This being a date. I want you to tell me down below Something cool about yourself. What do you love about yourself? What are you interested in? What makes you interesting? Let me know down below question number one comes from Logan answer me Nicholas like TV damn, okay?  I like a girl That is genuinely nice She she's respectful of not just me but herself and to others Say we go out to dinner. She's respectful to the waiter if the waitress is nice to me She isn't get an attitude at the waitress I've actually had that happen as far as titties and ass goes you could be as flat as my death note Honestly, I really don't care as long as you have a nice face. I'm a face guy if anime was real Who would you choose as your wife?  That's the loudest But everybody thinks it's hot, but I think isn't but I think power is hot so that doesn't make sense your your forger She would be my waifu because she has that dark side, but she's also a sweetheart and you need to have balance in life I need you to be evil enough to kill somebody for me But I also need you to be like my my my cuddle partner. What's your favorite movie?   Why did I pick this question? I dated girls with hentai titties and then I dated ones that were like just the sidewalk Like they were that flat and honestly, I see no difference. So whatever whatever size is good for you for you It's good for me site Thomas. Well, why am I picking these questions?  I'd smash.  I love all the openings. It's my favorite anime opening Anime and rezero just has my attention Because of what you just said mental health and it's my friend's favorite anime of all time So I figure I should give it a chance. What anime animes are you most looking forward to for the 2023 season? All right. All right, so we need attack on Titan. I miss it so much I feel like I mean it is my first anime experience. I need it back and it's the final season part 48 number two one punch man season three knowing that map of might be attached to it that excites me and shichichu kaisen Jujutsu kaisen. I'm really excited to see what they do for season two I love these characters and I miss it especially with panda coming back I think there's something called solo leveling and then there's the Genshin impact anime. There's so many things I want to check out next year. We're gonna check out new things Maybe some sports animes who knows but I definitely want to check out more stuff Did you ever expect your anime reactions would do as good as they are doing and be able to make a living out of it? No, I was praying that it would work because I was living in hell in my mind Doing all of those k-pop reactions and Taylor Swift and Ariana Grande as much as I still listen to that music Oh my god It was torture man like going through different songs every single day keeping one fan base happy And you somewhat do that. I somewhat do that with an anime Like I gotta make sure I keep different parts of the fan base happy like the one punchmen fans Attack on titan fans the spy family chainsaw man the one piece like I have to make sure sometimes But I stopped doing that I started doing whatever the fuck I wanted to do and it seems to be working But I was praying it would work and it turned out it did work. So I love you guys. Thank you for saving my life Did it hurt getting that butterfly neck tattoo because it's literally on your Adam's apple Also, why is it there in the first place always was curious? It didn't hurt that much Surprisingly it felt like I was shaving You know like I had a razor blade. I was Going like this. I love butterflies And I I feel so egotistical at times. I'm like, you know what I need to change I need to be reborn and when I think of rebirth I think of a butterfly. So I'm like, you know what I'm gonna show everybody I'm changed I'm gonna show everyone I'm different. I want to be seen I want to be seen as you remember that kid with the butterfly on his neck like nobody's gonna forget that motherfucker So I said, you know, I'm gonna get it and I got it and here we are whenever the stream's coming back When I buy a house because I got noise complaints for doing no streams My videos are different because my videos I could record for 20 minutes to an hour And that's fine But my streams were different because it was like two hours three hours And it was on different days and it was at awkward times because y'all are on different time zones And I had to work with that but I have to wait till I get a house.  Is there an anime you thought was kind of boring? You know, you think I'd be afraid To say this because I might anger some people But you think I care there's one anime that I had a boring experience with at times, but in the end really loved Demon Slayer There were times in that anime where I was like Why is this so loved like I just don't get it like I hear everybody talking about it All my friends talk about it online. It's always trending. It's breaking movie sales and I was sitting there like It's good. It's all right But then as it progressed I understood and I know it's very Not controversial but debatable But I actually really love it. All right. I actually really Appreciate it. I have fun with it It's my demon slayer reactions on my chainsaw man reactions always get the dislikes always because I guess there's people in the anime community that see it as over hyped and over exaggerated like myself But whatever I I enjoy it Look look look look at my look at this. I have time. I have two tangeros I have a rangoku and I have a nesco chan And chat that oh like like are you serious?  No No, I've not I mean I've rewatched attack on titan two times. I've rewatched demon slayer um, I always rewatch the chainsaw man episodes chainsaw man's like my I feel like it's my personal favorite I know it might sound crazy to some people like this guy's favorite Animates or attack on titan and chainsaw man.  I understand bro. I understand I understand who I am in this fan base.   So I understand you guys, okay? But those are mine. That's what I enjoy the most and it will change. Maybe it will change over time So first tattoo why start to get in tattoos? Maybe some tattoos a meaning and explained by the way. Love your stuff I love your stuff riku first tattoo was this one 1995 in case I forgot what year I was born I was rapping at the time and I had a show my friend travis in la It was our first big trip.  It's a tattoo who cares? And yeah, that's my first tattoo as far as meaning goes I'm not like the believer that you got to get a tattoo because of its meaning You have to have a meaning for it. I just get whatever looks cool Like you think I got this alien head because there's a meaning because I'm an extraterrestrial and I believe in Intergalactic communications.  You see that channel art. Yeah They made it my question is have you emotionally recovered from chainsaw in episode eight because I know I have it No No, I have not ever since you once said I need a blunt for my react. Oh my god Where's this going? I wonder do you have like a really funny stoner moments? You like to tell oh you ever just do a vid for shits and smoke one.  So one day Me and my friend Travis you're gonna hear this guy's name a lot because Me and him go way back best friends forever. We did music together grew up together We're still talking we have group chats and I hope those group chats never leak So one day when we were like 18 19 years old, we decided to smoke some weed under our bridge We didn't know this bridge was a restricted area because we usually go here We just bring our skateboards. We just talk listen to music or we just rap freestyle under the bridge turns out the night before a girl was uh our worded down there And yeah, the cops found us under the bridge and we were arrested and I was high As a duck and I had a hoodie on and the cops wanted me to take the hoodie off And I had a I had a shirt on that said the high life I was definitely in the clouds that day because when I got home my mom. Oh my god. She Whoo, you know that wasn't funny then but it's funny now Do you plan on reading berserk? It's referred to as the best manga, but the anime adaptations suck apparently I never really watched it myself, but I never heard anything good about them either Besides the soundtrack, which you should check out sometime. I'll check out the soundtrack. God damn. Yes as far as a manga goes You should Stay tuned for a video I have coming up that will talk about my first manga experience I think you'll be happy.  I heard that or it's just not that great the animation in general For the animes. I heard I could be totally wrong. What do you guys think?  As your favorite anime. Oh my god. Those are fighting words.  So it's just these two kids, right? You have the firstborn child It's your firstborn. You love it to death.  