 Okay, good morning, so thank you for being here early again. My second favorite subject, capsule of mega-pastification. So again, we have a laboratory at the fourth floor that I co-direct with me, and then we have Nathan and Joshua as fellows and both of them are here today, that's very nice. So before we go into the subject, just a small introduction because we have to know where posterior capsule of pacification comes from, right? So this is the normal histopathological structure of the chrysanthemum lens. Then you have here the anterior capsule, the posterior capsule, the equatorial region of the bag. And we have a monolayer of cells, the E cells at the equatorial region. They are in continuity with the A cells at the inner surface of the anterior capsule. And then what happens is that those cells, they do not behave exactly in the same way. So when you have surgery and you disrupt this structure, the A cells that are residual inside of the capsule of bag, they have the tendency to remain in place and then they undergo transformation. They proliferate in multi-layers and they start producing collagen. However, the E cells, they have a tendency to actually migrate and they are going to sit at different places, including on the posterior capsule. You see that normally on the posterior capsule you do not have cells. So they migrate there and they become bloated cells. They start forming the pearls, L-shiny pearls. So these two cell types are the cells involved in the process of posterior capsule pacification. And actually we will go beyond that. We are going to talk about the pacification within the capsule of bag. Because when the residual anterior capsule pacifies, this can also be problematic. And that's essentially a fibrotic entity. However, when we talk about posterior capsule pacification, you may have a mixture of pearls, proliferation of these E cells and also a fibrotic component. So again, these are the cell types involved in the difference process. And today we are going to be talking about posterior capsule pacification but also anterior capsule pacification. And I'm going to end with what we call interlinked tissue pacification. That's a pacification between two intraocular lenses if you put both of them in the capsule of bag. So there are many advances in surgical technique, eye well design, materials. Everything helped in decrease the incidence of posterior capsule pacification but it's still a major cause of decrease of visual acuity after cataract surgery. And depending on the time you consider it can go up to 50% which is really important. And of course you can treat these with YAG laser. You all know that. You do a posterior capsule autonomy with the laser. It's relatively a simple procedure but it's not without risks. You could have eye well damage, look at the spitting. You could have sublexation dislocation, retinal detachment. You could have secondary glaucoma, et cetera. It's also a very important cost to the healthcare system. So but nowadays we cannot just think like in a simple way, okay, you can do YAG and that's it. You have new intraocular lenses with new properties. You have premium eye wells and you have development of different projects related to accommodating intraocular lenses. And mostly these lenses are designed to be moving within the capsule of bag so then you cannot have a pacification of fibrosis inside of the capsule of bag. There's so much research going on on posterior capsule pacification including the basic level. My subject of my PhD thesis was to coat intraocular lenses with Teflon. It was extremely cool and it worked so well in cell culture and then when you go to the rabbit model it's really a different thing. There are some antibodies that they link to the eye well to prevent that, some coatings. I mean there is a lot in terms of basic research to prevent that. However nothing is really 100% effective so we are still researching many things. However in the meantime, what you as you're going to be surgeons, what can you already do to help prevent this complication? So Dr. Apple actually described three surgery related factors that really help in preventing the complication or at least decreasing the rate of the complication and we are talking mostly about posterior capsule pacification here. Hydrodisection enhanced cortical cleanup in the bag IOL fixation and a small capsule rex so they add you cover the periphery of the optic for 360 degrees to form the shrink wrap around the eye well. We are going to discuss about one by one. However I want to show you these are from cadaver eyes we get in the lab and before we have these factors that's what we would normally see. You have asymmetric fixation in the bag and in the cell cos you can see a lot of posterior capsule pacification you can see a lot of the centration and then when you got to those factors applied by the surgeons that's what you see. So it looks already much much better but there are still ways to improve that. Okay so let us start with the first one. Hydrodisection enhanced cortical cleanup so this is mostly important to remove all of this cortex and the e-cells at the equatorial region of the capsule