Hello and welcome to NewsClick. Today, we're going to discuss the app ban. And this is the third set of apps which have been banned by government of India. The first wave comprised of about 59 apps. The second was 47. And this round seems to have included 118 apps. The bulk of this apps which have been banned, or those which have a very large user base, are from 10 cents. Of course, we'll come to what are the implications of this ban later. But let's look at first, broadly, what are the apps which have been banned? And if you look at it, there are a number of WeChat versions, different versions of WeChat which was there. So this has been targeted at closing whatever loop holes might have been there in the earlier banning of the apps, of specific set of Chinese apps. All these, or almost entirely all of these are essentially Chinese apps. So WeChat effectively is banned in all its avatar from the Indian market. This ban seems to have been more targeting the 10 cents ban. 10 cents apps being banned. And out of this, the biggest in this range was what is called the gaming app. Now, we have to understand two things about the market banning of apps. One is, of course, the grounds on which it is in ban. The second is, what are the implications? For instance, the Chinese companies who have also invested a lot of money in the Indian stock market or making investments particularly in the startups. 10 cents has made a lot of investments in Indian market. One of that is in Ghana, the music streaming app owned by Times of India. It seems to have made $150 million investment in this particular app. And 10 cents owns 35% of the company. Similarly, it has also bought in to another Times of India media streaming company, what's called the MX player, and has invested 110 millions in this app. Now, it's interesting, the Times of India, which is with the beneficiary of 10 cents has also been asking for India's, India taking strong action against China, banning apps, and so on. So the money is welcome, but otherwise they should be kept out of the market. Seems to be Times of India's position. So there seems to be a certain degree of ambiguity with which the market players are reacting to that, appearing to be nationalistic, but behind that is a concern, particularly the startup community that it stars the Indian entrepreneurs of a particular kind of investment which are coming from 10 cents, Alibaba, and these kinds of Chinese companies who are interested in the startup market. In fact, the startup market in India has benefited a lot from Chinese investments. So that investment is really going to come to an end. And comparatively, other companies, other players in the international market has not invested heavily in the Indian startup business. Second part is, who are the beneficiaries of this particular decisions? The government of India has talked about that defense is the reason that these apps have been banned and the reason they have given, and that's an important one, the reason they have given is that this is targeted at those companies who give apps to us and various complaints have been received according to the government of India notification about the misuse of the apps for stealing and surreptitiously transmitting users' data in an unauthorized manner to servers at a location outside India. Now, this is almost word for word, the same that was used against TikTok even in the United States. The problem with this formulation, and this is a blanket formulation, that this would apply to almost any app that most apps do take users' data, they do not take authorization, and they have locations, the servers are located outside India. So this is, therefore, selectively being only used against Chinese apps, and obviously it has to do with a geo-strategic battle, particularly in the border, northern border of India, where we are having a standoff, and this app ban is more or less a tit for tat, as it were, of what is happening on the northern borders. If there is a tension that is rising, India seems to be taking action, not only in the northern border, which has been reported, that we are trying to block the Chinese over there, we believe they're doing unauthorized action, I'll leave that out, because I think that's a much bigger issue, but our response seems to have been to punish the Chinese by blocking the Indian market, both for investments as well as for data. Now, as I said, if data is the issue, we'll come to that. What does it mean for India, and particularly for Indians residing here? How do you protect our data, not only from Chinese companies, but all international companies located outside India? Are we saying that Indians data, this is perfectly okay to transfer it to places abroad, surreptitiously, but it should not be done by Chinese companies only. So this is an issue that we need to explore a little further, which I believe. But the key issue is that this is a geostrategic response, punishing Chinese companies for the tensions we are having on our northern border, and this therefore is something which is not going to be resolved by any Chinese company coming to India and saying, look, we could have all our servers here, allow us entry to your market, treat us like any other Indian company, we can invest in India as well, and so on. This is not the basis on which we are really banning the apps. Apps are being banned specifically as a geostrategic response to China. So that I think should be clear. What are the consequences of this that if we do use our national security as an economic argument, then is it possible that China can retaliate? India's position seems to be that we sell much less, China sells much more to us, therefore we can hurt them much more than they can hurt us. Therefore, if we do this kind of action, the quid pro quo will not harm us that much, it will harm China more. Of course, it is also true that while it's correct that India buys much more from China than it sells, but it's a proportion of Chinese trade, Indian trade is relatively much smaller, there's a percentage of its total trade than Chinese market is to Indian exports. We export nearly 15%, I told 15% of our export goes to China, that means their share is 15% in our exports. India share on the other hand, from Chinese exports is relatively much below 15%, it's about 6% or so. Given that China does have also the ability to punish India in a cross sector retaliation. So we leave that point out because essentially should you be using trade as a means to punish China for these northern skirmishes, northern border skirmishes, this is something that we have to think about because it seems to be going down a path which might lead to a reaction which will then again lead to an Indian reaction and the stick for that battle can mean economically disengaging from China. And if we do, then let's face it, a lot of our exports to other countries in the world depend on imports from China. And if we have to substitute those imports, then it could also affect our markets elsewhere. So this is something we have to think through very carefully, not the way we are going in which case, in which we are really banning apps after apps in the belief that there is no sectoral retaliation they can do because China does not use much Indian apps. Coming back to the basic issue that has been raised that apps transfer data, users data in an unauthorized manner and to servers outside India. Now, this was, as I said, was also the TikTok argument that Trump gave in his notification why he wanted TikTok to either close operations or to sell to local companies, local companies meaning American companies and Facebook, in spite of the fact that Facebook was the one who had campaigned against TikTok and wanting TikTok to be thrown out of the American market, said, hey, this is not a good argument because if this is the argument given, then we, as well as Google, as well as any other American company which deals in data, can then also be penalized exactly on the same conditions because we do exactly what TikTok is supposed to be doing. So the question is transferring data outside the countries in which they're operating. If that is supposed to be something wrong, then every American company which deals in data and will come to the importance of data today would also be the same boat. So this argument is being very selectively used arguing only Chinese apps have this problem as if other apps don't. We have a data localization framework that we are trying to build in which we are also talking about critical data, certain class of data being localized in India. Now, if it happens as a part of a larger set of Indian laws, I think that would be welcome, but making laws on the basis of immediate provocations or immediate tensions on our borders is perhaps not the best way to go when you're trying to build a legal framework for people's privacy. And let's face it, data, personal data is basically data privacy issue on which you have a law that is supposed to be passed in the coming months. We'll not get into that today, but let's get into the other issue. What are the financial implications of this ban in terms of who gains who loses?  