Glaucoma clinical trials influence medical, laser and surgical decision making for the clinician. During this live webinar, we will review recent clinical trials and their impacts on patient care.
Lecturer: Dr. John Thompson Lind, Associate Professor of Ophthalmology, Indiana University, USA
[John] Good morning, everyone, thank you so much for joining me this morning. It’s quite an honor to be with such a diverse and talented group. My name is John Lind and I’m a glaucoma specialist here at Indiana University School of Medicine in the United States. My topic today, to discuss with you, is incorporating glaucoma clinical trials into clinical decision making.
First and foremost, I’m a clinician. I take care of a lot of patients with glaucoma. A little bit about my background. I’m an associate professor of ophthalmology. I did my residence in St. Louis at St. Louis University in 2008 and my glaucoma fellowship at the Bascom Palmer Eye Institute in 2009. Right now I serve as the director of Adult Clinical Ophthalmology and assistant director of Medical Student Education. But once again, my primary focus is on glaucoma clinical care.
Conflict of interest regarding the information presented in this presentation, I was an investigator in the OHTS 3 trial which we will be discussing, as well as the Primary Tube Versus Trabeculectomy Trial. I do have some interest, I guess, in those studies. But my goal is present an unbiased view of all the clinical trials and try to really hit the high points and give you some take-home messages regarding a lot of clinical trials, not just these two.
The objectives of today’s presentation is to learn how to incorporate glaucoma clinical trials into everyday practice and to analyze current glaucoma trial results and understand the main conclusions. There’s a lot that goes into this, both in planning clinical trials, as well as reporting on the results, as well as incorporating the results into our daily clinical care of our patients. We’ll go over a lot of different factors as well as specific trials during this presentation.
Some things to keep in mind during this presentation. And this is specifically useful for this group because you’re from all around the world and I’m biased. My bias is that I’m going to presenting studies that were predominantly centered in North America and Europe, and clinical trials I use because they most commonly mirror my patient population. Fortunately, we have some other trials that are centered in other parts of the world that we’ll be presenting today. But when I present how I use clinical trials during this presentation, I’ll try to point out times where I say well, this may not necessarily represent the patient that’s sitting across from me that I’m trying to take care of.
Other study factors. It’s important to reconcile what stage of glaucoma that these clinical trials that they’re recruiting participants for. Certainly different clinical trials will have patients at all different stages of glaucoma. Some were focused only on ocular hypertension, some more are focused on early glaucoma, and some will be focused on later glaucoma. It’s important to realize what your target pressure is, what the likelihood of success with different interventions may be when trying to incorporate the results of clinical trials to help your patients. Another really important factor we’ve already spoken on is patient demographics. Is this a very diverse population, is this the type of population that sits in front of you in your clinic?
Also there are other patient factors that are important to consider. Does this patient come from three hours away and has trouble with follow-up appointments? Do they have trouble getting their medicine and using your medicine? All around the world we have these issues. And it’s important to, you may have the best intervention in the world but if the patient can’t do the intervention or participate and be followed correctly, that intervention may not be the best for the patient. Understanding patient situations, their current health, are they too sick for incisional surgery? Are there other options that can be done for your patient?
I think most really good clinical studies have one predominant question that they’re trying to answer. I think when I read studies I always think what was the author trying to study when they set out to do this research? I think that’s always an important thing. There are multiple conclusions and there are multiple results that we all interpret based on study findings, but really try to get at the heart of what was the basic question that the investigator was trying to study.
This, I think, was really interesting. This was a paper presentation at the American Glaucoma Society a few meetings ago and it mirrors some of the factors that we were speaking about before. This is a great study, really important surgical intervention study, that defined success as the intraocular pressure post-treatment being 18 or below. Complete success without glaucoma medications and qualified success with medications. But if you actually look at the preoperative intraocular pressure in this study the average intraocular pressure started out at 16.6. Obviously, this is going to be a highly successful study whether the intervention works or not. It’s always important to look at the pre-intervention demographics, as well as how success is defined in each study. Always keep that in mind, just don’t go with the one sentence hit that comes out of the study. Always try to be critical when assessing studies.