bag because PCO comes from proliferation of anything that's residue inside of the bag. So if you leave a lot during surgery you are going to have a lot of PCO. And in terms of research of course you do that with BSS but there is research using different solutions to do that. So we tried in the lab one time preservative free like docain and there are some anti-mythotics that you are tried with some success. Of course the problem here you can see is that you're injecting these solutions in the eye you may have some toxicity, right? So you have to be careful with that. So that is mostly to eliminate the cortex, the e-cells is there a role if you eliminate the a-cells attached to the inner surface of the anterior capsule if you do extensive polishing. So that was researched by different people and they observed that indeed you improve anterior capsule pacification because you're eliminating those cells that are going to form fibers tissue. However, they could not find any difference in terms of posterior capsule pacification if you do that. And actually Dr. Spauldon believed that we should not polish a lot the a-cells because you'll be good to have the cells proliferating and forming some fibers tissue. You see that's the anterior capsule here that's so pacified where it keeps contact with the IOL. And then this will contract the bag and it will push the optic posteriorly to enhance the barrier effect of the optic in contact with the posterior capsule. So he believes that's actually a good thing. So we tested different things in the lab. We tested this epilope which is wire that goes all around the capsule bag instead of doing hydro dissection use this wire and it's really very interesting. And Alan Crander right now is using a similar device and he uses that not only for this but also to crack the nucleus. So that could be quite interesting. We did some studies and we could demonstrate that you clean the capsule bag as effectively with this device as with the hydro dissection. In the past we tested this sealed capsule irrigation system. It was very interesting. It's a silicone device. After you finish to evacuate the capsule bag during cataract surgery, you put this in front of the capsule rexes and you seal the capsule rexes. So basically you have an inner compartment of the capsule bag that's sealed and then you can inject any kind of solution to treat that capsule bag and you do not have the problem of toxicity. That was all very interesting and here is with a dye to show that it doesn't leak after you seal. They try different things including just distilled water because if you put distilled water any cell is going to, biosmosis is going to explode. So you can see the difference here in terms of anterior capsule pacification. There is no fibrosis here where they use the device. However in some studies they could not demonstrate any effect. And what's the major problem here is that you have a cataract surgery procedure that's like 10 minutes and then you have to add a device like that, irrigate and everything. You add another 10 minutes so nobody really wanted to do that. That was a pity because it was really very cool. We tested also something very interesting. The photolysis system is a modified Yag laser. So again when you evacuate the capsule bag by irrigation aspiration, you get that probe and you start lasering the inner surface of the capsule bag. This German surgeon did that in these patients. He did it on the right side only to show the difference. And it was so interesting because with time on the left side he had anterior and posterior capsule pacification but it's like stops in the middle and in the right side you do not see anything. So this is really effective and we tested in cadaver eyes and you can very easily see when you remove the lens appeal cells the residual lens appeal cells but not only that, you also remove fibronectin or any protein that's used as a substrate in the capsule too for the cells to attach and to grow. So again very effective, very interesting but the same story. I mean you have 10 minutes surgery. This is going to add another 10. So it's pretty much abandoned which is a pity. But all of this shows that if you eliminate all the cells or at least the majority of the cells you really slow down this process a lot. What about in the bag IOL fixation? That's extremely important. Any study you're going to check in the literature you'll tell you that a posterior chameleon should be inside of the capsule bag for PCO prevention because if you have the IOL fully in the bag you are going to have the optic in contact with the posterior capsule and that acts as a barrier for the cells that comes from the catarison and they have the tendency to migrate to the posterior capsule but they stopped right there. However, if you have an asymmetric fixation with bag and sulcus in the side where the haptics in the sulcus there is a free avenue for those cells to come from here to grow behind the optic. So that's where the IOL should be in terms of posterior chamber IOLs. And the last factor is the capsule rexes. The majority of studies you are going to check in the literature will tell you that