 Okay, so we'll get going here, first off I'd like to thank Dr. Tessie for giving me a bunch of slides to adapt it from a lot of his biggest power points. So we're just going to go over a small topic like diabetic retinopathy. So, it's something we rarely see, but no, it's just pretty common. This is bread and butter retinop. You know, it's a relatively large section, it's almost a whole chapter, and because it's pretty important and it's getting more and more prevalent. So, we'll just get started. Here's my disclaimer, I'll leave it up for a second. These are my views. The Department of Defense had nothing to do with this. So just a few facts about diabetic retinopathy. First, it's more common in type 1 than type 2 diabetics, and it's the most prevalent cause of legal blindness in younger people. The factors for diabetic retinopathy are duration, and these are both from the Wisconsin Epidemiologic Study on Diabetic Retinopathy, or the WSDR. So there's a bunch of studies which we'll all go through, and I've got slides for each one of them, but the studies are kind of a large section of this. So we'll go through each one individually. But after 20 years, 99% of type 1s will have diabetic retinopathy, and 60% will have diabetic retinopathy of type 2s. And then, if you look at, after 20 years, 50% of type 1s will have proliferative diabetic retinopathy, whereas only about a quarter will have it after 25 years for type 2s. And the important metabolic control is obviously a big risk factor, and there are all these other risk factors, pregnancy, hypertension, which was shown by the UKPES study, nephropathy, obesity, andemia have all been shown. And feel free to stop you with any questions, just raise your hand or say, excuse me, or I'm just going to kind of keep going through this. So the pathogenesis, all these things lead to endothelial site, endothelial damage, and pericyte damage, which is kind of the end game, and then you get these vascular occlusion events. So increased platelet adhesion, there's erythrocyte aggregation, abnormal lipid levels, local upregulation of VEGF, viscosity problems, there's a huge inflammatory component to diabetic retinopathy, and then you get local abnormal levels of growth hormone as well. So all of those end up causing significant damage, and that leads to the entire process, so that these are kind of the very first steps that you get with hyperglycemia, and these end up causing the damage that then starts the whole cascade. So then you get this microangiopathy, which is you get the loss of pericytes, or what regulate and keep the endothelial cells healthy, keep them functioning well, keep the blood red in the area or blood brain barrier intact, and once you lose those, then the endothelial cells can proliferate, become abnormal and leak fluid, you can get thickening of the basement membrane, and then you end up getting these occlusion events on the capillary level. So you get capillary occlusion, and then once you get these occlusions, then you start to get AV shunts, which is what you can see with internal microvascular anomalies once they get severe enough, but before that you'll even have small shunts that are obviously not noticeable. You'll get capillary dilation in areas that still have good capillary function, and so you'll get some shunting of blood so that you continue to get normal blood flow from the artery to the vein, and so those capillaries kind of take up extra responsibility, which can lead to leakage of fluid. And then you can get new vascularization, which is kind of the end game for us, where you get new vessel formation due to anti-geogenic factors. You can get it on the disc, you can get it in the retina, and then you can also get these shunts in the anterior segment, as you guys all know. So what causes vision loss? So capillary leakage of macular edema is a huge reason for vision loss, okay? And so that's probably one of the most common causes of vision loss in diabetic retinopathy that's mild to moderate. The severe vision loss is less associated with macular edema, excuse me, and more with macular esteemia or sequelae from proliferative diabetic retinopathy, but the number one cause of vision loss in diabetics overall is going to be macular edema. And that's what we see at the VA, we see it here, and that's what we're treating most of the time. And why do we use so much abasin, recentesin, IVF? So you can also get capillary occlusion, which is going to cause macular esteemia, and just that ischemic process will cause vision loss. And that is irreversible, so that's a big thing we try to avoid. And it also tells you whether or not you're going to respond to anti-veget therapy if you have corresponding macular edema. It's how much ischemia they have, because that's going to limit their final visual improvement, even if you can get rid of the edema, excuse me. That also causes diabetic papillopathy, the capillary occlusion. And then you've got your sequelae from vascularization, which is mostly surgical in nature, and you have your vitreous hemorrhage, which is probably the most common cause of severe vision loss in diabetics. And then you have your tractional retinal detachments, and also neovascular glaucoma can cause significant vision loss, so your neovascular complications there. So for classification, you all know it's non-proliferative diabetic retinopathy, what also used to be termed background diabetic retinopathy, so you see PDR a lot, but the technical term should be non-proliferative diabetic retinopathy. It's more specific, and then you've got your mild, moderate, and severe, very severe categories, and we'll go into each of those, what defines each of those, and then at the end we'll talk about the follow-up based on the different forms of diabetic retinopathy, which makes a difference in how often you see these patients. And then proliferative diabetic retinopathy, and the most common terminology is low risk versus high risk. And we'll talk about the study that that came out of, and what constitutes high risk versus low risk, what constitutes treatment, thresholds, and things of that nature. Questions so far? I just want to make sure. So non-proliferative diabetic retinopathy, the microvascular changes are emitted to the confines of the retina, otherwise they would be proliferative with new blood vessels growing into the space that they're not supposed to be. The characteristic findings most commonly you'll see microangerous, and these are typically the first things you'll see. And doppelgut hemorrhages, you can get retinal edema, heart exudates, dilation, and beating of the retinal vessels, which at