 Hello, everyone. Hello, everyone. Is that working? Is it working? OK. We're going to get started. Our speaker today is Joshua Ford. He's one of our ophthalmic pathology and research fellows. He's working with Dr. Mamelis and Dr. Warner. He grew up in Sylvester, Georgia, went to Yale for his undergraduate and graduated from Dartmouth for medical school. He's in the process of applying to ophthalmology residency now. He's going to be presenting on light adjustable lenses. And so. All right. Can you all hear me just fine? All right, thank you. So thanks for the introduction. So I'm Josh Ford. I'm going to be presenting to you all on light adjustable lenses and other adjustable intraocular lens power technologies. And just before we even start, I want to make it abundantly clear. I have no financial interest in any material or methods presented this morning. Y'all can look at my bank account and make the same conclusion. However, I do work in the lab with Dr. Mamelis and Warner. And through working with them, I do interact with one of the companies that will be presented today called CalHoon. We're working with their light adjustable lens. And so I have gotten free meals from them, about $20 worth. So I just want to cover my bases here. Some of my co-fellows are Scott Cole and Justin Cole. I'm sure some of y'all have gotten to know them quite well. Also working in the lab is a first year medical student, Gareth Gardner, as well as Dr. Fasavada, who comes by every Friday and helps us out with our studies. So as Brian Sag mentioned, I am from a little town called Sylvester. It's located in Southwest Georgia, North County. Now, what we pride ourselves on down in South Georgia is our ability to make some of the finest peanuts in the country. We are actually home of the Peager Pan Peanut Butter Factory. And every year, we have what's called the Peanut Parade every second or third, Saturday of October. So that's coming up for us. It's always a fun activity for you. So some famous folks are from Georgia. I'm sure y'all all know about President Jimmy Carter. He's from Plains, Georgia, right near me. He was originally a peanut farmer who then grew up and became president of the country. Any of y'all are San Francisco Giants fans. We're also home of Buster Poseys from Leesburg, Georgia. He was on the 2010 World Series winning team as well as the 2012 team. We're also home of Philip Phillips. He's also from Leesburg, Georgia. He was the winner of the 11th American Idol competition. Ann Paladine, she was originally born in Albany, Georgia, but she made her empire out in Savannah. So if y'all are ever in Savannah, I highly recommend y'all go into her restaurant. And we're also known for producing the Shirley Temple of Our Generation in Honey Boo Boo. She's from McIntyre, Georgia. So what I'm presenting to y'all today is from a review article that doctors Mamless and Werner and I are working on. We're in the final stages of completing it. And we hope to submit it in the next several weeks. We just have to run through one or two more egetings of it. So hopefully, y'all will be able to read that in the next several months. So what we'll do first is we'll elucidate a problem within ophthalmology. Then we're going to introduce the concept of what an adjustable intraocular lens is. And then there are about 10 modalities that I want to try to run across just very briefly. Go over all the clinical and preclinical research that's available on those technologies. Go over any questions or comments that y'all have at the end, and then that'll be it. And hopefully, we'll get y'all back in clinic all in time. So one of the problems in ophthalmology that has been identified is that incorrect intraocular lens power still remains one of the most frequent causes of IOL exchange, despite all of the advances that we've seen in the past several decades. Owing to this, or a few studies by Branser and by Murphy, Branser 1997 showed that of 298 metropic patients having FACO or extra craft surgery, when they emerged from that surgery, only about 45% of those were within half a diopter of intended refraction postoperatively. And a bigger study by Murphy in 2002, consisting of 1,676 eyes, only 72.3% were within one diopter of planned refraction, and 6.4% were beyond two diopters. But I think some of the more compelling research on this topic are Dr. Manlens' foldable IOL surveys. So just to remind y'all very so politely, there's foldable IOL surveys in every OR. Figured Dr. Manlens for a lot for y'all to know that. But he's been doing this foldable IOL survey and has been publishing that ever since 1998. He publishes it once a year. And you can see here with a three-piece silicone IOL, the reason for explaining that was very commonly incorrect lens power. And that was in between 20% and 50% of explatations over a course of 1998 to 2007. For three-piece hydrophobic acrylic IOLs, lenses were expanded, or somewhere between 20% and 60% of those cases, or lenses were expanded because of incorrect lens power. And then for a one-piece-plaked silicone IOL, somewhere between 10% and 