The first study I’d like to discuss this morning is the Ocular Hypertension Treatment study. This was a study out of Washington University in St. Louis. I was on faculty there for six years and was spearheaded by Michael Cass and May Gordon. And this study was conceived in the ‘90s, so many years ago. And the original study question was does treatment of ocular hypertension prevent primary open-angle glaucoma? So that was the heart of the study and Dr. Cass is a wonderful clinician. This was a big question and still have a little bit of a question mark still. But I think that the study has really influenced a lot of our practice patterns throughout the world.
It was a very large study. There were 1636 patients randomized to medication versus observation to see if actually treating high eye pressure prevented open-angle glaucoma. Fortunately, we have 20-year results of the study which are currently being analyzed and reported on and published. It’s very rare in ophthalmology or in medicine to have 20-year results of any study. But Dr Cass and team were able to get follow-up information on all almost 1,000 patients at twenty years. Really a great guide study to help guide are practice patterns.
What were the baseline characteristics? To enroll in the study you had to be between 40 and 80 years. Slight predominant female population, obviously you couldn’t have glaucoma because that’s what they were trying to study was conversion to glaucoma, they had slightly thick central corneal thickness. One of the pre-meeting questions was the role of central corneal thickness and we’ll try to hit on that a few slides from now. 35% of the patient population had a family history of glaucoma and it was a relatively diverse patient population.
Just baseline characteristics, they had to have a normal Humphrey Visual Field Test, normal optic nerve head, and the pressure in the study eye had to be between 24 and 32. You may ask why wasn’t OCT included? Back in the ‘90s, OCT what’s a study tool and not in clinical use. If you were designing a study today with our current technology, certainly I think OCT would be a very important tool for the study like this. But in the 1990s, OCT was being invented in Boston so that was not included in the study.
There have been three OHTS phases. OHTS Phase 1 was looking at treatment versus observation. And the treatment group developed glaucoma at five years How do you rate all of 4.4%, while observation group developed a rate of developing glaucoma at approximately 10%. This showed that the risk of developing glaucoma was cut in half with treatment. In OHTS Phase 2, where they treated patients, they had an equal rate of developing glaucoma in the original treatment versus the observation group. And this was looking at the 10-year numbers.
As described before, the risk of developing glaucoma with treatment was cut at approximately about 50% but the number needed to treat to prevent one case of glaucoma was approximately 20. The 10-year study in the OHTS 2 study, really risk stratified patients. And it showed that there was greater benefit to treating patients that were at severe risk of developing glaucoma, which is not surprising. I think risk stratification is one of the major results of the OHTS study. Not every ocular hypertension patient that is sitting across from you is created equal, so you have to look at the patient and look at their risk factors. Risk factors include central corneal thickness, penetrating deviation, high cup-to disc, family history. So there are multiple risks that are involved with ocular hypertension. And if you Google “Washington University of St Louis OHTS risk calculator” you can look at your patient’s risk for developing glaucoma and individualize your discussion with the patients.
The OHTS 3 trial, which is a 20-year results, is just now being analyzed and published. What are some of the major conclusions from the OHTS 3 trial? 46% of patients developed glaucoma at 20 years. African-Americans in the study had a higher risk at 55% of cumulative incidence of development of glaucoma. The patients that were originally treated had a lower risk of developing glaucoma at 20 years. 25% of patients had visual field loss, 3% had very severe visual field loss with a median deviation of less than 22 decibels. About 8% of patients required tube shunt surgery or trabeculectomy surgery and 75% of the patients were on topical medications. And once again, the incidence of developing glaucoma increased as the risk factors mounted. Patients at higher risk tended to have a higher development of primary open-angle glaucoma. Very influential study conducted by Dr. Michael Cass and team.
