 Hi everyone, my name is Sneha, I'm the other ocular pathology research fellow, and today I'll be talking to you about a new IOL that has a membrane on it to prevent PCO. And the study that I'm going to talk about today was done in the Mammalus-Warner lab, and I just want to have a moment to thank Dr. Mammalus and Warner for letting me be involved with the study and for all of their support as well. It's a little background on PCO, posterior capsule pacification. You're right. Thanks. It's the most common long-term complication after cataract surgery. It's formed by residual lens epithelial cells after surgery, and you can see here in this picture, these lens epithelial cells from the equatorial lens blow tend to migrate to the posterior lens capsule down here. And they tend to form large, volume-like bladder cells. And of note, these are also the same cells that form a summering ring. So some factors that can reduce PCO include changing the intraocular biocompatibility, having a square-shaped optic edge, maximizing the contact between the posterior optic surface and the posterior capsule, expanding the capsular bag itself, and modifying the surface of the eye well. So when talking about a square-shaped optic edge, this decreases PCO. And there's two theories why this happens. One is by contact inhibition. And the thought is that a square edge is going to, and Sean already kind of explained it, is going to produce a bend in the posterior capsule itself. So once the lens epithelial cells kind of hit that bend, they can't grow any further than that. And the other thought is by capsule compression. Having that square edge can increase the pressure within the bag itself. And that increased pressure will compress the posterior edge of the eye well to the posterior capsule. So there's no place for the lens epithelial cells to grow. And in this picture, you can see a square-shaped edge over here. And then in this picture is also the Miyaki Apple view. And you can see that there's considerable summering's ring formation around here. But the optic itself is pretty clear of PCO. And as I said earlier, summering's ring and PCO come from the same cells. So we can see that the optic kind of acts like a barrier to prevent PCO from growing. Another factor to decrease PCO is by expanding the capsular bag. And this allows for increased aqueous flow. And the increased aqueous flow can decrease kind of like the deposits of the epithelial cells and also decreases the activation of stimulatory cytokines. And two IOLs that kind of go along with this theory is the Zephyr IOL and the Synchrony IOL. And these are capsular attention ring-like devices. On the top, you can see the Zephyr IOL here. It's a single-piece hydrophilic acrylic monofocal IOL and it has sort of a wheel-like configuration. And the IOL optic is suspended here and connected by a pillar of this haptic material. And this ring itself is what rests up against the capsule. So it prevents the optic from touching the capsule. So the haptic acts as, or expands the capsule bag and also there are some holes within the haptics itself. And both of those increase the aqueous flow in the bag. And you can see here after six weeks that there's no PCO formation in a rapid eye. And then another IOL, the Synchrony IOL, is a single-piece dual accommodating silicone IOL. And you can see here that these optics are attached to the haptics by kind of a bridge. And the haptics itself has a kind of a spring function here. And the anterior optic has two projections. And these projections push on the rexis edge itself. So it prevents the optic from touching the capsule as well. So not only does it prevent touching the capsule but expands the bag. And then there's also holes within the haptics to increase aqueous flow. And you can see here in a five-week slit-lamp exam there's no PCO formation. So another way to decrease PCO is by manipulating the surface topography of an IOL. And that's the method that this study chose. So usually cells migrate through interactions of focal adhesions. And it's thought that micropatterns itself can control where cell migration goes, depending on the, by controlling the focal adhesions. And one of them, one of these patterns is actually inspired by shark skin, which I thought was pretty interesting, since sharks are resistant to certain fouling organisms in the water. And that includes algae and barnacles. So this shark skin, like microtopography, has been shown to inhibit bioadhesion more effectively than other patterns. Specifically in other medical devices, it's been tested in an endotracheal tube and a Foley catheter. In the endotracheal tube, it's been shown to decrease biofilm formation and ventilator-associated pneumonia. And up here is a pattern that this endotracheal tube used. And down below is a pattern that the Foley catheter used. And in vitro studies showed that it inhibited E. coli growth. In pictures A, B, and C, here that's the sharklet pattern. And then in D, there was no pattern, or was a smooth membrane. And so you can see that there's much more growth here than in the other three patterns. So since this was shown to be effective in vitro studies in other medical devices, it was thought that this pattern could maybe decrease lens epithelial cell migration. So in vitro, study was done to compare the sharklet membrane versus a smooth membrane in a modified scratch wound assay. And in the study, all the sharklet topography showed significantly reduced lens epithelial cell migration in comparison to the smooth membrane. And in the pictures here, you can see this is a smooth membrane and then B, C, and D are the patterns that they used. However, since this was in vitro, they couldn't replicate the bending of the bag in vivo. So our lab was actually able to test this sharklet pattern in conjunction with an IOL in vivo. Three groups were tested. One was the patterned membrane with an IOL. The other was an IOL with an un-patterned membrane. And