the capsule rexes should ideally be smaller than the IOL optic centered. So the edge of the rexes will cover the periphery of the IOL optic for 360 degrees. And if you do that you're going to have better results in terms of posterior capsule pacification. This is a very important study that was done here and they, with different IOLs they compared eyes that had the complete overlap meaning 360 degree coverage versus incomplete overlap. And in all cases they found if you have a complete overlap you have better prevention of posterior capsule pacification. The majority of studies will show that there are very few exceptions like this study here could not really show a difference but the great majority will tell you that that's what you should have. So with the standard IOLs again you have the IOL inside of the bag, the smaller rexes, shrimp wrapping, the capsule around the IOL optic. That's a very important concept for standard IOLs. Later we are going to discuss about totally different concept that we are seeing in the lab. Okay but not only the surgical technique is important. I mean the IOL is also very important. Of course it has to go together. You can put the best IOL for PCO pre-invasion but if your surgery is not good there is no way the IOL alone is going to act preventing the complication. But what is important to have in the IOL to prevent posterior capsule pacification? So people talked about the material. It would be good to have of course a biocompatible material that you do not stimulate inflammation but the material should have some adhesive properties to stick very early to the capsule. Anything you can do to the design so the IOL optic will have a very good contact with the posterior capsule would help prevent posterior capsule pacification. And again I'm talking about standard lengths. You can do that for example by putting an angulation so the optic is moved posteriorly. And the most important factor is the square optic edge on the posterior optic surface. So again let us check one by one. So we studied with Dr. Lee Knowler he had this sandwich theory that was very interesting. And he proposed that if you have an IOL with a bioadhesive surface this would allow only a monolayer of lacyptyl cells to attach to the capsule and the IOL which will further prevent any proliferation inside of the bag. And we tested this with him by using cadaver eyes implanted with all kind of different IOL materials. And what was observed is that fibronectin is a protein that's readily available in the A-cosumer after surgery. And some materials, some IOL materials would bind to this protein much more than other materials. So in our tests we saw at the time the hydrophobic acrylic lens available was the acrysoph material and the binding to fibronectin was much superior than any other material meaning that that material really sticks to the capsule much better. And he proposed that that would prevent PCO. It turns out later that the most important factor for the IOL to prevent PCO is really the square edge but the material may have mostly an effect on anterior capsule pacification. And what we are seeing here are histopathological sections cut at the level of the anterior capsule. You are seeing here the capsule rex's edge. And you see here in some cases nothing or just a monolayer of lacypterial cells and with other cases a very thick fibrocellular tissue in the inner surface of the anterior capsule. And that's when this fibronectin and this adhesive theory makes really effect. So what we observed is that with some materials you have much less anterior capsule pacification than others. The worst was the old silicone lenses that were plate type design. And you can see the lenses in total contact with the anterior residual capsule and it's completely opacified where it keeps contact with the anterior capsule. Notice here also the whole anterior capsule that's residual there is actually clear but wherever it touches the IOL it's opacified. So it's used like an index of biocompatibility actually. And what's the problem with anterior capsule fibrosis? In the past people would not consider that much also a problem with the standard IOLs. It was just a problem when you had excessive fibrosis, asymmetric fibrosis, things like that like a phymosis of the opening of the capsule rex's and you had IOLs with very flexible loops and that would lead to a very extensive de-centration of the intraocular lens. So that was a big problem. However again nowadays you cannot think like that because in our lab we are working with a lot of projects for accommodating chocolate lenses and mostly these lenses are designed to be flexible to be moving inside of the capsule bag to mimic the accommodation. So if you have a capsule bag that's fibrotic this is not going to work. So we cannot just think like that anymore. So how can we prevent these fibrosis and especially this anterior capsule pacification which is essentially fibrotic? So we learned a lot with this project that was a dual optic silicone accommodating chocolate lens. Very good project AMO bodied and then they abandoned the project and that really worked. There was some clinical studies