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Ike K. Ahmed, MD (Prism Eye Institute/University of Toronto) delivered the Drs. Henry and Frederick Sutro Memorial Lecture at the 7th annual Glaucoma 360 New Horizons Forum in San Francisco on February 9, 2018.
His topic was “Interventional Glaucoma: The Why, The Who, and The How.” The keynote started a full day of presentations and panel discussions on innovations in glaucoma. New Horizons Forum is presented annually by Glaucoma Research Foundation.
Andrew Iwach, MD: Now I’d like to introduce our keynote speaker. The lecture is named in the honor of Henry and Frederick Sutro. Dr. Sutro was one of my patients and I actually had no idea that he had this capacity, very nice gentleman and he donated $3.2 million to the Glaucoma Research Foundation for research but also, he felt education was very important. He was a faculty member at Pacific School of Dentistry, he practiced in Oakland and he comes from a long line of leaders. His great-grandfather was the former mayor of San Francisco, one of the largest land owners back in 1898 and in fact, there’s a tower called Sutro Towers that emanates from one of the hills that they used to own.
Our keynote speaker is Ike Ahmed who all of you know. Ike has a stellar history and reputation. His studies began at McMaster University and then on to University of Toronto. He spent critical time at the John Moran Eye Center in Utah, where he did his glaucoma and anterior segment fellowship. He’s published over 600 manuscripts, delivered almost 30 visiting professorships. He’s authored over 120 chapters and articles. He’s also an editor for a number of different publications, including the Blue Journal Ophthalmology and a reviewer for many others.
He has, along the way, been given a number of well-deserved awards and the list is quite long but the one that caught my attention was in the Canada’s Top 40 Under 40 in 2009. I think he was about 20 years old then and what that tells me is as peers, we recognize his excellence and leadership but when you look at an organization that looks across all of Canada and brings him into that very special group, I think that really says a lot.
Currently, he holds several academic positions. He’s the Medical Director of the Prism Eye Institute. In addition, the University of Toronto and also continues his relationship at the Moran Eye Center in Utah. And with that, let me ask Ike to come up and I’d like to present this token of our appreciation, a plaque to commemorate your delivery of the Sutro Memorial Lecture here today at the New Horizons Forum.
Ike K. Ahmed, MD: Thanks, Andrew. Thank you, thank you very kindly, thank you. Thank you, Andrew, for the wonderful introduction and congratulations to both you, Adrienne, the GRF and all of you here that are part of this program. It’s hard to believe it’s been seven years — when you started, and I remember that first session, and you’ve grown tremendously, and this is one aspect where it’s good to grow, and I’m very excited to be here.
The field has changed tremendously, and I thought I would start off the day talking about where I think I see glaucoma going, at least a certain part of glaucoma going, which is interventional glaucoma. We have a lot of industry partners here and I’ve been very proud to work with industry and collaborating to move things forward to bring things to our patients and many years ago, we didn’t have a lot of these innovations. I mean, we see almost a billion dollars of money raised within interventional glaucoma, we see strategics purchasing and acquiring these companies and companies going public.
It’s really been a lot of buzz and I think we need buzz. Glaucoma needed buzz and that’s why it’s hot and getting hotter. By the way, those of you who are complaining about the heat, I took this picture just as I was driving out of my house up in Toronto. It’s a little cooler up there so if you need some air conditioning, that’s where you can go look.
Now glaucoma, of course, we know is a global issue. It is the leading or one of the leading causes of blindness. Estimates put the numbers up to 60,000,000 people at risk or who have glaucoma around the world and that number is continuing to grow, estimated to be over 80,000,000 people. In this space or in glaucoma, it’s estimated the amount of - the market amount in this area has grown and continues to grow. As you see, a $6 billion market around the world and the US probably accounts for about half of that. But it’s interesting, when you look at that global market share of drugs versus device, the vast majority of that market is in the drug market or at least it’s been. Now it’s certainly growing more so in the device and diagnostic area, but you can see, the surgical devices have really remained a very small portion, despite some of the innovations we’ve seen in our field.
When we look at surgical procedures by specialty, we see of course cataract surgery being a very large area of surgery and surgical volume. Refractive, of course, is fairly large, retina a small portion and glaucoma has always been a smaller portion of the pie in terms of surgical specialties within the space. The next slide was just going to show you the relative complications amongst the surgical procedures, in terms of cataract, refractive, retinal and oculoplastic and as you see here, we all know that traditional glaucoma surgery has been associated with a fairly high complication rate over the first early post-operative period and late post-operative period.