first I didn't know exactly how to see, but that's what you've seen some, because it's pretty obvious. Interretinal microvascular anomalies are ERMA, neurofibrillary infarcts, and then capillary areas of capillary non-proliferation, which are really best seen if you have a fluorescein. Sometimes you can tell there's areas that are non-profused, but the fluorescein is the best way to see that. And then again, it can affect, either through macular schemia or macular edema, the vision. This is obviously the most common form of diabetic retinopathy is non-proliferative. So for mild non-proliferative diabetic retinopathy, they really only have scattered microangerisms. Some people would debate and say they can't have maybe one or two doppelgut hemorrhages if you see them, and they're very small, but the classical teaching is that its microangerisms only will be mild diabetic retinopathy. And then if they have microangerisms and doppelgut hemorrhages with more than 20 of both of them combined in any field, that would be considered moderate diabetic retinopathy. So, for a while they used to count these things. I don't know, I didn't go to residency. It's pretty hard to classify some of these based on who they are because you can't sit there with a stare and count. You sort of get a gushall feeling by looking at it, and that's from practical standpoint. But yeah, if you do a good diabetic series of photos, you can read them and then probably go to the classifier. Basically, if there are a lot, I usually say moderate, or if there are more than one or two doppelgut hemorrhages, I'll call it moderate, if there are few doppelgut hemorrhages, I usually just call it mild. Kind of as a practical if you're doing an exam. And then the severe, that's the 4-2-1 rule. And again, we'll talk about the study that came out, we'll go through it again here. If you have four quadrants of diffuse MAs or doppelgut hemorrhages, so basically everywhere you have a lot of diabetic retinopathy. Just background stuff. If you have two quadrants of venous beading, or if you have one any intranetal microvascular anomaly that puts you in the severe category. And it's very important to look for those features. So really, you're looking for a ton of background retinopathy. You're looking for venous beading, and you're looking for intranetal microvascular anomalies and neobascularization when you're doing your exam. Because any of those are going to put you in a category where you have to be more concerned about the patient. And again, we'll talk about why, but it increases their likelihood of progressing to proliferative significantly. And then very severe, obviously, if you have two of those criteria, they're at extremely high risk. So severe, it's about 15% will progress within a year to proliferative. And with very severe, it's 45%. So you've got to coin flip if they have very severe retinopathy that they're going to have proliferative retinopathy within a year. So now we're going to macular edema, which is a second part of the non-proliferative diabetic retinopathy. And some important definitions. Clinically significant macular edema came out of the ETDRS study, and we'll review all the criteria for what's considered CSME. And that's used mostly for, it was used for studies, and until more recently and now they're using OCD criteria, which will be the center of all the macular edema. But initially, that's what it was used for, and then also it was used to guide treatment for laser treatment. Okay, it's not so much used to guide treatment for AFMFGF. You typically use a central involving, a center involving macular edema criteria. So that's based on OCD, if the phobia is thickened or not. So you'll hear us talk a lot about whether or not the center is involved as to whether or not someone will be treated. So we're not just saying if there's any swelling, you have to treat it. It depends on where it is, what their vision is. Whether they have agitates or not, because that'll change your paradigm on whether or not you're going to treat these patients. So then you've got two other terms, focal macular edema and diffuse macular edema. And that's dependent really on floor scene criteria. Okay, so if you look at these patients and you do a floor scene, and I'm sure you've all seen enough floor scenes now, that you can, sometimes you'll be able to pick out individual microangerisms in the beginning and then they'll leak late. And other times it just seems like everything just kind of starts leaking. And that's the difference between focal and diffuse. Okay, and it's a floor scene criteria. And it really decides if you were to do laser, what type of laser you're going to do. Okay, and we'll talk about the different types of lasers as well. Questions so far. So macular edema treatment. So you've got your pharmacologic, which is our most common. And you've got your anti-vegeta medications there, including macagin. Although none of you have ever seen macagin used, either of I. But it was, well, I did it in med school. I don't know who sent us trials, but not used really by anyone that I know of anymore. It was the original VEGF inhibitor. And it inhibited only one isoform, which is VEGF 165 alpha. So not something you need to know. But it was much significantly less effective than any of the other compounds. So once Lucentus was approved, or Ranobismab was approved, macagin use dropped and pretty much isn't used anymore at all. And then you've got your corticosteroids. And you've got Intervitural Triaxilone, which in the U.S. we use triacids unless you want to wash analog, which you can't do. And then you've got your dexamethasone implant, which is the Ajadex that most of you are familiar with. And then there's a new one, the Flucininide implant, under 90 micrograms, and that's Aluvian. And that was approved for DME. And at this point, that's all it's approved for. So they're working on getting approval for UVitis. But right now, the approval is for diabetic macular edema. And interestingly about this, it's the only medication that hasn't, or it's the steroid that has an indication that you can't use it unless you've already used a previous another steroid. And they have to have a documented non-steroid response. From insurance? That was the FDA approval. So the FDA approval states that they must have had a steroid and not had a steroid response prior to using the UV. And does it last longer? It's 36 months. So it does. It lasts much longer. So it's a non-biodegradable and biodegradable? Yeah, so it's a little teeny plastic. A fraction of the size of the body? Yeah, it's 1, 2, maybe 1, 10, besides project S. It's