 Our next presenter is Joe Alunzi. He's an ocular pathology fellow and he's going to be presenting on preventing PCO by intraoperative treatment of the capsular bag. Hello, my name is Joe Alunzi. I'm one of the ocular pathology fellows at Dr. Malamuss and Dr. Warner's lab. I have no financial disclosures. So one of the major issues of cataract, modern day cataract surgery, is post-operative capsular bag with pacification. When we explore modalities that decreases this type of complication, it shows, it's very needed at this time. Before I start, I would like to just bring your attention to the schematic view of the crystalline lens. We know that it's made up of three layers, the capsule cortex and inner nuclear portion. When you look at the, when you're looking at the pathogenesis of capsular bag of pacification, it's best to divide it into two types of tissue where you have e-cells and a-cells, and that's just based on the zone that they're in, so in interior versus equatorial, and they behave very differently. These two cells, within the cataract surgery, we're doing, we're creating a capsule rectus on the anterior surface of the capsule, and when, when these particular cells are disrupted, they, the a-cells in particular, they stay stationary and then undergo a pseudo fibrous metaplasia. Now with the e-cells, which are located on the, the equatorial cells, when they are disrupted mechanically, they migrate posteriorly and then undergo pacification. A couple examples are summering's ring or pearl formation. So it's, it's obvious the intervish, the perfect intervention for PCO. We could just go back to the traditional method of intra-capsular cataract surgery. Any volunteers for that? So probably extra cap cataract surgeries that are here to stay. So because of that, we're going to continually have this residual lens epithelial cells that are present to cause, to cause havoc in the form of capsule vagal pacification. So it's been well described, six types of factors that help decrease PCO. Three of them are surgical and three of them are Iowa related. Now surgical factors are going to remain constant. However, if we, if we approach this issue from a different angle, there's a way we can circumvent the Iowa related factors all together. So this presentation, we're going to talk about solutions that we could inject into the capsule vagal within the surgery intraoperatively that will decrease the pacification, adding very little, little time to the surgery at home. Genesphere is one company that created a nanocarrier. Here's a model of that nanocarrier where it's essentially a scaffold that allows connections to to maybe antibodies or proteins or other form of proteins as well as a cytotoxic agent. So in theory what this is, what this allows is internalization and cellular damage to specific types of cells. In our case, it would be the A cells and E cells within the capsule vag. And so our study design included five groups listed here. First group was just BSS, second group was just Doxy, and then the third to fifth group included different components of the three components that I spoke of. And there were, and they were injected into the capsule after evacuation. So this is a flow of our study design. So we had 16 little patients that we used. All of them had the control lens, which is a hydrophobic acrylic single-piece lens. And we performed sit-lamp exams on a weekly basis for a month. Upon completion of the study, the animals were humanely anesthetized and then emucleated. Upon that, we were able to analyze the capsule bag of pacification using both the Myakki apple technique as well as histopathology. And so these are images from week one. And basically what you want to take away from this is that all the eyes had a very mild inflammatory reaction. So this is at the, this is the final week. And there's a big difference. Let me just go back to the previous slide. So it's pretty clear there's a little bit of fibrin, but when we look at the eyes at week four, significant PCL has already started being formed. But I want to draw your attention to the images that contain Doxy-Rubycin. So it's going to be the second, third, and fifth. When you compare that to the other images, there's a noticeable difference in where you see a very little to no opacification compared to the control models. And so this translates into a statistical analysis as well where we found that among the five groups, there were statistical significance, particularly when you examine the P-value. So these are great posterior views. Looking at five of the different treatment groups, and again, the same thing is translated post-mortem, where you have the second, third, and fifth image, which are the ones that include a Doxy-Rubycin in different combination with a nanocarrier compared to the control, where in control there's significant opacification that's seen centrally in that first image and forming in that fourth image there. So I particularly found this finding impressive because both of these IOLs were placed in the same rabbit, where the right eye was treated with just the antibody and DNA nanocarrier, and then the left eye was treated with all three components. And there is a clear difference here, as you can know. So we did further statistical analysis, post-mortem, and the statistics were even more telling with even a stronger P-value here. Now, a second company that we've been working with is CODA. And CODA created a gel-like substance called nexagon that has already shown great promise within the field of wound care, tissue recovery, and inflammation. And we're now adapting that into ophthalmic care, particularly in decreasing opacification, copsovibagopacification. So nexagon, there's been preliminary studies that has been already been used in glaucoma treatment, particularly in tribes, and that shows great promise. Our study design is very similar to Genesphere, but instead we use seven little patients this time. And so this is the layout in terms of the treatment groups. And I want to just focus your