done here and the patients were actually quite happy but they figured it would cost so much to continue that they unfortunately abandoned. But we worked a lot because this design had very interesting aspects. So the lens had these eyelets on the anterior optic and then the anterior capsule would not be in total contact with this silicone optic. The contact would be very limited and also the whole IOL being dual optic would keep the bag open and very expanded. So we put this in the rabbits and then it was so interesting that not only there was no posterior capsule pacification and you can see in comparison to the control but there was also no anterior capsule pacification because if you do not have contact between the IOL and the anterior capsule, the anterior capsule actually does not pacify. So later we are going to discuss about the problem of interlanticular pacification that may happen between two lenses if they are in the bag. So with this design, of course you have two optics, we were worried about that. So we tested the rabbits, but it turns out that this is really a problem with two hydrophobic acrylic lenses such as the Acrysoft that has this adhesive surface in the bag. So this was not at all a problem with silicone type of lenses. So the last aspect of the IOL design is the square posterior optic edge. That's really the most important and it has been incorporated in the great majority of all IOLs that are called modern intraclal lenses and some of them they have square edges everywhere anterior and posterior surfaces and single piece lenses may have even in the haptics. The importance here is really the posterior optic surface. So again, don't forget that even for this square edge optic IOLs to really function nicely they have to be fully in the capsule of bag because if they are out of the bag you still have proliferation. But here you can see a better berry effect of the optic that has a square edge versus an optic that has a round edge. It's much easier for the cells from the equator region to gain access behind the IOL optic. And again, it has to be in the bag. Even a very good square edge, if it's not in the bag, it's not going to act as a barrier. And the square edge is very important does not matter really the material. So at the beginning people thought, okay, is the hydrophobic acrylic with the square edge that makes the difference? Not at all. There are very good silicone lenses with a very square optic edge and those lenses perform really well in terms of posterior capsule classification prevention. Here you have, oh yeah, Mike you're here. Look at that. So here you have round edges IOLs and you see the posterior capsule here being very opacified or with a huge aglaser here. And here you have a lot of summaries rings. So the summaries ring is the proliferation of these E cells at the equator region of the capsule bag. And that's what it grows behind the IOL optic and opacifies the posterior capsule. So there is a huge summaries ring everywhere here but the posterior capsule is perfectly clear because of the barrier effect. And what you're seeing here is fibrosis of the edge of the capsule axis, okay. So I spent some time in Germany and then we did very interesting studies there because this square edge became such an important thing and then suddenly all companies were stating they had square edge IOLs but then the results of the clinical studies were not really showing a comparable level of prevention of posterior capsule classification. So we're like, okay, but who is controlling if they are really square? Is that someone controlling? Then figure out that nobody was really controlling. That was very interesting. So we came up with this idea to get IOLs in the market that were sold as square edge IOLs. We got some specific diopters and we got a very standardized way to evaluate these lenses under a scanning letter microscopy getting a very high magnification photo showing the lateral posterior edge standardized magnification. Then we project in this image with a program that's used by architects. A circle that had a known radius based on the size of the lens of the cells. And with that what we were measuring is how much of that edge, lateral posterior edge deviates from a perfect square. So of course the higher the number, less the square is the edge. So let us compare these in the IOLs their market as square edge lenses. And we were very surprised. So you can see the numbers in yellow there. There is a huge variation of what is called square edge lenses. And here are the images. So believe me or not all of these lenses here were equally sold in the market as square edge lenses. But you just glance at the images and you see that they are definitely not the same. For the silicone lenses, the same thing. Some were very square, very, very good. But others, not so much. So again a huge difference in what the marketing was calling square edges. And nobody was really controlling that. And of course there is the stream trapping of the capsule bag of the IOL by the capsule bag. And if the capsule bag contracts you enhance the contact between the optic with the posterior capsule that may make