the other group was the IOL alone. And of note, so the membrane was implanted first and then the IOL was placed within that bag, within the membrane, sorry. So those were two separate things. From the study, we were unable to determine whether the pattern itself reduced PCO because PCO was prevented in both the pattern and un-patterned membranes. And we think that's because of the geometry of the protective membrane itself was expanding the capsular bag. So in this current study, our lab was actually able to test a membrane embedded into the IOL. We tested three groups of IOLs in 12 rabbits. Group one was that un-patterned clear-side IOL. Group two was a sharklet pattern clear-side IOL. And group three was a commercially available control IOL. We did weekly slit lamp examinations, testing the biocompatibility and looking at ACO and PCO. And the study lasted about four weeks. And then the rabbits were humanely sacrificed and enucleated. Afterwards, we evaluated the anterior segment using the Miyake Apple view and also evaluated the histopathology. And once again, like Sean said, we used a rabbit model because they have accelerated PCO development. You can see here it took about seven years to form this summering ring and some PCO is starting to form at the haptic optic junction. And then just in two months, you can already see PCO formation in the rabbit eye. In six months, it's pretty much completely classified. So just to give you some more background on the IOLs itself, the un-patterned and the sharklet patterned IOLs have the same base IOL. They're a one-piece monofocal IOL with two haptics. It's a hydrophobic acrylic polymer. The optic zone measured 5.5 millimeters in diameter and it had this 0.75 millimeter membrane surrounding it. The lateral wall had a height of 0.59 millimeters and that's higher than your typical standard IOL. And just to clarify, the sharklet pattern had an actual membrane on this peripheral membrane while the un-pattern had the membrane but didn't have a pattern on that membrane itself. And both IOLs were injected with an acu-jet reactor. And this is just to show you a close-up of the sharklet pattern. And once again, the thought is that this micro pattern can control where the cell grows by guiding the focal adhesions. So it's supposed to grow onto this pattern instead of growing onto the optic lens capsule. And the control IOL used was a hydrophobic acrylic acrosoft lens. It has two modified L-loops. Overall diameter is 13 millimeters. Optic diameter is 6 millimeters. And it was injected with a monarch III injector. So this video is showing the placement of an un-patterned IOL into a rabbit eye. So the IOL is injected fully into the bag. It's unfolding nicely. You can see the optic is fully covered by the rexis. And this video is showing the placement of a sharklet pattern IOL into the rabbit eye. Pretty similar to the first one that we saw. Fully injected into the bag. It's unfolding nicely as well. And then this one is the control lens. So all of them were fully injected into the bag. And the optics were covered 360 by the rexis as well. So after four weeks with this slit lamp view, you can see that there was no statistical significance between all three groups in terms of scenic eye formation and PCO. However, PCO view is limited with this slit lamp view because of the optic and the iris can kind of cover up what you can see. So it's better evaluated with the posterior Miyake apple view. So although there is no statistical significance for PCO, you can already see that these numbers tend towards more PCO in the control group than the sharklet and the un-pattern group. Also, there was statistically significant more ACO in the control group in comparison with both the un-pattern and the sharklet group. And here you can see in the slit lamp view that there is less PCO in the sharklet group than in the control group and the un-pattern group. In the posterior Miyake apple view, there was significantly more central PCO, peripheral PCO and summering's ring formation when comparing the control group to the sharklet group. However, there was no significant difference when comparing the un-pattern group to the control group. Of note, since multiple comparisons were done, the p-value was set with the Bonferroni correction, so the values of the un-pattern and control groups are not significant in this. And then in this posterior Miyake apple view, you can see that the control group had more PCO here than the sharklet group and the un-pattern group also had more PCO than the sharklet group. You can also appreciate how the iris can limit your view of the PCO as well. In this histopathology side, you can see that there is more PCO and summering's ring in this control group than the sharklet group, which is pretty clear, and that there's a little bit more in the un-pattern group than the sharklet group as well. So this study showed that PCO was reduced in the sharklet pattern group versus the control group, and we think that the micro-pattern was effective in controlling the lenzopothelial cell migration. Also, the ACO and summering's ring was reduced in both the un-pattern and the sharklet group versus the control group, and we think that's because of there being slight capsular bag expansion. If you can see here, the bag is a little bit more expanded than in the control group here. That's because the lateral wall of the IOL was higher than the standard height, and this limited the contact between the anterior surface of the lenz and the inner surface of the anterior capsule. So in conclusion, the sharklet pattern group had reduced PCO compared to a commercially available control IOL, while the un-pattern IOL with the same membrane did not, and this is because the sharklet pattern enhanced PCO prevention through controlling the posterior migration of residual lenzopothelial cells. These are my references. I'd just like to thank you for your attention if there are any questions. Take them.