 Great so good morning. Thank you very much and before I start just a reminder of the structure of our laboratories So we can either co-direct co-direct the lab the laboratories in the fourth floor We are specialized in intraocular lenses, but also it can be any kind of ocular implantable devices So we are going to talk about IOL power adjustment by Centosecond laser and Last year one of our fellows actually briefly presented about this subject Because we had a small experience with this project at the time However since then we have been working much more on that so I wanted to provide you with an update and Because in this presentation we are going to talk about IOL adjustable technologies I would like to acknowledge that our laboratory performed Contract research studies with at least three companies dealing with this subject, which are perfect lens, californ vision and Clarvista So in 2014 we published this review article at the JCRS on adjustable intraocular lens power technology A review of everything that was available or under development And we decided to do that at the time because of this particular problem In despite of the advances in cataract surgery incorrect intraocular lens power remains one of the most frequent causes of IOL exchange and this is shown by different studies including the survey that Nick sends out every year So of course a very good solution for these among many others But one very good solution would be the event of adjustable lens technologies So lenses that can be adjusted Posteriority to provide the patient with an atrophic refraction And then in that paper we review everything that's available or under development and there are a bunch of invasive Adjustment technologies, but also under development are non-invasive Adjustment technologies and at the time we briefly mentioned about the application of Fentasecond technology in this arena, but we did not have experience with that yet Since then we started to collaborate with the company that's developing this technology And also since then there was the publication of this paper describing the basis for the creation of a refractive lens within an existing IOL using the Fentasecond laser And even more recently they publish this paper and we're going to discuss about that because this describes the real chemical basis for all of these changes So just to start with an overview the project is being developed by Perfect Lens is a company in California and the laser system they have uses green light So 520 nanometers the wavelength and this is a system that operates with energy levels That are below the threshold for ablation or cuts This is actually very important because each time we talk about that the first question of Automology is that are you cutting ablating the IOL not really you're going to see that So in a nutshell, that's a very brief overview. There are laser induced chemical reactions in a very small targeted area within the IOL substance in that area This chemical reaction induces an increase in hydrophilicity of the area associated with a decrease in the refractive index and that area that's changed has a specific shape Which is the shape that's going to give the refractive power So this all happens at the same time the laser builds the refractive index shaping lens within that Targeted area. We are going to go into details In this this is just for you to see that what is happening is nothing on the surface of the lens Not until your surface or posterior is really within the lens What the laser is doing here is not cutting anything The blue area is the area that's changed by the laser based on a chemical reaction. So there's no ablation or cut So starting the day is what happens This system is based on the IOL being inside of a cruise medium So if you have an IOL inside of the eyes, which be surrounded by water when you have for example Any hydrophobic acrylic lanes that you put inside of water and you apply this laser In that targeted area. What's happening is that it's increasing the hydrophilicity of that area And in that very small area there is a decrease in the refractive index It's a very thin area in the substance of the lens What I want to highlight here is that for you to know if a surface or a material is Hydrophobic you can do tests like the contact angle or in water So you put a drop of water and you measure the angle. So this characterizes a Hydrophobic surface an angle of 87 degrees This was treated by the laser. So this surface remains hydrophobic The area the substance of the optic that was not touched by the laser remains Hydrophobic the only area that change and that changes is the area Targeted by the laser, which is a very thin area. So there is no other change in the IOL This can also be done in hydrophilic acrylic lances. So that targeted area is going to be rendered even more Hydrophilic. So what I want to highlight here also is that I'm talking about commercially available Hydrophobic and hydrophilic acrylic lenses. I'm not talking about a special lens that the manufacturer Produced to be used with the system. It can be anyone that's commercially available So I separated these steps, but this is actually simultaneously in that area where there is the chemical reaction And the change in refractive index the laser is giving this special shape This is called the phase wrapping Phase and basically it shows a collapsed IOL that small layer That's very thin contains the full power of a standard IOL refractive or diffractive And you see that's very thin area. So a phase wrapped structure Contains the entire curvature of a traditional convex or concave lens in one single layer That's very thin and why this is done because this is the way for you to create a very significant refractive change in such a Limited area. So they did the calculations to have a refractive index change of point Zero one in a conventional lens. You only get point four diopter of change However, if you do that using a phase wrapped lens, you get three point three diopters of change So this is actually very significant that you can get