What are the other take-home messages from OHTS? We discussed risk stratification is very important in making clinical decision. We know that thin central corneal thickness tends to underestimate eye pressure. And so this was rediscovered. It was actually known and published on well before the OHTS study, by Dr. Argus, I think, during his fellowship at Iowa. But central corneal thickness was rediscovered as a risk of its own, a thin central corneal thickness for development of primary open-angle glaucoma.
We also found through subsequent studies that cataract extraction is very good at lowering intraocular pressure in ocular hypertension patients, at least for a few years. The effects of cataract surgery in most patients, the pressure lowering effects tend to wear off over time. We’ve also learned through the study in the multiple stereoscopic disc photos, and visual field tests that we’re done routinely and analyzed, that it’s important to confirm visual field defects. If somebody has a new or progressed visual field defect, not necessarily in the OHTS trial, but it’s always important to confirm that the defects are actually there. We know that chances are more than not that visual field effects are not confirmed on repeat visual field testing. It’s very, very important to confirm visual field defects to make sure that what you are seeing is actually true, especially if it doesn’t fit the clinical scenario. If your OCTs are stable and your optic nerve is stable and the pressure seems well-controlled, they might have progressive glaucoma. But it could just be a bad day taking visual fields. Always confirm, you always want to treat patients and not tests.
And then lastly, glaucoma specialists, some of the best glaucoma specialists in the United States were involved in this trial. And this is how you show that we’re really bad at picking up optic disc hemorrhages. It’s very important to be critical in evaluating the optic nerve. How do we know we were bad? Because in the study, investigators had to circle is a disc Hemorrhage present? Yes or no? And more times than not, or sometimes when the doctor said no, and then the photos were taken, disc hemorrhages were on the photos but the clinician did not pick that up. So it’s very important to be very critical in assessing optic nerve head status.
The next study that we’d like to speak on today is something called the selective laser trabeculoplasty versus eye drops for the first-line treatment of ocular hypertension and glaucoma: the LiGHT trial, which was based in Europe. It was 718 eyes that were randomized to medications versus SLT. Patients included 18 years or older, they could have open angle glaucoma or ocular hypertension, the mean deviation had to be less than a -12 decibel, so mild to moderate glaucoma. And it excluded patients who had intraocular surgery except for patients that had cataract extraction more than one year prior, The average patient was on the younger side, 63, the vast majority of patients had open angle glaucoma, although 17% of patients were moderate-to-severe. So they accepted moderate-to-severe glaucoma in this trial, and then 23% had ocular hypertension. 70% were Caucasian, 20% were patients of African descent, and 7% Asian, 55% were male, 24 was the average intraocular pressure, and 6% of the patients were pseudophakic. These were the baseline characteristics.
Here’s some information regarding treatment versus control. 75% of the patients in the laser-only group had one SLT and we’ll talk about why that’s important. The medication burden was significantly reduced in the SLT group, both groups, the eye drop group and the SLT group, had a greater than 90% of the visits at the target pressure oh. This is part of the results at the bottom of this chart. The disease progression was lower in the SLT group, 3.8% versus 5.8%, and the patients in the eye drop group were more likely to have surgery, both cataract surgery and trabeculectomy surgery, as highlighted by the chart at the very bottom.
What were the clinical endpoints in the visits? The vision intraocular pressure and visual fields were maintained well in both groups at 3 years. And excluding the two week SLT visit, the total number of visits were similar in both groups. It wasn’t an increased clinical burden to do SLT versus drop treatments. What were some adverse events? Most adverse events were limited in transient; this trial did look at systemic side effects with the eye drop group and more localized side effects with the SLT group. But as you can see, the groups were pretty well-matched as far as limited in transient complications.
One thing that was studied was also repeat SLTs. There was a good survival of repeat SLT compared to initial SLT. This is something that we’ll come back to in the conclusion slide, but I found this to be something very interesting and it has changed my practice.