these differences in edge a little bit less important. But I mean it's just up to some extent. Some of these differences are very, very important. And then the third part of the study got really worse because then we evaluated the hydrophilic acrylic lenses which are not so popular here in the United States but you do have some. But in Europe they are very popular. So we got a lot of hydrophilic acrylic lenses and we did the same thing. But we used an environmental scanilator microscopy to not dehydrate the IOLs while they were checked. Because if you remember from yesterday the water content of these lenses may be from 18% and up. So if you really dehydrate the lenses what you may be seeing in terms of edge may not be the final product. So we tried to keep that not dehydrated and we were totally surprised. It's even worse. So these are all lenses in the market that I sold as a square edge lenses. So you look at the edges and some of them do not look square at all. And what happens with these lenses that they are manufactured in the dry state. So the edges are cut in the dry state. And then what the companies do they take these beautiful SEM photographs of the lenses dehydrated and they put in these booklets and it looks very square but however when you hydrate the lenses they do not look like that. They look like this. And why is this important? Because as a whole if you consider silicon hydrophobic acrylic and hydrophilic acrylic lenses as a whole in terms of groups all the lenses are not the same but as a group the hydrophilic acrylic lenses will have much less square edges than the hydrophobic acrylic and the silicon. And if you check the literature you'll find a lot of papers here's just some examples where the authors are saying okay this is a clinical study comparing two square edge lenses one is hydrophobic acrylic one is hydrophilic acrylic and we just want to see what's the effect of the material. And then the hydrophilic acrylic always have the worst PCO ever and they are like oh my god hydrophilic acrylic material is very bad and everything but they were not comparing apples to apples. Yep. There is something in the manufacturing process that does not really make this practical or even possible in some cases. So that's the thing in the sequence of the manufacturer and I visit some of them in Germany. You have to do that dehydrated then later in the last steps you hydrate the lens. There is issue with contamination by bacteria there is issue with sterilization also. So in the process that's not what you do. You do dry and then you hydrate but it makes a huge difference. In the literature you have all these papers published in very good journals arriving to conclusions they are totally not valid because they are not comparing apples to apples. So you should do an analysis of the edge before you enter in a study like that to make sure that you're comparing something that's comparable and the only variable is the material. So if someone says hydrophilic acrylic lenses have the worst PCO I mean it's not the material maybe just that the edge is totally not square at all. So another interesting point that we figure out also in rabbit studies and also in cadaverite studies and that's something you can clearly see in clinics when you check patients under slit lamp. So you know that those single piece lens became so popular because they are so easy to inject and manipulate and everything. So when there was a transition from three piece to single piece the way the PCO form became different because these lens here for example has the square edge all around including the haptics. However if you analyze the optic haptic junction it's going to be a very smooth ride for the lens reptilian cells. So there is no barrier actually here and because the haptics are so thick you are not going to have in this location a fusion between anterior and posterior capsule outside of the edge. So it's very easy for the lens reptilian cells to migrate here. So with these single piece lenses the PCO almost always it starts at the optic haptic junction. So we check that in the rabbit and then in our collection of cadaverized that's exactly what you see. So everything here is clear and here's where the PCO is just starting at the optic haptic junction. Here again histopathology showing the same here the same thing PCO is starting here PCO is starting right there. And with the three piece lenses we did this study showing that if you analyze where the PCO starts would mostly be where the capsule axis edge is not covering the periphery of the optic. So the pattern of PCO initiation is also different. However the incidence some studies checked does not change much. It's just the way if you have PCO where it really starts. So we did some interesting studies. This is a hydrophilic acrylic lens made by Rainer. It's actually available in the United States the center flex. And at the very beginning of this lens that was the design and there was a very smooth transition between the optic and the haptics here. So same thing PCO will always start right there. So the company decided to change just that specific region. They added an extra step there