teeny, teeny. But it doesn't biodegrade. It just sits there. It's plastic. Usually it's pretty difficult to understand. I've only used it on one patient. I'm very impressed with it. But for me, the criteria for that is usually people who have responded well, say, on your necks. But I'm repeatedly having to do them every three months. They do okay, but it's another object. So it's okay. It's going to work well in them. Let's try something that's a long duration avoidive direction. That would be your primary. You're never going to use it initially. It's about $10,000. Yep. So in the long run, it, you know... You're not likely to get insurance companies to okay it unless you've shown them a good response. I remember. You just injected the... Yeah, it's got a little injector just like on your necks, except smaller. That's like 27 gauge, I think. Yeah, I think it's 27. It's a tiny little thing. It's very hard to see. If you load this, you push it up into this little window, and you have to make sure that it's in this little window. So I guess I've got something to unload. Because you're never going to see it again. Yeah. Seriously, once you inject it in the eye, and then it's very difficult to see in the eye, because it sits over the parts of the eye, and it's very small. So it's in there. Yeah, you got to assume it's in there pretty much. And the effect takes longer to kind of come on because it's a very slow release. So a lot of... At least from a practical standpoint, a lot of people who have used it have said that they need to treat continuously with anti-veg F, or with some other medication, while the effect is taking on over a couple of months. Whereas Oz, you'd actually get a response within a month. Olivia, it's like three, four, or six months until you're kind of reaching the maximal response that you would expect to get. Sometimes it will get worse when you transition into Olivia. At least that's kind of the dogma right now. But it's pretty early. You know, a lot of these are just being put in. So we, you know, other than the study patients, we don't have good data over the long term of how the, you know, how macular nema does with Olivia. But it's exciting to be able to, for some of these chronic patients who are constantly getting injected on poor sugar fat, who don't have any problems with getting in Oz your necks or trying to send them to go ahead and put this in. You know, have them be able to have some long-term effect. And then you've got your laser, and you've got focal laser and grid laser. Okay, and the difference between focal and grid is whether or not you're targeting focal enema or diffuse enema. So focal is you literally are shooting and you're trying to whiten them slightly, which over time will allow them to stop leaking and it'll clot them off and then the leakage will improve. Whereas grid laser, you're just creating a grid in about one half to one spot in spacing between them, and they're about usually 50 to 100 micron spots in the area of edema. And you're just saying, I'm just going to grid the whole area. And focal has been proven to be more effective. So if you can do focal, you should be doing focal. And if there's really nothing to target and your patient really, really, really wants laser, then grid's a fine way to go. But focal's more effective in treating regular enema in the long-term. So now we'll go into proliferative diabetic retinopathy. So proliferative diabetic retinopathy comes in four flavors if you can, you know, or proliferative eye disease or diabetic retinopathy. Neovascularization of the disc, NVE, neovascularization elsewhere, NVE, neovascularization of the iris, and neovascularization of the ankle. So those are the four types. Neovascularization, excuse me, neovascularization of the disc is defined as neovascularization within one disc diameter of the disc. So even if it's not directly touching the disc, within a disc diameter of it, that's considered neovascularization of the disc. That's important because the criteria for when to treat are based off size and the sizes vary between neovascularization of the disc and neovascularization elsewhere, whether you have ventric hemorrhage. And again, we'll go into all the studies which I'll tell you about the treatment protocols. So, the PDR has multiple stages. So, extra-retinal fibrovascular proliferation and first you get neovet blood vessels with just kind of a very minimal fibrous matrix that they have to grow inside their extracellular matrix. And then you get increased size and extent of these vessels and you can even get pericyte formation on the vessels where they're more mature and then you'll get more fibrous tissue and more extracellular matrix coming in with those. And then eventually you usually will get regression leaving that fibrovascular proliferation and you'll get contraction which is what can cause retinal attachments and ventric hemorrhages as that's contracting you can care those blood vessels of your ventric hemorrhages. So, that's the most common pathway there at those three stages. We're going to keep that with me when we're seeing in the operating rooms positions of extraction blood vessels to be bigger than the mobile blood vessels massive. Yeah, we had one that we were dissecting for an hour because we thought it was a stock coming up with a all along the superior arcade because there was just this vessel that looked exactly like the arcade that was running in the exact same thing and finally when we got to it and we figured out that the retina was actually down below it it was a vessel that was definitely larger than the arcades. So, they can get pretty robust over time and very mature normal-ish blood vessels even though they're in a wrong location and it's tough to tell because you've got all that fibrous posterior highway and so you can't see underneath it so you don't know if that's a retinal vessel or not. So, here's kind of some typical pictures of PDR, you can see just a little bit of de-abasterization of the disc and then some de-abasterization of the disc with some fibrosis there on the right and then in the middle you've got a couple more areas of de-abasterization elsewhere and then you've got some de-abasterization with some fibrous tissue and then you've got mostly fibrous tissue down in the bottom right where you get that tractional appearance and that is what lead to tractional potentials. Okay, is that really fibrosis and you get this a lot of contraction. So, treatment, what do we do for proliferative diabetic retinopathy? Well, still the treatment paradigm is laser. Pedernal photocoagulation was created or was performed first in