Chapters Transcript New Developments in Glaucoma Tubes Course: Current Concepts of Ophthalmology 2025 Good morning everyone. Thank you so much for inviting me to New York and thanks very much, Joe, for inviting me here because we have lots of interesting discussions through the ideas and our love for glaucoma tubes, but also our love to improve glaucoma surgery, which we think there's still a lot of uh a way to go. I have some financial disclosures. And of course, also for the residents, this might be interesting because glaucoma tubes has been on the market for a long time now. The first one was invented by Twin Maltino in '69 already, and after that, a lot of different tubes came onto the market. And now the most widely used are the Balfo glaucoma tube and the armored glaucomba valve. Um but um all those tubes have in common that they are made of silicon. Uh, they all have silicon tubes and mostly attached to a silicon end plate as well, but uh some uh variations have other material for the end plates, like some of the newer maltinos with polypropylene and the arm which sometimes have different uh um. Uh plate material. The really the big difference between all those tubes is that the, uh, most importantly, the bar valve is not ligated. So if you use this, you get hypotenine nearly phase if you don't do something to prevent this. So mostly tube is ligated with uh dissolvable suture or like an intraluminal um rip suture. The other glaucoma valve is different because it has a one-way valve to prevent early hypoteny. And all those tubes during the years are somewhat similar to those two inventions, and I think in mostly in Europe now, the Paul glaucoma implant is a newer refinement of these previous earlier tubes. It has a thinner tube lumen, but it still has a large plate made of silicon, but still it's an improvement. And another design that's now coming onto the market is the armored clear path, which has a free reed intraluminal suture in place and it has a different bay design. It makes it uh probably easier to implant into the eye. So what have we learned from previous studies on tubes, and most studies have been done comparing the armed klakorovov and the Bafel tubes. And what they found was that larger end plates, it is logical, may lead to early greater IOP reductions in fewer medications, which is great, but it comes at the cost of more complications, especially hypoteny. But similar rates of surgical success can be achieved in both the barfels and the armor tubes, with the powerful, leading to greater IOP reductions and the AA more often failure because of high IOPs, and this is because it's a smaller implant. It is more prone to fibrosis and scarring. But the Barvel most often give more hypoteny and should be carefully used in patients with uveitis, especially juvenile arthritis patients, because they might really get bad hypoteny, so take care of using a bifel in those young patients. So he needs new designs, well, and new modifications or new materials, and that's important because there is an influence of the biocompatibility of the plate material on the IOP. And silicon we we use it, but it's not a great material because it has a high affinity for plasma proteins and it promotes inflammation and fibrosis. And well, we of course we saw that already the ball has a smaller tube. It is great, but we're still not there yet, and we have seen some plate modifications through the years. So that's great, but we're not there yet. So what do we still need when we want to design new tubes? You need tubes that be safe and effective. It should be straightforward and implanted and easy procedure as seen from a previous speaker, I'm. I really love his skills, but we should, uh, I think comma surgery needs to be simple and, and, and think attainable for a lot of surgeons because not only Joe and I should do this surgeon's surgery but also lots of us. So, uh, to be straightforward and easy and smart, it should be customized for the individual patient. And for this we need new and innovative materials that should be biocompatible, leading to less inflammation and leading to no erosion of tissues. We do not want patching with donors sclera or other materials. We don't want any patching at all, and it should be flexible and it should be stable, non-degradable. We also want flow modulation, and that we want it to be as minimally invasive as possible, so that's a lot of things on our plates that we need to do. So what has been done in the past? A lot of people have already tried some kind of flow modification. There's some papers out there on that, but the only procedure that had already made it to the markets is the eyewa implant, which is still made from silicon and it's a little bit comparable to the bar valves, but it has a magnetic disk which can be rotated with a magnet magnetic pen. To squeeze the tube to get a higher pressures or release the tube to decrease the pressure again and so that's very nice to get some flow modulation, but still it is a bit of a bulky device but promising is that I think the designers are already working on refinement of this thing, but it's a first great step. So the other thing is new material. So in the last 10 years we have seen two minimally invasive tubes come into the market, and first is the zen stand, uh, which is, I think, uh, used a lot of times here in the United States. Uh, it's made of pine gelatin, so that's something completely different than silicon. And the other one that has come into the market is the pressure for microgen, which is it's a pity not still not FVA approved, but it's coming, I think, a little bit more popular in Europe, but we need more evidence on this tube as well. But if you do it well and if the procedure is successful, you can see beautiful blabs as shown on the right sand. Um, uh, low lying, um, diffuse laps without leading to uh complications like uh uh lap erosions or hypoteny. But that's not always the case. These are two of my patients, one with a fibrose zen stent and the other is a hoary fibrosis first of all my cushion. So you still need improvements to get it right, I think with the zen we have about 50% patients in need of kneeling or other procedures to get the tube working again. And still they might fail both in the end, and with the pressure flow, I think it's about 30% or in need of needing or open revisions to get it right. So we're looking into other possibilities like higher concentrations of mighty mighty sea, etc. to improve outcomes. So even with lovely new material we're still not there yet in terms of fibrosis and scarring. So a few years ago I got very lucky and got a lot of funding to try to have a go at designing my own glaucoma implants. So this was really nice because we got access to a large team from the technical University of Eindhoven in the Netherlands and uh my other partner was Len Bin Chuuk and his team in Florida with Santon in focus, and of course Len invented the SIS material. So it was logical that we started