Direct Selective Laser Trabeculoplasty in Open-Angle Glaucoma

(upbeat music) Hello and welcome to the Ophthalmology Journal podcast. The official podcast of the American Academy of Ophthalmology's Family of Journals. Ophthalmology, Ophthalmology Retma, Ophthalmology Glaucoma and Ophthalmology Science. On this show, we interview authors about their recent articles and research. I'm your host, Dr. Emily Shehline. I'm a Glaucoma and Catarex surgeon in private practice in Michigan. Before we begin, please remember to follow us at @aojournalonx, formerly known as Twitter and Instagram for more podcast news, articles, new issues, editorials, and more from all our journals. On today's episode, I am thrilled to interview Professor Nathan Congdon. He is a prolific researcher and a giant in the field of ophthalmology. Among several affiliations, he is a professor at Queens University of Belfast and is the Orbist Director of Research. He is the lead author of the Glorious Study, randomized non-inferiority trial of direct selective laser trabecular plastic in open angle glaucoma and ocular hypertension, in press for ophthalmology. Thank you so much for joining us. - I'm delighted to be here. Thanks very much for the invitation. - Well, I'm so excited to talk about this study. And I think many of our listeners are already very familiar with selective laser trabecular plastic SLT and the light trial. And I'd like to start off by asking you to describe how direct SLT or DSLT is similar or different from conventional SLT that we've been using for many years. - That's a great question, Emily. So it's worth stepping back from it and just briefly talking about SLT. SLT, of course, treats the trabecular mesh work and offers the opportunity as light as shown as to be a very cost effective and patient-friendly way of lowering the intracular pressure. The economists are almost telling us that we should be using SLT more. One of the things that stands in the way of doing that particularly in low resource settings. And that's what got me interested in this study. Most of my work has done in low resource settings in Africa or Asia. The challenge of delivering standard SLT is you have to have access to and know how to use ogonial lens, which I'm sure our audience all know is basically a lens designed to bend the light that comes through it in such a fashion that it can get into the part of the anterior chamber where the trabecular mesh work resides. Without that, you'd have what we call total internal reflection. Just couldn't get there. Those lenses don't exist everywhere. I was based at the largest eye hospital in China for a decade. When I would ask for one, I'd often be told that-- sorry, the director has had locked in this desk and he's out of office today traveling, so you can't have one. And then, of course, once the problem of having the lens is solved, then people need to be comfortable on how to use it. And it does involve coupling gel often and has to be placed in the right way on the front, on the corner of the patient. So there's a lot of stumbling blocks to making that happen in low resource settings. The major difference, the treatment is effectively the same where we're delivering the same kind of light to the same structures in the trabecular mesh work with DSLT. But the big difference is that it's being done externally. So it's going across the limbus as opposed to having to go through a lens, a gonial lens, sitting on the front of the eye. That makes the whole process quite a lot easier, not only for practitioner, but also for the patient. The device basically automatically acquires the limbus. It figures out where it is with a quick scan. And then, with a matter of a second or two, it delivers either 180 degrees or 360 degrees of treatment. So the whole thing becomes easier. You don't have to necessarily have the same level of expertise to use it. And it also becomes more manageable for patients. And that's important as well. Many of our folks that are that we're encountering in our practices, who need treatment for glaucoma, they might have mental health issues or physical issues, back pain, neck pain, a variety of things, maybe even limited mobility from the stroke. And for them to hold their head still for a couple of minutes to complete a traditional SLT procedure might just be more than they can manage. Whereas with DSLT, that's over in a matter of second or two, that can be the difference for some folks between being able to comply and not. So ultimately, we're talking about kind of delivering the same treatment, but in a way that's much more accessible for patients and much easier for practitioners. And particularly in areas where ophthalmologists who are familiar with conoscopy and had the ability of that kind of device, it opens up a new world. It eliminates a lot of limitations. And potentially, both in low resource and high resource settings, can mean that a lot of patients that wouldn't have been able to access SLT care, maybe they can access it now. So it sounds like DSLT is solving several challenges in the glaucoma treatment landscape potentially, right? So