30% were expanded for incorrect IOL power. And so going into some of the reasons why lenses are expanded, I mean, you can group them into various categories. But some of them are due to technological inadequacies, such as incorrect axial length, incorrect corneal power determinations, incorrect a constant. So it's just looking in the technology and the formulas that are used to determine the IOL power preoperatively and some of the assumptions made, as well as mechanical issues. So when you put the lens in the bag, does it go in the correct or the presupposed position that it should go into? And then especially with TORQ lenses, you have to consider access deviation. And then some reasons are just unacceptable. The fact that IOLs can be mislabeled by the manufacturer or the wrong IOL might be inserted. And so in a study by Drs. Jen and Dr. Crandall back in 2007, they identified incorrect axial length and incorrect corneal power determination to be some of the most common reasons for post-up IOL power, incorrect post-up IOL power. So considering where we are today, where millions and millions of people are getting lacy surgery, where in our current arsenal of IOLs, they generally come in half a power, half a dioptric power of gradations. And the fact that patients' expectations are increasing, do we think that these certainly won't help with this problem? And so that's where adjustable lens technologies come into play. And what an adjustable lens is, it's any sort of lens that can be adjusted postoperatively to provide the patient with hematropic refraction. Now these lenses can be adjusted either invasively through some sort of insert surgery after they've been implanted or non-invasively through perhaps changing the properties of the materials of the lens after it's been inserted. And so I'm gonna run through all of these lenses. We're gonna start off talking about those that can be adjusted invasively. And then we're gonna start talking about those that can be adjusted non-invasively. And we're gonna conclude with the light adjustable lens as manufactured by Calhoun Vision. And one of the things that, one of the take home messages I want you all to get from this is that these tend to be, these seem to be the more superior technologies. And if I were a begging man, which I don't know, after losing $70 on a slot machine one time, I don't really think I'm a betting man, but I would think that these will have the most promise for becoming part of the mainstay of cataract surgery in the future. So we're gonna talk about the multi-component lens. So this lens, the multi-component, just as its name implies, it's made of different lens components that can come together and make a whole lens. So here is the base and lens. And this was first conceived back in the early 90s and published by Dr. Werbel in 1996. But the base lens right here is a PMMA lens. It's about six to seven, it's about six millimeters wide. So it would have to be inserted through a pretty large incision. So it's implanted first into the capture bag, outside of the eye, the middle and the cat lenses are brought together. And then you see this groove right here on the surface of the base lens. It fits perfectly the haptic on the middle lens and that's how it all comes together. So why this technology is a good idea is that if the patient's refractive needs change over time, the surgeon can go in at any point thereafter, take off the middle and cat lens and replace it with a new middle and cat lens. Another reason why this is important or why this is exciting is because if you consider all the different lenses, if you consider what the patients need when an entire population's needs are, if you consider that in 0.25 dioptric gradations, you need about 15,000 lenses to suit everyone versus this technology through just by exchanging the middle and the cat lens, that number would be more manageable be it just on the order of a few hundred. So Dr. Werblin published just a proof of concept study just to show that if you implant this whole lens into a caga that would remain stable within the capture bag that it wouldn't come apart. And eight caga is over a six-month period that he did demonstrate that to be true. Infinity Vision Optics is a French-based company that has used that concept of a multi-component lens, changing it ever so slightly. So for example, they've made a lens that has the, where the front lens has two IOL components held together by HydroStack. Also the front lens since in front of the interior capsule. Reason this is because our very own Dr. Werner here has published extensively on a concept called inter lenticular opacification, which is a known complication of piggybacking two IOLs together. And so if the front lens sits in front of the interior capsule has a much less chance of happening. So Dr. Pertaglio, she has published a study which was recently published in JCRS in 2013 where it's a two-year follow-up study of six adult patients receiving the Infinity Vision multi-component IOL. What she demonstrated over the course of two years is that no inter