It's amazing And you're not just being biased at times you probably will be because it's your firstborn And then you have your newborn baby, which is like me and my family. My brother was the firstborn But I was the newborn little bastard and I became the favorite That's exactly what it's like right now where chainsaw man is that newborn baby And I've grown very familiar with it. I could relate with denji a lot of us can I love the characters I love the animation the storytelling the action the depth of of the The character development everything the music Everything about chainsaw man is something I'm really loving and I don't see it falling off I see it getting better and better So I believe you when you say there's more and more shocking moments because that's how I see it every week It shocks me. I don't need a big death to happen Do you think you'd ever go to an anime con type adventure and do a meet and greet type thing with your fans? I loved anime nyc so much. I loved anime expo Especially when people came up to me and just knew me and they said My videos made their day that they love me that Oh my god, that was Out of this world for me honestly God, I love you guys so much. So yes. Yes. Yes. Yes to your question. Yes. Yes.  I said a question not a powerpoint presentation, bro I'm sorry. I got two and can't decide which one to ask so I let you choose if you even answer a single one I'm gonna answer both because I love you out of the anime.   I don't want to be like him similar question wish antagonistic or evil organization person Marley world government light yagami or l so you hate the most as an wish would truly gets under your skin To the point where you actually root against it more than any other That's a great question. Wow.  Whatever they're involved in Anime especially like in death note even in chainsaw, man.  I root against the government Every chance I get so the government are you working on your anxiety issues? You know, we love you, right? So don't stop believing in yourself You've got what it takes you will make a great streamer. So resume it We will support you all the way love from bangladesh.  I wouldn't be able to go to conventions And walk through crowded people Now I was fine I just act like myself. I had to learn that My who I am is perfectly fine And I didn't have to go about it the way I did where it took all of your love 800 000 plus of you saying you love me and subscribing to me It took all of that for me to love myself And that's the wrong way to go about it because it showed me that it's in me all along that I have the power For others to love me as long as I love myself as long as I'm myself. I don't have to be anybody else.  You're my favorite reaction youtuber. You're just saying that before I did my anime videos Like before february. That's when I started my anime journey on the channel I never edited Like you know how I do the zoom ins and everything I never did that I put on a Taylor Swift song. I do my normal intro. Hey guys Taylor Swift today. I love her and then I'd react to the song Say my thoughts outro done. No zoom ins. No edits. No jokes. I was just like Yeah That was good.  I love what I do I love that I include jokes when I do my reactions. I'm not forcing it I'm not cutting think it of a joke and like all right makima Uh wolf like I'm not like that. It's just it's it's just comes off the dome. You go on my patreon There's no cuts sometimes there are if I say a word that I shouldn't have yeah, but that stays in a group chat Some people say I miss things and I do it's a sacrifice. It's a sacrifice. I'm sacrificing missing or seeing all the details For entertainment and a lot of people won't like that or some people won't like that But I love it. It's personally what I enjoy doing. I love being different You know, I respect all my peers some of them I don't respect But there's a lot of reaction channels probably ones you watch they don't do what I do And I could proudly say that I could confidently say that they don't Do the jokes they don't try to put Comedy and entertainment into the things and let me let me bust the truth out Every reaction channel is fake and something every single channel you watch Because if you're watching a reaction channel If they turn that camera off and they were watching the same thing. This is how they'd be Huh Not even that noise that it's just made that would be the whole reaction channel all these reaction channels like oh Oh, oh denji. Oh, bro They're they're pushing it out of themselves, but not like forcing it But we're we're trying to be entertaining, you know We're pushing out these emotions that we're keeping inside when we're alone, you know when we're alone We're just enjoying it sitting back It's like you go to a movie you think when I see a demon slay movie.  No, I'm just sitting there like this. It's part of being a youtuber. It's why I believe I've made or I've Earned your subscription It's because I'm different and I pride myself that way you recently share on your instagram that you'll be visiting Japan early next year march by the way How do you feel about jumping into a new and different culture? Do you plan to prepare like learning a few words to make sure? Oh, yeah, definitely make sure I don't get lost Definitely. Definitely. I want to Be respectful of the culture. I joke when I say I'm gonna get off the plane called everyone up back Dough stuff. I'm not gonna do that. Okay. That's a joke. I'm gonna be very respectful of the culture before I arrive in Japan I want to know words. I want to learn the basics. So When I go to a restaurant, I'm just not like this And I love Japanese culture. I've always loved it even before anime and manga. All right video games music I've always loved Japanese culture especially video games and Nintendo. Oh my god. Nintendo fan since I was a literal baby So Japan is my dream destination and another thing you guys probably don't know about me Godzilla Nintendo and Godzilla were big parts of my Growing up my my my my adolescence my childhood everything. It was just I love it. I still watch it I love go gojira and I cannot wait to experience that stuff plus studio jibbly stuff I love studio jibbly so I can't wait to see all the stuff now We have anime and anime into the equation imagine how I'm gonna be in Japan I'm gonna go there for like two weeks or three weeks Hopefully three weeks or a month. I can't wait. It's gonna be so much fun And I want to meet you guys so we'll plan that when the time comes but March March 2023 Nicholas light comes to Japan. Do you get goosebumps when you rewatch a clip from an anime that you loved? I have adhg too, and I'm so happy to see someone to react to anime the same way. I do.  I love you. Oh my god. I love you guys. There are three scenes in anime so far That have hit me on a different level And I'm not saying other scenes are not good Because some scenes that I've seen are god level but these specific three scenes just transcended my Brain and my soul number one was attack on titan the whole erin kruger thing The way that episode ended with him mentioned in mikasa and armin to grisha while they're on top of the wall that That scene will I think it'll forever be my number one? Maybe not forever, but it will stick in my heart like a firstborn child Second another attack on titan scene would be the transformation scene It's not even them just transforming. It's the casualness. Oh, yeah, so we're the colossal titan the armors I like the casualness. It was so different. That's what I like that Even just saying it. I gotta rewatch it three the chainsaw man episode just the other day or two weeks ago actually Everyone dying dying makima gobeni denji Amen, oh that took an anime that I was already falling in love with or already fell in love with and just made it like undying love like unconditional love like I'm A simp for this now So those are like my top three scenes right now that really What gave me goosebumps gave me goosebumps continuously if you had to organize some of the anime and animated shows You've watched recently on your channel into a top three or five list How would you rank them attack on titan chainsaw man? Vinland saga but vinland saga and chainsaw man All three of these positions could switch up right in between each other But those are my top three definitely How would you say your life has changed over the course of this year? Love your videos. They always cheer me up if I'm feeling down. Keep up the good work and take good care of yourself Thank you rabbi cool. I love you. My life has changed 100% Before this year. I was living with my parents I didn't have a car or I had a car, but I was my brother's So it wasn't mine and I drive his car everywhere I wasn't making that much money because I was doing music reactions and all the record labels would take that money So I wasn't making any money Up until like 300,000 subscribers. I didn't even have a patreon. So anime I was able to get my apartment. I'm working on getting a house. I bought my my tesla I Sent my my parents on a trip to venice. It changed my life. I'm doing smarter things. I'm smarter with my money I'm a smarter person. I'm growing every day And next year is gonna be even better But anime I feel like I found my lane.  