it is solving the issue of adherence, because if you have SLT, you're 100% adherent. It's making the procedure more accessible and feasible for providers, especially in the resource limited settings, like you mentioned. But it's also potentially improving the patient experience, because nothing needs to touch their eye at this point, which is a big stumbling block for some patients when something has to come touch their eye. But I also think that it is the natural next step in the evolution of glaucoma technology. It really seems to make sense of how do we sort of level up our current treatment. I think what you've said summarizes it well. And the other thing I would add, I suppose, is just that it's when we compare SLT, for example, to incisional surgery, where even now in 2025, our best standard efforts, the most commonly used procedures, still include things like tribectomy and tube-shunt surgery, which are incisional operations. And can be associated with substantial risk of infection, particularly a functioning blip. It's created a whole in the eye that does allow the possibility of increased risk of infection. And when we're doing any kind of SLT procedure, we don't have that problem. So if we can allow this kind of low cost, safer, essentially infection-free procedure to become more available to practitioners and more available to patients, yeah, there's a lot of advantages. And then of course cost effectiveness. That's important as the economist will tell us. All right, well, let's get to the meat of the article. This was a large multi-center randomized non-inferiority trial comparing DSLT and SLT. So can you discuss the results for our listeners? Sure. Let's start with the design. I think probably most of our listeners, the basic idea of a randomized control trial is probably pretty familiar. You make a decision as to which treatment someone receives at random by flipping the coin. The power of that, the strength of that tool is that it allows us to be certain when we have something like glaucoma treatment that there could be hundreds of factors that might impact on whether the treatment is successful or not. When we use randomization to assign a treatment, we can be confident that not only are all the factors we know about are the same in between groups, but also the factors we don't know about, which is pretty powerful. I mean, there could be something out there in the diet that has a massive impact on the success of glaucoma surgery. We don't know about it. And yet, if we do a well-designed randomized trial, we're still going to have balance for that unknown factor between the groups. So I think that idea of the trial is probably pretty familiar. The non-inferiority design might not be quite as familiar. Usually, when we're doing trials or any kind of study, we're trying to figure out what's better than what. Sometimes, though, we'll have a situation like with SLT and DSLT, where there are certain inherent advantages to a new technology that are so striking, that even if the new technology and the old technology had the same result, we'd still prefer the new technology because of whatever it is, convenient, safety, stuff like that. So DSLT, being so much more convenient and being able to be delivered externally, not requiring a conial lens, not requiring the level of expertise, that's a pretty strong inherent advantage. And so we thought a non-inferiority design was appropriate. And non-inferiority is kind of what it sounds like. It means as long as this isn't obviously worse, then that's good enough. That's all we're trying to prove. The new technology is not worse than existing technology because it has certain inherent advantages that would make us potentially prefer it, as long as it's just about as good. So when you do a non-inferiority study, you have to choose a non-inferiority margin. How close does the new technology have to get to the old technology? And we chose a non-inferiority margin of 1.95 millimeters of mercury. And that might seem a little mystical or confusing. Basically, what it was is we thought clinically and there's been consensus statements about this that a difference within two millimeters of mercury is gonna be clinically roughly the same. So that's why we chose two. And then 1.95 was just slightly less than two. So the result is that we found out at six months, which was when the main outcome was meant to be measured, that actually we didn't quite fall within the margin of 1.95, that is, it wasn't strictly speaking non-inferior. And the reason for that is interesting, it's because the standard deviation was a little bit higher than we expected. That means that the difference in terms of how much impact we got was quite different between individuals, a little more different than what we expected. That seemed to be driven by some folks using more or fewer eye drops. And it's not difficult to imagine how folks that are taking a number of drops, they might be not as receptive to other treatments because they've been receiving treatment for so long. Even though those treatments are washed out during the trial. So what