And who are the gainers? Now, here is the issue that all companies, all major internet players, what I call digital monopolies today, they essentially use data. What is the data they use? Users data. Their strength comes from the users data that they have, the network relationship between users they can see and using that to drive either advertising revenue or in the case of Amazon, for instance, marketing. Of course, Apple is a slightly different company in this. Apple has its Play Store, which of course it gets a cut out of that, but Apple has a very large position in terms of the hardware, software combination, products itself. But when you come to other companies, whether Amazon, when you come to Google, when you come to Facebook, the three other main companies that were held up before the US Congress, all these three companies depend as their lifeblood, so to say, on users data. So if users data is a commodity and today it is, it is the one which is fueling the rise of the digital monopolies in the world. If we look at just the size of 10 cents, for example, this is a nearly $700 billion company in terms of market capitalization, as opposed to Facebook say $800 billion. So it's very close to Facebook in terms of size. What we are doing is, we are saying Facebook is okay, but Alibaba is not, WeChat is not, 10 cents is not, we are really choosing sides. That Indians data in the hands of American companies is okay, but the hands of Chinese companies is not. It's really making gift of India's users data to companies like Facebook. Of course, Facebook has been in the news recently, particularly with this relationship with the ruling government. We also know that in fact, the move against ByteDance TikTok was also pressed by Zuckerberg. Facebook was interested in a campaign against it so that it would be kicked out of the American market because a felt TikTok was a threat to its user base. Is something like this happening in India today? Are the companies who are being identified as the companies who have to be sanctioned in India? Are they being identified by due to basically based on our needs? Are they being identified companies which are hostile to the Chinese companies, see themselves as competition? Are we also fulfilling their agenda? That's a question we need to answer. Hopefully this is something which is specific to our interest as perceived by the body government. But then the question is that while we are willing to freeze out the Chinese from the Indian market, what is it that we are doing to provide a market that will help Indian industry? It's very clear the Chinese, the great firewall of China, protected their users data. That is what allowed Alibaba, that is what allowed Tencent to grow in the size that they have or even ByteDance and the TikTok app, for example. Now, if we don't protect our users market, and if we say the Chinese are not welcome to it, Americans are, then what we are doing is we are bartering our users data, Indians' users data for basically nothing that we are going to get out of it because we are handing over the advertising revenues. Let's not forget Facebook's main strength, main revenue comes with advertising. So does Google's. So we are handing over an internal advertising market to these companies completely. And in the long run, it means the Indian media is going to become more and more weak because it cannot confront what the Facebook's and the Googles of the world are doing. Let's not forget that the main threat to the media anywhere in the world comes from Google and Facebook. And therefore we are handing over our media in the long run to these companies. And that is a huge consequence for democracy. It is a huge consequences for our independence itself. So I think we have to read the app ban, not simply as app ban, but you have to read the app ban that we are trying to choose sides globally, but we are not willing to choose our own side, how to protect our people's data from any foreign company. And I think that's the key issue that we need to address right now.


to aunt scripture like I told you before we have shaynees right here in the studio and of course she's a budding artist and she'll be telling us more about her journey in music welcome to the show thank you oh my god you look so amazing you look so nice thanks all right so check us through your journey in music maybe you can give us a little background about yourself and about how you got started the music and how this has been for you okay officially I started in last year yeah but I tried to tell but yeah so I go back last year I recorded my first song now go back yeah then in like three months from then I recorded my second song then but now I have four songs oh yeah nice four songs so how has the journey been for you since last year until this moment how has the journey been I know but but it's a little bit in a town yeah yeah because you remember you told me um about some of the things that were happening in the industry you didn't like them maybe you can tell us some of those one of those things that happened maybe in the in the short time you've been here that you didn't like about the music industry okay the fact that a lot of people in the like presenters the days want to play a song unless unless it gives in to their demands yeah demands like uh money I'm a what kind of demands from ladies mostly they're really sexual it's from bj yeah that's awful all right but still you told us I yeah you said it back in 2010 and then you stopped okay definitely when I have the money so I plan that I go back to school finish up get my money then get back to studio yeah yeah so you already graduated yeah I'm working oh nice maybe you should tell guys that that is why do you think it's important for people to like as much as you're talented to also go to school why do you think that is important okay knowledge everything yeah it's power and it's everything yeah so I went back I did a diploma in clinical editing yeah and right now I'm working for myself in county all right so um you have a new single out now it's called the scene uh tell us about that how did that come about yeah okay scene is about okay it's a true story about okay it was some years back I was in a relationship with someone when we were down but when we got the money yeah he left me for someone else yeah awful but as much as it's awful it actually happened a lot and that's what people don't understand because people are out here telling ladies all the time look for that one guy you build a life with him it doesn't work but I don't know do you need money? yeah they try something else they try to something else yeah all right so in your case give us a little bit give us more what happened this back to me to an amali because I actually saw that in the video I saw in the video how your heart and then he met okay just give us details okay like it was 7g now but so much what do I do but new point or a new point do I do am I right okay like one of the five One of the fun, the groupies actually, let's call them groupies. That's quite unfortunate. But anyway, you're here as a song guy in Bertha. So tell us about the writing process for you as an artist. When do you write? Because you're working and then you're also an artist. How do you find a balance actually between music? Okay, between singing and then writing and then school, work. Okay, just spend time. If you have passion for anything, you'll spend time for it. Yeah, I spend time. Okay, I also, let's say, do you want to send a letter to a Jay. Jay and Betty from Tanzania. Oh! Yeah, that's a super blessing about a lot of Swahili in my song. Oh, so he helps you write the music. That is nice. So in the Kenyan industry, you've worked with anyone so far? So far. There's another song coming out very soon. I've featured a rap artist called Patuz. Right, are you looking forward to working with more artists? How many years have you been working with them? How do you inspire people in the Kenyan industry? In the Kenyan industry? Right now. Not really, but who knows, I'm going to work with him now. Like Nadia. Nadia Mokami. Yeah, she's amazing. Yeah, Ochile Brown. Chikuse from Basak. Yeah, I love Chikuse. From Kenya. Yeah, I know him. We've heard him a lot. Why on different shows before? Yeah, he's amazing. Yeah, and Kinka. Yes, he just dropped an awesome album, definitely. Alright, so moving forward, what do you want to achieve? Because obviously you tried music in 2010, it didn't work out. But you're back and you want to pursue it. What are you doing differently currently? To make sure like, I top up at 2010. Okay, one of the things is working on my finances. At least I won't have to do someone a favor for them to record for me. Yeah, yeah. These are things I want to do music different from the other artists. Right. So for you to grow, do you find time? Do you have vocal training? Or how do you work on yourself to make sure that you get better? That you sound better than you did on the last song? Or just to make sure you do better music? How do you practice? Just tell us about that. Not really, but I'm planning to. When I go for my liver, I'll start vocal training so that I can get better. Oh, that's amazing. Also, so this karaoke, obviously the show is karaoke. And everybody who comes here, you have to do a little acapella for us. We want you to make doggo. Billy L. S. Autea Studio, Nyan Nyan, Nkhtungu, Naroiko, no? Just you, they're all you. You guys want to hear that. So maybe you can choose any of the songs that you've done before. I'd like you to make doggo. Just a bridge. It's a bridge. It's a bridge. Yeah, it's a bridge.


