 It was my great pleasure to introduce our speaker this morning, Dr. Nell Grigori. Nell was a star medical student here at the University of Utah when I had brown hair and some of our tenings had hair. She went on and did her residency training at Baskin-Palmer, followed by a fellowship in retina. She is now an associate professor now. At Baskin-Palmer, she runs the VA hospital, she's involved heavily into teaching, and we're happy to have her back here. She's going to talk a little bit about artificial retina work. So I'll sit down and I'll let Nell go on and start chatting. Thank you, Nick. I think this works right here. Can you all hear me in the back? Yes, perfect. This is really exciting for me. I'm just really, really happy. Oh, okay. You're going to laugh. This is my computer because I have two boys, 15 and 9, and of course they're into Call of Duty. So I hope my guns are not going to show because this is my kid's computer. Mine decided not to work. So let's see if my slides advance, maybe. Anyhow, I'm really excited to be back. I spent 13 years here at the University of Utah and did my undergraduate and medical school and internship, and this is where I was introduced to the wonderful world of ophthalmology through Paul Zimmerman, who was the happiest person I met at my career day. And I said, wow, ophthalmology table is like the happiest people. They're all smiling. They love what they do. I said, wow, I've got to check it out. So I called them the next day and I said, Paul, Dr. Zimmerman, I said, can I please come and see what you do? He said, sure. So I went over and I mean, I saw cataract surgery and I thought, that's it. This is all I'm going to do for the rest of my life because this is so delicate, so beautiful. And then, of course, Randy was able to take me on as a student because he only mentors one student a year and his other student dropped out so God was watching out for me. And then he just did such a great job mentoring me. So internship here is amazing. I was so prepared when I went to Baskin-Palmer. Actually, I was teaching my colleagues who didn't know what a corneal ulcer was or how do you tell that from a corneal abrasion and it was just amazing. So I'm in awe of this place and this new building is just amazing. So I'm really happy to be back. It's been 14 years. Now my children are 15, so I left when my younger, the first son was one year old. And it's wonderful to be back. So now I hope my slides are up, perfect. And I was thinking, what talk do I give? I'm fortunate to be involved in ground-breaking research, stem cells and gene therapy. But I thought the bionic eye and the artificial vision would be a good topic because I hear that Paul Bernstein is about to do an August 2 implant. And so I think that this will be kind of a nice overview of the work that's been done and implants that are being developed around the world. So my talk then is advances in artificial vision quest for the bionic eye. So I need to disclose that I'm a consultant to Second Sight Medical Products. That's the company that makes the August 2 implant. So what I would like to do in this one hour then is to discuss various artificial vision implants under development in the world and then describe the August 2 retinal prosthesis in detail. Indication surgical procedure, post-operative rehabilitation, possible complications, and future directions the company is taking. Here are my take-home messages, and they will repeat at the end. So hopefully this early on everybody could pay attention. But epiretinal, sub-retinal, supercoital, introscleral, optic nerve, and cortical implants are being developed. August 2 is the first retinal implant approved by the FDA. It provides, and all implants really that are being developed right now provide pixelated vision, limited visual acuity, mainly shades and contrast. No color vision is possible at this time, and number of electrodes and resolution are expected to improve in the future, most certainly in my lifetime. Future work is being done right now. So just to again list all the layers where various implants are being developed into, and let's just talk about the various retinal implants. There's an epiretinal, sub-retinal, and supercoital approach. The epiretinal implants that are being developed now are non-light sensitive microelectrode arrays. So the signal comes from external camera that's placed on the glasses. The signal then is sent to a night-light sensitive array which stimulates ganglion cells, and that's how August 2 works. The sub-retinal approach could either be light sensitive or non-light sensitive, and again, these are just designs that are being out there right now. The signal then comes from the photodiodes in the array itself, so there's no external camera. These are then amplified and sent to the electrodes, which stimulate, they're under the retina, they stimulate bipolar, mainly bipolar cells, but also amocrine and ganglion cells. The alpha-IMS implant in Germany is developed like that, and it's a light sensitive implant. The supercoital approach is inserted through a tunnel in the sclera. It's not commercially available just yet. So let me kind of go through the major sites in the world and the implants that they're