Some take-home points from the LiGHT trial. Patients should be offered, in my opinion, laser trabeculoplasty as a primary therapy. This study, I think, has changed practice patterns. Laser trabeculoplasty works in the majority of patients, patients still need to be monitored, and it needs to be explained that this is not a cure for glaucoma or high eye pressure, because we do know that the effects wear off. But many times that patients have trouble getting eye drops in or even in patients that can do eye drops, patients should be offered laser trabeculoplasty and encouraged if they do want to go that way.
Patients with severe disease were less likely to be controlled with the medication laser group, so that was in one of the charts earlier. But as the disease became more severe, hitting pressure goals with both SLT and drops was decreased. I think we see that clinically where many times we try an intervention on more severe disease whether it’s MIGS surgery, or SLT, or drops, as indicated in this trial as well, the efficacy is just usually not as good, unfortunately.
One thing that’s changed is considering repeat SLT even if no prolonged effect from the first laser. I was taught almost 15 years ago that if you didn’t get an effective SLT don’t go back to the well, it was unlikely to work a second time if it didn’t work the first time. But this study shows, and I do do this in my own practice, I’ll say unfortunately with the one SLT you weren’t part of the 70 to 80% of patients that normally respond. But new evidence shows that repeating SLT that there’s a percentage of patients that tend to do well with repeat SLT. I’ve had a few patients that we’ve repeated SLT on and this is really a big take-home point for me from the study.
Also laser trabeculoplasty is a cost-effective alternative to drops. And then the authors make a point to say that maybe we don’t need to do an earlier than one month visit following SLT. I think that generally that’s true. Certainly if a patient has a history of a pressure spike, if they have very severe glaucoma, that you’re worried that pressure spike might cause a problem, if they’re monocular. Sometimes I’ll see patients three or four days after an SLT just to make sure they don’t have a pressure spike but really the chance that a pressure spike in the study was very, very low which I think is reassuring.
The next trial that I’d like to discuss is the ZAP trial, which was a single-site perspective trial of 889 patients that received LPI and then the other eye was observed. So it was a six-year trial which is a really good length trial, maybe not good compared to the OHTS trial, but six years is a good length of keeping a patient in a trial. The inclusion criteria, the patients were between 50 and 70, they had to be primary angle closure suspect with greater than 180 degrees of appositional closure without ocular hypertension, synechiae, or optic neuropathy. And then they did have an exclusion criteria of greater than 15 millimeter rise in intraocular pressure, with dilation or dark room provocation testing. The eyes that were studied in this trial were short in length, they had mild hyperopia with a cup-to-disc of approximately 0.4. So once again, you could not have had glaucomatous optic neuropathy.
These are the Kaplan-Meier plot endpoints. There are three endpoints to this trial and as you can see the proportion that reached primary outcome was extraordinarily low. The three endpoints were an intraocular pressure at a couple of visits greater than 24, more than one clock hour PAS that developed a peripheral anterior synechiae, or an acute angle closure glaucoma attack. What was the incidence per 1000 eye years? Reaching endpoint of the pressure endpoint there was a .66 per 1000 eye years incidence in patients that had laser iridotomy versus a 1.11 incidents per 1,000 eye years in the control eye where they had not had an iridotomy. A similar reduction with PAS formation and acute angle closure. So the incidence of all three endpoints is extremely low at six years but reduced in the iridotomy versus observational eyes.
When you compare the eyes that did and did not reach endpoint, what were the differences in the eyes that tended to reach endpoint? It was a risk that if you didn’t get an LPI that you were likely to reach an endpoint more frequently. Other factors were age, so the older you were the more likely you were to reach endpoint. If you had a smaller anterior chamber depth, you’re more likely to reach endpoint as well. These were looking at different factors in this trial.
The good news is there’s very low risk to doing iridotomies, there was hyphema which we all see, a very rare risk of a pressure spike or corneal burn. Endothelial density didn’t seem affected by iridotomy, which is important to note especially with glaucoma intervention these days. It is important to note that. So some really useful information coming out of this trial.