lenticular opacification occurred. There was no corneal damage induced by the lens and the lens was stable rotationally within the capsule or bag. She also showed that decimal visual acuity improved from the uncorrected decimal visual acuity, improved from point 11 to point six eight and the corrected decimal visual acuity improved from point two eight to point eight three over that two-year follow-up study. One of the things that she advocates for is or she advertises that this could be a very awesome technology in terms of managing a congenital cataract because you think of putting a lens into a baby's eye and over time their axial length and their refractive needs change. So if you could insert this lens into the child's eye and then over time change it out the front part while the child's refractive needs change. So going on to the mechanically adjustable lens and this is developed by Acratec and published on accessibility by Dr. Yon. This is a German based lens. But this is the way that this works is that this is a PMMA lens. It's about six millimeters wide. The optic is about six millimeters wide and so it would have to be inserted through a huge incision. But as you can see on the edge of the optic there's a one millimeter high cylinder and on the edge of the haptic is a piston. The piston fits within the cylinder and the way adjustment is made is you put this in and then with some specialized optic manipulators you adjust this in the anterior posterior direction with those manipulators and that's how you get adjustment. What Dr. Yon showed was that you have an adjustment range of about two to two and a half diopters so about one and a half diopter per millimeter. This has been studied extensively in animal and in human studies. So for the short term and long term rabbit studies they showed rotational stability, easy removability of this lens, mechanical stability during adjustment and they didn't show it seeing any evidence. And those were in short and long term rabbit eye studies. In human studies consisting of 35 eyes they showed that there's no difference in visual beauty, inflammation and intraocular pressure between this and just a conventional PMMA lens up to 15 months. They also showed that mid-reagate refraction improved from about one plus one to zero diopters. What they did however fine was that there was an increased incidence of posterior capsular of pacification that happened in about 18 of 35 eyes but fortunately that was treatable with yacapsilogamy in all patients. So going on to repeatedly and magnetically adjustable lenses and you can see I sort of brought them together and then you'll see why. So this is a repeatedly adjustable IOL which was developed by Dr. Eggleston published on extensively by Dr. Matthews and these folks are based at the University of Missouri. What this consists of is a PMMA lens with an interoptic and outer ring. The interoptic can be adjusted by moving it in the anterior and posterior direction but in a screw like fashion within that outer ring. Dr. Matthews published a paper just to show that just to prove for proof of concept basically showing that the rotational force required for power adjustment was well below a target maximum of one and a half ounce inches. Now why is that important? Well that's important because if you're rotating this thing if you have to apply a lot of pressure you're gonna maybe you rupture that capsular bag you're gonna mess up the zonules and you'll cause some damage and then interior chamber but the force required to do that wasn't significant at all. So imagine using that same lens and then fashioning some magnets within that lens and having an external source and being able to adjust that with that external magnetic source. So and that's what Dr. Matthews did and he published this paper the same years as a repeatedly adjustable lens. So using a magnetic spindle consisting of samarium cobalt and external source consisting of neodymium iron boride he basically showed that you can get you can screw this interoptic within the outer ring six-dipter lens you can focus that within .04 doctors and for a 16-dipter lens you can focus that within .01 doctors. They also did some leaching studies on this lens to show that over time if you put this in solution over time the magnetic components are gonna just come out. And that's what they did. They showed that in leaching studies that compared to you get about the same concentration of leakage as you will with a bare magnet in solution. That was the very question I had and it wasn't mentioned on that. I don't actually know. I don't really know much about samarium cobalt I would think that that would be important. The thing with this lens is it hasn't been published on since 2003 and as far as my knowledge goes Dr. Eggelson who designed this he's since retired. So I don't really think that this is going anywhere but it's an interesting concept, nonetheless. So going on to the liquid crystal lens with wireless control. And now we're getting into lenses that can be adjusted non-invasively. So just before I even go on