such a change with such a thin layer in the substance of the IOL And this is the recently published paper where they define the chemical basis of this change So they use different microscopic methodologies laser induced fluorescence Coherent anti-stokes Roman scattering this basically all techniques that are used to show changes in the molecular structure of polymeric materials So what they demonstrated is that there are photo induced Hydrolysis of polymeric material in the aqueous media in that area where you apply the laser With creation of two hydrophilic functional groups and then as water is slowly diffuses to that area You have increasing hydrophilicity forming hydrogen bonds and then decrease in the refractive index But this is not an immediate Change so it takes at least one day for the water to slowly diffuse diffuse to that area Then you have the change in power So if you apply the laser and you measure the power of the lens you'll not be changed immediately So you cannot measure on the same day and then of course with this technology We have to ask ourselves is the optic quality of the lens change by the laser And we did different studies and I would like to cite this one We had commercially available single-piece hydrophobic acrylic lenses and we evaluated them before the laser and after the laser by different techniques including light microscopy So you can see here before and after And there is some water there because the lens has to be water all the time for this to work And on the right you see after laser it looks like the fractive rings But again, these are not the fractive rings on the surface of the lens These are changes in the lens inside of the substance of the optic so we measure the light transmission through a spectrophotometer and Light scattering using shine a shine flip camera and we have this device which is actually an eye model so we put it I will inside and You can do the measurements inside of water. You have like a corner artificial corner artificial iris So this really simulates an eye And we use the PMTF device to measure power and modulation transfer function The MTF is really what indicates the optical quality and it's important to mention this device because there are eyes Standards defining how you evaluate the optic quality of a lens This is the device that fits the eyes with standard. This is the device that is used by the FDA So in terms of light transmission, you can see the graphs and there was a minimum change Which is absolutely negligible in terms of values in the light scattering What you can see is the pattern on the right side of the Pattern applied by the laser so it increase the back scatter inside of the optic substance of the lens which matches Exactly the laser application We perform many different studies using the back scattering machine and with these levels of increase We are not expecting any change whatsoever And this has already been confirmed by the measurement of the MTF again the modulation transfer function indicates the optical quality The curves of all lenses before and after the laser pretty much the same So you can see here all the results with the 10 lenses And you can see that the targeted change for this study was minus 2 diopter and that's pretty much What we got and you see the changing MTF is like almost non-existent So in vitro these words like very very well But then since then we had the opportunity to do the first in vivo study using this technology Because you may ask okay. There are chemical reactions involved is this laser Durating some toxic factor Unpolymerized molecules inside of the eye they are going to cause inflammation or toxicity or so on so we evaluated the biocompatibility We did the first preliminary study using just six New Zealand rabbits They study lanes was implanted in both eyes and again I'm talking about the commercially available single-piece hydrophobic acrylic lanes that has absolutely nothing special in the material Slit lamp was performed every week for six weeks and The laser adjustment procedure was performed at week two the targeted changes plus 3.6 diopters After the follow-up the rabbits were sacrificed and the IOLs were Explanted for the power measurement and the eye was underwent was prepared to undergo all histopathological analysis to see if there was any sign of toxicity So again commercially available single-piece preloaded in tropical lanes nothing special about that So here you see a video of Nick actually did the surgery so he's implanted in the lanes Nothing special about the lanes implantation Injection in the bag implantation and fixation through Capsule axis smaller than the optic. I mean very very standard Then I want to show you our in vivo setup It seems very easy to say is more preliminary study six rabbits, but It took months to prepare this because first of all they had to create with a 3d printer a support for the rabbit Because even though in clinically sit in the clinical situation you do this adjustment with top co anesthesia Of course for the rabbit. We had to fully anesthetize the rabbit So they created a support for the animal and we could tilt the animal in all kind of directions They use again a 3d printer and you see here the whole setup for the in vivo study It pretty much I could buy the entire operating room that we have in the vivarium They came with everything they built up the laser there the whole system the bed everything so it took really many days to do that and And also the rabbit eyes have many Characteristics that we can use to evaluate I wills with the same size of I wills as the Human situation, but there are many differences between the human eye and the rabbit eye So we have done preliminary studies evaluating the differences in size the differences in geometry And you can see here for example the size is very different But look at the corneal diameter for example of the rabbit is actually larger So the geometry of the entry segment of the eye is different So they had to create an entire interface for the laser to fit the rabbit eye because of these differences