developing. Pixium Vision is a French company. It collaborates with Vision Institute in Paris and Stanford University. The signal is generated by an external camera on glasses. It transmits it to intraocular array of electrodes, and the patients that are being targeted are retinitis pigmentosa and macular degeneration. And you see RP and AMD are the two population of patients that are being targeted with these implants. This company is developing two different implants, the subretinal iris system for retinitis pigmentosa patients. It's currently in clinical trials. Ooh, go back. And commercial launch of the product is going to happen this year in Europe. And the second implant is the subretinal prima implant for wet macular degeneration. That's currently in preclinical development. The first human is implanted this year. And as you could see that the subretinal implant has more than 2,000 electrodes. So the goal for this company is to move towards facial recognition, not just pixelated sort of shades of vision, but the actual details. That's the goal. This company, Retinal Implant AG, in collaboration with the University of Tübingen in Germany, developed subretinal light sensitive implant that I mentioned. That is a small camera microchip that has 1,500 electrodes directly in the eye, not on glasses, under the retina, stimulates bipolar cells, produces these slightly flickering signals up to nine great levels developed for retinitis pigmentosa and other outer retinal degenerations, commercially available now in Europe since July of 2013. The best visual acuity with that implant is Lugmar 1.69, which is equivalent to SNEL and 4 over 200. The visual field is just from the retina that's being stimulated by the array. So it's only 10 to 12 degrees. So it's a very limited tunnel vision. This is how it works. There is a subretinal polyamide foil with microchip. There are golden wires that are kind of exiting the eye into this cord, which then goes under the skin into the sub dermal electronic box behind patient's ear. And that controls electric circuits in the chip. The patient is holding this battery-driven power supply, which allows them to manually control the contrast and the brightness of the stimulus. This paper was published in 2015 with 29 blind participants with this implant in one eye. 25 of them had retinitis pigmentosa and four had cone rod dystrophy. Pre-implant vision was light perception without projection or no light perception. Results were 72% had an improvement in activities of daily living and mobility. 86% had significant improvement of visual acuity, light perception, and or object recognition. They used these landlord C-rings and what scale. So they documented visual acuities of 20 over 2000, 20 over 606, and 20 over 546. So again, it's a significant improvement if you think that these patients completely don't see light. They're NLP. Australia is developing a supracoridol retinal prosthesis, which is targeted for patients with retinitis pigmentosa and coridoremia. It's implanted under general anesthesia, just like the Argosim plant. The surgery lasts three to four hours, and this is the implant here. Essentially, it's an intraocular array that goes into supracoridol space. There are the stimulating electrodes to return electrodes here. A wire that then is connected to this percutaneous behind-the-ear connector and also percutaneous or subcutaneous return electrode behind the ear. It's placed through a slit in the sclera, and the array is shown right here, right under the coroid here. It's a silicone array with 33 platinum-stimulating electrodes. The main disadvantage is that because of its location, it's further away from the retina, and it's been shown that the closer the electrodes are to the retina cells, the better the threshold, the better the signal that the patient perceives. So we have to see how this pans out. Here's the first in-human trial of this implant, and as you can see, you do get some hemorrhage, which then clears by day 55, and you see these electrodes right there under the coroid. Interest-clerol retinal prosthesis is being developed by the Osaka University in Japan. No human data is published so far, only proof of concept work in dogs, and three months after implantation, the authors showed preservation of retinal perfusion by angiogram and retinal function by ERG. So again, this is far away from commercialization. This is the implant and the figure from this patient. It's a 49-platinum electrode containing array with an intravitrile return electrode and an extraocular microstimulator. Again, it's placed through a scleral pocket. Optic nerve implants are being developed. Intraorbital, intracranial, and intravitrile routes are being explored. No clinical trials so far. No human cases were planted to test feasibility, and again, it's far away from commercialization. Belgium implanted two patients with intraorbital and intracranial optic nerve implants, and again, this is retinitis pigmentoscia patients with NLP vision. In Japan, they're developing direct optic nerve electrode intravitrile implant. As you can see here, it enters the eye, goes through the vitreous, and kind of inserted into the optic disc. The idea is that it's not stimulating one