This obviously has impacted the adoption of these procedures and as we think about traditional glaucoma therapy, I don’t have to put a slide up here because you know, we have, of course, a very heavy medicated initial therapy paradigm mixed in with some later trabeculoplasty. We of course know the issues around medication, the challenges of compliance, adherence, local side effects and other cost issues as well and on the other side of the equation, of course we have traditional surgery which we know, of course, can be very powerful and effective but also associated with significant risk early and late as well as post-operative recovery.
So, there’s obviously a large treatment gap that we have within the glaucoma space when we think about the US alone and this has been, of course, where MIGS has kind of come to fore, still evolving, still developing where we’ve seen this gap starting to fill. Now it wasn’t like this a few years ago, when I finished my residency or during my residency. I remember looking at the different specialties and poking around, seeing what my interest was, talking to glaucoma folks and asking about how do we treat glaucoma, can we change things? I remember hearing, you know, this is the way we’ve done it, it’s been drops first line, second line, third line and we really, surgery is really reserved to the latest and I mean I think one of the most dangerous phases, as this quote shows, is the language, we’ve always done it that way. So that’s why we’re here, because we don’t always do it that way. We think out of the box and we do it differently.
So will glaucoma therapy change? Well, I think it will change and it’s changing already and dramatically and this is, of course, because we know the development of a disruptive market is a creation of new spaces where patients, physicians, others are not met by the current opportunities that are available and this is really what’s developing into an interventional space, what I like to term interventional glaucoma. This is overtaking, I think and will overtake the current treatment modalities that exist.
So, interventional glaucoma or IG, of course those of you that know and are on social media know that IG is typically Instagram, right? So it will be easy for you to remember what interventional glaucoma is about. Interventional glaucoma, we’re going to talk a little bit about here what I think it means. We’re going to hear from different presenters today about different ways where glaucoma is looked at more as an interventional opportunity, whether it’s diagnostically, whether it’s therapeutically, whether it’s procedure-related or follow-up or any other technology related to this, we are changing our attitude and that’s what I really want to focus on. I look at this as an attitude adjustment for us in glaucoma and we are enabled, because of what we have available to us and what’s coming in the future.
Proactive, being proactive in looking at disease versus being reactive. Using advanced predictive analysis in terms of diagnostics and screening, actively monitoring with advanced technology, intervening earlier and more aggressively in a safer and lower risk way while addressing adherence as well. That’s what IG and interventional glaucoma means to me. We have technologies that I think allow for safer IOP-lowering. Drug delivery, MIGS is what this is about of course, whether it’s delivering drugs to lower IOP or wound healing modulation, combining procedures together and micro-stenting approaches of course is where we’re at.
So I think it is a time for change and one of the reasons we see this is because it’s not only a hot area but of course, I think we really realize that the current treatment paradigm is not working well. Many of you may disagree with this, that we have a pretty good - we’re in a good position - I’ll beg to differ, and I’ll show a little of the data on this. I think we have tremendous challenges still in monitoring patients properly and this creates confusion and procrastination and I think one of the reasons why we still fail, and we fail our patients over long term, not the short term, is because we’re insufficiently lowering pressure, controlling for fluctuation and addressing the adherence issues and this is the opportunity.
And so, this is what we mean between being a passive observer and watching patients unfortunately getting worse versus actively intervening, whether we’re on internet and just perusing and watching and being a lurker or whether you click on every pop-up, basically, there’s pros and cons. We don’t recommend doing the latter, of course. But active manage is, I think, what we’re after here. And I think this is based upon the fact that glaucoma progression and blindness rates are still a problem. Glaucoma remains the leading cause of blindness in many parts of the world.
The long-term risk of blindness has reduced, we’re happy to see this data from one in four to one in eight in unilateral blindness, looking at some reasonable population data but one in eight is still too high and of course this can be quite variable and we look at patients at lifetime risk of going blind, patients for example who have been followed by excellent practitioners, you know, up to 40% are blind in one eye by the time they pass away. That’s a very sobering thought. This is European data, we may think we’re better than the Europeans, that can be debated, I guess, but I think this number is reflected in many places around the world and the reality is that we’ve come to accept that progression is a reality. It’s not a matter of whether a patient is going to progress or not, it’s how fast or how slow they’re going to progress and then we adjust therapy. I really think that this is a problem, and this is an issue and of course, we need to recognize that.