we found is at six months, we couldn't say with confidence that the new treatment of DSLT was non-inferior. It still might be, slightly inferior, it was very close. But what we did find is at six and particularly 12 months, that when we followed them for a little bit longer, that those differences became quite a bit less. And we certainly had a consistent picture out to 12 months that the result that we could get, the pressure lowering benefit that we could get from DSLT laser treatment was still quite good. It was quite substantial. So the result would be, we can't state at six months which is our pre-specified date that this is definitely not inferior, but it was very close and it still worked well, DSLT still worked quite well. And at 12 months, we saw quite substantial a reduction that was quite comparable to SLT. And again, the reason for it not quite meeting the non-inferiority margin is because there was a little bit more variation, a higher standard deviation than expected. And we think that was driven by differences between people who were taking more versus fewer drops. - Well, I think that was such a great explanation of a non-inferiority trial. And I think it will really help our listeners to interpret the results here. I wanna ask also, I think one of the reasons that we all really enjoy using SLT and our clinical practice as well as because it's effective, but also patients do really well, right? They have minimal adverse events. And this was demonstrated in the light trial as well. So can you review SLT versus DSLT in this study, how their safety profiles compared and if those differences will be clinically meaningful? - Yeah, very, very good question. Obviously, whenever we think about any kind of a treatment technology, we have to have two things principally in mind. First of all, does it work in second, is it safe? So I would probably talk about this by mentioning the safety issues which are the same, which overlap between DSLT and SLT and those that differ. So let's start with the ones that overlap. You know, obviously we are treating the regular mesh work. That's the business end of the sort of drainage system for the AQIS. And so there's always the possibility, we're always careful to watch out for pressure rises. With both SLT and DSLT that risk is similar and low, particularly when we give a bit of pre-treatment. There's also the possibility of getting a bit of inflammation and they come with treating ocular tissues, with energy. There's gonna be some inflammatory response, that's just the body's natural response. Just the same way as, you get an injection, or you get a jab for health reasons, flu shot or whatever. There's gonna be a little bit of redness and stuff, a little bit of inflammatory reaction. So those types of inflammatory reactions and pressure rises are rare with both DSLT and SLT and they're kind of similar between the two because the treatment modality, ultimately, what the treatment is achieving is similar. What's different is that with SLT, we're needing to place a lens, a gonial lens on the cornea, either with usually with the kind of lenses that we're using for laser treatment, there's gonna be some coupling gel there. And that lens is gonna be rotated generally as the mirror is being brought around to achieve either 180 degrees or 360 degrees. And it's not, you know, it's a pretty intuitive idea that if you're taking something even very gently, even with coupling gel and you're kind of rotating it on the cornea, there's some risk of damage to the cornea-lephalian and the possibility that a patient might get a little abrasion and wind up with some discomfort as a result of that. That risk doesn't really exist for DSLT because we're not using a gonial lens. So that kind of cornea-lebration thing is much less likely to occur. Now with DSLT, we are doing a couple of things that don't happen with SLT. The first thing is that we, in order to make sure the patient's lids remain open, we're usually putting a device into hold the lid's open and there's some possibility of getting, you know, some redness or abrasions on the lids from that, although those things were very rare. Perhaps slightly more common because we're delivering treatment. In this case, externally at the limbus, there's the possibility of possibly having some light absorbed by a vessel that could lead to some bleeding, contact level hemorrhage, something like that. Those events were also quite rare, but that's something that you might see in DSLT and be less likely to see in SLT. Looking across the whole range of different problems, though, we found that they were really quite comparable up between the two modalities and quite low. And that reflects, you know, what I think we all kind of know in practice that laser is a pretty non-invasive treatment. And if we compare that to some of the things that beta blockers can do when it comes to medications, or if we compare it to infection risk that we can have with certain types of insusional surgery in SLT and DSLT come out looking quite good by comparison. Absolutely. You know, I think you also covered this a