This is the fatherless football. For $32, you too can own one. Let's see how it works. It's overrated. Excellent for training. Will not bring your father back.


Greg, how do you reconcile eating flesh with the fact that sentient beings are being killed without giving their permission to take their life? Well, Dolores Cannon spoke about that. When you ingest meat, it's giving that animal the opportunity to experience humanity through you. You have been all these animals, plants, insects, you've been everything just to get to where you are right now. And this is the animal's first opportunity to experience what it's like to be human. When you eat vegetables, that's a living sentient being as well. So it's doing the same thing with the vegetable, it's giving the vegetable the opportunity. And of course, you know, as empath, we feel the empathy of the animal, but we also bless the experience. So if you can find some kind of peaceful understanding between the two, it'll be okay. But if you're being guided not to eat it, then don't.


You will not die, but there is an old version of you that must die to step into a new version of you. Today we're going to be talking about how to have a breakthrough in your life. And to be a little bit honest with you, there's parts of this episode that might be a little bit tough for you.  So I was watching a movie not too long ago. It's called Honey Boy. I recommend it if you guys like Shia LaBeouf. And he speaks in this, it's kind of a rough movie on his childhood of being a childhood actor. And I watched it and whenever I want to, whenever I hear something in my life, I'm listening to a conversation, watching a movie, seeing a video, listening to a podcast and an idea comes out of my head. I'll put it inside of my notes tab and I'll look back later on and be like, hey, I could do an episode on this.  And he said this quote, it says, a seed has to completely destroy itself in order to become a flower. Let me say that again real quick.   You cannot bring an old version of you into the new version of you.  You literally have to become somebody different. And so when I think about myself, for instance, and you could think about yourself as I'm talking about this, because I know my story, you know your story. If I think about myself today versus who I was five years ago, who I was 10 years ago, who I was 15 years ago, who I was 17 years ago before I got into personal development and realizing that I was fully in control of changing my life and nobody was going to come and save me. I'm a completely different person today than I was when I didn't have an idea that I could change myself. When I looked at the world as a victim and I had a victim mindset and said, oh, I'm just this way because I grew up with an alcoholic father and it's the world's fault. It's the government's fault and I had excuse after excuse after excuse after excuse. When I look back to who I was, let's say 17 years ago, I have actually destroyed who that person was. I destroyed my habits. I destroyed my way of thinking. I destroyed my way of talking to myself. I destroyed my way of talking to other people. I have mentally, physically, emotionally, energetically destroyed who Rob Dile was 17 years ago compared to, in order to build up into who I am today. And I want you to think about that because it's exactly the same for you.  I had an identity of myself of who I thought I was that needed to be destroyed in order to build myself into who I wanted to be. I built a new version of myself and brick by brick by brick by brick just like building a wall. I built myself into who I am and you can build yourself into who you want to be at any point in time. So you're listening to this podcast. You're in self development. You're dipping your toes into the self development thing because there's a part of you that thinks, if I work on myself, I might be able to build myself into who I want to be. If I work on myself, I might be able to create the future and the life that I want to. But the life that you want is absolutely impossible and will never happen unless you change first. Your life will not change unless you change. Your life will always be the same if you are always the same.  And so if I can look at myself today, I can see everything that's in my life. Everything that I have, everything that I am, all of the people in my life are based off of who I was in the past. That can be a good thing for some of you. That could be a bad thing for some of you. That could be, you know, looking at it and going, well, damn, yeah, I do want to change some aspects of who I am because I do want to change aspects of my life. And it's, I don't know how many times I've said this in the podcast. I've done over a thousand episodes, but so many times I've said this. The Einstein quote is to expect different results, but stay exactly the same as insanity. To think that your life can be different, but you continue to do the same thing over and over again. And expective results is absolutely insanity. Sometimes, and this is why it might be a little bit tough, sometimes you have to have a breakdown in order to have a breakthrough. This is the benefit of life. This is the benefit of relationships, great relationships, failed relationships. But the problem with that is a human's resist change. The human brain will always resist change. You will subconsciously resist change. Always. You can consciously want change. You can consciously want a different life. You can consciously want to build a business. You can consciously want to have a deep relationship with the person that you're in relationship with. But change is always a threat to the brain. And so the mind will resist change because change means a destruction of who you are.  And that alone is scary to the parts of your brain that are not with us. In our old, old, old, old parts from our ancestors 100,000 years ago, 200,000 years ago, all of that stuff. There's still parts of our brain. The amygdala, which is an, you know, in the limbic system, which basically is the animal part of your brain. There's just like survival, survival, survival, survival, survival is going to resist that. So you can consciously want to change, but subconsciously hold yourself back. And this is why, and I don't hear people talk about this enough, especially not in self development. You can feel like you're at two ends of a spectrum with yourself. Like you can want to change so much. And you're just like, God, I don't want to be in this situation anymore. But continuously self sabotage, self sabotage, self sabotage, self sabotage, self sabotage. Because there's a subconscious programming running in the background that's going to try to subconsciously self sabotage you. So therefore you don't change because change is automatically seen as a threat.  But there is an old version of you that must die to step into a new version of you in order for a butterfly to become a butterfly.  And it's got to literally completely transform itself to become a new version of itself. And so I want you to think about this as I'm talking. Are there parts of yourself that you're resisting the change?  In order to change my life, I need to wake up and have a morning routine.  Right. That's the little part of you, the little inner voice.    Life is a beautiful thing. There's beautiful things that happen. There's terrible things that happen. There's tragedies that happen. There's successes. There's amazing moments. There's terrible moments. But we have to look at it and through the lens of everything that comes to me is an opportunity for me to transform everything that comes to me is an opportunity for me to change myself. If I have a great relationship with somebody that is calling me into a greater version of myself to show up better for this person so that I can have this relationship to stay in this relationship, to change myself, but also to change them. I've also been through some breakups. I'm sure you've been through some breakups before that are earth shattering. And sometimes those relationships need to happen in order for us to wake up and go, you know what, I need to change. It can be that person's fault in many ways as well, but it can also be our fault in many ways as well in our lens needs to be what happened to me happened. And this is what one of my favorite quotes from Peter Crone. He says, what happened happened and could not have happened any other way because it didn't say that again for everybody. What happened happened and could not have happened any other way because it didn't. I believe that everything happens for a reason. I've gone through the ups and downs of being like, there's no such thing as fate. Everything happens for a reason. And then not everything happens for a reason. And I've gone through every up and down and nooks and cranny of my mind to try to figure it out. And the older that I get, the more I start to realize, damn, that thing did happen to me so that I could make a change. That thing happened to me as another version of growth that I need to step into. I was in a, I'll be honest with you. I was in a psychedelic journey one time. I was, yeah, I won't tell you what I was doing, but I was in a psychedelic journey one time. I'll leave it at that. And I saw this like visual of a flower, a rose, a red rose is what it was a visual of. And I saw that, you know, a rose will bloom from the center. And then in order to make room for a new leaf to come through, the leaves on the outside must die. They must crinkle. They must fall off in order to make room for the other one. And life as a human is that life as a human is an order for that new version of me to bloom from the center, the new fresh, great smelling version of the flower that is me.  