In follow-up, what changed with an iridotomy? The angle seemed to deepen with LPIs and in eyes that did not have an LPI tended to shallow overtime. But the vision and the intraocular pressures stayed pretty similar with both groups at six years.
What are the take-home points from the ZAP trial? I always chuckle to say, you probably do too many peripheral iridotomy, I don’t, but you probably do. I probably do too many too. When you’re sitting across from a patient if they look really, really shallow, if they have risk factors, if you don’t think that they’re going to need cataract surgery soon. If they have other risks that you’re really worried about them going into angle closure, or other risks, sometimes because the intervention is low risk. We probably, as a group, do do too many iridotomies. But the risk can be vision threatening, so that might skew how many iridotomies that we do.
The patient population in the study probably does not match what I see here in Indiana. And then some questions. Is six years really long enough to look for necessity of PI? And I think the answer to that is when does a patient need cataract surgery? If a patient’s really, really shallow and has appositional closure and they’re 50 and they have a clear lens, I might be more likely to do an LPI than in a patient that’s 69 and has a two to three plus NSC with a vision of 20/40, which I’m thinking about taking their cataract out.
Trying to stratify, once again, which patients need that. That’s a tough part of being a doctor sometimes is trying to put yourself into the patient’s shoes and trying to feel out what their risk aversion is, look to innovation versus observation, and trying to figure out what’s best for them individually. And, once again, just talking to them about the risks and benefits, alternatives with this procedure. I’m not paternalistic as a physician so many times I say both options are reasonable. I try to do my best, as we all do, to educate our patients and then having them buy into what they choose and answering any questions that they have.
The next study that I’d like to speak on is the effectiveness of early lens extraction for the treatment of primary angle glaucoma or the EAGLE study. This was 419 eyes that were randomized to clear lens extraction versus LPI. Different study population, obviously. These are 50 years or older patients with no visually significant cataract. So that’s very, very important to realize these were clear lens extractions. They had to have primary angle closure with a pressure more than 30 or primary angle closure glaucoma. They had to have one of those diagnoses. They could not have a symptomatic cataract, or be post-LPI, or have a past history of acute angle closure glaucoma. The average patient with 67, slightly predominant female population, average pressure was 30, the axial length, once again, shorter eyes with a mild hyperopic prescription, mean deviation on visual field was a -3.3 decibels.
At three years, eyes that had clear lens extraction had less medications, had less likely need to have glaucoma surgery, which is great news, and had better quality of life. As you can see from the results presented, the clear lens exchange is in the first column and the laser peripheral iridotomy is in the second column. Medication burden was less like we discussed and needing trabeculectomy. There were six patients in the LPI group that ended up getting trabeculectomy, there were actually 16 people that ended up getting cataract surgery, and then one patient with an Ahmed tube, it looks like. Here clear lens extraction really had benefits to both intraocular pressure and medication burden and quality of life, which is what we all try to improve with our glaucoma patients.
Very low complication rates. 1% posterior capsular rupture rate, about 1 in 200 had vitreous loss. It was interesting that in this trial when the glaucoma actually occurred more commonly in the LPI group compared to the clear lens extraction group. Obviously being a hyperopic population puts you at an increased risk with any sort of intervention. But as you can see, both groups had pretty low risk. Also interesting, loss of vision was higher in the LPI group compared to the clear lens extraction group.
What are take-home points from the EAGLE trial? Clear lens extraction can greatly improve intraocular pressure, lower medication burden compared with LPI. And in the United States, at least, we struggle with this because of the challenge to convince insurances, government that clear lens extraction is a potentially great treatment for a potentially blinding disease such as glaucoma. But that’s a challenge that we have here in the United States, other countries are more progressive in relationship to this. Clear lens extraction can definitely be a glaucoma treatment, certainly. I think the study is a really nice study that shows this.