Have you genuinely enjoyed every anime if you reacted to or have you continued some series solely for the channel No judgment if so just curious. Love the videos. Hope to see more op reactions soon All right, so demon slayer already went over where it got me a little Confused during some parts of it because I was like why do people love it so much? But then it got me back and I understood death note After one of the alphabet letters die. It took me off. It took me away Like I had to push myself to do those I guess last 10 episodes and it was better It got better towards the end like those last two episodes I loved But the whole thing went mellow and near Oh Oh, I honestly had to force myself and I'm not saying I forced my what I was feeling and what I was saying But I had to push myself to do the reaction like to actually sit down and react to it What was it like having to switch from so many types of reactions and the fandom they come with as far as anime goes There's a lot of fandoms in anime. It's like music. You have the Taylor Swift You have the Ariana Grande's you have the Shakira's You have the attack on titans the demon slayers the digits of kaizen's the mushuko 10 size the re zeros The sword are on lines the hen ties the um high cues You have so many different animes and everybody wants me to check out their favorite anime and believe me I appreciate that and I got overwhelmed for a bit I was like damn there's so much and I don't want to get burnt out But I don't want to upset anybody I don't care anymore Now I'm like I'm going at my own pace and I'm gonna react to what I want to react to And I'm gonna give stuff a chance though.  This is still fun for me And I want to keep this fun because the second the fun is out of it and it becomes a job That's when I go to ups and I work there. What is your workout routine because you're looking really good lately Thank you ray. Also, do you have any tips for people who are trying to work out and getting shape? Well, if you saw me in the middle of this year, I was getting a little plumpy I was in a depressive state and I gained about 40 pounds. I was getting fat.  I was getting fat I've since I've lost all that weight still losing weight It's all about routine and I tell my friends this all the time get yourself into a routine Don't go to the gym tomorrow 8 a.m. And then the next day skip and then the day after that go at 10 p.m Don't do that. Have a routine Monday through Friday. I'm gonna go 8 a.m. Before work every single day Start that routine you do something for 30 days.  If it's gonna be a favorite of yours. All right, let me answer that one first characters You have to have good characters because a lot of Film a lot of video games You have a good story But the characters suck And it just takes you out of it. You need someone That you could stand behind Or stand against you need somebody like that. For example airbender last airbender you had Zuko I feel like that's one of the greatest written characters ever, but he's such a great character I don't look for these one-dimensional characters that are one note like always bad twirling the mustache That's if you I hate that it it's cringy to me. It takes me out of it I like when there's depth in the characters and it feels real You know what I mean? And I'm not saying they can't be animated in their expressions or in the way they feel and think but Just just don't be one note I hate one note and that just doesn't go with characters. It goes with everything I love to know who your favorite characters are from some of the stuff you've watched And what type of characters you tend to like the best. I love Saitama. He's funny I could relate with his dry humor and he's not even trying to be funny That's the humor and the magic of the show the love of the show the heart of the show I love Saitama one of my favorite characters Zuko I already praised Zuko. I think he's number one for me.    I love denji Honestly, it's it's like a kid And I could relate with a lot of his qualities even now I'm sure a lot of us can titties Honestly jokes aside denji definitely denji final thing. This is just my own curiosity But would you ever consider doing a video where you try to draw? No, no, you don't want that. You know what? I'm gonna try I'm gonna try to draw Saitama There's my art. That's as much as you're getting from me rate my art down below out of 10. There we go Rated, how do you have so much energy in each and every video? You never seem low in any of them.  I take a lot of pre-workout before the gym I know you shouldn't but I take like two scoops and then I have coffee I swear to god, I'm gonna have a heart attack on camera one day, but to be real I have fun with it. That's why I can't fake it You know, it's the only thing that makes me feel alive That I feel like I'm good at making people laugh smile have a good time taking them away from their thoughts or their bad day Just for a few minutes That is what keeps me energetic knowing that I'm good at it and I'm not forcing it. It's just what I love doing It's like people love drawing Love skateboarding love making music. I love entertaining people and making them happy if you were born in japan Decided to start a write a manga. What's your initial plot gonna be about? All right. Well, why do I have to be born in japan? Like I can't write. Wait, could you read? Could you write manga if you're not born in japan? Do people write manga if they're not in japan? I don't even know guys. Let me know But all right, say I say I was born in japan. Okay. Decided to write a manga. All right So let's pretend I actually have talent.  It would be about a bird a bird just like chantero It's a bird that you can't pick apart from any other bird Right, it won't be like a main character bird. He won't have a scarf.  He has to stick out.  Full of life forms that look exactly like you so that would be to plot Finding what makes him different. Which road will he pursue? We follow the birds when they fly south. Do they fly south for the winter? Wherever they go, wherever those fuckers go. Does he follow those birds? Does he go his own way and risk starvation?   Tell me if you'd read that or watch it put it down below I might write it actually. Do you still plan on watching haiku at some point? There's not rush at all since you're already watching so many shows right now But if you do then I think it is a great first anime that has nothing to do with powers or supernatural things And it's just about some high school volleyball. I love you nick and keep up the great Well, I love you. I think when I do a first Sports anime, it will be haiku. I'm definitely or haiku I'm definitely interested in checking that out and I like that that there's nothing super powers or supernatural Not that there's anything wrong with that, but I feel like you need a balance, you know, I like watching different things Maybe I want to watch an anime about romance Who knows or an isekai or whatever like I want to watch different genres within anime I feel like that is how I will grow as an anime as a weeb I'll actually be a weeb right now.  What is the most tragic scene you've ever seen aesthetic studio jibbly films? Nothing beats that aesthetic, but if we're talking anime, I really love the jujitsu kaisen aesthetic Don't get me wrong demon slayer.  So I'd have to go with jjk most tragic scene. I feel like it's agonizing takes that too What grisha screaming in a performance where erin's talking to him Like when he's when he's talking to him when his face you y'all know the meme y'all know what I'm talking about that scene Wow, but then i'm thinking about the villain saga scene thorfin on the boat in like the first few episodes after thors dies Spoiler alert. Have you seen any studio jibbly movies? I've seen them all I wanted to enjoy something animation wise by myself all for reactions And that's what I did with studio jibbly one day this year I just watched all the films in like two sittings. My favorite one is grava the fireflies I watched out on a plane. I was coming from hawaii And I just put that on the plane And I was tearing up in my my flight seat.  I'm watching death That's what I'm watching. What's the most important lesson you've learned from one specific anime Don't trust these hoes.  I'm never gonna have a family like that attack on titan taught me a very valuable important lesson that i'm never gonna forget A lesson that I was taught before But didn't really fully believe in until I watched the anime you see gabby you see erin two different worlds But they were both affected the same way But it was by each other's Nations kind of you know what I mean like erin was attacked by gabby's people gabby was attacked by erin's people And then we all learned the truths and the what who is who and everything and towards the ends but that hatred Like erin understanding erin gabby trying to understand him and then erin or Mikasa and armin understanding gabby You know what I mean like just two different sides everything's not black and white And I like that and I always understood that But it made me understand people differently Like why do they act this way everything's not black and white unless it's just pure fucking hatred and pure evil Then nah last question It's not really a question Wow so much for the last question But I just wanted to tell you that you are one of my favorite youtubers of all time like top three and top one favorite reaction Channel Why am I not you're in top three you're top number one in general then you make me laugh at every single video you make So thanks I love you guys.   This was different Y'all get to know me more You know outside of the craziness And all the reactions, you know, I'd like you to know me more because you guys are the biggest part of my life And I love you so much how many times did I say that in this video? I'm so sorry. I'm sorry for saying I love you so much. Oh, Merry Christmas. This is your gift getting to know me more Because I am the gift