little area of the retina, it's stimulating the whole optic nerve, so the idea that perhaps we could stimulate a wide visual field so that the field of view is not a tunnel vision. This paper then showed that 25 months later, this patient that was implanted had visual sensations and no complications. Laterally, genucleus and cortical implants are being developed as well, multiple sites far away from commercialization. I was excited to see that University of Utah actually is developing an implant, and I'll show you a slide about that next, but Second Sight, which is the company that makes the Argus II implant, is also developing one of these cortical prostheses. It's called Orion I, and it has been implanted last year in a dog, and it's about four years from commercialization. Other groups are involved as well, but this is University of Utah thought it was really exciting to find out that this had been done here. They implanted it in three cats in 1999, and it's Dr. Norman's lab. You could see the size of it, and essentially the conclusion from this paper, again, it's very early on, but although a few early implants failed, cerebral cortex stimulation to evoke a behavioral response can be achieved with the penetrating University of Utah intracortical electrode array. So, stay tuned. Now, other senses are also being used to see, so there is a company in Holland that takes a camera image and converts it to a sound stimulus that the patient perceives as louder sounds if the image is brighter and higher pitch, perhaps, and then less of a sound if the image is dark, so patients use other senses. This is more for patients whose optic nerve eye is completely destroyed, perhaps, from trauma. There's also now a brain port device here in the United States. It's a Wicab company in Wisconsin that converts camera image to tongue stimulation, so it feels like champagne bubbles. We've actually written several grants a few years ago trying to get funding for FDA approval from DoD. They didn't get funded, but it's interesting to know that Google actually funded the study, and FDA approval was secured last year in 2015. So, really neat. So, again, just to summarize what's commercially available, Argus II retinal prosthesis now is available in Europe since 2011 in U.S. since 2013. Alpha-IMS German implant is available in Europe from 2013, and brain port V100 is FDA approved in the United States from 2015 and in Europe from 2013. Just to say that these devices are not cheap, and one of the hurdles that these companies have to jump through in order to make these implants available to the patients is work with the payers to fund and to pay for the surgery and for the implant. So, I think one of the main hurdles in order to make these implants widely available and used. Brain port is 100, no, a brain port is 10,000. Argus retinal prosthesis is 92,000 now. It was 144, and just this year the price came down. Alpha-IMS, I don't know how much it is, but I know that it's not widely used in Europe because of the cost. So, let's talk, the rest of the talk that I would like to spend just to really get into the integrated details of the Argus retinal prosthesis. So, the first device was implanted in Europe in 2011 by a talented Italian surgeon, Stanisla Orizzo. We collaborate with him, and that was done in Pisa, Italy. And then in 2013 it was FDA approved as a humanitarian use device. So, what that means is that you have to have an IRB to implant it, and now the FDA is also collecting data for post-approval to see how patients are doing. So, you usually have to have two IRBs in order to do this for patients in your institution. As of May 1, 2016, 182 Argus II prosthesis have been implanted worldwide. 64 in the United States, 111 in Europe, and 7 in Saudi Arabia. So far, 3 out of 182 have been implanted. Doctors always want to know how long do they last. Two of them were either partially or completely implanted because of conjunctival erosion. Conjunctival closure is really, really essential. And one of them was implanted because of patient psychiatric issues. But the implant provides benefits in localization, motion detection, orientation, and mobility. January 22 of 2016, President Obama presented the National Medal of Technology Innovation to Mark Humayun, who is a great surgeon and researcher who collaborated with Second Sight to develop the Argus II implant. He's a great person to work with, very humble. And this award is given to recognize those who have made lasting contributions to America's competitiveness and quality of life and helped strengthen the nation's technological workforce. So it was really exciting to see an ophthalmologist get this award. So, what are the FDA-approved indications for the Argus II? These have to be adults, 25 years of age, or older. Vision loss has to be due to retinitis pigmentosa only. Also, I just found out that it could be Libra congenital amurosis, because the LCA patients are almost indistinguishable from RT patients later in life. As long as they have a history of youthful vision as children, they qualify for the device. So it's not for patients with central retinal artery occlusion, retinal detachment, or any other causes of visual loss. It's contraindicated in patients