and tell you about this lens I just wanna sort of go over what a liquid crystal lens is. When you think about this you have to think of just going back to journal chemistry the three phases of matter solids and liquids. Solids and solids the molecules are oriented in a parallel life action. Their positions relatively relative to each other are fixed versus a liquid which there's more random positioning of the molecules with respect to each other. For a liquid crystal a liquid crystal basically has the features of a solid and that of a liquid as you can see roughly parallel lines but some movability. Because of that the liquid crystal lens is amenable to adjustment via electricity and by magnetism. And that has actually led to a lot of applications so far such as the LCD screens on cell phones and the big screen TVs that we all have in our homes that watch football games. So Dr. Siminoff this is based out of the Netherlands here. He's made a lens just basically out of liquid crystals that can be adjusted from the external source. So the way he was able to do this you take a functional generator connected to a modulator which the signal is then amplified and then with a transmitting antenna signal is sent to a receiving antenna which is on the lens surface that signal is then demodulated into a voltage which is then applied to the liquid crystal lens surface. And here's just a schematic of the lens that he's been able to produce. So you can see right here this is a liquid crystal lens it's about 40 micrometers thick. This is a scary thing to go in your high, I know. I know, I'm not even going to joke around here about that. So, but the liquid crystal is between a high ohmic and a low ohmic material which applies the magnet to change the refractive ability of the lens. And so here's the lens as you can see wrapped around or coiled around it is the antenna. And right here is the rectifying diode. Now he's been able to show in initial in vitro studies that you can get about 2.5 diopters of adjustment. And they're currently working on encasing this whole thing within a silicon based material so that you're the contest of your interior chamber aren't exposed to all of this junk right here. And I just wanna give a shout out to this lens called the Alenza autofocal lens. This is actually being developed and it's an autofocal accommodating lens which doesn't really go into the topic that I'm talking about today but it does exploit the uses of liquid crystals. This lens right here, basically what reason it's so awesome is that there are sensors in the optic of the lens that measure pupillary dynamics. And so that if the patient needs, it can measure if the pupil is trying to constrict and it can help with accommodation. So maybe we're thinking about doing a paper on accommodation later on in the fellowship but that it's not really applicable to this surgery to this presentation but I figured it was worthwhile mentioning. Going on to femtosecond laser technology, I know that's been a hot topic in ophthalmology in the last decade or so but what's so, okay. Thank you. So with the femtosecond laser, this is just in brief, it's femtosecond lasers are able to, they have high pulse agility and they're able, you're able to focus on a very small microscopic target and without having producing much collateral damage. And so they've been employed in various procedures during a cataract surgery. So for example, they've been, they have applications to astigmatic limbo relaxing incisions to interior capsule agonies into lens fragmentations. So the question is whether or not they're well adjustments. And so these, what I'm about to present on you, the next few things I'm about to present on you, these are in their very early stages. We weren't able to obtain much information from the companies because they're keeping their lips shut on all this. But Alcon has a patent where they, and this is just a schematic of how it works. It's not quite clear as what's going on here but they're able to fashion a lens with concentric rings that are connected with this internal microstructure. And on this internal microstructure is this heat absorbable material or dye. So just looking at the zoom in of this, the photons emitted from the femtosecond laser, if they are, if they hit that dye, they call shrinkage. And so then you get tension development between these concentric rings and so that it becomes thinner. Conversely, if you apply the photon to the internal microstructure, you break it and then you relieve that tension and allow for fattening of the lens. Now that's about as much as they were able to tell us about their lens or as much as is available in that patent that we found online. Aaron Scientific is also working on using the femtosecond laser to make postoperative IOL adjustments. And most of their stuff has been done by Dr. Joseph Beale. And so he's developed this technology or has helped develop this technology called refractive index. The femtosecond laser is applied to a thin layer of immutable material within the optic. And by applying the femtosecond