I must have other parts of me that need to change it, need to go. There is only so much room on a flower and a rose. So in order for me to make room for the new version of that flower, for the new petal to come out, old petals that do not serve that flower anymore, anymore must die off. And that is exactly how life is. But it's really, really hard. So much of what we do is rooted in our identity of ourselves. So much of what we do is rooted in our identity. And if we don't have our identity, what do we have? And at that point in time, it becomes very hard for a human to figure out, like, I've gone through very tough times before that, you know, people in the spiritual world will call it dark night of the soul, where it's like an order for me to figure out who I truly am. I've got to go through some really hard stuff. And that is the world or the universe or God or whatever it is that you believe in presenting you with things that make you change in order to have a breakthrough. Sometimes you have to have a break down. And I remember there was one time. It's about four years ago at this point. I started really thinking about what I do. And at this point in time, I was already in self development. I was already a coach. And there was about three weeks where I remember I was like, it's just something doesn't feel right. I feel like I'm like I'm leading from who I am, but there's a part of myself that isn't my truest version of myself that's still sticking around. And I had to go through this journaling and meditating every single day, every single day and be like, what is it that is sticking around that is not a part of my highest potential? And I need to get rid of it. I need to identify it. I need to get rid of it. I need to work through it consciously every single day and be very intentional about working through those things. It's like in order to build a new building, sometimes you got to destroy the building that's there. You've got to destroy a building and build a new building. That's the backbone of personal growth. The backbone of personal growth is you have to lose yourself in order to find yourself.  You have to lose yourself to find yourself.  You know, sometimes you're painting, if you've ever painted before, I've done painting before and I'm not a good painter in any sort of way.  This thing looks like trash. And it gets the point where it's like, yeah, this, I'm too far down the line of this canvas.  I've gotta throw this canvas away and I've gotta go for a new canvas. I've gotta literally put a brand new canvas on and start painting again. That's exactly how life is sometimes.  It might be great. And you just know that there's more potential or you might be looking at your life and it might not be that good. And it might not be that great. And you know that you have to look at that canvas and go, this canvas has to go. Like I can't just make changes on this canvas anymore. I've gotta throw this canvas away and I've gotta get a brand new canvas. I gotta go to the art store. I've gotta buy a new canvas and I've gotta buy a new paint and I've gotta start painting again. Sometimes that's what is required of you from personal development is to be that way. And one thing that is very important that I don't hear talked about enough in personal development and another thing is that sometimes you might have to mourn the old version of you. The old version of you got you to where you are. And that's a good thing. It's never a bad thing. It got you to where you are and it did its job. But it's gotta go at some point in time. I remember I had this really deep meditation one time and I realized all of these fears that were in my way of my highest potential. And I had to mourn these fears, not mourn them in some crazy way, but almost like a mini death of these fears of going, you know what, these fears that I have that are holding me back, they are a good thing. I have these fears for a reason. They protected me for a really long time. Like these fears protected me emotionally when I was a younger kid and I was going through a lot of stuff with my father. These protected me. They're like my friends that have been with me for a really long time. And you know what, they're a part of my identity. They're part of who I am. But in order for me to step into who I want to be, I've literally got to get rid of these things. So what am I gonna do? I'm gonna mourn these. I'm gonna let go of them. I'm gonna say, you know what, thank you so much fear of emotionally getting invested into somebody. Thank you for that fear because it protected me. But in order for me to step into new relationships that I wanna have with myself, with people around me, with everyone that I wanna impact, I've got to get rid of these fears of allowing myself to open up and be emotionally vulnerable to other people because I won't be able to step into that new version unless I get rid of it. And so I had this whole deep meditation of like, this is a fear I need to get rid of. Hey fear, thank you so much for everything that you've done for me. Thank you for being here. Thank you for protecting me as a child. Thank you for helping me get to where I am. Because without that fear, I would not be who I am. And I love who I am, but I know there's another side that I want to grow to. So in order for me to get to my next level, I gotta let go of you. Thank you so much for everything that you've done. But we can't be friends anymore.  Change is not easy. Sometimes it needs to be more, but change is necessary. And the one thing that I know about humans is that progress equals happiness. I have never seen somebody that is in true alignment with who they feel like they need to be in this world and what they need to do in this world. I've never seen somebody that's in alignment with who they need to be and they're making progress day after day after day. Even if it's just a tiny bit of progress and they're having real progression, I've never seen somebody who is making progress towards the life that they want that is unhappy. Progress equals happiness.  There is a version of you that wants to bloom, that wants to come through, but there's just not enough room on the rows anymore. And so in order for that side to bloom, you've gotta let some of the pieces, some of the petals die. It might be fears, it might be thoughts, it might be identity shifts that you need to have and you need to look at them and say thank you for being here. Thank you for what you've done for me. Thank you for this relationship that we have. Thank you for all of the perspective that you've given me but it is time for us to break up. We can no longer be friends. I gotta let you go. And you've gotta let go of those things to step into a new version of yourself. To loop this all back around, I'm going to leave you the exact same way that I started you with this quote.  So if you want to become a flower and you want to grow into that version of you, you have to ask yourself what pieces of me need to be destroyed so that I can step into my true potential. Hey, thanks so much for watching this video. If you wanna learn even more about Master Your Mind, click right here and watch this video as well. Do you follow your dreams or do you watch Netflix? Do you work for the business that you wanna create or do you scroll on Instagram?


