 All right, good morning, everybody. We'll go ahead and get started. We're really excited to be able to have our new pathology fellows come and speak to us this morning. We're going to hear first from Sean Kennedy. He's going to be speaking to us today about uvial and capsular biocompatibility of a new hydrophobic acrylic microincision IOL. And then after that, he'll be followed by Sneha Bantu, our other pathology fellows. He's going to be speaking to us about posterior capsule and pacification prevention by an intraocular lens incorporating micropattern membrane on the posterior surface. We're really excited about these two talks. So Sean, why don't you go ahead and come on up and we'll get started. So like Chris said, I'm Sean Kennedy. I'm one of the new acupunctology and research fellows. And today I'll be talking about a new microincision cataract surgery lens, or MIX lens. And this study was done at the Mamelis Warner Lab up on the fourth floor. So thank you to them for providing this study, all this information, all the help in making this presentation, and then also for everything else they've done. So some background, I know this is the kind of wordy slide and I apologize for starting with that. But there are a couple of ideas that are important to understand before you kind of can get why this new lens shows promise. So the size of incision used in cataract surgery has trended down over the years. And right now, most surgeries are performed through a incision smaller than three millimeters, which is already very impressive. It takes a lot of time to get there. But the next step in continuing to decrease the size of these lenses is what we call microincision cataract surgery. And this is generally defined as a sub two millimeter size incision. And it's challenging to develop lenses that can fit through incisions this small. The material has to be compressible enough to fit through these really small incisions, but also has to be rigid enough that postoperatively the fibrosis that occurs with the capsule, the lenses won't get deformed, they won't tilt in the bag, they won't move anterior or posteriorly in the capsule. So it's difficult to develop material alone that can fit these demands. And then in addition to that, these lenses also have to perform similarly to the standard lenses in terms of the complications. And when talking about complications, it's important to note the rate of PCO formation. So PCO or posterior capsule opacification is the most common complication after cataract surgery. And it's caused by proliferation of lens epithelial cells that are left in the bag during surgery. They grow down and form groups that will affect visual acuity. And PCO is affected by lens material type and shape. Most notably generally, I'll just be talking about the shape of lenses as plate versus open loop lenses and hydrophilic versus hydrophobic materials. And just as a general introduction, most mixed lenses have been made of hydrophilic plate type materials. So going through the evolution of some of the mixed lenses, this is one of the earlier mixed lenses that was developed. It was a hydrophilic plate. And you can see that it doesn't have the open loops that this standard lens has. And it's also made of a hydrophilic material compared to the standard lenses hydrophobic material. And while it was able to go through a sub two millimeter in size incision, it developed significantly more PCO and this caused significant differences in visual acuity. So one of the next iterations was a hydrophilic lens with haptics. And this was done because we know that the plate style lenses generally develop more PCO. So this lens was tested in comparison to the standard hydrophobic material and it also had more PCO, unfortunately. And this slide's just showing a couple more hydrophilic lenses that were developed. These are both plate styles. Like I said, most mixed lenses have been plate style hydrophilic lenses. And the studies compared it to the hydrophobic one piece with haptics. And again, the mixed lenses had more PCO than the standard lens. So why are these hydrophilic plate lenses getting more PCO than the hydrophobic lenses? It's complicated. There's a lot of factors that go into the development of PCO. So now we'll talk about a couple of the other ones. But one of the reasons, one theory is that hydrophobic lenses maintain their shape better than the hydrophilic lenses. And specifically, they maintain a square edge in the bag. So when you think about how the lens is placed in the bag, the capsule bag is holding the lens and then you want a square edge to the optics so this can help keep lens epithelial cells from growing inwards and forming PCO. And both hydrophilic and hydrophobic lenses can be made with a sharp edge. You can cut the edge as sharp as you want. But the hydrophilic lenses, which you can see on the left up there, they kind of act like a sponge. They can absorb water. And even with that sharp edge, they can round off. And then the lens epithelial cells can kind of grow in downwards. And the hydrophobic lenses, you can kind of think of them more as a block of rubber. They maintain that edge a little bit better and they theoretically will reduce the lens epithelial cells from growing inwards. So this slide, it shows some pictures from a study Dr. Werner did in Germany where they looked at a scanning electron microscopy of different lens types. On the left, you see the hydrophilic lenses and after hydration, they get just that rounded edge. They tend to get rounded edges and the hydrophobic lenses tend to keep a better square edge. So some people decided that if they developed a hydrophobic lens that was able to go through this micro incision, then maybe this