little bit earlier in our talk in terms of how DSLT can really allow potentially expanded access of care. Do you have any other comments about how it can or will potentially fit in that treatment landscape for glaucoma? - Yeah, that's a good question. The work that I do, by the way, so I spent half of my time and half for about 20 years between an academic appointment recently now at Queens University Bell Fast as you mentioned. And then with NGO working for the last 16 years with Orvis. So my focus really, both on the research and NGO side, is very squarely on low resource settings. And that's why I've signed on to do this study. And I think that's perhaps one of the reasons that, you know, the bell can reach down to me to begin with. So particularly in those kinds of settings, this has the potential to really be transformative. And one of the things I'm really interested to do, I have a fellow who's just finished up her PhD with me, Shola Olaway from Nigeria, very well trained glaucoma specialist. She's keen to get some funding now from Welcome Trust to do a fellowship training, which would include research to do a randomized control trial, trying to look at DSLT as a treatment option in Africa. She's very well trained, knows how to use a gonial lens, but obviously many, many folks in a setting like Nigeria would not either wouldn't know how to use it or wouldn't be able to access it. So there's the potential of broadening the base in terms of the delivery of the treatment. So yeah, I mean, it's pretty exciting, I think. It obviously, as we mentioned before, in any setting, expands the potential access for interest of patients because there's folks that would have a real hard time complying with a two or three minute treatment, might find a two or three second treatments and then they could manage. But there is also this idea of being able to expand access into low resource areas, including parts of Africa, parts of China. And that's a particular interest. I think most of our audience probably knows that people of African descent have four to five times the risk of glaucoma and glaucoma damage, including blindness. And that pushes it into the working years. There's potential of knock on effects of that blindness on the families and communities that depend on those folks for their economic well-being. China, we all know, has got very high rates of glaucoma partly due to angle closure glaucoma. The ability to come externally potentially could expand this to folks that have very narrow angles that might not be accessible for traditional SLF. treatment. So there's a lot of real interest and potential benefit possibly be able to expand these treatments now as SLT treatment in a variety of geographic areas like China and Africa where the disease is, the disease burden is even higher than what we experience in America and Europe. Well, I have certainly learned a lot over the course of this conversation. So thank you so much for joining us. I just want to give you one additional opportunity. Do you have a closing message about this study for our listeners? Yeah, I guess my closing message would be, I think this is an exciting technology. I think that there's going to be further work. I think the message from this paper, which will be coming out soon and off the mology, is that while not strictly speaking non-inferior, we can see that this is a technology that offers a substantial benefit in the treatment of alcomam and the opportunity to expand that treatment to patients and potentially to practitioners who might not be otherwise able to wield standard SLT. I don't know how many of our audience, you know, are either sitting in or working in or have an interest in more middle-income countries, but the ability to expand that treatment into those areas is potentially a huge game changer. So a lot of excitement about this treatment, it's the lot of reasons to want to see expanded use of SLT, a healthy economic reasons, safety reasons, patient preference reasons, the light trial has really helped to bring that into relief. DSLT may offer us an opportunity to make that expansion a reality. Well, thank you so much. I feel like we could talk for another 30-40 minutes about this or even longer, but this was really wonderful. I know our listeners learned a lot. And thank you for listening. If you liked this podcast, please rate and review and tell your friends and colleagues about us. We'll be back for our next episode in two weeks. Until then, follow us on X, formerly known as Twitter and Instagram @aojournal. The Optomology Journal podcast is hosted and produced by our team of social media editors. Doctors Edmund Choi, Andrew Carey, Matt Fang, Rixana Mirza, Regis Rao, and Emily Shaline. It is produced and edited by Web Editor Greg Pellkovsky and Executive Editor, MAPio Trowski. Special thanks to our editors in chief, Russell Van Gelder for Optomology, Andrew Shackit for Optomology Retina, Henry Jampell for Optomology Clocoma, and Emily Chu for Optomology Science. Music by I Robinson SDS from Pixabay.com. For more from all our journals, follow us on Instagram and X @aojournal.