So glaucoma is still a leading cause of blindness even when patients are under our care, which is an issue. Now this is not a new idea, Morton Grant, many years ago, wrote an editorial, Why Do Some People Go Blind from Glaucoma? Fast forward, Susanna and others continue to talk about why patients still go blind from glaucoma for the same three reasons - underdiagnosed, improper treatment for many different reasons and lack of compliance. There’s many reasons why these things happen, we underappreciate the severity of damage, we’re not lowering pressures enough, we’re not measuring pressures adequately, we’re not looking at peaks properly and difficulty in evaluating progression.
So the premise here, and I’ll be a bit provocative, I think our guidelines are a little impractical and they’re insufficient and I do think that in my experience and will present some data on this, I think driving patients to low IOPs is not just for advanced glaucoma, it is the best way to protect our patients from going blind. The problem is that we have had issues with adherence in getting down that far, in side effects but things are changing and I’d like to really continue to put up the EMGT trial, which of course we were all happy to see that the risk of progression reduced with treatment, from 76 to 59% but I think what is really alarming here and continues to still, you know, I think be the talk of the study, in my opinion again, is despite a reasonable treatment, 25% IOP reduction is basically what the American Academy Preferred Practice Patterns has recommended as target pressure targets.
Still, over the long-term follow-up, medium-term follow-up in the patient’s lifetime at least, 60% of patients still progressed. I mean, I think that is very sobering. Now again, there’s many different reasons why and that was not necessarily, that was not advanced glaucoma. Recently we saw the UK Glaucoma Treatment Study, randomizing patients to latanoprost versus placebo. Certainly saw a pressure reduction between both groups. We certainly saw a reduction in progression but even at one year - even at one year, 20% of patients with very early glaucoma still progressed at one year. So we can celebrate progression is reduced with therapy but we need to do better than that and we need to ask ourselves why to patients still progress in these treatment arcs, why do we see this happen?
Well, it’s not just about IOP, I know that, of course, there are many reasons why, but I think we have to reflect and ask why we see continual issues on that and we’ve seen the risk calculators and we’ve seen, you know, reduction of risk, 10 to 20% per millimeter of mercury and we continue to see data that’s both old, like this data from Odberg in Norway, showing patients who are kept less than 15 progressed less, patients who are surgically treated progressed less and we of course see other data population, prospective population study from Canada showing patients who are in the lower tertile of pressure, average pressures, do better in the long run, still unfortunately seem to progress but do better in the long run than those that are higher. And of course, there’s a very well overplayed AGIS Study showing keeping pressures less than 18 and keeping an average of around 12, whatever we can argue about the validity of this, certainly seems to reduce the visual field progression in patients with not only advanced disease but moderate disease as well.
So it is something to ponder, you know, is 12 the new 21? It used to be 21 as a target before, we were all about target pressure so we’d be thinking about getting down closer to 12. Well, we see in the general medicine studies and data that in diabetes, intensive control, not only keeping averages low but keeping fluctuations low in blood sugar seems to result in less end organ damage. We have better ways to treat diabetes now with continuous monitoring and infusions pumps and that has allowed for us to be aggressive without overplaying some of the risks. Having this intensive therapy seems to have some benefit, keeping patients to the low end of normal in a chronic disease. Hypertension not to different, of course, as well, in terms of sustained aggressive intensive therapy, reducing end organ damage. The problem, of course, is the side effects and compliance and adherence issues that remain with medically treated diseases.
So who do we need to be more aggressive with? Is it only in advanced glaucoma? Well, I’m not talking about fake glaucoma, first of all. So I’m not talking about ocular hypertension or suspects, I’m talking about real manifested disease but not just advanced disease. That’s important to remember that, thinking about life expectancy. As one of my friendly colleagues from Europe once said, glaucoma is only young once. We only have one chance to keep that glaucoma young, so to speak, or early, more than ever. And of course, our traditional therapy paradigm has been a stepwise approach, setting modest pressure targets based on consensus, not a lot of data to support that and then we watch and wait and we observe with techniques that are not the best. We’re getting better with progression analysis but still, we lag behind as far as robust analysis in an earlier period of time and then we basically then have to aggressively treat patients.