Good morning guys. Good morning. I can't believe it's July 30th. I mean the kids going back to school are saying, summer's over. Oh my god. I feel like summer began. Anyway, so we're going to kind of pick it up where we left off. And I'm going to provide you with an overview of treatment of UVIS. Plug it in. Fundamental to treating UVIS is establishing a diagnosis. So as we were talking about last time, it's really essential to establish a diagnosis, even if it's idiopathic to exclude an infection or a legacy. If you have an infection, it's treated with appropriate anti-microbial therapy. And then if it's a non-infectious or disease-specific implications of treatment, which we're going to kind of go over a little bit. And then kind of a step-lighter algorithm.  But it's an approach. It's basically a kind of philosophy of taking care of patients. I think one should always be willing to step back, reconsider your diagnosis, particularly if you have an atypical response to treatment or if new findings emerge. The diagnosis may be different or you actually may be treating something that you don't want to be treating. So the goals of treatment, okay? We want to eliminate inflammation with prompt control of acute activity, suppress chronic or recurrent disease, and an attempt to reduce an induced remission, which is difficult to do in a lot of cases with UVIS. This whole approach is an effort to prevent, reduce ocular structural complications, which can interfere with vision, such as cataract, macrodema, scarring, quadrilateral scars, and to minimize potential systemic complications or ocular complications of therapy. So in essence, we want to have our cake and eat it. And I think that in many cases it's possible, but it takes some doing and a little bit of, you know, empiric therapy sometimes. So this stepladder approach, basically very broadly speaking, is we start out with steroids, okay? Steroids are the first line treatment for patients with UVIS. Frequent steroids, topically or systemically, but for edgier segment inflammation topical steroids and psychoplegics. I don't really use oral non-steroidal anti-inflammatory medications very often, except when they are indicated for a patient that already has disease from which they're taking it, such as certain types of spinal or throat disease, in which I think in some cases it may be somewhat steroid-sparing. Then periocular and intervitrial steroids, which will go over brief systemic steroids, you know, dividing the length of time with oral prednisone, usually about a milligram per kilogram, tapering, and then the early implementation of steroid-sparing immunomodulatory therapy in patients that are not responsible for development of side effects. And then finally there is, I think, a role for retracting in UVIS, although that is really not well-defined therapeutically. So we have the route and the choice of medications really determined by the anatomic location we were talking about last time of the inflammation. The accurate complications that it can induce, and really the systemic health of the patient. So tapering steroids, for example, are adequate for purely anti-ov-UVIS, but they will not penetrate to the back of the eye. So here are our choices, topical periocular implantable devices, systemic steroids, immunomodulatory therapy. We use them depending upon the location of the UVIS, so anti-UVIS, topical steroids are really the choice. In intermediate UVIS, usually, we begin with periocular injections and sometimes systemic diseases, and then advanced therapy is needed. Post-UVIS similarly, and then in pan-UVIS, this inflammation affects all segments of the eye. We can use, we have everything available to us. So just topical steroids, I don't want to insult your intelligence or anything like this, but when we use topical therapy, if you have inflammation in the eye, use it frequently enough to put out the fire, to put out the inflammation, so don't start out with BIT topical steroids. Treat it frequently, a high dose delivered directly of the anterior segment, and then once the inflammation is under control, taper it sometimes slowly, depending upon the disease, but taper it and then there is limited delivery of the posterior segment with the exception of a couple of situations. So diphenyl prednate does have pretty good posterior segment delivery. A caution about that is four times more potent than predfortag, and is much more steroid, side-effect-inducing with elevated interaction pressure and cataract. And it particularly produces those problems with age children. The other thing is that in a betrachromized eye, you may have better posterior segment penetration of wall drops, so non-stroidals as well. So as I was saying, you start out with high-frequency taper over about six to eight weeks. Frequently, we will employ cycle-pleagian that cases of anterior uveitis for comfort for the patient to avoid ciliary spasm and also to prevent sneakiness. I prefer to use a sure-acting cycle-plegic such as home matrimony or cycle gel, cycle petalate to move the pupil rather than to keep it in a fixed dilated position where I think the sneaky would be more apt to perform. Regional steroids provide local sustained delivery for about three to four months and minimize systemic adverse events, and they're very useful, particularly in acute non-remitting disease that is unilateral, particularly intermediate uveitis, and the kind of indications are obviously an infectious disease, so you would never want to administer a periocular or an inferior steroid in a patient that has toxoplasmosis or in whom you might suspect of having arm scolitis, or you would be loathed to do this in your circumspect in a patient that has a really large steroid, high steroid responder. So the preparation we most often use is a triapicillone acetate of 40 milligrams per mil. You can deliver it either in a posterior subtenance injection or an orbital floor, and they have equal efficacy. It is effective in both reducing inflammation and in macular edema in about greater than 50% of the time, and there is additional benefit for repeated injection. There is, of course, the risk of steroid-associated side effects of cataract and intraocular pressure, which are not actually minimal. Similarly, with intravitual corticosteroids, triapicillone acetate has been used most frequently in two to four milligrams. It is quite effective in reducing CME in about 85% of cases, improving vision, and decreasing vitritis in the duration is about depending upon the eye or eye as it protects my astronaut in about three to six months. There's no tachyphylaxis to repeat injection, so it's equally effective each time, but the cataract, it induces cataract and intraocular pressure more often. One study showed that basically cataract requiring surgery occurs after the fifth injection in a large percentage. You're familiar with the Ozardax or dexamethasone delivery system, so it's a different steroid in dexamethasone. This was approved for use in uveitis through the Huron trial. It had advocacy in reducing haze, macular DMA, and as opposed to sham with, you know, at least initially where it got approved with minimal intraocular elevations of pressure and cataract, but this was a six month trial. Patients that were steroid responders were excluded from the trial, so they had to wait for kind of post-marketing experience where the efficacy is actually still effective in patients with even greater inflammation that was required for the trial with reduction of macular thickness in patients with macular DMA. Elevation in the intraocular pressure a little bit more, you know, 40% of patients, more instance of filtering surgery and cataract surgery. And while the studies show, you know, a reinjection frequency of a mean of about six months, I think in clinical practice most people find that you have to re-inject people more like three or four months. When you're determining whether or not to use something like ozardex, like intravitrile versus periocular, like what are you thinking about, like in terms of like when would you use periocular versus ozardex? Yeah, well that's actually a good question and it was something that we attempted to you know, there's a study called the point trial which was included which I'm going to talk to you about a little bit that may answer that question. But in general, okay, I am using periocular stearers a lot less frequently than I was previously. I think periocular stearers have a role in patients with very mild macular DMA that may for example be macular DMA that is peri-phovial but not quite underneath the phobia in which you don't, the patient may be adverse to an injection because it is effective, post-operatively after the tractomy surgery in patients that have vitreous haze with no macular DMA and intermediate uveitis you know, it's your first encounter with a patient, they may have a little bit of leakage from their on their angiogram, they may benefit from a periocular injection. So that's what I'd be thinking but in more severe inflammation, I think more go to is intravitrile. So, I'm, Ogedex has actually shown efficacy you know, in the pediatric population and in, it is it has a similar disillusion rate in a vitrectomized eye and not a vitrectomized eye. So, I mean, I think that is helpful in a patient that has a vitrectomy for example and if you put an intravitrile triacinth into their eye, they're going to have the dispersive effect of all this with these crystals in their eye and they won't be able to see very well for a day or two or maybe longer whereas in Ogedex this thing is floating around and they're similarly effective. So, regional corticosteroids the problem, they're relatively short acting they're less effective for chronic inflammation