the diabetic retinopathy study or at least validated first in the diabetic retinopathy study I should say and they used greater than 1200 spots 500 microns in size and separated by one half burn length was what they were trying to create. It destroys the ischemic retina which decreases demand and it increases oxygen tension from increased diffusion. So you actually can measure the vitreous oxygen concentration and it goes up significantly locally over these areas that you do laser on and so you get better diffusion from the chloride because you're taking out some of the RPE, you're taking out the overlying retina so it allows it to diffuse and then also there's decrease of demand in that area so that all of that ends up translating into decrease angiogenic factors which will allow new esterization to regress over time. And the DCR seen that noted that there's no statistical difference between single session all 1200 spots or multiple session PRP. Now obviously if you're using like a pattern scanning laser 1200 spots is not going to be sufficient. One your spot size is not 500. Normally if you're doing PRP you should have a 200 micron spot size on the laser because most PRP lenses are around a two times magnification so you're going to double the size so if you're going for 200 because you can't usually set 250 then you're going to get about 400 micron spot size so you figure you have to up the number of spots a little bit and then even with that they've shown that the pattern scanning is a little you need a few more spots probably because some of them aren't taking because you're using if you're using a multiple spot pattern you've got nine if you get seven takes you're going to feel like that's pretty good but you know 1200 spots you're going to be short to 300 or 400 spots The reason the 500 micron in fact in the DRS there were no like broken stock white I would like to name it because that was a three mirror lens so it was a direct so instead of 500 it was a 500 micron spot so there was no magnification effect like now we have this inverted wide angle lenses so So bottom line is that's what you're looking for somewhere around that level and then obviously if you're using the you know the usually I see that the Pascal is usually set to 100 microns which is fine if you want to do that you can do 100 micron spots but you're going to have to do many more you can figure that 1500 is total PRP that's not even near enough you know you probably have to get to 2500-3000 shots so sometimes you'll do that though if patients feel it if you decrease the spot size you can decrease the power and the duration quite a bit and they won't feel as much so sometimes you have to do that but if I can I usually start with a 200 spot size and then you've got your pharmacologic your anti-vegetary treatments and protocol S from the DCRC that noted non-inferiority to PRP and in some instances questionable superiority although that's you know I think debatable they're using area under the curve for visual acuity so they looked at patients who had DME and who didn't and if they had DME if you took the vision area under the curve they did better so they did somewhat better but never statistically significantly better over any time point but if you take all the time points together and add the area under the curve you can see the visual significance so the question is is that clinically significant to patients if they're seeing one or two letters better every visit it never meets that statistical criteria for the individual visit and so you know some people say yes that's absolutely significant and that's quality of life measure over the entire study and others say you know what you didn't ever show that any time point was better so question will bear but they did also have a decreased rate who had the anabism at as opposed to those who have laser so it was I think 6% or 7% versus 18% so they had a significantly decreased risk of needing the track to meet for for the patient but the basic of the study was that it was non inferior they didn't really prove any superior but there were certain criteria that they said well it seems like maybe it's superior in this aspect or this aspect but definitely not a bad option especially if someone has concurrent DME it doesn't you don't necessarily have to PRP right away you can say I can treat as long as they're going to come back I can treat for a few months with anti-fedge F then new vascularization will regress at the same time I'm treating the DME and then down the road we can do PRP and the reason that's important is because it's been shown to increase macular DME in both the DRS and the NTDRS studies and they they did vocal before PRP or simultaneously in those studies and showed that it decreased the rate of macular DME and transient vision loss so you get a transient increase in CME in DME when you treat with PRP especially if you do a full session where they said that they were equivalent doing a full session and separate sessions but there was kind of a sub-analysis that showed that doing multiple sessions you might get a decreased risk of transient vision loss but over the long run it doesn't affect visual acuties in any way it's just a short-term short-term spike in macular DME so again if you can't wait for PRP you can treat with they said treat with focal grid and do some PRP or treat with anti-fadge F agents and do PRP in a week or two weeks simultaneously if the patient can talk to you Questions about that? Okay Maybe I'm just that boring I don't know So surgical management of diabetic retinopathy this way it gets us excited you know indications for an atractomy non-clerin vitreous hemorrhage anything greater than one to six months and that was shown by the diabetic retinopathy study that patients did better especially type 1 patients with early vitrectomy as opposed to waiting greater than six months or even greater than a year so they determined that it's superior to not we need that wrong if they have a tractional retinal detachment that's involving or threatening the macula if there's a combined retogenous tractional detachment then you definitely need to do something recurrent vitreous hemorrhage despite maximal PRP we see that reasonably I'm sure all of you have seen plenty of people who seem to have as much PRP as possible and have been seeing us for years and they come in with hemorrhage every now and again and if it doesn't clear it's certainly a reason to go ahead or if it's just happening frequently enough that it's bothersome and then usually you can find some areas to do a little more PRP but even if you can't they've shown significant