Right, so I guess we'll get started on the best topic you will ever be lectured on, just diabetic retinopathy. I think it's really fun to treat diabetic retinopathy because it's so diverse and it's kind of presentation, it's phenotype, and also it's severity and how we can treat it. So diabetic retinopathy is most common in type one with 40% of patients developing it versus type two is 20%. And notably it's the most common or most prevalent cause of legal blindness between the ages of 20 and 65 in the United States. I think it's a really important thing to consider because that's working age people who are trying to raise children and so protecting their vision is particularly important to society. The risk factors are the duration of having diabetes, so after 20 years, 99% of type one patients and 60% of type two patients have some degree of diabetic retinopathy. For type one at 20 years, 50% will have PDR and at 25 years, 25% will have PDR, which is really remarkable. The other risk factors are poor metabolic control, things that may be or are complicating factors are pregnancy, high blood pressure, kidney disease, obesity, hyperlipidemia, and endemium. So the general pathogenesis is that there's different factors that cause endothelial cell and pericyte damage. This leads to an increased platelet adhesion, increased erythrocyte aggregation, abnormal lipid levels, a parodilation of VEGF, general abnormal viscosity of the blood, inflammation, defective clot breakdown, and then abnormal levels of growth hormone. This is clearly a complex milieu of inflammation and ischemia that leads to this thing we call diabetic retinopathy. It really is a microame geography. Its most characteristic problem is that there's a loss of pericytes and that leads to a proliferation of endothelial cells. There's a thickening of the basement membrane and that's causing ischemia. The microvascular occlusion leads to a number of things. Early on it leads to AV shunting, which is Irma, so intra-retinal microvascular abnormality, and then eventually leads to neovascularization, which are new blood vessels that form the retinopic disc and the iris. And it's thought to be caused by the antigenic factors for retinoschemia or the release of VEGF. Vision loss from diabetic retinopathy really can be broken down to two main problems. You have leakage from the blood vessels, or you can have just a lack of blood flow. So the leakage from blood vessels leads to things like macular edema. And then the capillary occlusion causes macular ischemia, so that can just be a long-term vision loss because of poor perfusion in the macular. Or things like diabetic papillopathy, or the sequela when you have neovascularization, so vitreous hemorrhage, tractional retinal detachment, and neovascular glaucoma. It's a great photo just showing proliferative diabetic retinopathy in a boat hem and hemorrhage. Now the classification of diabetic retinopathy is for non-proliferative diabetic retinopathy, or MPDR. It could be mild, moderate, severe, or very severe. And then for proliferative diabetic retinopathy, the two classifications are low risk or high risk. And we'll go through those. So an MPDR, microvascular changes are limited to the confines of the retina and never extend beyond ILM. The characteristic early fight in its microaneurisms, and this moves on to dot-bot hemorrhages with retinal edema, heart exudates, eventually you get dilation and bleeding of the retinal vessels. You can get the formation of ERMA, which is a lot like neovascularization, but it doesn't break through the ILM. And then you can also have RFNL. In FARC so-called mole spots and capillary non-perfusion. As we talked about, the way that this causes vision loss is two-fold. One is macular ischemia, so that's capillary closure. And then the other is macular edema, and that's this capillary hyperpermeability, so the leakage we see leading to intranetal fluid. So to classify MPDR, you've got mild, which are just MAs. You've got moderate, which are MAs and dot-bot hemorrhages, but less than 20 per field, so the four quadrants. Severe has the 4-2-1 rule, so any of these will get you severe diabetic retinopathy, not proliferative diabetic retinopathy, and that's four quadrants of diffuse MAs or dot-bot hemorrhages, so that's greater than 20 of these in the quadrant. Or if you have two quadrants of venous beading or one quadrant of Irma, in terms of very severe, it's just if you have two of the three that you see in severe. The reason this matters, and we'll see this in some of the results of the studies, is that it is predictive of severe vision loss in these patients. This is definitely OCAP's stuff, and it's on it every year. Immacular edema has a number of names that you'll see in the chart. And so from the ETDRS, you have clinically significant macular edema, and we're going to talk about this criteria in a second. You also have something called center-involving macular edema, so that's edema or thickening by OCT of the fovea. And it's important to make this distinction because center-involving macular edema has been criteria used for more modern clinical trials where we have OCT available, versus the early work was done just by fondoscopy, and that was where the term CSME came from. Focal macular edema is a good term to use when there's a focal area of leakage that you have an X ringdeck to say around the temporal area of microaneurysms. And then diffuse macular edema is extensive leakage, and that's widespread breakdown of the blood retina barrier. So as it's become very common in a huge part of retina practice is treating macular edema, and we can do that with a number of treatments. Most commonly, what you use in clinic now is anti-Vedgev treatment. And there are a number of options. Pretty much we use three of these options today, and renabizumab, bivisizumab, and flibersept. But the original trial was on Pagatinin, which is macugin. And it really didn't have that hive of binding affinity with Vedgev, and it wasn't as effective as these later treatments that we have now. But it was the first one that was published to show that mechanism could be worked to treat macular edema. In addition to anti-Vedgev, we can use steroids. And the three approved options are the intravitulatramicinola, retriacinth, ozardex, which is a dexamethazone implant, and then the fluocentanide implant, which is alluvian. The reason that there are differences in how we use steroids versus anti-Vedgev is the risk profile within the eye, with steroids causing cataract and glaucoma, or elevated pressure in the eye. So they can be very effective treatment, but they do have a slightly increased risk profile. In terms of if we're not going to use pharmacologic treatment, a treatment for macular edema is focal and grid laser. And before we had these injections, that was all we had, which is before I ever did. So it's all Dr. Teske had. And while this can be very effective even today with focal macular edema outside of the fovea, focal laser at the end of the day is destructive. And we don't think of the pharmacologic options we have as being destructive. So oftentimes, we use it in directed cases that are amenable to it. But we are in the last few years at a time where laser's making a comeback in the form of this micro pulse laser or endpoint management laser by the Pascal system, which is the idea of laser that's subthreshold. Typically, when we do laser, we like to see an effect. So you can see light blanching in the macula. Or what some companies are doing now, and there are some evidence to say that it works, is to essentially get that light blanching and then cut it to 20% or 30% of that and treat in a grid pattern throughout the macula. And you can potentially decrease your dependence on injections. So moving on to proliferative diabetic retinopathy, there's different areas of the retina or the eye that can neovascularize or convert to proliferation. And so we break them down into these terms. And we normally always just use the acronyms. So you have neovascularization of the disc. You can have neovascularization elsewhere, which is just on the retina, one disc diameter away from the disc. You have neovascularization in the front of the eye, the iris in the angle. So those are just the terms to know since we normally just write down those three letters. So what is proliferative diabetic retinopathy? So it's extra retinal fibrovascular proliferation that expends beyond the retina, so beyond ILM with three stages of evolution. So first, in its earliest form, you can see new blood vessels forming with minimal fibrous tissue. And when we're saying fibrous tissue, we're saying, you know, not red. It's white. It's scar. In the second stage, the new vessels increase in size. And there's an increase in the fibrous component. And then in the third stage, the vessels regress, leaving residual fibrovascular proliferation along the posterior highlight. And I can create traction leading to detachment of the retina. These are some great photos looking at these different forms. So I think as well, I'll zoom in a little bit. So in this upper right image, you can see that there's neovascularization of the disc. And this has super temporal quadrant of the disc. And while in the second picture, you can see there's kind of complete