as you can see here. And sure enough prevention of PCO was much better. We did that in rabbit eyes and later all the authors confirmed in clinical studies. So it really makes a big difference. Okay so now let us start talking about things are not really standard right. So what is the standard so far that I told you? Have an eye well like here. You open your anterior capsule did your anterior capsule rexes you evacuated the capsule bag and then you put the eye well inside of the bag. That's the standard. In these we want a shrink wrapping of the eye well by the capsule. But Marijoseta Sinon in Belgium decided to do something totally different. She decided to organize the capsule bag as a function of her eye well. So she designed an eye well that's very different. It's called the bag in the lens eye well. So in the surgery you do the anterior capsule rexes and then you do a posterior capsule rexes of the same size. And then you put the eye well. There is a groove on the periphery for 360 degrees and you fit the residual edge of the anterior posterior capsule right there. So then with this she pretty much eliminates posterior capsule prosecution. And I want to show you some images because a few years ago she had some patients die of cancer and she got them to donate the eyes for her for research after their death and then she sent the eyes here. So this is the first one and actually this was from an ophthalmologist who was very, very interesting. So you see here the eye well inside of the capsule bag. This is perfectly clear because the fact is there is no posterior capsule right there. So in this eye if you do the pathology we saw a residual outline of the eye well here and you have here the groove and you see anterior and posterior capsules directed to that groove. So later she sent other eyes that had longer followup and you can see that in the residual capsule bag there is a lot of summaries or information. Again this is residual pearls. Lens of tilliocells that form pearls, residual cortical material that proliferates and summaries ring is at the origin of posterior capsule pacification. But as this is confined in the equator region because anterior and posterior capsule are inside of the groove of the eye well there is no way this material can migrate to the area behind the eye well. So even though you have this huge summaries or information PCO is zero. And this is what she uses in all her patients especially in all the pediatric population because you know the pediatric population if you do not take some extra measures in the surgery PCO is going to be 100% so she doesn't have PCO. However there's not exactly a very easy technique to implant. She trains her personnel so everybody's very nicely trained in her department for that so they do this routinely. So for them it becomes very easy but for surgeons worldwide to adopt that it's not very easy. Say it again. You know she discussed that with the buttonhole technique by Rupert Manapachi and everything but with these lengths it seems it's pretty much okay. She didn't see that because the material cannot escape that area here. So there is a fibrotic tissue that forms between the edge of the anterior and posterior capital inside of the groove and that becomes sealed. So the material remains there. So now we talked about Mahijou Zeta-Sinon lengths and then I would like to talk about these IOL designs maintaining an open or expanded capsule bag. So we started working some lengths in our laboratory and suddenly we are like these are behaving very very different. So in 2010 they created a whole symposium on these and we were talking about that and I think I'll use just this specific project to elaborate a little bit on what is that. So since many years we have been studied these round lengths this shaped lengths which it has these rings. The lengths suspended between haptic rings is a hydrophilic acrylic lens and at the beginning they gave us this drawing and say okay when you put the lens in the rabbit it's probably going to look like that. The optic will be posterior in contact with the posterior capsule but the anterior capture rex is going to be floating there is not going to contact the IOL so you are not going to have anterior capsule pacification. So this is a rabbit eye five weeks after implantation this is a high frequency ultrasound that you use for the anterior segment and that's exactly what we saw. So we started doing some small preliminary studies with few rabbits short term studies like up to five sometimes six weeks and these lengths will be implanted in one eye and the other eye will have a standard single piece hydrophobic acrylic lens. And the difference was so impressive that we were like we never actually saw that. So of course in the rabbit eye is an accelerated model for PCU. Six to eight weeks in the rabbit model may be more than two years in a human eye in terms of lens up to your cells proliferating. So in the rabbit eye as you give time it's just like the capsule bag fills up again and look at the difference with the test eye. No PCU and the anterior capture axis is absolutely clear. So here you have from the posterior view and all the