decreased time of VEGF sitting in the eye with vitrectomy so you're going to remove all of the antigenic factors that are likely causing these little tufts to be there and you're going to take any traction off any remaining tufts so it can definitely decrease the rate and they also think it may improve macular hemorrhage I think that's a lot to do with it when we do vitrectomies it's rare that they have vitreous detachment, most of these diabetics they're eye ones pretty well and even in eyes that have had a lot of PRP and there's no obvious VEGF causation when you're in the operating room when you're getting the vitreous off the retina it's very common to get a little hemorrhage or probably a little larger rest areas of neopathy so it's probably what's happened in clinically vitreous kind of pulls the hemorrhage properly even though there's not a lot of obvious evasperation on the exam but there's still vitreous attached there sometimes it's very anterior sent through so you'll get decreased you'll get decreased VEGF as well in the vitreous so you can get some of those blood vessels or even the macular through because people worry about the anti-VEGF being washed out with her but more than anything it's actually the VEGF itself that is allowed to clear faster because it's not sitting in the vitreous and they've shown some good studies of significant decreased VEGF levels after protracting and then if they have go-cell glaucoma that's a indication for having you seen go-cell glaucoma before I've seen several most of the time people don't let vitreous hemorrhages go that long but even small hemorrhages that have settled can end up giving somebody go-cell glaucoma and you can really do you can kind of see these khaki cells that are floating around they've got this vitreous hemorrhage and their pressure will be 40 so it's pretty interesting for board purposes that's the buzzword if you say khaki colored cells that's what it is you can just find go-cell glaucoma if you don't have to look for anything else there's nothing else that's going to ask you that has khaki colored cells okay and then NVA, NVI without the ability to perform PRP sometimes people have such bad neovacerization of the iris that they just don't dilate any PRP and so that would be an indication to take them to surgery open that up do full end-of-laser PRP after you're done after the treatment and then if they have a dense cell highway hemorrhage like this guy then you would consider it because that's going to not clear for quite a while so you may have fingers vision for a year any questions about any of those facility on the the second bullet from the bottom you're now going to anti-vedge after a lot of these NVI's you can temporarily clear it pretty well pretty rapidly actually on the bastard injection still in the long run you can get a PRP and that's what what do you think Dr. Teske about there are some people that I've seen or who advocate doing anterior chamber a bastard or anti-vedge instead of vitreous if they have I have not injected the anterior chamber you get a response from injecting the viscous cavity I mean the jet was probably coming from the posterior segment anyway so I don't inject the anterior chamber you get a response from the viscous cavity yeah I've just seen some people talk about doing that you know I haven't seen it happen I figure the clearance might be too quick as well alright now on to the studies this is the fun stuff okay these are the studies that you need to know the last one it just got put in this year and it doesn't have a section on the studies it's just kind of in a lot of the macular demon a few other places they just kind of talk about protocol B protocol D so we'll go through the protocols and discuss and not any others except for protocol S they did not they said protocol S is in enrollment and they've enrolled 305 patients so as they created the book they hadn't had any preliminary results from the PDR with only anti-vedge F which is protocol S but the other ones you definitely need to know the DRS the U.K.PDS ETDRS DCCT and the DCRC so it's a bunch of letter madness word salad stuff but and those are the dates that those trials were initiated those are not the dates they were completed the U.K.PDS wasn't complete until 2008 2007 it was a 30 year study which is pretty awesome you don't get very many ophthalmology studies that are longer than a year or two years so we can get anything out five even ten years we're doing pretty well and that's been one of the major complaints about ophthalmology until more recently is that the studies weren't there for a lot of the things we were doing and we just had small or retrospective or very small randomized controlled trials for a lot of the things we're doing but I think we're getting better with that and especially I think in retina we're getting better with having better studies for some of the things that we do and we'll go through each one of these individually and we'll go through what they were and what the results were so you don't have to write it all down right now so the diabetic retinopathy study what was it so it was one of the big question was is PRP an effective treatment for diabetic retinopathy so what they did was they did PRP to one eye of patients with advanced N-PDR or who had PDR in both eyes they had 1700 patients and then they followed them out after they did full PRP in one eye and why I observed the other and they saw a 50% decrease in severe vision loss over five years so PRP doesn't eliminate vision loss so you definitely need to consult patients when you're doing PRP or when they have PDR that no treatment is going to eliminate the risk of them having a vitreous hemorrhage needing surgery, further vision loss down the road, macular ischemia macular D-my-mean you know it's not a treated PRP and you're good and bye bye and they need to know that especially for the type ones because they're 40 years old they're 35 years old and you know you're going for 30 years and they'll probably be blind at some point it'll probably continue to progress they'll get continued macular ischemia and they'll end up being legally blind if they have bad PDR and early macular ischemia in their 20s or 30s so you've really got to get home control your sugars because that's what's going to keep you seeing for as long as possible okay so DRS said that high risk PDR was if they had mild NBD with vitreous hemorrhage moderate or severe NBD with or without vitreous hemorrhage so that's one third to one quarter of the disc area there's a standard photograph standard photograph 10A which is they said if it's more than this