neovascularization disc and then this NVE with this fibrous component. Moving down to this image, this beautiful area, I guess neovascularization isn't beautiful. But when you look at it, it can be really interesting to look at. And you can see this neovascularization elsewhere. So over this diameter away from the disc, coming off the arcade. And then in a more extensive neovascularization elsewhere. This is a really good photo showing that as these blood vessels that had form coming off, the arcades down here have now started regressing. And there's some active blood vessels here. But it's created this fibrous band. And that's creating traction. And it's tenting the retina here. Tenting the retina here. Which then, moving on, you can see that this is neovascularization on the disc that has created a ring of traction, sometimes called wolf jaw fibrosis. And it's because the two arcades connect. And then they close and they detach the macula. And you can see that this retina is detached. The macula is detached. The treatment of PDR is first and foremost, and for many, many years, is pan-retinal photocoagulation. This is something to know for boards is that it's greater than 1,200 spots of a 500 micron spot size, separated by a half burn width. Which is, that was the initial treatment or protocol. Often times, now we're using 200 micron spot size. But not quite as hot as it used to be. But the idea here is that you're destroying the ischemic retina. And the peripheral retina, which is not as valuable to the patient. And hopefully what you're causing is a decrease in oxygen of the total retina. So this diffuse microangiopathy that's preventing blood to come to the retina by sacrificing the large real estate of the peripheral retina, you can hopefully continue to perfuse the macula and decrease that secretion of inflammatory signals, one of which is VEGF. So that increases the oxygen tension in the eye. And for decreased consumption of the increased perfusion, all these inflammatory meteors cause evasive constriction diffusely throughout the retina. And so as you improve that inflammatory milieu of the vitreous and the retina, you're actually going to have increased perfusion. So it's not just that you're killing dead retina. You're actually hopefully increasing the blood flow to the healthy retina or the retina we're trying to maintain health. And so that's interesting. There's no difference in single versus multiple sessions of PRP. I think that I know that's debated by different attendings. I had attendings that always did PRP, never more than 800 shots in multiple sessions due to the risk of contraction. But there is good evidence to say that you can do a full treatment of 1,500, 1,800 spots in a treatment. I think that's one of those things that, like a lot of what we do is you're going to manage risk based on that specific patient in front of you and kind of set their expectations of how much they can get done that day. And you may be more incentivized to try to get a full treatment in than someone that has limited access to care or is unlikely to come back versus someone that is showing that they can follow up. What it's very interesting is a couple of years ago, the protocol S from the DCRC net was released. And that was a non-inferiority trial of Ranibizumab versus PRP, so Lucentus versus PRP. And there's been many papers that have come out afterwards because the trial did conclude that you could use Ranibizumab as treatment for PDR. And that actually those patients, when you did an area under the curve analysis, had improved vision through a year and then at two years it pretty much regressed back to the mean, is that that would create maybe an undue burden on patients and on providers if we were to treat PDR with long for a lifetime of injections. And the big debate around this is when you stop injecting the patients, what happens to the new vascularization? Does it come back or doesn't? So that's still a debated topic of how to use it. But certainly in a patient with macular edema and a new vascularization that using anti-veg F alone will at least through two years make the new vascularization go away. And that's where it all came from, right? I mean, we treated macular edema in the past. Before we had anti-veg F injections, we'd have a patient with PDR that needed laser for the macular edema too. And it was like, well, if you just do PRP in eyes that already have macular edema, most those eyes, the DME worsens. So we would have to say, well, we've got to drive your macula first. Problem is we didn't have good ways of drying up the macula. You do sort of grids and full goal. And you kind of wait and hope that it would dry up so you could start your PRP. But you often didn't have that much time. So really have been a bad type of edge if you're kind of killing two birds with one stone. And you can control the proliferative retinopathy, at least in the short term, you can control it as you treat the macular edema, whether I think the jury's still out long term, whether the lack of PRP in these eyes is going to be an issue. There's increasing evidence that maybe it's not going to be, but I don't think we really know that yet. Absolutely. And a really interesting part of Procholes is many of these patients that were in the PRP arm presented with Diabac macular edema and received injections of ranobizumab for their macular edema. And I think it's 38% of the patients. So this wasn't really a trial where you had PRP alone versus ranobizumab that would then get rescued with PRP. It was patients who were treated for DME. And some of them got PRP as well. And so I think it was a pretty tough trial against ranobizumab to say that because so many of the patients weren't going to get ranobizumab anyway. And it showed non-inferiority and incursion. It was a powerful say, but it absolutely juries out. And that's what we just talked about. So PRP and the reason that I brought up that point on, it said it's OK to do a full session of PRP on one visit is that lasering the entire peripheral retina causes inflammation and that can cause an exudative retinal detachment and that inflammation in the eye can cause macrodema certainly to get worse. And I can have patients that maybe don't have CSMEs and they may have a little bit of temporal intraretinal fluid. But then after you do PRP, then all of a sudden their central vision's gone down. And they think you've caused them permanent vision loss. And so it's very important to know when you're talking to these patients that they are diabetic. They have a likelihood of getting macrodema. And if they have very mild macrodema, it may get much worse. And the tough patients to manage are those that have excellent central vision because they have little or no macrodema, but they have significant proliferative disease. Now they need PRP. There's a good percentage of those eyes that are going to lose some vision through the course of treatment. It takes a lot of educating the patient and making them understand what's happening. It's not as much a problem now because we have anti-bed Jeff. But in the days when we had to manage everything with laser, it's like, what do you do? You do a focal grid. Maybe slowly start the PRP. But you were always at risk of flaring up the macular edema. There are a number of papers out. It's not in... We're trying to focus on what's in your books. There are a number of papers out on the tractomy for macular edema in the cases of the taut hyeloid or in medically refractory, or so it's patients that's macrodema doesn't respond to injections. And the data is fairly weak and when they've done that analysis, it doesn't support that that works. But so we can move on to the surgical management of diabetic retinopathy. So this is what I think is super fun. So first indication is a non-cleric vitreous hemorrhage, which is greater than one. It's going to one to six months after you've developed a vitreous hemorrhage. Certainly if there's a tractional retinal detachment involving or threatening the macula, absolutely if there's a combined regmetologist's tractional retinal detachment. There are certain patients that you'll have that will have adequate PRP, but they just keep getting vitreous hemorrhages and they may clear, but they've had multiple vitreous hemorrhages and you just have not been able to get that eye under control. As you know, in clinic it's, the far anterior retina is somewhat difficult to laser and you can have times where you can very anterior neovascularization and ischemia that's difficult to get at until you get them to the operating room and can really do that peripheral laser. And another case would be if you have vitreous hemorrhage and then go slow glaucoma, you would want to remove that inciting problem which are the red blood cells in the vitreous. It is not uncommon to have a patient with neovascular glaucoma or NVI or MVA and they also have a vitreous hemorrhage. So you can't do PRP and you can, or this, and so you may need to take them to surgery to remove vitreous, the blood, the inadequate laser. Some of the paradigms for this have changed because of the ability to use anti-Vedgev agents. For instance, if we have someone come with neovascular glaucoma now and there's too much vitreous hemorrhage to get PRP, we'll often treat them with anti-Vedgev to see if we can