And you see here the animal comfortably sitting in the bed and Anesthetized and you can see the interface there that was specially designed for the rabbit eye and The eye of the animal had to be aligned under the laser system And the laser has an OCT system to allow for this alignment and also a video camera So this helps control the alignment of the eye But of course this is happening the animal study took like a long time because of course it was anesthetized So we had to do the alignment with the help of the system the human situation is going to be much simpler And here's the treatment. I mean once you push the button for 3.6 23 seconds and it was quite amazing So then we performed slightly immediately after the laser treatment and Almost each hour because after the laser treatment there is this bubble formation this gas formation You see this in cataract surgery the femtosecond laser to these bubbles were behind the eye well between the eye well and the posterior capsule and they progressively Progressively decrease until they disappear the longest time that takes to disappear is five hours after five hours There was nothing. There's no mark on the eye well No, no Pete like when you have a laser and you beat the eye well by accident There is no pity is a change almost in the color where the The laser treatment was performed And then we follow them and there was no inflammation induced by the laser treatment actually we did not even need to treat with Drops or anything we follow in terms of UVO by compatibility capsule by a compatibility You see the PCO formation in both eyes treated or not treated eyes was exactly the same There was absolutely no difference then we did posterior view analysis growth analysis complete histopathological Analysis of all eyes and there was no difference in terms of inflation toxicity whatsoever And I wanted to show you then the power change because that's what's so interesting That was the first in vivo study We were expecting that the target would be really off because it was not so simple to set up And still with a target change of three point six diopter You see that it got really very close. So that is actually very impressive for a first study I want to call your attention for these measurements here, which are all a little bit different But then all the lenses we implanted in the rabbit eyes and all eyes They had a power labeled as 22.5 Diopters as you saw in that table there was variation in the power measurements done with the PMTF device So what you cannot forget Is that there are current standards? You know the eyes with standards and orders that they allow some tolerance for the measurements of the power and labeling of IOLs For example, you have a tolerance of point three diopters for IOLs between zero and fifteen Diopters it is even higher with IOLs between 15 to 25 diopters So basically if you have an IOL with a power measured as 19.6 diopters and another with 20.4 diopters Both of these lenses will have a label diopter power of 20 diopters So you see that this by itself may contribute to postoperative refractive errors after IOL implantation And by itself make this kind of technology quite interesting But of course when you analyze the studies the most important cause of very large refractive errors Are basically the incorrect measurements of the biometry of the eye So I put some slides on the light adjustable lens because I want to make a direct comparison with it So the light adjustable lens is a non-invasive way to adjust the power of the lens It's almost commercially available. It's undergoing the last phase of FDA clinical trials And I know you are familiar with the project I just want to highlight that with this lens we need with this technology We need a special lens. That's a 3D silicon lens that has a material that's special It has this photosensitive silicon subunits that are going to move inside of the lens when you apply the light So not only is a special lens you can only use this one, but also the silicon lens So silicon lens are not so popular if you put silicon lenses in And the eye of a patient who has retinal issues one day you may be in trouble because if you use silicon oil That oil may attach to the silicon lens if you put the silicon lens in an eye with asteroid high-laws You may have calcification of that lens So it's not that simple And then if you remember how this works you shine the light for example in the center of the lens to add power and Polymerize the subunits and by diffusion the unpolymerized Subunits are going to move to the center change the shape of the lens and that's the change in power This process also is not immediate. So it takes 12 to 18 hours for this complete diffusion To to be final. So in this project as in the center second laser You cannot measure the power that you get immediately. You have to wait at least one day But what is very important here is this with the cal rune vision Project the patient has to wear this special UV protected glasses Until you finalize the entire thing until you adjust the optic and then if you are happy with your Power then you have to lock in the eye well, which means you shine light in the entire optic and then after that The the power can actually not be changed But until that time which may take a few weeks the patients have to be wearing these glasses otherwise he goes to the Sun there is There is uncontrolled polymerization of these subunits Also the light application for the light adjustable lense is also very easy you put contact lanes and then You dilate the pupil and you enter everything in the computer and then at the time we were so excited We did so many adjustment of rabbit eyes and the adjustment and lock in would take 120 seconds and we thought that was so fast But actually to be holding that lanes there for all hundred twenty seconds It's not that easy and now we defend concept of second laser it lasts 23 seconds for an adjustment that's actually larger than that and another very important thing is the lock in So with the second laser you do not need to lock in the power