So right now we’re going to get a little interactive. I have a couple quick questions. The first quick question is and we’ll give you about 30 seconds to vote, we’ll put up the voting in just a second. But it’s a 50-year-old with neovascular glaucoma, presents on maximum tolerated medical therapy, with a pressure of 40 and a vision of 20/80. Unfortunately I get multiple of these patients a lot a month. What is the most appropriate surgical therapy in this patient? We’ll put up the choices, we’ll give you at least 15-20 seconds to vote, we’ll go over the results, and then we’ll go over a study that addresses this question.
Kind of all over the place on this. Most people wouldn’t do a XEN. I would certainly agree with that and then between Ahmed, trabeculectomy, Baerveldt, there’s kind of a split decision with Ahmed’s winning. And I would go with the majority here, frankly, and I’ll try to tell you why with reviewing the next trial.
Let’s look at the next trial that we’re going to speak on. These were parallel trials that pooled their results because they were so similar in nature and they were run about the same time. The Ahmed Baerveldt comparison study, or the ABC trial, which was spearheaded by Don Budenz, who’s now the chair at the University of North Carolina, but he did this work predominantly when he was glaucoma specialist at Bascom Palmer. And then Ike Ahmed at the University of Toronto conducted the Ahmed versus Baerveldt study. But these were both multi-centered perspective international clinical trials that randomized patients to Ahmed FP7 versus Baerveldt 350 tube implant.
Patients had to be over 18 and had to have uncontrolled intraocular pressure. This was a very high-risk patient population. 65-years-old, average intraocular pressure of 32, over three medications on average. And a fairly diverse patient population, which is, once again, great to see. 50% of patients had POAG. But about 40% of patients had what’s considered high-risk glaucoma: neovascular glaucoma, UVA glaucoma. Traditionally tube shunt surgeries were reserved for high-risk populations. Some physicians felt like, well, two shunts don’t work as well as trabs. But the study populations in those earlier studies were difficult patient populations. We’ll talk about that a little bit with some other studies down the road. This was a very high-risk, high-pressure patient population with bad diagnoses.
What does the IOP in the pooled data show? It showed that Baerveldt achieved lower pressures, so you can see pressures were typically below 15 with the Baerveldt, slightly above 15 in the Ahmed group. But at five years pressure control was really pretty good in this pool of data. Survival rates over time. At five years, Baerveldt seems to do better as a whole but Ahmeds also did very well at five years as well. But Baerveldt is statistically significantly better with less medication usage. So the Baerveldt group tended to use about half a medication less compared to the Ahmed group at pretty much every time point.
What are take-home points from this trial? Baerveldt Implants had a higher likelihood of success, have lower intraocular pressure, have lower medication burden, but did have a higher incidence of complications and hypotony. A really important take-home point, in my opinion, that has changed my practice was a result of the study as well, that showed that in neovascular glaucoma Baerveldts having much higher risk of progression to no light perception vision compared to Ahmed implants. I almost exclusively use Ahmed implants for this reason, not always, because I like the initial pressure lowering Ahmeds. Even, I think, it’s more predictable than with fenestration of the Baerveldt implant, as well as the fact the patients tended not to have devastating complications in the neovascular glaucoma populations.
Going back to our quick question, I’m biased, probably, to do an Ahmed implant in that situation. But I think a Baerveldt implant is also justifiable in that situation. Be aware that serious complications with Baerveldts in that patient population
Let’s switch gears a little bit to the tube versus trabeculectomy group which was spearheaded by Steve Getty at the Bascom Palmer Eye Institute. This was reported probably about 10 years ago, the final results, the five year results. But this was a study of 212 eyes randomized to trabeculectomy versus a Baerveldt 350. And patients had already had cataract extraction and/or trabeculectomy. Once again, wide age range, pressures had to be between 18 and 40.