control that eye before we take them to surgery now, which is great, operating on a hot eye with a pressure of 60 is difficult. And the posterior highlight, so the attachment between the vitreous and the retina or the macular and diabetic is often very fibrous so they get pretty impressive ERMs. And then if they bleed under these fibrous, taut posterior hyalurid, they can really be plastered on the macula and kind of a bone hemorrhage you see here and that might de-hemoglobinize and might begin to clear, but sometimes they just don't. So taking them, peeling that membrane off and clearing that blood, we'll get the region back for them. So we'll kind of go through the studies to know kind of the big works. There's one that's not on here I always like to share when I talk about diabetic retinopathy because it was from the early fifties and it was when before we had any treatment or laser for the treatment of diabetic retinopathy for PDR. And so the neurosurgeons had come up with, and they were working with the retinologists at the time, that hypofysectomy, so removing the pituitary gland may be a treatment for PDR. And so there was a trial where they went and they did neurosurgery and removed the pituitary gland to see if that would cause PDR to regress and then it didn't work. We've come a long way from chopping out sections of brain to need more focus since the, you know, 70 years ago. So the first one is to look at is 1972 and I think it's just so impressive to look at how long ago some of these studies were now and they're still really important how we practice, which is the diabetic retinopathy study. Many of the diabetic retinopathy have attracted to me study in 1976 and the UK PDS in 1977, ETDRS, 1979, DCCT in 1983, and then many, many trials from the DCRC net, which are a while ago to even going on right now. So the DRS study, the first one, 1972, and that is, is the real question that they're asking is PRP effective for the treatment of diabetic retinopathy? They did, was PRP to one eye patients with advanced NPDR, PDR in both eyes. And then they looked at the rates of severe vision loss between the two eyes. Now as defined as visual cue, less than 5,200 on two consecutive examinations, four months apart. And then compared to that control, I did not get PRP. And they were able to look at these patients for five years, so really impressed a study of almost 2,000 patients. And what they found was that there's a greater than 50% reduction in the rate of severe vision loss. As we talked about in the population we're looking at of people who are 20 to 65, severe vision loss can really be dramatically life altering for them and their whole family. So that was pretty amazing. I know that Dr. Teske may know this because there's a story about what laser they were using back then. Well there were, the Argon laser was relatively new and it was a far ground blue, green, and then there was a Sinon, which was really a photo coagulator. It's not truly a laser, it was multiple wavelength. I would leave these. It was done with a direct, it's a big machine with a monocular direct view. And the spots were about the size of the disk or bigger. And there were massive spots. When I first came here, I mean, there was an old Xenon photo coagulator in the back room somewhere. I don't know what happened to it, but they all had to have a retropolar block. It was very painful. But that was part, that was in the study. They were using Xenon or Argon laser at the time. So the next study is the diabetic retinopathy study. And this is what defined high-risk PDR. So when you come and present to, and certainly it's on the board, you wanna know if it's high-risk PDR or not. And that's defined as mild NVD with vitreous hemorrhage. And mild NVD would be less than a quarter to a third of a disc diameter. Or moderate to severe NVD, which is a quarter to a third disc diameter or bigger. And that would be without vitreous hemorrhage. Or moderate NVD, so a half disc diameter or bigger with vitreous hemorrhage. And it's as or any of the three following. So that's always the three I remembered. So vitreous or pre-rentinal bleeding, presence of neovascularization, disc neovascularization martyrtism. Yeah, I think the top three are really what you wanna know for OCAPs and boards. What's really interesting about this, because this wasn't the neovascular glaucoma study, this was the diabetic retinopathy study, that they didn't look at NVI or NVA. We pretty much treat NVI and NVA automatically as if it's high risk PDR, if they have diabetic retinopathy. So this put that one on your mind in the list, but when you answer the questions on the test, this is what you wanna answer. So next was the diabetic retinopathy vitrectomy study. So this was looking at severe vitreous hemorrhage. They wanted to answer the question is early vitrectomy. So within the first six months, preferable to deferred vitrectomy, for at least one year in eyes with severe vitreous hemorrhage from PDR, or those without vitreous hemorrhage, but very severe PDR. And what it showed is if you have type one diabetes, there was a clear benefit to doing early vitrectomy. And in other words, early vitrectomy is defined as one to six months. So this isn't tomorrow, this is in the next month or so to see if this clears. And then type twos and no benefit from early vitrectomy for vitreous hemorrhage. But if they had very severe PDR, early vitrectomy was beneficial. I think that this says, interesting, I'm very curious if this was redone today with modern vitrectomy techniques. This is in the late 70s and vitrectomy back then was, or mid-70s, this is a little different. So it was not uncommon to wait six months for vitreous hemorrhage to clear. What they said was no benefit to early vitrectomy, but these are eyes that would, I mean, in type two, but you also have an eye with no vision for six months or a year. But this was when vitrectomy was 19 or 20 gauge. I mean, it was a much riskier procedure per se than it is now, so. So I think that this, it's important to know, but we're more aggressive than this. And I think if we repeated this study today, we would show early vitrectomy was probably beneficial to. I think the main takeaway of this is that they did show that early vitrectomy is advisable in type one diabetics when they have hemorrhage. Sitting on these eyes for more than six months is not a good thing. So whereas in type two, it didn't seem to make much difference if you delayed vitrectomy. Their outcomes were similar. So. It's a slight side note. I always filmed as a resident when you're in the emergency room and you have the diabetic who's never had an eye exam comes in. They're 60. They had flashes and floaters. They have diffuse vitreous hemorrhage. You can't see the retina. And you're, in the other eye has, you know, moderate, maybe severe NPDR. And you're sitting there asking yourself, do they have a tear because they just had a PVD or they just diabetic with a vitreous hemorrhage because they're 60. And then there's, so they've looked at studies where you did vitrectomy on every vitreous hemorrhage, even if you thought it was hemorrhagic PVD or anything, and it's 80% have tears. But then if there are severe diabetes, you know, it's always hard but late at night. So, you know, getting them to retina, you know, in the next couple of days is a good idea for us to look at it and get the ultrasound in.  So, let's look at some of them. I think this one's great. Venus beading, when you see it, it's exciting because you've always memorized it but you don't always see it. And this one's a really good example of Venus beading. So, if you look at this inferior, okay, do you can see this? If you look at some of the standard photographs for Venus beading, some of the really ones, they're not grossly obvious like that. It can be more subtle than that. And on a exam, on a live patient, it can sometimes be difficult to see. It's always easier to classify at retinopathy, looking at some photographs, right? You photograph the patient, you can look at them and stare at them as long as you want. In a live patient sometimes and they're photophobic, it's not as easy to see all this stuff, but. There's also clear NVD in this case. And as you're looking at more and more eyes with NVD, you'll see the shunt vessels and the CRVO patients. And so, not every funky looking blood vessel on the optic nerve head is NVD and you'll get a sense, but typically they're very fine. They have a three-dimensional quality to them coming up off of the nerve. But it can be a little, so it's like it's the same patient. And even on the projector, we can see what I think is really interesting here. So one, if you see an FA, like on my exam, you see a dark spot like this with severe retinal vascular disease. So you know this is blocking. If it's blocking, it's pre-retinal hemorrhage and you know that this is gonna be high-risk PDO. So blocking can be an indicator of chest-taking situation of knowing that that's high-risk. But I think what's really interesting here is, so macula, as you can see the degree of capillary non-perfusion out here, there's just no capillaries. And of course, they diffuse microangerisms. And then the NBD is showing up as hyperfluorescent. So it's probably the patient's other eye and this is this so severe. It's, and you can see