attention on just the last five you notice that in the left eye, received standard of care. And in the right eye, received the nexagon gel-like substance, which was injected into the eye intraoperatively. So standard of care just means no injection at all. So they received BSS. So again, this is images from post-week one. Just showed a mild inflammatory process, which was seen in practically all the eyes. And then at week four, I just want to draw your attention to the first of control group and you see just clear opacification that is covering the posterior surface of the IOL. But in the right eye, the eye that was treated with nexagon, there's significantly less opacification. And our statistics also confirm that it correlates with what we saw grossly. So this is at the end of week four. However, when we did the post-mortem analysis using the Myaki Apple view, there's grossly significance there. However, when we did the statistics, sorry, however, when we did the statistics for post-mortem, it wasn't statistically significant. This is histopath of the right eye of one of the little patients. And you see very little proliferative cortical material present. And here is the control eye. And if you look at the bottom, to your right, there's significant proliferative cortical material present there, as well as cortical material that is growing around the haptics, which are in the top two images. So when we... It's clear for Genosphere that there was a trend towards decreased opacification. And grossly, so for COTA, this is a novel idea, a great idea, and we're moving in the right direction. Next steps would be optimizing concentration of these substances that we inject into the eye and just finding a ideal concentration. Other things to note is just evaluating the role of the carriers and seeing the significance of it. And also just seeing how this technology could be applied to other areas within ophthalmology, not just decreasing capsule vagal pacification. I want to thank Dr. Mamelis, Dr. Warner, also my fellow co-fellows in the lab and everyone else that's part of the team. Here's my references. Any questions? Yes. The next presentation is another topic that has a lot of potential to get pediatric. But my question is, how exactly does this target lens epithelial cells, but then not corneal epithelial cells? Corneal cells or angle cells or irons cells? Do you think, I'm sure there's a mechanism or a theory, but do you think that actually is perfect in that? It seems like it should have some risk to all of the other cells in the interchamber. All right, thank you for the question. So his question was, how do we know that it specifically targets the lens epithelial cells versus any other cells found within the eye? Great question. Genosphere has done preliminary studies where they have been able to elucidate the pathogenesis of PCO. And what they found is, a lot of these lens epithelial cells will undergo a metaplasia where they transform into myofibroblasts. And these myofibroblasts have specific proteins that are found on these cells. And so when they created the GA antibody, those antibodies are for those specific proteins that are found on those myofibroblasts that occur during this metaplasia process. Does that make sense? Yeah. Yeah. Any other questions? Yes, Niko? You only get one question. Do you think like that your results in the first part of your talk is mainly due to Dr. Rupusin alone? And then the second part is for the nexagon. I didn't see what it's composed of, but for your control, instead of BSS, can you use a gel-like kind of inert substance that the nexagon is made of as well? We'll see really clearly. Okay. That's a great question, actually. So Niko's question was, is the results that we're seeing, and particularly the Genosphere study, is it just due to Dr. Rupusin being there, or does the nano carrier, this 3D DNA carrier has a role in the results that we're seeing? I think that's a fantastic question. When we look at the statistics, all the groups that had Dr. Rupusin showed decrease of pacification. But the groups that didn't, the BSS, the group with just the antibody in the nano carrier showed increase. I think the answer to that question is very alarming, particularly to this group, because it would be hard to just market Dr. Rupusin. I'm just gonna stop there. But that is a very good question and it's a great observation. We do have to do further analysis and seeing the role of the nano carrier. But yeah, I think that's a great observation, Niko. And your second question was referring to Nexagon? Yeah, good question. And so, I mean, a lot of research is, I mean, you go there and you're trying to brainstorm, trying to come up with the best method, trying to create the best control. So during the time, we did decide to use BSS. So we had seven rabbits in total. The Nexagon does come with a vehicle. So the first two rabbits, we used the vehicle for both eyes. And then for the subsequent five rabbits, we decided to use BSS as opposed to the vehicle and the control eyes. Maybe Dr. Malmuss could elaborate a little bit more on that, but it's still in the preliminary phase and that's something that we're definitely thinking about. You know, when we were doing the direct comparison, we're doing BSS, but we did do four eyes just the vehicle to see what the effect of just using the vehicle was. And interestingly enough, with just the vehicle, you actually had more PCO. And I think the reason for that was the fact that this is a very thick, jelly-like substance and as you inject it in the capsule bag and the rabbit, it separates the capsule bag from the edge of the aisle and actually allows more space for the PCO to grow. So the vehicle without the actual treatment material in it actually led to even more PCO than it did just BSS. So that is a sign to us that the actual material is working as opposed to having the vehicle have any prominent effect. Did that answer your question? Yes, thanks. Any other questions? Thank you for your questions. Thank you for your attention.