so you'd have to continue to repeat the injections there's theoretically and I think that in practice with each relapse of inflammation that a patient may have or with chronic inflammation there's this kind of sawtooth decline in retinal function with each relapse or in chronic disease progressive dysfunction so you, a approach where you're injecting a patient every two months is probably not really a viable approach for chronic therapy so those patients might need systemic therapy which we'll discuss. And then of course is the cumulative risk of ocular side effects, right, cataract and glaucoma and also the cumulative effects of endothelitis. So to your point Brad, there was a trial that we were the PIs for here called the point trial, the periocular and intubitrile corticosteroids for umidic macchiordema trial with clinical impression that intubitrile therapy may be more effective than periocular therapy but may have a less favorable side effect for a trial. And that the impression, clinical impression is that objects in intubitrile time cell may be similarly effective but you know the studies that went for the approval of the medicine seem to indicate that maybe objects were safer. So a less controlled trial was conducted to evaluate, you know, what's the best first line treatment for macchiordema in patients with either inactive or active inflammation. And I don't have time to go through all the nuances of that trial but the bottom line is that all three are effective, but that intubitrile approach is more effective in reducing macchiordema, both azuredex and dexamethasone than stearoids. And that that was clinically and statistically significant and that that was at the cost of a moderately elevated intraocular pressure rise in the intubitrile group that could be managed with stearoids. Again, this is a pretty short study. The other interesting aspect of this was that the intubitrile dex was not inferior to the intubitrile approach. In fact, although it was empowered this way, we're studying it seemed because of some of the complications of the study design it seemed that the may have a not statistically significant advantage over intubitrile therapy terms of efficacy. The other thing that we learned was the peak efficacy of the seems to be about 8 weeks rather than 8 weeks. And that intubitrile dex monthly implant did not seem to have an advantage with respect to intraocular elevation of the pressure. There is another trial that is a sister trial to this with related to macrodema called the Merrick trial that is ongoing. Again, we are principal investigators for this site and there have been some other non-steroidal agents that have been shown to be actually useful in the treatment of macrodema including anti-veg agents, both Avastin and Lucentus and intervirtual methotrexate which has been used as you know in the treatment of intraocular lymphoma but also in terms of patients with uveitis. And one large retrospective cohort showed that induced a durable remission in over 70% of patients. So what is the best treatment? So one of the big problems in uveitis is that patients with apparently controlled inflammation can still have persistent macrodema up to 40% of patients in fact. And in the MUST trial 62% of patients in systemic therapy are additional periocular or intubitrile injections. So what is the best treatment for patients with controlled inflammation who have already had an exposure according to steroids? So your choices are to give another steroid in the eye or maybe try something else, so that's what we're studying in that MUST trial. For more longer acting steroid delivery, there's the red assert. This was approved back in 2005 and it showed definitive efficacy with respect to reduced recurrences and compared to the fellow eye, decreased requirement for junctive therapy and improvement of stabilization in vision eventually in 80% of the patient. But at the cost of not unexpected, frequent eye-ocular complications by marinating an eyeball in steroids for two and a half years. So this implant will release flucinolone and setinine for just moderately potent according to steroid for two and a half years. So everybody in my experience gets a cataract. Medical therapy is required about three quarters of patients. That's pretty why. And filtering surgery both in the trials that led to the approval of the implant and in the MUST trial was necessary in 30 to 40% of patients. So that's not insignificant. I think that we'll talk about this and we can talk about it offline as I say. But I think this is a great device in terms of the cost of significant eye-ocular side effects and you have to this is where individualization is important. So our job I think particularly younger people is to prevent eye-ocular complications and create them. There is a long term people will say what's the big deal of cataracts and you can always do a cataract with it. I would agree with that. But there is a big deal about glaucoma surgery I think. So there is a long term risk of that. There is also an alona set-night insert which is an office-based delivery. Sorry, the red assert is a device that needs to be implanted in the operating room. I just have a minor detail so the patient needs to go to the OR and you know there is a you have to implant this with a paris plana incision into the eye and suturing it into the eye. So it would be great to have a similarly effective implant that you could inject into the office. And indeed this has been developed by alomarous sciences and by eye point. The aluvian implant is confusing but aluvian was from alomarous sciences. This is the implant that was approved for the use of diabetic macular or the eye point product. It has been approved recently in October for uveitis. So there are slightly different there are different companies that own them. And there is no indication for the use of aluvian in uveitis although some people have used them. But now we do have a device as you can see here which is an office-based inject injection of flucinolone into the eye and it's a bioerotable device that is it's contained in a polyamide cylinder that elutes in phase one kinetics into the eye once it's injected. So you are left with this little thing that kind of floats around in the eye but it usually lodges in the vitreous. I personally do not have enough experience to tell you whether or not patients see these things or not. But Glenn Jaffee who pioneered this has not really had that experience. So it's the efficacy of this has been shown in pivotal randomized controlled clinical trials with significant reduction and lowering the currents rate as compared to sham decreased incidence of loss of 15 letters of vision and it allows less adjunctive therapy to be used but then a higher rate of cataract development and note again this is fairly early I am sure that you are going to see more cataract development and probably more elevated intravenous complications in this device. Just with respect to macadamia in the one year 12 year results about 74% versus 48% patients in sham had resolution of their macadamia so as we will see this may end up becoming actually a very useful device but patient selection is really important so it is the slowest releasing of the devices and it may be useful adjunctively in the office in patients that are on systemic treatment that have persistent macadamia or in patients with moderate inflammation in their eye and unilateral disease such as in patient with intermediate EVIs there is another delivery system that is being pioneered supercruital delivery of a triumphal by clear side biomedical and there is animal model that supports this versus intermittent injection that this may give you a higher amount of medication to where you want it to the core and RPE cells with a lower exposure of medication to the anterior segment so when you plan to read a certain into the eye it is right behind the ciliary body so it is thought that location is important with respect to the induction of cytokinesis we are not in this trial but I did try using this device it is pretty fast some patients will report some pain associated with this injection by injecting medicine into the supercruital space as they do when they develop supercruital hemorrhages but it is a very actually unique device and again there are phase 3 randomized controlled trials NDA has been submitted to the FDA for its approval remain known by academy of time whether or not this is the approval and it reached its primary outcome measurement which was basically visual duty outcome 46 or 47 percent of patients versus 50 percent of sham team layers of vision it is also a significant reduction in central macular thickness and it reduced a requirement for rescue that is local steroid rescue versus sham so sham patients were not treated they were treated with periocular and so far there is a low incidence of intraocular pressure and cataract so far stay tuned so systemic corticosteroids are really the main state of severe disease particularly when it is bilateral prednisone has a terrible reputation among patients and maybe people don't use it but it is a very effective medication used properly I think without creating a lot of the litany of steroid side effects that you would read about if you were to open up all the side effects of this medication I think that they are manageable and in our clinic we weigh patients, we check their blood pressure we check their blood sugar and their fasting limits and we don't have patients on steroids for super long periods of time so we have a defined interval of about 3 months we set goals with the patient in terms of how much we always supplement them with D and calcium because one of the major side effects of the medication is blossom calcium