these sub-hyloid haemorrhages kind of mixture of age plastered on the retina. So ETDRS study is a randomized clinical trial sponsored by the National Eye Institute. Three goals, compare early photo-calculation versus deferral treatment in eyes of mild to severe N-PDR or early PDR with or without DMV to evaluate the effect of photo-calculation for DMV. And I wanted to look at aspirin would change the disease course of diabetic retinopathy. One of the things that gave us was the ETDRS chart, which is the number of letters you can read on that chart which has become standard for many ophthalmology studies since. Almost 4,000 eyes, 1980 to 85. So I was born in 84. So I was technically alive, very nice. But I don't think any of the, oh yeah. I forgot we have one other old person. I'm one year over you. Yeah, all right. And so it looked at the real of the spectrum of mild N-PDR all the way to PDR. And visual acuity had to be reasonable in each eye. One eye got photo-calculation scatter and or focal and the other got known. And they got randomly assigned to aspirin or placebo. And it's defined the 421 rule and it defined clinically significant macular edema. Its findings were progressing to, the risk of progression to PDR. It also found that early PRP reduced the risk of severe vision loss. And focal definitely includes visual outcomes and focal improves retinal thickness. So the reason these classifications are important is if you have severe N-PDR over one year, there is a 15% chance that you're gonna progress the high risk PDR. Sorry, so severe N-PDR progressing to PDR. So when you see the 421 rule applied, know that that patient needs a different follow-up and we'll go through what those follow-ups are because you don't wanna miss that conversion. I'll say from personal experience because when this was done by expert retina doctors and at the time not having some of the imaging modalities that we have now, that golden age of fundoscopy was really there. And so many patients that I think have severe N-PDR or very severe N-PDR, if you do a wide field angiogram, you'll be amazed the amount of NVE that's hiding in there that you just didn't quite see. So it's, I think, something to think about when you see those patients as well. Very severe, so it's two of those criteria. It's almost 50% chance at one year. So when you see Irma and Hemorrhages everywhere and I'm a person with diabetes, know that they're on that precipice and they might not always have macular edema, so they might be sitting there 2020 thinking they're fine, but they're really approaching that cliff of severe vision loss. So early scatter was not indicated in mild to moderate N-PDR. The risk of laser outweigh potential prevention of severe vision loss. So what is the risk of laser? So back then, certainly this was hot laser. There was a much higher incidence of things like exudative retinal detachment and severe macular edema that you then didn't have steroids or anti-veg to treat. But the thing even now is there is visual field loss when you do PRP. And so taking someone with mild N-PDR N-PDR doesn't make sense. So we used to use this data a lot more before the Herig's anti-veg F and you know, you had either eyes in a very severe N-PDR you can certainly justify initiating PRP before they develop proliferative retinopathy because of their risk. And again, that partly depended on the individual to follow up likelihood, et cetera. Or they already have PDR in one eye and the other eye had severe N-PDR or very severe. We would often initiate treatment in the fellow eye. Nowadays, a lot of those eyes often have some macular edema. There's certainly evidence that you can treat severe N-PDR without macular edema now just with anti-veg F. So we don't, the idea of doing early PRP is probably not one way. You know, PRP's becoming less and less done. But back then, you know, we would treat eyes before PDR if they had pretty severe N-PDR. Yeah, I think that's a great point. And there's been a number of recent studies, I think in Texas by Dave Brown and why, Charlie Wyckoff's group where they've done wide field optos and geography on patients with DME and then the PRP directed at those areas of catapult or non-profusion in the peripheral retina to see if they could decrease the dependence on anti-veg F injections. And they've all been negative so far. So, but it's not uncommon to start trying things when you have patients that are refusing injections and they're still having, you know, moderate to severe macular edema. And there's certainly case reports of it working but in trials it hasn't worked out. So, and then early PRP resulted in mild re-reduced severe vision loss. Yeah, so that's excellent. I think my thought now as a fellow when I look at this is before we were trying to decide is it worth it to do PRP and these people with either very severe N-PDR or in that PDR. And now I wonder with the safety profile of atrectomy now is really early of atrectomy and removing the hyeloid in some of these patients with that if you have a 35 year old type one. And I don't think that trials been done yet but it's the thing I think about now. Oh, and yeah, really importantly the clinical definition of CSMA. And this is absolutely important to memorize. So it's the beginning of the retina at or within 500 microns at the center of the macula. Heart exudates at or within 500 micron at the center of the macula. If it's associated with thickening of the adjacent retina in a zone of thickening one disc area or larger, any part of which is within one disc diameter of the center of the macula. So those are the classic photos showing you those three different situations. So you have thickening within 500 microns at the center of the fovea. You have a one disc diameter of thickening within one disc diameter of the fovea and then heart exudate with adjacent thickening. So OCT was not around at this time so this was all done with contact macular lenses. And I think that's impressive. When you get that perfect cornea and no cataract and you clear fitreous and you can see macular fields and then when you go and look, you're like, oh, I can see it. And then you go look on the OCT and it's like massive. It's like 700 microns thick. And I think Dr. Teske and his colleagues were able to see pretty subtle things. It's a little bit of a lost art because we don't spend the time putting the fundus lens on it doing biomechroscopy because we basically don't need to. We have OCTs now and we have OCT guided macular demon more than we do that. That's good for historical purposes. And that was the criteria that was used. I mean, if you were going to treat somebody, they had to have, they had to be one of those criteria before you would initiate treatment. And so the focal results were focal for CSME reduced the risk of moderate vision loss, which was doubling of the visual angle. Focal increase, the chance of moderate visual gain, having the initial visual angle and focal reduced radical thickening. So focal works. So these are just good photos of focal. You can see the focal burns and then you can see this group. We see some of these patients that were in ETDRS that have lots of atrophy and lots of bigger spots. Early on in the criteria, if you were treating patients, you had to whiten all the microandrism. So you could have a spot over one, but if you could still see red in it, they sent it back and said, you need to retreat that microandrism. And so you would treat it again until it whitened. So you would get these retreated areas and much heavier. So we'd never do that to the macular now, but that was part of the protocol back then. If the microandrism were not completely whitened, you had to retreat them. Wow. I feel, I haven't done focal too many times, but I've done it enough. And I feel like if I get just any blanching of the red on, I'm getting good. Yeah, and that involved, we didn't follow. I mean, that change, even before the anti-vegetable drugs became available, our way of what we treated macular and even with laser evolved into much less treatment, much less heavier treatment, more just barely threshold burns. Any quick question? Yep. So for focal grade, you're not actually focusing on the NMAs necessarily, but you're just kind of all the way around the phobia. Well, are you asking me which one is it? Yeah, which one is it? Well, there was a combination of both treatments. With GRID, when you weren't treating specific microandrisms, it was much lighter, smaller spots, and that's probably why some threshold micropost works. You know, you said, well, why does that work? You're not closing the microandrism? Well, it's probably some photochemical stimulation in the RPE and the POP mechanism, however magically it works. But so they saw that effect, even in eyes that weren't or had more treatment or, I mean, that was kind of an incidental finding. You know, we thought you had to close specific microandrism. We found that, well, as it had more microandrisms that had more laser did better. You know, could be just anecdotally, so we were basically getting a grid too. So it kind of evolved into light grids, and then specifically trying to close microandrisms. Then we kind of evolved to say, well, you don't actually have to whiten the microandrisms to get the effect of this. So we didn't treat this heavily anymore, but