Let’s look at the average patient. So 71 with a pressure of 25 on three medications. 81% of the patients had open angle glaucoma, and a very diverse patient population which is great. Once again this was a multinational study, multicentered study. Let’s look at the five year results of the TVT trial. In this study, trabeculectomy groups achieved lower intraocular pressures but the tube group also achieved pressures below 15 throughout the five years of follow-up. Both Baerveldt implantation and trabeculectomy achieved very low intraocular pressures, which was great. Failure rates though were higher in the trabeculectomy group, compared to the tube shunt group. You can see them diverging at about six months and then getting wider throughout the study protocol.
What’s the take-home message from The TVT Trial? Trabeculectomy was more likely to fail at five years, trabeculectomy had a greater chance of reoperation in hypotony than tube shunt surgery, which is the Baerveldt 350. Tube shunt surgery had a lower risk of serious complication, trabeculectomy achieves a lower pressure with similar medication usage. Perhaps trabeculectomy had a higher risk of failure since 55% had undergone a prior trabeculectomy. So maybe the study population was a little skewed against trabeculectomy because a certain percentage of these patients had already failed at prior trabeculectomy. I think this was a really big landmark study to show that tube shunt surgeries just weren’t for refractory glaucoma as a last ditch effort, which I think has been the predominant throughout the eighties and nineties. That tube shunt surgeries could be done after cataract surgery and/or failed trabeculectomy surgery. I think probably among glaucoma specialists it was to do three trabs first and then if three trabs failed then you can do a tube shunt .But I think this study may have pushed tube shunts a little bit further up in the surgical decision-making tree.
One more quick question, this is our last quick question of the day. 65-year-old surgical naive patient presents with progressive severe glaucoma despite SLT times two, a maximum tolerated medical therapy, with an IOP of 18. What is the most appropriate surgical therapy? We’ll put up the pole here, give you 15 or 20 seconds to vote, we’ll share the results and then we will discuss some thoughts and a trial to help us address this.
All right. Here’s some results. It seems like trabeculectomy with mitomycin C is the clear winner. I think there may be a couple answers to this that I think are reasonable, frankly. But most people I think in this situation would go with the trab. Which is probably what I think is best based on this next clinical trial. Let’s look at the primary tube versus trabeculectomy or PTVT trial
This was a study looking at 242 eyes randomized to trabeculectomy versus Baerveldt 350. I was an investigator in this trial. And once again this was spearheaded by Steve Getty at the Bascom Palmer Eye Institute. Very similar data collection and study design. But in this trial patients could not have had any prior intraocular surgery so these were in surgically naive eyes. The pressures had to be, once again, between 18 and 40. Younger patient demographics, with the TVT it was 71 years old, here it was 61. Intraocular pressure was 24 on three medications. Very diverse patient population, which is great. 90% of the patients had primary open angle glaucoma.
The three-year results of the PTVT Trial. The five year results are going to be presented by Dr. Getty at the American Academy of Ophthalmology meeting in November. But let’s look at the published three year results. At three years, tube shunt and trabeculectomy both lowered intraocular pressure well below 15, with trabeculectomy achieving lower intraocular pressures. Here’s the difference though, the trabeculectomy group had an increased survival rate compared to the tube group so the inverse result of the TVT trial. At three years the tube group had a higher risk of failure.
What are the take-home points so far with the PTVT trial? At three years, tube shunt surgeries have a greater risk of failure, have a higher intraocular pressure, have a higher rate of reoperation, and greater need for medications, but lower postoperative complications. The complication rates in the PTVT trial show Baerveldts tended to have less complications but here there’s a higher failure rate. Which is different for this different patient population. There’s a thought, when you look at different tertiles of starting intraocular pressure in this trial, patients failed at a much higher rate in the tube shunt group if they started out with lower intraocular pressure. Going back to the quick question, you know the patient had a treated pressure of 18. In this situation, trabeculectomy, based on the results of this trial in this patient population, was able to achieve greater success compared to tube shunt surgeries.