laser, you basically excite the electrons. They create a plasma. Bonds are then restructured. And so the way adjustments are made are by altering the refractive index of that material within the optic, as well as by altering its geometry. And so going on that principle, he's also developed what's called dividing the surface of the optic within various concentric diffractive zones, simplicity of the power adjustment that you're able to achieve. So if you consider a single 50 micron lens layer, if it provides five doctors of refractive diffraction, then if you split that into four, you could get 20 doctors, it's quite significant. But I have to say so myself. He's also said that you can get just by, and here's some pictures that he was able to provide us. You look here, this is the thin layer within the lens, within the lens right here. He's able to micro, to fashion some micro gradient patterns on to that thin layer. And here's looking at that pattern, sort of looking down interiorly. And then I'm gonna talk to you about two-fogon chemistry. This is also another exciting thing that's being developed. No, me showing these organic molecules, probably you're recalling horrible days from organic chemistry, but this is as simple as possible. So if you consider, so if you apply covalently attached to what's called cumulon, this is like a dye molecule. The nice thing about cumulon is that it's amenable to just like phogochemistry. So if you apply phogolons right here, this causes dimerization of the cumulon. When you get dimerized cumulon, you decrease the refractive index. However, conversely, if you apply a light with a different wavelength, you're able to break this bond and reef. And so this is being reported on by doctors, Shraub and Hamp. And with this two-fogon chemistry technology, they've been able to show that you're able to change the refractive index up to 0.03, allowing a fine tuning of up to two and a half diopters. They also conceived that torque corrections would be available with this technology. And the nice thing about this, and as you'll see later when we talk about the Calvin-Lager-Justice lens, is that this reaction is instantaneous. So once you apply that light to the patient, this reaction occurs, and you're able to refract the patient the same day. Another thing about this lens, or this technology, is that if you're thinking of light being able to change its properties of it, well, the theoretically ambient sunlight doesn't have enough energy to cause this reaction to occur. So theoretically, it's not going to change the refractive index with your patient being out in the ambient light. So now I just wanna go on and talk about the Calvin-Vision lens. This is probably the biggest topic, or the biggest subtopic today that we'll talk about, just because it's an FDA, a satiary of FDA clinical design. And so it's about to be out, or about to be commercially available probably in the next few years. And what the light adjustable lens is, it's developed by Calhoun Lens. It's a silicon-based lens that's amenable to, that can be adjusted with the use of a digital light delivery system. As it features square optic haptics, those are meant to help with PCO prevention as modified CPMMA haptics. And then the silicon macromer within the optic of the lens, that's amenable to light chemistry and able to be able to get adjustments that way. So this is just a schematic showing how it works. So consider this is the optic of a lens, and if you wanted to add power to that, you apply light to the center of that lens. The light causes polymerization, which doesn't change the refractive power of the lens. However, over time, just based on sheer thermodynamics alone, when this silicon polymerizes the silicon macromer in the outside or more in the periphery, the concentration isn't similar to that in the middle. And so it diffuses down a gradient and with it brings water and so you get sort of fattening of the lens. Now this process takes about 12 to 18 hours to occur within the time of actually applying the light to it. So you do have to wait a day or so to refract these patients. And then at some point thereafter, you're able to lock in the lens. But this whole process takes about two to four weeks to do. So if you're going to get a patient to do this, they need to be very amenable to wearing light protection because while it remains, it was originally a theoretical risk that ambient light could actually change this, but there's a case report coming out of Europe where this patient didn't do as her doctor said and her refraction just basically tanked within two weeks and so they had to exchange the lens. And so if you wanted to subtract the power from the light adjustable lens, what you do is you apply light to the periphery. This is called this polymerization and through the same thermodynamic principle that I mentioned previously, you get fending in the lens you get change in the radius of the curvature and then thus change in power of the lens. And so the way, the technique for applying light to the lens is that you have a light applicator