with severe optic nerve damage. Why? Because the ganglion cells are stimulated and they have to send the signal through the optic nerve. Vision has to be bare light perception or no light perception in both eyes. So no current, useful vision. Again, that's because the image is of low resolution. It's not your high definition television. So if you have count fingers or even hand motion vision, that will conflict with the vision that you get from the artificial from the artificial device. And patients have to have history of past useful vision. So it's contraindicated in patients with profound embliopia. Just a few words about retinitis pigmentosa, just to kind of make sense of why this implant is placed, where it's placed. As you know, the outer retina atrophies in retinitis pigmentosa, so cones and rods are gone. But the inner retina, which is comprised of bipolar cells, amachrine and retinal ganglion cells, are relatively intact. And so that's really key here for patient selection is we need to confirm that they are able to perceive light or they have measurable chronically evoked visual response. Usually the light perception, even in patients that are NLP in clinic, can be elicited. The flashlight test that is done at screening is a really, really bright light in a completely dark room. And patients usually see some. And that just indicates that, yes, their inner retina is still working. Of course, OCT. One could look at the OCT and see that the inner retina is preserved. Although it's not... the OCT is not an ideal test, in my opinion, because you really cannot see the cells individually. So usually the flash test is the test that is used. And of course, there's this sort of a special test that SecondSight has a protocol for. It's kind of like the evoked visual potential test that could be done if you're not completely sure if the patient has inner retina preservation. But this is how the Argus II works. There's a camera on the glasses right here. Through the wire, the signal is sent to a VPU video processing unit which then sends the signal back to this transmitter coil on the right or the left side, depending on which eye is implanted. And then wirelessly, this signal is then sent to the implant on the eye. So the implant on the eye has this coil which is the receiving coil or the antenna. The signal then travels into this electronics case and then through this cord is sent to the array of electrodes. Now there are 60 electrodes in this Argus II implant. There used to be 16 in the Argus I. Now the FDA approved the one with the 60. And that's placed on the macula. And it yields a 20-degree visual field. One important aspect to remember is that their patients have to be aware of what MRI system is being used on them later on. It's a pretty scribble sort of MRI system. You can usually this covers most MRIs, but it's just something for them to mention to their neurologist if they need an MRI, a brain MRI. So this is a video from Second Side. I hope the sound we need to turn it on a little louder. Whereas thank you. I could go back so we could replay. I think so. It's not, this video just describes everything that I just said. So it's not that critical. But later on there are videos that would be nice to have louder. Sounds great. Okay. So it just shows that the image then goes into this implant and onto the retina. So I'm going to just move on as soon as this is over. And through the optic nerve into the brain. Alright. So this is what it looks like on the eye. It's placed under the lateral rectus, the coil. And then the metal case is positioned in the suprotemporal quadrant. And as you can see here, the cord is then enters the eye through a sclerotomy. The sclerotomy is 5.2, 5.5 millimeters long. And when it enters the eye it sort of makes a nice S shape. The array is placed over the macula. So when one thinks of the surgical procedure for this it's really placing a buckle. It's sewing a barbell implant. It's doing a reticert. And then it's tacking. So it's kind of multiple steps. And I was so thankful that I had in my residency enough glaucoma surgery and enough buckles and you think, I will never do this. You will. And it's amazing. So learn as much as you can in all your different rotations. And then of course it looks like this in real life. And this is a picture from Lisa Omos, actually is assistant professor at USC. She works with Mark Humayun closely and she was one of our graduates and she gave me this picture, of the array. So just to point out that the optic nerve is here and the array is a butting but not covering the optic nerve. This is a tack that was used in 1980s for repair of the retinal detachment. Most younger surgeons have never used a tack in their life. And so this is kind of a new skill that folks have to develop prior to the surgery. It's difficult and there's a handle on the array that I will show you why that's important in a couple of slides. So it really takes a team to screen, implant, fit, rehabilitate these patients. And this is our Vascom Palma team. Byron Lamb is the principal investigator. Probably Kathleen DeGreene knows him really well. He's an amazing neuro-automologist who is also a genealogist. He does retinal degenerations, ERGs and so