At higher pressures, tube shunts did very well in this trial, but there’s a lot of failures in the lower tertile patients that received tube shuts in the primary tube vs. trabeculectomy study. We’ll see what the five year results show, just wanted to point out a difference between the two trials.
One more study to speak on is the COMPARE study. This is a really great study, prospective randomized trial comparing Hydrus to the original iStent implants for standalone treatment. This was not combined with cataract surgery, which a lot of the MIG surgical trials are. Once again, this was a little bit off-label in the United States because in the United States, typically we are limited to one iStent implantation. But this included patients with two iStents. And once again did not include cataract surgery.
The inclusion criteria, wide age range, you had to have open angle glaucoma but you could have pseudoexfoliation or pigment-dispersion. Intraocular pressure had to be between 23 and 39, post washout. A younger patient population, age was 67, pressure was 19 on 2.6 medications, a diverse patient population, 94% of the patients had primary open angle glaucoma. Not a lot of pseudoX or pigment-dispersion. Kind of the mild or moderate median deviation loss on visual field testing. And 64% of these patients were phakic, so important to note that.
What do the studies show? It showed that two iStents versus one Hydrus had good pressure-lowering reduction and reduced medication burden. Although the Hydrus tended to have slightly lower intraocular pressures and less medication use over the time course of the trial. I believe that there is new data being presented from this trial as well at next month’s American Academy of Ophthalmology meeting. The safety profiles above the Hydrus and the iStent were very good.
Take home conclusions from the COMPARE trial. Both surgical modalities we’re really good at lowering pressure and reducing medication burden. The iiStent that was used in this trial was the “older generation” where most of the time in the United States we’re not still using the same iStents that they were used in this trial. And that most surgeries had excellent safety profiles, which is very important, especially in minimally invasive glaucoma surgeries.
Some tips in analyzing clinical trials and incorporating results into your practice. Try to match patients with clinical scenarios when trying to assess recommendations to the patient. I think giving the patient some options and reviewing some of the positives and negatives that these clinical trials have highlighted, I think are important in giving patients and empowering patients to pick which option is best for them. There are definitely differences between studies, you can’t really compare study-to-study because of patient populations, definition of success. And then, obviously, surgeon expertise and experience may dictate superior results. Most of the good trials are perspective, multicentered, multi surgeon trials, but your technique may be really good with one of the surgical options. That certainly should weigh in on your decision-making in recommending something to your patient.
It’s been such an honor to be able to speak with you today, this morning, here in the United States. And once again, such a talented and diverse group. I did want to take a couple questions from the box and then we’ll go ahead and sign off.
One of the questions was what makes cataract surgery a good intraocular pressure agent in patients with ocular hypertension? What’s the proposed mechanism? I think that this is a little bit for debate. Some people have advocated that perhaps the ultrasound does something to the trabecular meshwork to get the trabecular meshwork working better. I think that some people propose taking a big lens out and putting a smaller lens in might somehow physically open-angle better. I don’t know that the mechanism is 100% proven why it works. We do want to know the effects, typically in studies that have looked at this, tend to wear off over time so maybe three to four years. Maybe someone else on the call knows the answer? But I don’t think that the mechanism has been completely validated about why we think that happens. I think there can be multiple mechanisms that might affect this.
There was another question about how many times do you go back to SLT before going to a different therapy? Like I said before, I was always taught if SLT doesn’t work in one eye, it’s not going to work on the other and don’t try it again in the same eye. My practice has changed a little bit. I would repeat the SLT probably twice in the same eye. If I’m not getting an effect after the second eye, I know that this is different than some of the studies show, but then I would usually go to a different intervention. Whether it might be an oral agent or a surgical intervention depending on the stage, that pressure where we’re at. I’ll typically do it, if I’m not getting the effects after the second SLT, I’ll tend to move onto an alternative therapy.
Once again, thanks so much for your attention, and it’s my honor to help be a part of this program for Cybersight and Orbis. And this is a really big honor for me to be with you today. So thanks so much and everyone have a great day.