would prevent PCO similar like to standard size lenses. And unfortunately this didn't work. These two papers, they looked at a couple of hydrophobic mixed lenses and they still had worse PCO in comparison to the standard size hydrophobic lenses. So something else had to be developed to prevent PCO in these mixed lenses. And one development that Dr. Matsumakashima developed was this what they call active oxygen processing. It's a treatment that can be applied to the posterior side of lenses and it'll make the lenses stickier so they stick to the bag better and theoretically this will prevent, it'll make a seal so that new epithelial cells can't grow inwards, it can't proliferate, causing no pacification. And these pictures, this is the sticky material that they talk about in the paper is it's fibronectin. And here they're showing that the UVO zone or active oxygen treated lenses have more fibronectin adhesions. They're stickier, they stick to the bag. And then over here, that's just some pictures taken with showing the lens epithelial cell adhesion. So even though the UVO zone treated picture looks a little dirtier, it's actually a good thing because you get that monolayer epithelial cells and it prevents other cells from proliferating. And this was the treatment that Hoya, the study sponsor for our study, applied to the lens that we were looking at and then we evaluated whether it actually worked. So getting to our actual study, we had, it was set up similarly to a lot of the studies we do here. We had eight rabbits, we injected the test IOL in one eye and then the control in the other. And then we had weekly slit lamp examinations looking for biocompatibility, evaluating PCO and ACO. And then after four weeks, the rabbits were humanely sacrificed and enucleated. And we evaluated the anterior segment postoperatively from the Miyaki Apple view, which I'll show in the next slide because this gives you a better view of the posterior surface of the lens. And then we also performed histopathology. So this is the Miyaki Apple view. It's a coronal cut through the eye and then it's as if you're sitting on the optic nerve looking forward through the eye. So you can see here's the ciliary body just to orient anybody that hasn't seen this view. Ciliary body here, capsule with the lens inside and then iris and pupil looking forward. And this human eye, it's pigmented, CC, ciliary body is pigmented, iris pigmented. The rabbits we use are albinos, they don't have the pigment, that's why they look a lot lighter. And the reason we use this rabbit model, specifically for PCO formation or any opacification is because that these rabbits have such accelerated development of PCO. This group suggested that one month and the rabbit eye is approximately equal to one or two years in a human eye. And you can see that evidenced here. This lens in the human eye, it's been in there for seven years and you see very significant summerings ring around it, but just the beginning of PCO here at the haptic optic junction, really not at this haptic optic junction. And in comparison, this rabbit, it's the lens is only done in the eye for two months, but you already see it's a little bit harder without the pigment, but you can see that the PCO is growing in from the haptic optic junction here. It's already almost halfway across the lens. And then down here by six months, it's completely covered. So that's the reason we use this rabbit model. So the lens that we were testing, it was developed by Hoya, they call it the NANX multisert. It's similar to the standard lenses in dimensions. It's a one piece monofocal hydrophobic acrylic. It's made of the same material that they've used in. Millions of lenses injecting different eyes over the years. And then they applied that active oxygen treatment that I discussed earlier on the posterior surface. And according to the manufacturer, they did studies previously where they showed that incision size could be as low as 1.8 millimeters. The lens is colorless and it has UV filter. Its dimensions are the same as our control IOL. They have an overall diameter of 13 millimeters, optic diameter of six millimeters. The control IOL, it's by Alcon, made by Alcon, it's their Acrosoft lens. It's most commonly implanted lens in the United States. It's also a one piece monofocal hydrophobic acrylic. And it can be injected through incisions as small as 2.2 millimeters. And when you look at these lenses, most notably the only difference is the blue blocker that the Acrosoft has, it just gives it a yellow tint. So comparing these lenses, they both, like I mentioned, they're very similar structurally. They both have that square optic edge that I mentioned as being important in preventing cell migration. And they both are hydrophobic, so hopefully it'll maintain that edge. They both have similar refractive indexes and the same power was used in our study. So when Poya developed this lens, they also had to develop a injector that would be compatible with the lens this small. And what they came up with was a preloaded disposable system. The outer diameter of the injector tip is 1.62 millimeters, which is the smallest in open loop hydrophobic acrylic lenses. And according to the manufacturer, like I mentioned, they can be injected through incisions as small as 1.8 millimeters. The injector can be a single-handed push or a two-handed screw and it can be delivered directly into the bag or you can use a insert shield to get a set depth. But in our study, we weren't evaluating the injection. We used a three millimeter incision and we injected directly into the bag. So this is just a slide showing the injector, the tip of the injector. You can see that the multisert injector has a very thin