it's high risk if it's not more than this it's not high risk and this is kind of what they decided was treatment criteria with these it was the high risk PDR patients that did the best with the most decreased rate of severe vision loss okay so or if they have one half a disc area NVE with vitreous hemorrhage so if they had a huge NVE with none they didn't put them in this category although most people these days would treat that but based on this study this is what they decided and that is those are important to know in terms of NVD with hemorrhage or large NVD without hemorrhage or NVE with hemorrhage or treatable PRP that's a test very testable question or if they have three of these so if they had basically you could not have any vitreous hemorrhage but if you had neovascularization of the disc and moderate elsewhere you would meet the criteria so if you had both NVD and NVE you would still meet criteria for PRP even if you had no vitreous hemorrhage does that make sense questions about that that's kind of a big thing that came out of the DRS they validated PRP and they gave us the criteria for high risk PDR which is the criteria for treatment of PRP so you can think of the DRS almost exclusively in terms of what questions they can ask you about it as a study that validated PRP and gave us criteria for treatment okay that's really about all you need to know about the DRS next one is the DRVS diabetic retinopathy vitrectomy study so they looked at patients with severe vitreous hemorrhage and those with very severe PDR without vitreous hemorrhage and they said it's early vitrectomy between month 1 and month 6 preferable to deferral for a year or more in those eyes and so they determined that type 1 had a clearly demonstrated benefit for early vitrectomy type 2 had no benefit from at least statistical significance benefit in terms of visual curies and then they also clearly showed that early vitrectomy for patients with very severe PDR without vitreous hemorrhage it was still beneficial to do vitrectomy with type 2 no we didn't I mean it wasn't that large of a study and there was a trend but not a significance the only thing to take away from that really is that you don't want to delay vitrectomy in type 1s generally now they're not clear within a month whereas sometimes in type 2s you can give it in type 2s you know it's there it's clearing a little bit they don't get in as much trouble with type 1s maybe you could try to get a little more clear no one would object it the studies were done this was earlier days in the track everything was 28 years a little bit more you have anti-vegeta agents that help them this is what they're going to test you on but this is not necessarily how the press works we had no treatment until we could get a little bit more clear so you have somebody who has vitrex hemorrhage if not have PRP how long you give them clear before you get laser if they already have laser you feel more comfortable quickly so that's why you don't delay but nowadays we might inject them they can clear so there's other options that's what the DVRS study showed however yeah pretty much if anybody goes a month or two without clearing most of the time unless they already had a small PRP and we're just kind of sitting on them most of the time we're taking them to attract me if they're not clearing at all we can't get more laser and you kind of either have to try to string them out with injections or you have to take them to surgery so most of the time if it's a couple months we're taking them to surgery but certainly in type 1 if they've had no laser you're waiting a few weeks maybe a month and then you're saying it's time to clear this out and get laser in before they have a more fibro-bascular contraction but this is what they'll test you on the DVRS showed apps showed that if you're attracting it's good for type 1 and type 2 type 1 only, type 2 only that's what it's going to be so there's some PR that will be funded to work on it so the ETDRS had three major goals compared early photobagulation versus deferral of treatment who had basically NPDR or early PDR so they're trying to say is earlier treatment and what the DRS showed beneficial then to evaluate photobagulation focal laser for divert macular hemat and determine the effects of aspirin so there were 3700 participants that's not real I don't think they're going to ask you how many people are in any of these studies but it's technically in the book so it's technically fair game but it's not a minutiae I would remember but knowing kind of the inclusion, exclusion criteria who they were, the population they were treating is probably important so knowing that it's patients who didn't treating them didn't improve and then the macular edema so they had to have relatively good visual acuity and then they were randomly assigned so they defined that 421 rule for severe, very severe so that's important to know that's from ETDRS and they also defined clinically significant macular edema or CSME so those are two questions that are absolutely fair game and then their findings they were finding they talked about the progression risk to PDR so that's that 15-45% for severe, very severe within a year they did show that early PRP reduced the risk of severe vision loss focal definitely improves visual outcomes and improves retinal thickness so they defined CMME and validated that focal works for it they showed that early PRP is somewhat beneficial earlier than the DRS criteria but there were also down, they said you have to balance that with the downsides of decreased night vision that sort of thing and then they talked about how likely it is to progress and that kind of guides how often we see a lot of these patients as how likely they are to progress to PDR and need treatment so questions about that so I know that's a lot but that's really, if you know that slide you're good on ATPRS so again, severe PDR 15% chance of transition to PDR within a year very severe 45% chance they said early photo-quigulation is not indicated for mild to moderate and PDR but they said, you know, severe is kind of where you're saying maybe it is but there are a lot of downsides so but they said definitely for mild to moderate it's absolutely no go and then, again, they showed that mildly reduces vision loss in early PDR and severe or very severe in PDR that last bullet mostly type 2 guide that's been exactly so if you have something severe in PDR or early PDR it doesn't meet the DRS criteria for PDRP justify doing PDRP in those eyes especially in a type 2 guide there's indications that it will be beneficial but it's a matter of side effects versus