we would still target specific microandrism. It's really only practical now, honestly, in focal areas of edema where there's like a surcinate area of macrodeme, and you'll have a cluster of little microandrisms within the edema, and then you can specifically target the microandrisms whiten them and you'll get an effect. But I don't know if that answers your question, but thank you. So aspirin did not affect diabetic retinopathy, but it prevents the patients from dying, so because it affects cardiovascular ability and mortality. So aspirin's a good thing, but it doesn't change the disease course in the eye. It doesn't alter it either. That was the bottom line of that. So if somebody needs to be on aspirin for other reasons that can be on aspirin, it doesn't have a negative effect on the outcome of the retinopathy either. So then there's the diabetes control and complications trial with that type one diabetics for one to five years, and if they can control their blood glucose, does it affect the progression of diabetic retinopathy? And the answer is resoundably yes. So intensive control reduces the risk of development of diabetic retinopathy by 76%. It reduces the risk of progression by 54%. And then the other things, or sorry, that diabetes really affects, it definitely has a disease, my fine course on neuropathy and kidney disease, and it decreased the patient's need for laser for treatment of their macular demon. So that's why every patient we see with diabetic retinopathy, it's important to help them control their blood glucose and communicate with their primary team. There was a similar study done for type two diabetics. This was done in the UK and intensive blood sugar control reduces development and progression of diabetic retinopathy in this group as well. The DC are seen that are multiple protocols driven by clinicians, so by ophthalmologists who decide that these are real world questions we want answered and they're not always questions that a drug company would wanna sponsor to get answered. And I think one of a very interesting trials in it. So protocol B was the treatment of macular dima with either focal or the intravitual triampicinolone. And it showed that the visual cutia was better in triampicinolone. But if you look at four months, but if you look at two years, the laser group outperformed them and there was less side effects. So this is really where we saw the side effect profile cataracts in high IOP from intravitual triampicinolone. Protocol I was the treatment of macrodigma with leucentus and prompt or deferred laser with triampicinolone with prompt laser. And we're in a mizumab with prompt or deferred laser was superior to laser or laser with triampicinolone. So that's showing the beginning of the anti-bedgef era for diabetic retinolone. Protocol T was comparing the effectiveness of a flibberset mizumab and ranibizumab. This is one I think is so interesting and important. It's similar to the cat trial. So, and it's hard to really have a randomized clinical trial comparing something that's generic to branded medications is because of the money involved in putting on a trial like this. And so I think this is a really impressive thing in our field that we're able to do this and show that mizumab is reasonable treatment for DME, despite not being FDA approved and despite not being supported by a company to do that. And so it's a more effectiveness of all agents, but it's also important to note that a flibberset was more effective in patients with worse presenting visual acuity to 2050 or worse. So that's why at the VA, sometimes when you bring a new patient, we don't always do three of a vast and then switch. There's reasons to start with ILEA and it's okay to do that.  Protocol D was a case series of PPV with PVD creation for DME. And that showed that their retinal thickening reduced in those eyes, but there was not a significant difference in vision. Protocol P was patients with MPDR and cataract surgery. And it shows that post-operative CME is more common if you have MPDR. So when you're doing your pre-ops and if they have any MPDR, certainly if they have a immaculate DMA, get it right now on board. We'll give them anti-bedge F before and then you probably want to treat them with an inset and steroid to prevent or bind gas. Protocol Q, patients with DME prior to cataract surgery. Yeah, half of eyes had no visual acuity improvement or worsening of the CME. So worsening with cataract extraction, sorry. Any patient that doesn't have improved vision after cataract surgery, and then afterwards has a problem that they may have had even before, they absolutely will associate it with their surgery. And so in some patients you can educate around that. A lot of them, it's really difficult to do that. So it's not standard of care in the US to have an OCT on every pre-op cataract patient, but ERMs, DME and people with mild DME that you might have just not seen on Fondoscopy, or sorry, on DiVec right now. Because of this, you really don't want to do cataract surgery on someone without at least talking about it beforehand and having everything in one. Protocol S, we already talked a little bit about, that was we're in a business map versus PRP for PDR. And this was the other result that I think is really important. There was a statistically significant decreased rate of vitrectomy in eyes that got anti-Vegeta only versus the PRP group. I think that's important to know. Avoiding surgery is a good thing. So that's the recap of the studies. I can get a screenshot and send that out. These are the examination schedule. First exams for type 1s are five years post-diagnosis. Type 2 is at-diagnosis, pregnancy, every trimester. And then you can see there, it gets broken down by form and whether they have CSME or not or PDR or inactive PDR, how often they need to be seen. And so that's good to know, especially when we're at the feeding. So any questions? I think we're pretty much on time. I just wanted to share a quick case. Oh my God, I don't know what just happened there. I just lost my screen. Treating diabetic retinopathy is, can be a challenge, because it's kind of like, can be like weeding. These patients are gonna live a long time with this problem, and it can require multiple types of treatment over a long time. So this was a patient of mine that, I met I think a year or so into her once she started coming to CS when I was a resident. So she had this pre-retinal hemorrhage and PDR in the left eye. Then a year later, she, after getting laser in the left eye and regression of that NVE, and she got lost to follow-up, she comes back and now she has another pre-retinal hemorrhage in the other eye. She gets a PRP for that. This appears for a while, and she needed fill-in, she never got it. She now comes in with worsening, pre-retinal hemorrhage is in the left eye, and we do a lot more PRP, and we have regression of all these hemorrhages came in, and probably the details in that FAA aren't as important as, what I really want to show you here is we, you can tell that there's been regression of the pre-retinal hemorrhages, there's probably some NVE, and there's all this pre-retinal fibrosis kind of in both eyes, but when you do the wide field angiogram, you can see that diabeck retinopathy is really a diffuse vasculitis in some patients, and this one's a great example of it. And you're going to see how diffuse in both eyes the leakage is, and some of that leakage in those fibro vascular areas, even as it regress will still happen, but you can see it's pretty much everywhere. And she at this point had pretty good PRP, but she still has a lot of leakage. She now has macular edema, and she was one of those people who presented with 20-20 vision, and now she gets macular edema, vision goes down 24, 20, 50, and we started treating her with anti-vegeth, and fill in PRP a year later, and continue to do anti-vegeth, and after kind of six anti-vegeth treatments, you can see these late FAs images, and she's had more fill in PRP, and you really start to get more control of this diffuse vasculitis, and now we're looking, and now we're four years after this all started, and she starts to kind of look like that, so she has these areas of pre-retinal fibrosis, she's got the laser in, she's got an ERM, she's 20-25 in this eye, and 20-20 in this eye, and I can't see that image quite as well, and her FAs not terrible, and that's when I kind of handed her off when I came here, and so kind of when she was starting, she looked like this, this is what she looks like now, sorry about that photo, then show up, but the idea back right now for these, for her, it'll be a lifetime issue. Oftentimes with PDR, it does burn out, and there's patients I've seen with Dr. Teske where he did laser 15 years ago, and now they're sitting there with 20-20 vision, and their macula looks pretty good, and the peripheral retina's gone, but you can stabilize these eyes, but oftentimes this is a really long-term process for these patients, it makes it really fun to treat, because you get to know the people really well, but if they're having this and they're either having other problems, and so it can be hard to get them to always follow up, but if you're gonna take care of them for 10 years, you'll get to know them, and it's a fun disease to treat, so. I think we ought to get to clinic.