forth. And he's the principal investigator for this. And we both screen patients, surgical team, the first case Janet Davis and myself performed. Then I did a second patient, a veteran, and that was neat to be able to give it to a veteran patient. And then device fitting and rehabilitation is done by multiple people. We're fortunate to have a biophysics lab at the Vascom Palma Institute. And those are engineers that work with second-side engineer who comes and they do the fitting and I'll show you there's some innovative work that's being done by the lab in terms of rehabilitation. So when I screen patients, of course I make sure that the vision is appropriate and that it's retinitis pigmentosum and it's not optic neuropathy or previous RD-CREO. However, another aspect is important and that's the axial length. So just so that the implant fits correctly on the eye, the axial length has to be between 20.5 and 26 millimeters and patients have to have realistic expectations. They will see shapes, objects, they will improve their mobility but they will not be able to drive, they will not be able to recognize faces with this implant. So that's something that I'm counseling patients on. And then they have to be motivated to work with the device and undergo long rehabilitation. I compare this as to having this artificial vision is like learning a new language. So it really takes daily work on the patient's part in order to use the device and get better with it and find use for it. So the screening is done in two visits. There's Berkeley Regimentary Vision Test and that's just to make sure that the patients have no residual, useful vision that they're only bare LPLP or NLP. This photo flash test that I already described is the main test that's used for the documentation of the visual acuity. Residual and functional visual interview is done. Patient has to try the device. The glasses do get warm after a while so it's not something that the patient wears the glasses the whole day. No, usually they wear it in spurts. They will wear it sometime and then they have to rest and so forth. And so they find activities in which the device is most helpful and that's how they use it usually post-operatively. The psychology is a really, really important point to make. Patient has to be a satisfier, not a maximizer. What I mean by that they have to be a half glass full rather than half glass empty kind of patient. Because again, this is not high definition and they have to be happy or else they will not use it. They must be willing to work hard to learn the Argus language. So what they can usually do is locate doors and windows, sort light and dark clothes, stay within a crosswalk, avoid obstacles, feel more social, reconnected, enjoy being visual again. Patients telling me oh it's kind of like my brain is alive so I could process visual information. Read large letters slowly and watch fireworks. All of those things have been really life changing to patients. They feel a lot more connected to the world around them. Patients however cannot expect to recognize faces. Read standard print at a normal pace or drive a car. It's important to look at the status of the lens before surgery. So a YAG usually is recommended if the patient is pseudophagic because you cannot do it postoperatively. The YAG energy can damage the array. So whether or not there is PCO, you know, YAG is recommended. And then the lens status is addressed. So if the patient is phakic, clear corneal phaco-mulsification is performed, patient is left a phakic and all the capsule is removed during vitrectomy. This could be done before or during implantation. If the patient is pseudophagic and the lens looks like it's not stable or might become subloxed, it's better to remove it, remove all the capsule and leave the patient a phakic. And if the patient is a phakic, then all the capsule must be removed during vitrectomy as well. So these are the key steps of surgery. And just like I mentioned, there's a buckle component placing the external components on the eye. And then there is intraocular components which, vitrectomy, sclerotomy, cutting the sclerotomy, inserting the array, and then tacking. And then the closure. One has to use graft materials just like glaucoma drainage implant where you use either corneal graft or tutoplast to cover the elevated portions of it and then the conjunctiva is closed and tenons is closed over it. So the array insertion is critical. It's possible to strip the coroid as one inserts it, so it has to go in perpendicularly. The sclerotomy closure is another critical component because that could lead to hypotomy and essentially side-el positivity after surgery. And then the tacking is described here. So the tack looks like a nail and essentially is delivered into the distal portion of the, I'm sorry, proximal portion of the implant and looks just like this. And that's what holds the array up against the macula. So just as this diagram shows. Now the reason I mentioned this is because second-side recommended sort of a one-handed approach, and you could see this video from Dr. Olmos where the tack is partially inserted right here into that circular opening in the proximal end of the array. And then it's dragged over the macula