and use angiobesortable agents is necessary immunomodulation immunomodulatory therapy is necessary in patients that fail to respond to corticosteroids in patients with unacceptable side effects of corticosteroids or diseases that are known to be poorly responsive to monotherapy with corticosteroids and we'll go over some of that or when you're tapering a patient often they get to 20 milligrams prednisone and they have recurrence it's just you're not going to gain anything by continuing to elevate their prednisone continuously and giving them chronic exposure steroids you need to add something else or spare steroids in the long run so there are certain diseases we know that need immunomodulatory therapy at the outset those include Bechette's disease severe ocular ocular supragenous chordopathy tyrosine scleritis and sympathetic ophthalmia there are some other diseases in which the experience suggests that really early implementation if not at the outset may be beneficial in the long run in terms of the progress of those patients those include birdshot, multi-vocal certain cases with JIA and some cases with HIV-AIDS so what are these agents so I like to think of them again because I think I try to think broadly stupidly but in broad categories so there are so many agents available or coming available so I think you one useful way is conventional therapy biologic therapy so conventional agents and biologic agents actually by definition modify some specific aspects of the immune system so conventional agents are more broadly acting they interfere with either DNA or protein synthesis and affect the body all the cells in the body like methotrexate will affect immune cells but also the gut other agents will have specific receptor ligand antagonism such as IL-2 for cyclosporin there is receptor blockade and there are others for which really the anti-inflammatory mechanisms are not quite known so the conventional agents again thinking in broad categories are the anti-metabolites that those include methotrexate mycophenolate, monochial or cell sept calcinerine inhibitors or T-cell transduction inhibitors such as cyclosporin and tecrolimus and then the alkylating agents chloribus cell and cyclophosphide which we don't use that frequently these days because we have more we have alternatives such as the biological agents these agents are actually useful in certain disease states in inducing remission to my knowledge there are not very many agents that actually do that the alkylating agents are the only ones that do really so for patients for example with Baciasis disease remission induction has been shown with chlorimus cell and cyclophosphide for patients with necrotizing scilaritis associated disease angiopositive disease we do have retuximab chlorimus cell and cyclophosphide so treatment principles you got a fire, you want to put out the fire with a fire hose not a squirt gun so you want to use a large dose by whatever as Nalcomax would say by whatever means necessary so by whatever route you need to use to put out the fire and then you want to keep the fire out so you taper the medication and then if there's recurrence think about immunomodulatory therapy or if it's disease that doesn't respond well to monotherapy then immunomodulatory therapy so in order to do that you need to know something about your drug so using steroids as a bridge is useful in patients for example for whom you're going to put on any metabolite because most medications will require two to three months to become actually biologically active so you want to have something on board tapering your prednisone while methotrexiders cell systems become biologically effective so with immunomodulatory therapy as opposed to steroids where we start out with a higher dose and then taper down we start out with a moderately high dose and then taper up with monitoring side effects so we want to closely monitor these patients both clinically to see how they're doing on their medications then with laboratory investigations at baseline and at regular intervals to exclude infection and then to monitor the hematopoietic side effects or renal side effects for example cyclosporin will produce renal side effects and those patients need to be followed for PUN creatinine whereas liver function is more metabolites so there was a very large registered study called the site study that is still kind of ongoing and it's collected a lot of important and informative data from five huge Iveitis practices in the United States on the use of these agents and it has shown that basically the anti-metabolites work about 60 to 70% of the time so that means that you have a fairly high percentage of patients in whom you don't have a response and at the remission rate for patients with anti-metabolites is fairly low whereas the remission rate for patients with cytoxin is high higher however it comes at a price of significantly higher toxicity there was a trial called the must trial the multi-centric Iveitis steroid treatment trial which is a very important study that I encourage you to read the reports on both their two and seven-year data which I'll just briefly here is a randomized controlled trial of the flucinolone implant versus standard of therapy that is steroids first and then the addition of conventional basically immunomodulatory therapy to see which is better or whether or not there was equivalence because a lot of people would say oh my god you're poisoning these patients with immunomodulatory therapy why can't we just inject something into the eye so the two-year results showed that both with respect to the implant and to the systemic therapy that the visual outcomes at two years the study was designed as a two-year study but there was a follow up for seven years I think that's an important point of argument that we can talk about some other time but the end point of the study was at two years and it showed similar visual outcomes their inflammatory control was statistically significantly better with the implant but vision was the same and systemic therapy was incredibly well tolerated so we learned some very important pieces of information so inflammation was slightly better with the implant vision was the same and patients really did well with systemic therapy other than having to have more prescriptions written for infection so a person's on methotrexate they get a cold, they go to their GP and they say oh you're on methotrexate here's an antibiotic prescription that's really what I'm talking about but it came at the cost as I was saying significantly increased the amount of cataract IOP requiring therapy and glaucoma surgery and a large number of patients the results at seven years were interesting so this is not a designed end point but a large portion of these patients followed up to seven years and what it showed was that at seven years there was actually a switch to a more favorable response to systemic therapy and that switch occurred at about five years and it occurred probably concomitant with the decrease in the efficacy of the implant implantation was not required in this trial although patients were re-implanted but it was not a requirement and that overall favorable visual outcome in the systemic arm and that there was a higher proportion of patients that had legal blindness in the implant arm benefit systemic arm so these graphs kind of show that with respect to inflammation there is a statistically significant difference up until about 54 months and then at about five to six years this switched your favoring systemic therapy both groups had anti-inflammatory coverage which is probably why the systemic arm did better because they had continuous anti-inflammatory therapy with respect to macurodema not so much only a statistically significant difference at about six months for the implant that again switched at about 54 months favoring systemic therapy all of your complications you know as I mentioned to you in the trial at seven years similar cataract glaucoma surgery then systemic adverse events were similar as in the two-year study with more antibiotic treatment infections and similar quality of life for both groups so what does that mean you know I mean you can interpret this data in two in two very different ways but that long-term visual outcome favor systemic therapy versus the implant and the reason for the decreased vision was thought to be the increased in the amount of macular damage and cortiretinal inflammatory lesions there was initials better control with the implant you know that initially with the implant then later on at seven years obligation rate as expected with the implant so I think that you know the treatment implications is that systemic therapy works okay that it may be better for a lot of patients as initial therapy but the implant has excellent control of information I think again I would never I can think about this data in two very different ways because I think it really needs to be individualized to the patient there are patients that are intolerable of corticosteroids there are patients that just don't want to be on systemic therapy that will do well with this medication there are patients that have had unacceptable side effects of systemic therapy for which implants are actually very good options as I mentioned the the adjunctive use of intervitual therapy with more longer acting maybe extremely useful particularly in patients that are on systemic therapy that have small recurrences of say for example macular so biological therapy the other large arm they are therapeutic bioengineered proteins that are antagonists against immunoactive molecules not that you should memorize this but this is really what is you know available these days that we use in patients with with their RISO inhibitors