scoring was very significant in terms of difference. And when you do the full histopathology the only place we saw some proliferation was in a very limited area between the two rings otherwise nothing else. Everything else was clear anterior and posterior capsule. So this was the first design and then in the second design they changed including holes on the lateral edge here because there was that hypothesis at the time starting at the time that if you leave the capsule bag open and the acres humor can flow all around the inside compartment of the capsule bag you actually prevent capsule bag of pacification. So this one had a much better flow of acres humor and sure enough we put in all the rabbit study in another rabbit study very small study short term in the prevention of posterior capsule pacification in anterior capsule pacification was even better with not even limited proliferation at the equator region of the capsule bag. And in that particular study something very interesting happens. So they gave us the lens and the lens had no mark or anything so it was very difficult to load in the cartridge and to know what was anterior and posterior surface. So I was loading at the time I probably screwed up and then that how you normally see in the ultrasound a standard IOL that how you should see these lanes with the optic posterior and no anterior capsule touching the IOL. And in this study two of those lenses end up upside down. So the optic instead of being down in the posterior capsule was up. So there was zero contact between the optic and the posterior capsule. So what did I tell at the beginning that the contact between the optic and posterior capsule is very important for PCO. So you would conclude, okay so it was horrible for PCO. No, it was zero. So with this configuration of the round disk shape design the capsule bag being open with the acres flowing inside of the capsule bag the contact between the optic and the posterior capsule is not even necessary. So this changed completely in our universe because it's really a shift in weight to think. So very interesting. And now you have this study that's impressed because when you have a new IOL, new material the ISO standards, the international standards require the company to perform six month studies. And the fellows will tell you that when we do six month studies in the rabbit it is horrible because after the second month there is so much proliferation inside of the capsule bag that almost like the proliferation starts pushing the optic out. You have popularity optic capture. You have synechia. The eyes look horrible. So it's just a question of having a control as far as the control look as horrible as the test we are pretty much okay. So we did the six month study. And this is what you see. I mean, PCO was scored as zero at six month in a rabbit model. That's unheard of. That's extremely impressive. So you see here the control with partial popularity optic capture, a lot of proliferation and this is looking really good. And most importantly, look at the histopath. So you have the control here. The capsule bag is filled with material. Where it's empty here is because the IOL was here and the IOL is actually dissolved during the preparation. So you have a capsule bag that's full with material again. And here's the test. I mean, the anterior capsule is here. Totally clear posterior capsule. The bag is very expanded. You see nothing. So this is literally unheard of. This is very interesting. We have another project. This accommodating IOL is also bulky and keeps the capsule bag expanded. It does not really keep the capsule bag open that the aqueous can go around, but it really keeps the bag very under tension and expanded. So that's the lanes that has silicone oil inside of the large haptics doing efforts for accommodation. This is squeezed and then the silicone oil goes to the optic and you have some accommodation. Clinical studies are underway for these lanes. And we did short-term studies and long-term studies. And again, the same thing. You see the control just going south very, very badly. And the test eye looks really nice. You see from a Miyake view, a two month, you can see a six month look at the difference. And here's again the histopathology. Very limited proliferation there, otherwise very expanded and clean. And here you have huge proliferation. So now just to finalize, we talk about anterior capsule pacification, essentially fibrotic posterior capsule pacification, surgical factors that you can use to prevent it, IOL factors that you can use to prevent it. We talked about these out of the bag concepts, out of the box concepts, like the bag in the lanes that change the relationship between the lanes and the bag, and these new IOLs that instead of keeping the bag very collapsed around the IOL, actually do the contrary and keep the bag very open. And now to finalize, we talk about interlinticlo-pacification. We don't see much of that anymore, but it's important for you to know because the pig-back procedure is becoming quite popularized because if you have, for example, a refractive surprise, instead of explaining to the lanes, you can just get an