to deliver the tack once you're happy with the position. But you can imagine the tack is really, really sharp. It's like a little nail. So you could scratch the ratknife, you inserted it too far and so forth, and that just made me too nervous. So we decided, you know what let's think of something else. And we did and I'll show you that so here once you position you just you deliver the tack, you push it in is inserted through ocular coats. And it does go into the sclera. But this is what we did. We published this bimanual technique for retinal tacking of a retinal prosthesis. And essentially what I like to do is grab the little nub that I was telling you with the Eckerd forceps place it with one hand either right or left, depending on the side whether it's right or left eye and then the other hand then delivers the tack. Professor Ritso in Italy we found out developed a slightly different technique where he uses the soft tip and he just sections as he grabs just by suction the array moves it and then delivers the tack. He tells me that that's how he used to do it and he's actually using this technique now. So we went ahead and published this so that other surgeons could benefit from the collaborative experience. And I'll show you the video how it's done in just a second. So this is the first patient that we did. Our first patient was a 58 year old female with retinitis bimintosa diagnosis at the age of 18. She was bare like perception for 16 years and received the Argus implant in her right eye in November of 2014. This is Janet Davis and Lisa Olmos who came. Second site always brings an experienced surgeon to proctor the first case because there's so many steps and one wants to do it just perfectly. And of course our nurses and technician. And this is the video. There's no sound so we could just watch it. So congenitiva is opened. The muscles are isolated. There's your buccal, scleral buccal skills that come in. And then the coil is placed under the lateral rectus. It's not a small device I must say. It's large and it's delivered and at first you think oh my goodness it's not going to fit but it does imagine it does fit around the eye. This is the array covering. We use a tip of the fecal sleeve to kind of cover it so we don't damage it during the surgery. And Watski's sleeve is positioned super nasally. And then the tabs of the essentially around that metal case are sutured. This is kind of a bar built implant suturing you could imagine it this way. It's measured precisely from the limbus according to a normogram and the axial length is what used to determine how far from the limbus to place your sutures and then on both sides the tabs are sutured with this is 5-0 nylon and the implant is tied down. Very similar to bar built. So that's done. There's a third tab and that's infrotemporal and that's the tab around the coil that receiving coil or the antenna. So now everything is positioned and one can do the trectomy. It's essential to use triescence to stain the vitreous. We find out that these patients have very sticky vitreous and it's impossible to induce a PVD easily. And then the sclerotomy through which the cord is going to enter this is Janet Davis's technique it doesn't have to be done this way this is just the way she prefers to place red asserts. One could just use one blade to enter it and here she's using essentially a 64 blade to outline the incision and then 75 blade to enter the eye completely. That's the key you want to make sure that this sclerotomy is opened completely before inserting the array perpendicularly in order not to strip the coroid. And then sutures we used proline vical or proline can be used we prefer proline and sclerotomy around the cord. This is the cord that goes into the eye is closed and the key is not to pucker the cord make sure that the cord is flat and it doesn't keep the sclerotomy open. So here is tacking coming next. The effort forceps is 19 gauge so we're using a 19 gauge mvr blade to enter this is the tack you grab it and then delivered into the eye first position yourself and this is the bimanual tacking where I'm just moving the array over the macula and then once I'm satisfied the tack is delivered it's a little tricky to let go there's a little down and out movement with the tacking tool and then you place one more suture to flatten the cord in order to keep it flat instead of puckering and then here I just not many people use 20 gauge anymore so I wanted to show to the younger surgeons that you do make an X suture with your vical to close these 19 gauge ports because these are 19 gauge ports and then cornea is used to cover the tabs all of these the 1, 2, 3 tabs around the metal case and around the receiving coil is covered with again this is very similar to barvelle and then the conjunctiva is re-approximated next so it took us 5 hours it was eat a big breakfast and then it looks like this now this is a neat OCT picture I like this because we have this web source OCT it's a wide angle OCT and you could see the array is sitting against the retina very nicely and of course that has been shown to improve the threshold that you get so the key is to place it so that's why for example stephaloma complication because the array will