Maybe it’s time to think about changing the paradigm by being more aggressive from the outset, particularly again patients who are at risk, patients with more than early disease and patients who have a longer life to live and this is the philosophy of interventional glaucoma. We must remember that glaucoma has a number of problems. IOP is fairly random. We measure it once in a day, maybe every few months. We know, of course, that the technique of measuring IOPs are not necessarily very robust or valid and we know fluctuation is an issue. So it’s a random measurement that we look at, of course. Severity is under appreciated, we know that, of course, structure and function relationships and progression, I still find at least that it’s not so easy. We have wonderful colleagues, Felipe Medeiros, who has done great work in looking at imaging and perimetry and I think developing better algorithms for this, but we have a long way to go still before we really have a technique that we can be confident in.
And what about target pressures? Well, this is a Canadian - these are the Canadian Guidelines based on mild-moderate disease and severe disease. Many of you would probably may say, you know, those are a little bit outdated, I probably am a bit more aggressive. The Preferred Practice Patterns, a modest pressure reduction as well and the same thing with the EGS Guidelines, again promoting a matrix of risk evaluation to set target pressures but still fairly modest. And this is basically the algorithm based on the EGS Guidelines so basically, we determine an individualized target pressure. Well, remember, this is somewhat random, in terms of target pressure, what is the IOP baseline? We know the variability on it and we know that, of course, we set generally pressure reductions, again, based on the best available data.
As we continue to come along here, we then prescribe therapy and we monitor patients and of course we monitor patients and we watch for patients over years with techniques that are not necessarily, again, robust and are not optimal in terms of progressing detection. Again, I think we’ll get better, but we still have some ways to go. And then we consider lower targets once we have progression and we have issues and by then, of course, we already have impacted a patient’s quality of life, we already have risked the patient as far as surgical risk. This very much is what I do when I’m not sure what to do at home, for example. We wait and watch. This is procrastination. We have a false sense of security, we make excuses, we’re in denial and then we have a crisis situation where patients are going blind and getting worse. I don’t have all the solutions to this, but I do think that we need to think about this in more detail here.
I think most of you clinicians out there who look at glaucoma would not watch somebody who presents to you with a pressure, elevated pressure and has disc damage and visual field damage. Most of you are going to treat and not watch the patient get worse and then treat. But if you look at these rates, they’re again, not so different than what we see in modestly treated patients. So if we’re going to watch and wait for modestly treated patients that are insufficiently treated, why do we not adopt the same philosophy for patients who are untreated? In fact, we should be pretty consistent. The reason we don’t, of course, is because we don’t necessarily have comfort in some of the additional aggressive therapies that exist.
We must remember the long game and the long game exists whether we talk about surgery or medicines. Our treatment in blindness is not to help the patient for the next six months or a year or two or three years. The effect of our therapy now will not be evident to the patient until eight to ten years later and the long-term risks of being too aggressive or not being too aggressive remain for this patient throughout the patient’s lifetime.
So as you can see here, I definitely feel that someone - if a patient presents to me with more than early disease, with a life expectancy of more than ten years, I look at that patient as somebody who needs to be treated more aggressively based on what the best available data is and my own personal opinion. But does that mean more medications? Well, we know that adding three or four drops to someone already on a couple of drops probably does not provide a meaningful clinical drop in many patients and we know even adding medical therapy, at least with prior drugs, that the diurnal fluctuation, peak IOPs and other aspects of measuring fluctuation in IOP don’t - are not the same with surgically treated pressures versus medically treated pressures.
And despite all the options here, we know that compliance and adherence remains to be a problem and intervention means taking that therapy out of the patient’s hands and putting it into their eye, hopefully through our good hands. And even if patients are able to put drops in or remember to put their drops in, putting them in is a challenge for many of our patients as well, whether it’s the tried and tested marination technique or the dive bomb technique, this remains a challenge for our patients and we know of course that patients who progress or patients who are not adherent have a higher risk for progression.
We also know that medical therapy does have an impact on surgical success as well, certainly with bleb surgery, we know the impact of conjunctiva. The elevated pressure is truly an interventional problem, one that needs to be dealt with in a more interventional manner and we need to reconsider where the place of surgery is and not just talking about a quick traditional surgery but some of the, of course, novel techniques and techniques associated of course with drug delivery can be combined as well, when we think about this. And the benefits of, of course, surgical therapy or non-medical therapy are again, IOP-related, compliance-related and hopefully quality of life as well.