system which is basically akin to a slit lamp that's coupled with a computer system. You dilate the patient so they have to be amenable to dilation. You put some topical anesthesia on the cornea and then you apply a contact lens and then you have the patient focus on a ready to target. At the same time, you enter the base power and the correction you get into the computer system. The computer determines what power or what intensity of light you need. The lock-in is done at a higher intensity at some point thereafter. And also I forgot to mention the lock-in procedure. After the lock-in, you can no longer adjust this lens. That's it. So here's the digital light delivery system right here and it's manufactured by Carl Zeiss Magatac. And you can see here, this, real right here is the pattern that it's going to place on the lens. So here, here's our very own Dr. Werner. Now this picture shows Dr. Werner basically applying this pattern onto the surface of the lens. And so after this was done, these lenses were ex-planted and so Calhoun, they took these lenses and they were able to show that this pattern that she wanted to apply to the lens, this is the power that she actually got. And this is Dr, and sorry, this is a, she's applying an astigmatic or a band-shaped pattern to the lens. So with this new digital light delivery system, you're able to get higher, you're able to correct for higher-order aberrations as well as for astigmatism. Now here's Dr. Mamelis. He's applying what's called a tetrafold pattern onto that Calhoun-like adjustable lens. And so just as what I described previously, this lens was ex-planted from the rabbi guy and the Calhoun vision showed that the tetrafold pattern that Dr. Mamelis intended to apply was actually applied to the lens. And so we know Dr. Mamelis affectionately in the lab is Kramer for, and I hope I still have a job after this but this is Dr. Mamelis sporting his Kramer hairdo with Dr. Werner and they're at the, I think this is the 2009 Aschers video awards presentation so you'll have to ask him about that. And so our lab was the first to do the various with the light adjustable lens. And so using 12 cats, Dr. Werner, back in 2007, and the reason she used cats in this, she's trying to show specifically that applying light to, or the intensity of light needed to make the adjustments with the Calhoun light adjustable lens are not going to one mess up the cornea or two mess up the retina. And so she designed this, so I'm using cats because they're cornea, the cornea endothelial cells have a regenerative capacity akin to that of the humans. Rabbit endothelial cells are very regeneratively robust so they're not amenable, but they wouldn't be a good model for this. And so what she did was she applied 250, this is the amount of light needed for the walking procedure. She applied it to the right cornea so we'll call those the steady eyes. And then the other eyes, she didn't apply it to. So, and then she sacrificed these cats at one day, one week, and at three months. And then using, she compared them qualitatively and quantitatively, qualitatively with Tri-Pam Blue and Alizarin Red and quantitatively with this EPCO system. And these are her data. So she showed that there's no for, there's no statistically significant difference between the steady eye and the control eye, suggesting that applying the light source to the cornea is not going to cause endothelial shutdown or effect. She also did a study using eight pigmented rabbits to make sure that the applying high intensity beam of light is not going to affect the retina. And so what she did was she used steady IOLs which were the Calhoun adjustable lens which have this UV blocking agent within the optic. And she applied up to five times the expected maximum UV radiation dosages. And then for the control eyes, they don't have this UV blocker in them. So she applied up two times that amount. And then one week after irradiation, she examined them with slit lamp and fundoscopic, she did a fundus exam. And then she sacrificed and nucleated and then submitted them for histopathology. And what she showed was that in the control eye, so those that don't have the UV blocker in them, that you get this retinal scarring. So you see this scarring event right here. But with those that had the steady lens suit or rather the Calhoun adjustable lens which has the UV blocker in it. You're getting retinal scarring in the study. So that's suggesting that applying the light, applying the highest intensity light possible during the adjust or lock in procedure is not going to affect the retina. And so a lot of the clinical studies on the Calhoun adjustable lens has been performed by Dr. Chaya. He is based out of Mexico. And he did some of the original studies using just with myopic and hyperopic adjustments. And he was able to show that 13 and 14 eyes are about 93% of those. You're able to achieve within 0.25 dot there's a targeted refraction one day after lock in. He got about a very similar result with those that required hyperopic adjustment. He also did some of the studies