IOL and put in the circles as a pig-back lanes, a supplementary lanes. And if you have two lances in the eye, you have to think, am I going to have interlinticlo-pacification or not? So basically this is the opacification between both lances that were in the bag. And if you think how this is formed, the material that comes from the Cotero region, the summary stream, instead of going behind the optical of the lanes forming PCO, if you have two lances in the bag, that material may go in between the lances and form IOL. It's the same material, the same cells, it's the same origin. It's just that it goes inside of the capsule bag between the lances. All the cases we analyzed were related to three-piece hydrophobic acrylic lances implanted in the bag with a small capsule axis covering the edge of the anterior lanes for 360 degrees. And all of them were acrysophal lances. So I particularly believe that the acrysoph has this adhesive surface. Then the material starts entering in between and it attaches to the IOL. And they have like a scaffold to keep growing and growing. Because some surgeons even put two silicone lances in the bag in this configuration. And they did not see this problem of interlentic lopacification. So I think the attachment of the material to the surface is important. But then you cannot even detach the lanes one from the other. It was really horrible. And that's what was happening. You have two lances in the bag. And these cells that start proliferating instead of going behind will go in between. So there are some surgical methods proposed to prevent this complication. If you would put two lances in the bag, it would be better if you do a larger capsule axis, larger than the optic. Because then that anterior capsule would fuse with the posterior capsule and sequester the residual cells to the cotar region. The second one is really the most popular one. You would still have one IOL in the bag via a smaller capsule axis. But the anterior lanes would be placed in the cell codes. And then you would not have a space, a real space, in between because this here is sealed with the one standard IOL in the bag. And that's what mostly surgeons do nowadays with refractive surprises that then they put an IOL in the cell codes. However, I want to remind you that you cannot put any intraocular lanes in the cell codes. You really have to pay attention. So some three-piece lances with lower power, they have square edges not only on the posterior surface. They also have square edges on the anterior surface. And they may have a lateral edge that's not polished. So it's very rough. If you put this type of three-piece lanes in the cell codes, you may have a very important problem of UGA syndrome-related ITS glaucoma hyphemus syndrome with a lot of pigmentary dispersion and even pigmentary glaucoma because of that. So you have to select an IOL for the cell codes that has smooth surfaces and round and polished and smooth anterior optic edges. And of course, we always have to remind you, the single-piece acrylic solves and all the single-piece lances like that, they have anterior and posterior square edges, at least the acrylic solve does. And the square edges on the haptics, the haptics are very thick. The side walls are very unpolished, very rough. You should not put this IOL in the cell codes at any circumstances. So you always should pay attention to that. So we had cases with a lot of pigmentary dispersion. So the research and prevention of capsule vagopacifications really increase in importance now because of especially these accommodating lanes. There are so many accommodating IOL projects going on there, some very interesting, some very crazy, but all of them that we test, this is a very important problem. The bag has to remain stable. If the bag starts proliferating cells and fibrotic tissue and opacifying, it really kills those interesting projects. So it's not only PCO anymore. It's especially, I would say, ACO because ACO anterior capsule classification is an essentially fibrotic entity. So you really have to think about the capsule bag as a whole. Now you have to prevent any fibroses inside of the capsule bag because of that. When we talk about these IOL designs maintaining the bag open and expanded, we may see a shift in the future towards those things because we are very surprised with the results. There is not only less anterior and posterior capsule classification, even when you see the summary's ring formation, there is less proliferation there. And that may be because of different mechanisms. And one of them is down here. So Dr. Nish believes that if you have a consumer that can freely go inside of the capsule bag and wash the inner compartment of the capsule bag, this is going to prevent some cytokines to reach a certain level. And these are the cytokines that stimulate length-of-cell proliferation, but if they not reach that concentration, this process is going to be stopped. So this is a very important concept that deserves further investigation. Again, we are very, very surprised with our results. Thank you very much. If you have any other question. Okay, everybody understood everything. Thank you.