careful follow-up but you can, a lot of people do they've already had one for the busies in one eye and they got severe or non-moved in the other eye a lot of people start treating the other eye and if you guys do a fellowship and you have a county hospital that's probably what you do we were treating a lot of severe and very severe in PDRs because they would come in and they hadn't come in for five years and they're probably not going to come in ever again, maybe so if they're there we do full one session PDRP we usually just do a retrobar block and then that way it's comfortable put in 1,500 spots in 20 minutes and be done with it it was just something they found they said that type 2s seem to do seem to have improvement whereas the type 1s really don't get a decreased risk of severe vision loss just kind of a subset analysis they said well it seems to kind of work so and then they define clinically significant macular dima this is absolutely testable so thickening of the retina within 500 microns in the center it should be hard exudates within 500 microns if associated with the thickening adjacent so even if the thickening is not within 500 if you have exudates within 500 associated with an area of thickening and then lastly a zone of thickening with a disc area ok so if you have a disc area in size within a disc diameter if you have 500 microns or exudates within 500 with thickening any questions about those it's a lost skill because it was all based on you know still not biomicroscope and funnest contact lenses and honestly with the 90 lens for field lenses it's not nearly as easy funnest lens on but real contact lens you can see this stuff a lot better for a practical standpoint we do with OCTs now we just don't use this criteria much anymore but it's still fine so don't be tempted by people ask you to go on OCT it's actually a significant macular dima OCT doesn't define it it's center involving if it's OCT remember the definition so but this is an important skill and if you can if you can know it and try to look for it before you look at the OCT you can really improve your skills because you can say I see thickening or not and where you see it and see if it corresponds with OCT it's kind of fun it's a good skill to have because it really makes you look and kind of assess how well you're able to see things so there's a local reduced CME for risk of moderate vision loss it also increased the chance that they would have improvement and it reduced retinal thickening so again it just showed that it worked so they defined C as a mean and they showed that focal worked in a 4-2-1 rule and progression and aspirin was worthless except for reduced cardiovascular and more talent so it doesn't affect diabetic retinopathy but it's a good thing for patients to be on their disease DCCT type 1 diabetics this is DCCT and UKPDES are relatively similar except for their patient population type 1 diabetics done in the US diabetic control and treatment complications trial does intensive control of blue glucose improve progression and slow development of retinopathy and the answer is essentially yes okay so that's where this comes from they had an intensive versus regular insulin protocol and intensive significantly decreased the risk of development 76% progression by 54 and decreased the risk of nephropathy albuminuria album albuminuria thank you and decreased the risk of needing treatment okay so basically blue glucose control works UKPDES similar except much larger study much much longer but showed they had 4200 patients with type 2 diabetes the other thing they looked at was hypertension in this study and that's where we get one of the big risk factors for progression of diabetic retinopathy is hypertension so intensive sugar control reduced development and progression of retinopathy and control of hypertension also reduced development and progression of retinopathy didn't matter what you used and they used all sorts of different regimens in terms of treating patient sugars but as long as they treated them well it didn't matter DCRC net this is a large group of academic and private practice centers they do multiple programs that are developed by clinicians we jam poles kind of ahead of this thing and they claim that it's more of a real world setting because they're doing it over a large multi center populations private practice patients academic center placement but it's still not in a study so it's not really a real world situation and that's one of the big downsides of the protocol as study and we'll touch on that very briefly so they have a lot of protocols but I'm going to go through the ones that they talked about so they briefly touched on the protocol B and they macular demon treated with focal versus triumphal and visual acuity was better earlier on in patients who had triumphal but it was better at two years for patients who had laser and that was after you factored in if patients got cataracts even then they still had improved outcomes from laser versus individual triumphal but they didn't look at any other steroids so this is just is laser better or worse and they weren't that much different but and in pseudo-painting patients it was almost identical but for those who had got cataracted in Guacoma protocol I was treatment of macular demon with ranivizumab and prompted deferred laser versus those who got try and synolone and proc laser basically they showed that ranivizumab or lucentus or the antivegaphs you can expand it to all of them if you like showed it was superior to either to laser or laser with try and synolone so bottom line antivegaph should be your first choice for macular demon okay protocol T was the comparative effectiveness of a flibrasep bethizumab and ranivizumab and this is why now you can typically generalize most of the previous studies that were done with lucentus they improved medication for by a while for treatment at DME and they all had similar effectiveness except if you subset it out patients who had 2050 vision or lucent baseline they did two letters better on the ETDRS chart than those who got ranivizumab or bethizumab okay but otherwise statistically no difference between the three agents about one year or two years and now still at three years okay and then protocol D there was a case series of patients who had vitrectomy and PVD creation for DME and I mentioned this because sometimes we do this especially Shakur talks about doing this a reasonable amount and the other attendees as well for those who have refractory DME or who have an epiretinal membrane especially to do vitrectomy and they showed retinal thickening reduction but they