So the patient can go on and later if another adjustment is necessary It can be done because the area uses very thin So you can keep adding that for a long long time and here the lock in also is not that simple It's not one lock in there are two sessions for looking at least So an adjustment of a diet adjustable lanes is at least three sessions for one Adjustment and then after that it cannot be changed anymore And also you may say okay the phantom second place is so expensive and everything but with the light adjustable lanes You also have to buy the digital light delivery system I do not know how much it cost of course I bet it's not as expensive as a phantom second laser, but it is also an expensive technology In another technology we are evaluating that's almost clinically available is already in clinical trials is the harmony Modular system is a lens with two components So you put one base in the capsule bag and the optic is very easy to change We performed already at least two is studies we publish on that is by compatible The exchange of the optics quite easy, but this is an invasive technology Each time you change the optic it is a surgery with all possibilities of Complications so I think if you have a good non-invasive technology, it's always going to be better So again to summarize that we have now this possibility of I will power adjustment by the phantom second laser It can be applied to any commercially available Hydrophobic or hydrophilic acrylic lens the company tested in PMMA lenses and in silicon lenses and it does not work But this especially hydrophobic acrylic lenses are the most used lenses in the world We are talking about non-invasive procedure that can be done very fast and under top cornesthesia Multiple adjustments can be performed right now the company is evaluating How many actually can be performed and also they are evaluating if there is a limit Above which the optical quality of the opt is going to change because if the optical quality decreased Then we should set up that as a limit Also, premium functions can be added and later removed if necessary if you apply a Multifocal pattern and the patient is not happy. You can simply apply another pattern that has a Contrary characteristics of the first one and then this is no You do not need to use this special protective Spectacles and that's really very important and What is very interesting also is that you don't need to have a phantom second laser just to do that a Phantom second laser can be designed to do everything the power adjustment Corneal and catra procedures. So I mean in summary we are very interested in that technology We are happy to be associated to the evaluation of it And everything going well, this seems to be a real game changer. So thank you very much if you have any question Actually, if you remember in the in vitro study I presented the in vitro study was a negative You can do negative positive. They are ready tested asthmatic Multifocal so pretty much anything We didn't do in vivo though yet in vivo. We just did the positive one It is so so stable I mean during the treatment is 23 seconds if you look at the video you can follow in the video and everything You don't see any movement whatsoever. Everything is very stable because the eyes in the interface. There is a suction very stable And then to Will there be like just a software update for any standard tablets or Platform all questions very good. Yes. So to the first one. They are ready to start clinical trials They are currently looking for sites. They're evaluating all sites in different countries and everything and basically what they have This company's developing is basically the software So what of course they want in the future is that some big name by them And then they can incorporate these to their femtosecond systems and then fit their systems to do this and Cataract and Corning procedures because the precision you need to do this is much higher than cataract and Corning procedures to further that along Randy Olson's on on their board as is Susan McDonald one of our Residents from Tufts. And so we're writing the protocols right now for the clinical studies And hopefully we will be the first center to do this So we're already starting to look at getting the protocols passed and actually do it here You know the term game-changing technology is an overused term especially given the hyperbole of our present administration But this really is a game-changing technology. You don't have to put a special lens in That you have to change from the first. They don't have to wear goggles They don't have to you know, be very careful not to be exposed to ambient light You could take a standard hydrophobic or hydrophilic lens and you can change it And for example the the idea of maybe you can put a multifocal pattern on the patient can't tolerate it Doesn't like the glare the dysphotopsies of the things associated with multi-focality. You literally erase it And change it and so there's going to be issues of how many times you could do this But this is a very small area. It's between 50 and maybe maximum 200 microns It's a very very tiny area that's done and I'm stunned at the accuracy of this. We're talking 0.0 5 diopters and especially in light of the data Liliana presented that when your standard 20 diopter lens can actually be 19.6 or 20.4. So we're talking the accuracy of the lens you put in the eye maybe plus or minus 0.4 And this is 0.05. So it's incredibly incredibly precise Yeah, and actually Dr. Olsen is trying to look at it. We hope. Yeah, because the IOLs are in existence, right? So I think they just have to really prove when it's already ongoing all these studies that there is no liberation of any toxin or anything So, yeah Oh We will he's gonna get rid of all the bureaucracy, so don't worry So that's the major limitations of geometry really so but you see being intrinsically each IOL if you're you feel have the label the power may not even be that one So there are so many sources this makes this type of technology very very interesting Okay, thank you very much