the CD20 inhibitors IL-6 inhibitors IL-1 inhibitors they are we have borrowed really heavily from the rheumatologic colleagues in terms of using these medications as they have pioneered the use of these arthritis but just to go over the things that you will see most frequently in clinic so the TNF inhibitors there are many of them but the ones you will see most often are N-Brol influx map and Adaluma map N-Brol is a recombinant fusion protein that really is great for arthritis it was one of the first to come up but it really has been shown to be ineffective in patients with with uveitis so we will see children for example more adults that have inflammatory arthritis that are being treated with N-Brol that come in for screening and they may not have any inflammation in their eye okay let's not rock the boat okay you're doing fine well if they developed inflammation I would switch them to another agent such as influx map or Adaluma map which is more effective there is evidence based medicine and there is evidence based medicine and so it's hard to conduct large clinical trials but it is useful to get people's experience and particularly when you're trying to get medications approved by insurance companies so prior to the visual one two and three trials it was published in which we had expert opinion with respect to the use of biologic agents and basically the bottom line was that influx map and Adaluma map are really the preferred first line agents for Bechette's disease nothing else seems to work very well with Bechette's disease everything's been tried but these agents seem to work well they are not remittive but they do get disease under control and then second line agents are patients with GA-associated urocyclitis and then potentially second line agents when you have failure of conventional immunomodulatory therapy in patients with severe intermediate posterior panheubitis so influx map is a chimeric monoclonal antibody that is a mouse-human combination that shows efficacy in heubitis with reduced retopical steroids from its IMT taper and is differentially more effective than in tenor sept it is administered by IV infusion on basically a monthly basis after an induction the fact that it's a chimeric antibody a little bit problematic and that one can develop antibodies to the molecule so that patients that are on this medicine usually require concomitant metabolites such as methotrexate one of the advantages to using this cellular drug is in a poorly adhering patient at least you know that they're getting their medicine right so they're coming in for an infusion every month and then the variable with respect to the dose and the frequency with which you administer it so rheumatologists like to administer this at a much lower dose than for ocular inflammation three to five milligrams per kilogram we usually start it out at about 10 we can go up to 20 and then infuse patients on a monthly basis rather than eight weeks and then extend their infusion interval out Adalimumab has been approved by the FDA is the first biological agent to be approved for use of intermediate post-European UBI's but on the basis of two visual one and visual two trials it is fully humanized so it's less immunogenic though people do develop antibodies to the medication it is delivered subcutaneously so it's a little bit easier to administer and to the credit of ABV supports this product they have a fantastic program for patients in terms of support and use of this it's usually dosed every two weeks although in ophthalmology there are patients that have recalcitrant disease in which we may have to dose them weekly and that can be a bear in terms of getting that approved so there are some concerns with respect to TNF inhibition the major I mentioned some of them to you you know there can be a anti-chomeric antibodies which can reduce the efficacy of the drug drug-induced lupus syndrome but really the most important thing is that patients are at increased risk for developing severe infections particularly TB and histoplasmosis so any patient that undergoes biologic therapy has screening for tuberculosis there are studies in the literature depending upon what body of literature you read that there's an increased risk of lymphoma in this group of patients particularly among patients with rheumatologic disease that are already at risk for lymphoma anyways patients with rheumatoid disease it has not been shown in the GI literature it's actually very there is actually increased risk of demyelination so this is actually an important point especially with respect to the treatment of UV-itis as we maybe touched on last time intermediate UV-itis one of the major differentials in intermediate UV-itis is multiple sclerosis which can occur in more often in young women that are HLA-DR2 positive in any case multiple sclerosis is not a diagnosis you make by a laboratory test but we know that those patients are at increased risk so you need to talk to patients about it and then as intermediate UV-itis or porous planets patients are at risk for development I would not start this without actually screening them with an MRI scan the latest and greatest is always met with great enthusiasm and just take a more circumspect approach and that is kind of wait and see I would certainly adopt new therapy not everybody responds to TNF inhibition right so there are other by launch agents that are available to us that work by different mechanisms so if a patient doesn't respond to one anti-TNF medication such as Adelum you might want to switch them to another one like infliximab where you control over the dosing there are a couple of other anti-agents such as golymumab and sirtoluminsumab which also may be effective but there are third line agents and we don't really have time to go through them but they work by different receptor antagonism such as abatosept or rituximab which is a medication that actually inhibits B-cells don't ask me the exact mechanism of how inhibiting a B-cell it's complicated but a B-cell inhibition seems to work in rheumatoid arthritis in which it's thought to be a bit insimilarly in certain patients with EVitis which we think is more of a TH-17 or CD4. There are other medications that will inhibit other cytokines such as IL-1. One promising which inhibits intralocon-6 which is a cytokine found in the eyes that are inflamed that potentiate the activation of T-17 cells is tosylizumab which is an IL-6 inhibitor. One of the other interesting aspects of this molecule is not only is an IL-6 inhibitor but also inhibits anti-veget. So systemic administration of this medication is not only effective but also for macchaedema actually there is a phase 2 trial called the STOP EVitis trial which was a multi-center phase 2 trial which looked at the safety and efficacy of IV tosylizumab in two different doses and it showed an improvement of best corrected visual acuity, decrease in vitreous haze and decrease in macular thickness which was significant interestingly in the lower dose rather than the higher dose of this molecule. So this there is a few more about ectema or tosylizumab just for the sake of completeness there are other biologic agents such as the interferons interferon and alpha 2a is a molecule that can be given three times a week or weekly and has been actually very useful in bachette's disease in the European experience it's really not useful here but it's actually very useful in recalcitrant macular edema I know of one patient that nothing worked other than this and that patient is still on interferon alpha 2a and then IVIG which has been useful based on autoimmune retinopathy so what about the outcomes you know there is no question that in JIA associated urocyclicitis that treating patients with immunomodulatory therapy decreases the risk of auto complications and blindness and the better CEI and the site cohort which is that large cohort that I mentioned to you there is a significant decrease in the risk of visual loss particularly worse than 2050 outcome in patients that are managed with there is a concern for what about the induction of cancer and mortality there have been a couple of studies on this and it's quite interesting and I think that the information is evolving about this suffice to say that in the published literature thus far there is no increased risk of cancer mortality or cancer risk in patients on anti metabolites or in metabolites or cyclosporine inhibitors there is a slightly increased risk of mortality in patients with cytotoxic agents although this seems to be driven completely to the right of the cell a word of caution is that and then just kind of like hot off the press kind of information is lost over this and that the site data the initial site data of the TNF inhibition did seem to suggest an increase of mortality and cancer risk in patients that are on biological agents although this is a very small number of patients and that subsequent data has suggested this does not actually hold patients that are on immunomodulatory therapy even patients that are on anti metabolites are at increased risk of non-mole skin cancer so you have to advise them about that and that is also another area of study so in summary there are disease specific indications for treatment we apply a stepladder algorithm with the early implementation of steward sparing steward sparing immunotherapy either is conventional biologic therapy and there is definitely a place for multiple diseases and hopefully with effective control we can modify the prognosis of uveitis with the early introduction of these agents and I think that will also require identifying allies that are at the most risk for developing a lot of complications and which limits marketing surveillance with randomized control trials thanks