not touch the retina in a stephaloma case alright so potential intraoperative complications corroidal detachment can be induced either sears or hemorrhagic inability to close the sclerotomy retinal detachment either from a break in the retina or scleral penetration or perforation during suturing of the extra ocular components hemorrhage during tacking injury and inability to close and I've seen this actually at Emory the tenons and conjunctiva just it gets stretched and sometimes it's really difficult to close it so whenever I screen patients I take a Q-tip and I just move it make sure there's no scarring anywhere and the conjunctiva and tenons look really healthy so what can patients expect outpatient surgery takes about four to five hours under general anesthesia after about one to two weeks a recovery custom device fitting occurs the vision is going to be different from normal and patients have to get used to that idea patients see spots, lines of light and they learn to interpret that and again I already mentioned it's like learning a new language so this is what this is a simulation video that biophysics lab at Baskin Polymer prepared this is what we see and this is what you can imagine the patient sees they don't really see necessarily dots they just see lights and they have to learn this is not high definition you have to start somewhere but that's what you can imagine they see certainly takes work to understand what you're looking at absolutely so let me just describe them to you and this is key because this is where the patient recovered you're feeling great about yourself you know you've done this beautiful surgery and what's next we're each electrode is tested and intensity of the signal is adjusted to patients comfort occurs in about one to two weeks after surgery one that's done the patient is ready for inclinic blind rehabilitation and this is where occupational therapist and low vision optometrist are essential it's about 10 sessions patients learn to handle the components of the implant implant and they learn the basic visual skills using these kits that second site provides and then orientation and mobility training happens and it's usually done by a certified orientation mobility specialist in and around patients home and workplace and patients learn to integrate Argus II into their life once that happens you can see that the patient here this is our first patient she's learning to use the cane and Argus II together so remember that the camera looks only where the patient looks so you cannot look down you have to look straight ahead in order to visualize where you're going so the cane helps the patient feel where they don't see and it's a very limited it's 20 degrees so patients have to learn to scan and to move their head instead of their eyes so this is what some kind of done to teach patients to do that the cylinder helps them understand that you don't just move your eyes you move your whole head and you scan because there is image is extinguished after a few seconds and one has to continuously move the head in order to keep the image alive so that's her working on some of the kits at home this is her quote and I listed it here because it really highlights the patients experience it was very hard to me in the beginning to accept the artificial vision the memories of real vision were conflicting inside my thoughts preventing me to accept the new vision I had unrealistic expectations regarding the artificial vision it's funny because we spend a lot of time talking about it but until you really experience it you don't believe it so and working with it where she sorts her clothes and prepares meals and she's using it in different situations helps her realize where the artificial vision is most helpful this is her playing with her grandson a ball and of course remember she was an LP for a bare LP for 16 years so she does really well and she's one of those work hard I want more help me rehabilitate more kind of ladies so more of the things that lines now once all that's done in 10 sessions the patients could feel abandoned because there's really nothing else usually the rehabilitation is done so what's next our biophysics lab with John Marie Perrell and his PhD students and Alex actually Gonzales he is the manager of the lab he's a computer whiz so they came up with this novel concept of remote guided computer based rehabilitation modules so these are computer modules that are sent to the patient via computer and the patient practices with them every day so this is our patient these modules are voice guided patients can work independently and there's feedback that's given to them yes you're doing correctly so they're motivated to do more of it and then also remotely sent to the lab so that the programmer knows how the patient is doing so here she is learning to recognize letters so now she could recognize majority of the letters of the alphabet and read simple words like cat dog on the computer so she's moving the letters until she's able to position it just right in her visual field in order to pick out the letter and if you could hear the computer is telling that is correct in this beautiful electronic voice so and here she is writing she loves to practice writing