with our design from the present present for micro fission, which is of course made of zips, and on the right hand side you see how lovely this material is. It is the first stretchy material designed specifically for long term implantation in the body. It's expected to outlive the patients, and it has been used in the body since 1999 in cardiac stents. And the beauty of this is that it should cause clinically insignificant inflammation and encapsulation, but we have seen from the earlier slide that still fibrosis is happening. So the first thing that my technical colleagues ask me is, OK, so we have to design a tube, but how do we do that? And what is, by the way, what's the resistance in the blab? And they said, Well, I don't have a heck of an idea. So the first thing that we did was build a model for designing intraocular pressure regulation, glaucoma implants, and miniature implants, and we simulated a micro shunt with an adjustable lumen diameter. And we showed very clearly that increasing the hydrodynamic, the resistance of the microin by reducing the looming diameter can effectively be helped to prevent hypoteny, but decreasing the hydrodynamic resistance of the implant will not sufficiently decrease IOP to acceptable levels when the is encapsulated due to tissue fibrosis. So to effectively reduce IOP, one adjustable glaucoma implant should be combined with the means of reducing fibrosis, and that's in practical terms that is mitomycin C. So what did we do in the end, we designed a magnetically actuated glaucoma implant, and for this we chose a tube diameter of about 100 microns and um which we can then reduce to reduce the hypoteny. And uh we designed a valve that could be switched, switched on and off and it was made of uh mag magnetic zips like a micro pencil as you see in the right hand slide. So we tested this valve in in virtuous situations in a microfluidic condition, um, in a chip with the valve containing uh uh on the chip with an outlet pressure mimicking the pressure in the lab in a hypotenic condition, for example, and also attached to a syringe pump which we could simulate the aqueous flow to the eye. And actually this this device worked quite well in vitro, so we could switch it on and off and we got uh acceptable IOP levels with a 40 and 50 micron tube um in in the range of IOP that we really should want in in real life. We also tested this in Gaddaver eyes and then we saw similar results, so we were quite enthusiastic about this. We also saw that if we wanted to test this um um magnetically pen we could still see it through a thick layer of um um uminons but um of course we have to test this further in vivo and see if this small lumen actually works and then have to fine tune the system and I'm very happy to say that we have obtained some additional funding to test this, uh, really. So it's the same uh group. Another thing that we wanted to look at is surface topographies. So if you have this end plate of the tubes, we know that a big fibrotic capsule can form around this. So if you want to change the surface topography, perhaps that could lead to better outcomes with less scarring. And we did this also with the technical university of Eindhoven with Topo chip technology. And Topo chip is uh is a system that has been designed. It has comprised of more than 2000 unique topographically patterned surfaces. So and this each topo unit can be imaged to determine the cell response with regard to inflammation and inflammatory cells. That this was done during COVID times, and we tested three available um to topography screens from literature and which we saw in a small pilot experiment is that it can be done. If you look at the right hand slide, you see the imprint of the topographies and the way that the macrophages and other uh cells are attracted to it. But in this experiment we found that the actual subsurface of the end plate did as well as a topography. So we need some further research to really find out if this is an interesting uh feature to further work out, but um it also shows us that the SIS material is probably quite good as it is. So from this big project, we got 2 patent files, which was one for the surface topographies, one for the flow control, and we also made an implant a drug delivery system with mitomycin C which I will tell you about later on today. So in the right hands, like you see the prototypes that we made in the first one was not so very um nice, but the second one looks already a little bit better and you see the magnetically uh just sips material um implants, uh micro pencil in the tube. So with this result, which was quite not favorable, we said we thought, well, let's try another design as well. The seams results, but that was the name of our project, showed that the end plate is useful to improve the wound healing response. So we thought, let's do something else, something crazy, and if we design a ring shaped device also made of sips, would this probably also work and perhaps we could attach this to a 70 micron loop lumen. Which may eliminate the need for flow actuation, but we could still, if we get have some funding in place, also try if we can get a magnetic activation or desire to do lumen for this also working. And the ultimate question that we still have is, do we still need mitomycin C is such a design. Uh, so we designed um a ring shape device in which we could also add mitein C or also uh uh DDS that could be put in the center of the ring. So in this second project, you made 3 prototypes. One was a ring of sips on a membrane with a smooth design. The other one was a ring on a membrane also from SIPs. The topographies attached to it. And the last one was an open ring and we uh we compared this uh three designs with the Ahmet FB8 in in animals and rabbits and in this experience we did not use any Mitan sea at all. And which we, which we, what we found is we got a different capsule in the ring group which looked really, really absolutely well, but a very thin capsule around the implant and with large aqueous pockets with vascularization in it which is what we really want in a glaucoma tube because the the tissue is still very nice looking and this was a better result than with all the others. So we decided to take this a little bit further, but this is how it looks like in the uh the last prototype. So we had a small hollow ring shape device made of zips with a 70 micron tube lumen. Which is successfully tested in animals and it's patented and now luckily we obtained some funding for research and flow modulation to take this a little bit further. We also began with a startup to see if we can bring this design to the market at last, but it's still a long way to go. So, um, I think that's what my first talked about. And that really thanks to my colleagues from Eindhoven University and London to and esteem in Miami. Thank you. Published January 24, 2025 Created by Related Presenters Henny (Helena) Beckers, MD
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