with the stigmatism with the newer light delivery system. And all his patients are all five patients who had the stigmatism. He's able to get them within 0.25 dot there's a targeted refraction at one day post lock in. Now, as I mentioned before, or folks with axial hyperopia and axial myopia, these folks are very difficult to predict what IOL power they need preoperatively. And so some of the newer studies by Dr. Hanger, he's based out of Germany. He's able to show that 93% and 67% of the eyes were within 0.5 adapter and a quarter of adapter of the targeted refraction one day post lock in. And with those with axial myopia, about 96% and 81% of those eyes were within half adapter or a quarter adapter one day after lock in. So there's very promising data right here. And then one of the newest publications for this is looking at folks who have history of refractive surgery. And this is a very promising study right here because it showed that he, Dr. Brealy showed that 74% and 97% of those eyes were within a quarter and a half adapter after lock in. And so, as I've mentioned before, those folks with axial hyperopia, axial myopia and those folks who have had refractive surgery is very difficult to predict whatever IOL power they need preoperatively. But this is very promising because it's showing us that we could implant a leg adjustable lens into these patients and get most of them within half a adapter of targeted refraction. Calhoun, they're doing studies with their adjusting how to incorporate the UV blocker in their optic. Originally with the first generation lens, the UV blocker was just scattered throughout the optic. However, with this next generation of lens, they're applying a, they just have a surface applied to the posterior aspect of the lens. And this is called, this is supposed to be the UV blocker right here. The idea behind this is that if you can thin it out, you can perhaps make it so that you don't need that many adjustments. So if you don't need that many adjustments, you might can shorten the time after implantation of the lens down to about two weeks that you are able to lock again. So to help with patient compliance, because as you all can imagine, asking a patient to put a lens having to wear UV protection for four weeks, it's a big thing to ask. And so just a synopsis of everything that we've talked about today, we've said that incorrect IOL power is a significant problem that deserves our attention, hopefully adjustable IOLs will provide a useful way to correct this problem. We've gone over all those IOLs that can be adjusted invasively as well as non-invasively. And then I think one of the recurring themes or where I've tried to impress upon you guys is that non-invasive adjustment seems to be superior to invasive adjustment. The Calhoun-like adjustable lens is in stage three of FDA clinical trials. And so as such, it's closest to commercial availability in the United States. However, and I know I'm opening up a Pandora's box here about concluding on this very final statement, but who's gonna pay for these technologies? These are very expensive technologies. The Calhoun-like adjustable lens, I have tried to get some financial data from them. They keep their lipstick on that, but I was able to find in various papers from Europe that the like adjustable lens costs about $1,500 for those patients in Europe. The digital light delivery system costs on the order of $80,000 to $100,000. So that's a very expensive endeavor. And you also consider all this femtosecond laser technology, those things cost on the order of half a million dollars. And who knows how upwards of $70,000 to for annual maintenance fees. And I couldn't get from Calhoun vision how much the maintenance fees would be for the digital light delivery system. So these are all my references, sorry. And I just want to think, first of all, all of you for attending this presentation, I know it's a significant time investment from your clinical responsibilities, so I definitely appreciate you being here. I also like to thank Dr. Manlis and Dr. Warren for taking me on in their lab. Dr. Cole with the K and Dr. Cole with the C, that's our nicknames for each. We have nicknames in the lab, so. And Dr. Vasavada, he is an international doctor here who's here just observing. And he comes to the lab once a day, once a week. Also Alicia Doxton for helping set this Grand Raleigh's presentation up. And Mary Mayfield, she's our histopath tech and she does a lot of the specimen handling and she has answered so many questions that has been an invaluable resource. So I just want to ask if y'all have any questions or comments? Yeah, these femtosecond technologies on the leg adjustable lens. So in vivo study, sorry, in vitro studies, it's about four adapters. I think we've asked, counting this question ourselves, it's about two and a half to three adapters. For the, yeah, silicone lenses are foldable. Yeah, the first ones with the mechanically and the multicomponent lens, they're made with PMMA, so they're not foldable. So you need a huge incision to even. Sorry about that.