so she's writing high and you could see how she is if you did this with your eyes closed not seeing anything it would be impossible so there are certain tricks that the programmer puts into the computer to know that the patient is really seeing and she's really proud she says hi at the end of the video so she's this is another quote from her these modules help me with my memory, vision, attention, motor skills processing data, alertness concentration, increased critical thinking and integration with other senses all while being entertaining so the idea and actually I was mentioning that we Baskin-Palmer is going to collaborate with SecondSight in order to make these modules available to other patients not just the patients at Baskin-Palmer so the idea is to create you know rehabilitation modules to create a network for these patients with Argus 2.2 play perhaps games and so forth just like Call of Duty my kids spend so much time doing that where you are actually integrating with other patients and feel connected socially and feel that there is a need for to use this device so just really briefly I know do I have till nine or am I going over time till nine okay so a few more minutes and we're done this is a paper that came out in ophthalmology in 2015 and it outlines long term results with this prosthesis 30 patients were done in order to get to receive FDA approval and this is the follow up from these patients in USA and Europe so patients scored better with the system on on square localization of motion grading acuity with the mean visual acuity at one at year one and three of 2.5 lugmars which is equivalent to four ETDRS letters lines improvement and 29 out of 30 are still functioning I mentioned that one was explained due to conjugal erosion this is data from one to five years showing that the mean error in square localization and that's where a patient has to pick out a square on a screen a computer screen is better with the system on than with the system off same for direction of motion where there's a bar moving across the computer screen and grading visual acuity does improve the y-axis is performance no better than by chance so it improves with time what are the complications the serious SAEs the conjugal erosion or dehiscence is the most common it's about 23% hypotony and it's the same maybe a little higher at year 3 13% presumed ophthalmitis in about 10% this is out of 30 patients and retinal detachment in about 6% either regmatogenous or tractional so the five-year data this is still in press it's not been published yet but it's about the same the numbers stay about the same and retinal detachment is a little higher at year 5 so most SAEs occur within 6 months after implantation and 4 out of 5 later occurring after one year SAEs were part of events that began earlier so patients should be monitored continuously while the implant is in the eye comparing the frequency of the serious adverse events to glaucoma drainage implants are very similar hypotony 10% versus Argus 6% conjugal dehiscence or erosion in about 11% 10% with Argus presumed in ophthalmitis 5, 16 depending on the study in 10% in Argus so it's about the same it's certainly not a trivial procedure to do and there are complications that could arise this is our patient she did have a retinal detachment she came in herself completely asymptomatic and had fluid between 3 and 6 o'clock so no breaks were seen during surgery or after the retina does look atrophic in these patients and it's very difficult to see a break so the macula was on the implant was sitting up against there was no fluid so we decided alright we're going to just demarcate it and see how she does so we did we used 532 nanometer laser at month 8 looking great the fluid is contained by this laser and the implant is functioning she's doing quite well so Paul be ready alright and so intraoperative observation then very sticky vitreous like I mentioned unable to remove all cortical vitreous of retinal surface beyond the macula and no retinal breaks were seen so it's probably atrophy so the future directions based on our collaboration with the company they just told us that essentially what they're doing is they're improving software of that computer that the patient wears on their belt they're putting in special circuits that will improve resolution just based on those 60 electrodes there's going to be thermal recognition so patients are able to tell warm objects people versus cold objects you know that bowl of soup that I shouldn't be touching or is this cold drink the glasses and camera are going to be improved and the intraocular implant there are thoughts of how to modify it it will take years to modify and get FDA approval so I tell patients you know what don't wait if you really want this you have the other eye and you know you could have the next generation improved which implanted which has been done in some patients take home messages you've already heard and I would like to finish with this fun slide why Argus, well Argus Panoptis is the name of a 100-eyed giant in Greek mythology and he was a watchman for the goddess goddess Hera so that's why the name Argus thank you so much for your attention that's the end and thank you for having me here