didn't have any visual cue to change for those patients who had the term to be protocol P showed that patients with NPDR and cataract surgery had a risk increased risk of CME compared to controls and then protocol Q was very similar patients who had DME prior to surgery so these protocol P had no DME protocol Q had DME prior to surgery and it showed that both had an increased risk of worsening DME or CME depending on what you think the etiology is after cataract surgery so it's routine it was pretty routine at this point if someone has pre-existing diabetic macular edema to give them a peri-operative treatment with anti-veg F even if they've had a history of DME some people will choose to treat them even if they're not currently inflamed because there's a pretty good chance you can see that half of eyes had no visual acuity improvement with cataract surgery due to macular demon worsening you know and that was only in a couple months and you know at the long term it may have gone down to baseline again but you're definitely going to be treating those patients so treating them right before they don't meet before surgery is a reasonable idea to decrease that and then protocol S which we talked about was randomism app versus PRP okay and randomism app was non-inferior it may have improved visual acuity if you look at area under the curve and there's a decreased rate of a chronic ventrectomy okay the downside and you know one of the big problems or issues with this study is follow-up okay in a patient population even in the study where they were they had to study coordinators calling these patients they you know had them all set up they all were getting you know they all had insurance okay they still had a 10% drop out rate in two years so you can imagine somebody with PDR if 10% of the best patients the most likely to follow up patients are dropping out your rate's not that good right so real world so real world yeah they had to come in every month they got photos every single month and they compared the photos to previous photos to see is the PDR worse is it the same or is it regressing and then based on that they would decide to treat or not and I think the first year they got an average of about eight or nine treatments and then over the second year they got about four I think if I remember right four or five so they got they definitely got fewer treatments as they regressed the problem is is they're still coming in every single month and 10% of people didn't complete a two-year study so if you got you know multiple diabetics in their 40s and 50s and 60s you can imagine there'd be a lot of people walking around with PDR we're not going to come back in a real life situation the biggest concern about this is the practicality of implementing this compliance and then the cost you know monthly rent is pretty quick even monthly a vastness is going to be as pricey as PRP at the moment for these young patients so so right now it's not a lot of times we're treating patients with P and B for a significant regression of their PDR and all these patients are getting six, seven treatments in the first year so their PDR on their arrest the biggest question I have is when you stabilize them do you need to head PRP at some point or do you need to be gone now do you want to bring it back with PRP possibly six treatments or seven treatments so there's the recap for the studies and we are about finished because I know it's about that time so that's the recap there of what these studies showed okay and then here's the recommended examination schedule okay so for first exam type one five years after diagnosis is when they should first be examined okay they don't need to be examined sooner than that so if you see somebody who is newly diagnosed tell them to come back in five years okay because these patients are diagnosed at the time they have diabetes right you don't have very many patients go two or three years with type 1 diabetes because they go into diabetic chioacidosis and aren't around anymore if they don't get the diagnosed but type 2s they can be 10, 20, 30 years you know pre-diabetic or diabetic or you know even significantly diabetic they should not have been diagnosed so at the time of diagnosis they should have annual exams at minimum and then if you're pregnant and they have a history of diabetes you should see them at least every trimester and that's if everything is good if they have severe or very severe NPR you should be following probably every one or two months so that's the difference and you know especially with type 1 diabetics now you see a lot of type 1 diabetics who are pregnant and you have to follow them much more closely okay and then the schedule on the other side is just kind of how we follow these patients if that based on their diabetic retinopathy okay so normal or minimal 12 months mild 12 months as long as they're pretty well controlled if they're not if they're A1C's 10 or 11 probably seeing back at 9 months maybe even 6 months just to make sure that we're having a little more engagement telling them they need to get in control stuff like that their rate of progressing to PDR in 6 months is minimal but it's more for continued follow up checking them for DME's moderates 6 to 12 months and again that depends on their control if they're very well controlled they've been moderate for a while 12 months or 9 months is reasonable they're not well controlled 6 months it's a good way to go severe you know 4 months ab at least failure 4 months and then non-hyrous PDR they say 4 months I'm not going 4 months I'm probably going more like 2 to 3 certainly at first if you are choosing to follow these patients and not treat them and then hyrous PDR they're saying every 4 months I assume that means they're treated and this is all coming from the annual guidelines and then in voluted PDR you can follow more or you can follow less frequently as long as they're not active and they haven't been active for a while so when you're first treating them you're obviously going to be seeing them frequently and then as they do better you can space them out further and further you can probably get them back out to a year if they have PRP 20 years ago haven't had any ventures hemorrhages or any other problems and they're all controlled but that's kind of the basis and that's why at the VA sometimes it seems like we're randomly deciding what people are coming back but mostly I try to go off that any questions for me sorry I'm a huge Calvin and Hobbes fan I think I end all of my presentations with Calvin and Hobbes I own like every single one of the books when I was a kid alright that's it