rim and this helps make it able to accommodate this lens. So here's a video of the, this is the control lens and these surgeries were done by Dr. Manuelis. So here you see the lens being injected. You see the yellow tint that's that blue blocker that I mentioned. Lenses injected fully, it's centered and you'll see that there's 360 degree coverage of the capsular axis. And this is the new test lens. Just note the small injector tip. Like I said, we didn't use that insert shield that was injected all the way into the bag. It's injected fully. It's the colorless material that I mentioned without that yellow tint. And again, inject without problems, unfolds fine. And there's also 360 degree coverage around the capsular axis. So when we looked at the rabbits post-operatively, there was no difference in post-op inflammation between the two lenses. And then also there was no difference in terms of, no significant difference in terms of PCO and ACO. The ACO is actually scored exactly the same. So there's no P value for the PCO. The test lens actually did do a little bit better than the control lens, but no significant difference. So not inferior for sure. And here's some pictures taken at three weeks from the slit lamp. You can see that test lenses and control lenses, some are a little bit cleaner. This one has barely any PCO invisible. This control lens is also pretty clean. And then some had a little bit of PCO. So this test lens, you see some growing from the haptic optic junction. And in this control lens, you see it also growing there and on the opposite side. So after inoculation, we did the Miyake Apple view. And like I mentioned, we do this because it gives you better visualization of the post to your surface. Here you can see that in this test lens that PCO starting to form at the haptic optic junction which you might not have been able to see in the slit lamp exam if the iris wouldn't die light fully. You can also see a little bit here on this side and then the control, you see it growing about halfway across. And in this test, this one of the test lens that had a little bit more, you see the PCO almost halfway across the lens and then they control three big groups of PCO forming. So when we scored these using that view, we saw some results similar to our slit lamp exam scores. The test eyes again showed a little bit better central and peripheral PCO than the control eyes but there was no significant difference. And then on histopathology, we found that the anterior segments were pretty unremarkable. There was no notable toxicity or inflammation. There's some sections of the eyes for histo. Just to orient everybody. Here's the cornea, here's the iris, ciliary body, and then the capsule bag. You can see the outline of the lens right there. Same with the control lens. And both these sections are actually clean for rabbit eyes. There's very little PCO forming on either, seen on the posterior bag of either lens. You do see some rings ring here in the test and then on both sides in the control. So discussing what we found in this study, we weren't looking at incision size or whether we could insert through a micro incision. All lenses were done through three millimeter incision without problem. And we know that this lens is made of the same material that's already been used millions of times. And this lens can go through incision as small as 1.8 millimeters. We were looking at whether this new treatment when applied to a micro incision lens prevented PCO as well as the standard lenses. And this is a video from the manufacturer just describing how this treatment works. So the lens material, they're just showing that it's a polymer here on the posterior surface. They expose it to some oxygen, which is exposed to UV radiation. This creates ozone. And the ozone also absorbs UV light and it forms reactive oxygen. This reactive oxygen interacts with the lens polymer and makes some sticky functional groups. And the functional groups should stick to the bag better. Lens up to the other cells better. And we've actually tested this treatment previously at our lab. We showed that it did work. This is a different lens that was not treated with the treatment. And you see that significant PCO here, big summering's ring, and then the treated lens, it's much reduced PCO. So the theory behind why this works, why this treatment works, is called the sandwich theory from Dr. Lanola and Dr. Werner. And the theory is that you have an adhesive, a sticky IOL and then a monolayer of lens epithelial cells stuck to the posterior capsule. This forms a seal, preventing any new cells from entering and growing of passifying. And the key protein in this is Fibronectin. It sticks to the capsule and ideally that UV ozone would increase the, how well the lens sticks to Fibronectin. And it's just showing how that tight seal will prevent that fetal cells from growing inwards. So in conclusion, we knew that, oh yeah, I had developed a lens that was compatible with micron scissor surgery, made of hydrophobic material. We knew that this is a safe material and we knew that this treatment that was applied worked in other lenses for preventing PCO. And what we found is that when they applied this treatment to the posterior surface of this, their mixed lens, they, we found that PCO performance was similar, if not slightly better than conventional hydrophobic lenses. And this is important that it's hydrophobic because you don't have the compromises that come with a hydrophilic lens, such as calcification and ideally maintenance of that square edge. This is just a picture from Labor Day. I went back to Iowa and canoeing early in the morning. That's my dog. Thank you for listening. I'd be happy to take any questions.