But our current paradigm in treating glaucoma is still, has been to operate late, certainly with traditional therapies. When we operate late for good reason, we have difficulty in assessing or getting predictable outcomes and we have an increased risk of complications and this is also a vicious cycle as we go back and forth, and we continue to kind of push surgery farther and farther away. We really have to break this cycle when we think about becoming an interventional specialty, again, instead of being reactive and responding to disease, being proactive and solving problems before they come.
And we’ve seen Cochrane Reviews, we’ve seen the nice guidelines, and these are starting to shift toward, again, suggesting surgery even first line for at least advanced therapy. And we’ve seen data in the CIGTS Trial, comparing surgery versus medical therapy, showing for the majority of patients with very early disease, there seems to be little difference but patients who have more moderate to advanced disease, with Mitomycin trabeculectomy and some of the issues around trabeculectomy still despite that do better over the long run than the short term.
So is surgery the answer? Well, certainly we’ve seen that surgical rates have continued to go down, at least traditional surgery. So if surgery was so great, at least traditionally, we wouldn’t probably have seen these rates. What will it take for surgery to become the norm? Obviously, invasiveness matters. This creates an adoption profile that makes it palatable for us and our patients. We know the example, of course with extra cap or intra cap versus phaco that really changed cataract surgery.
Safety, of course, is paramount and this is what really makes a difference and this has, of course, now resulted in a significant uptick of glaucoma surgical procedures now we see in the United States. And I do believe that the shift to safer glaucoma surgery allows us to be comfortable to shift to lower targets and I think that’s what interventional glaucoma means, it means intervening earlier, more aggressively in patients with real disease, less reliance on topical medical therapy and being proactive versus reactive.
And I was to give the Binkhorst Reflector back in 2014 and what my topic was, MIGS, an idea whose time has come. And MIGS has been talked about a lot and I won’t go through all the details of MIGS, of course. We’ve seen, again, the different outflow pathways and we’ll hear a bit about this conventional outflow pathways, supraciliary pathways and subconjunctival pathways. I like to call this internal MIGS and subconj MIGS. We have different targets that we see, depending on what outflow we reach and we see these therapies that can be used either as medical therapy alternatives or safely getting patients down to 12, at least that’s theoretically what the idea is, a smoother safety profile. And I think certainly MIGS fits very much into the philosophy at least of interventional glaucoma, much like many years ago, we started seeing coronary stenting along with drug elution start to create a field of its own.
And I do believe that we’re starting to see this in glaucoma, with many practitioners now looking at glaucoma in a very interventional mindset, which again really, I think, takes advantage of the technology as we’re going forward. Obviously, the ability to combine cataract and glaucoma surgery is an opportunity and I often say that MIGS is the phaco as toric lenses are to IOLs, that we no longer think about leaving someone with astigmatism when they go into cataract surgery, at least we consider that, we don’t always treat it and the same thing relies with glaucoma therapies.
You know, I also see drug delivery as being an advantage, particularly when it comes to synergy with MIGS. Some of the internal MIGS procedures can get us down and we want more sometimes, and I think the ability to combine IOP-lowering medications with MIGS I think is a great opportunity to synergize the interventional approach. We also know that we have limitations with regards to wound healing and fibrosis that continue to evolve and I think the ability to combine these drugs together with MIGS therapies helps.
So what I’ve hoped to share with you is an interventional mindset, leveraging the technologies that are out there in terms of IOP-lowering in a safer manner. Certainly it’s probably more of a mindset right now than reality, but I think that’s the philosophy that I think was captured within what we’re talking about today in many of these instances. Whether again it’s sustained release delivery combined with MIGS, whether it’s MIGS with cataract surgery, whether it’s other novel glaucoma procedures that are out there, including micro-stenting approaches.
And I will say that within MIGS, even, indications are expanding. They continue to expand, they continue to move earlier in the treatment paradigm and we’ll continue to see these new devices later in the treatment paradigm. It’s really changed the mindset, it’s actually given, I think, ourselves hope and excitement. We hope it’s not false hope. It’s given our patients the ability to, again, believe in a more active approach and a less passive approach and that’s the mindset that we look at.
It’s a proactive approach, it’s getting in and getting our hands dirty earlier on, rather than waiting and watching with uncertainty. It’s aiming lower, addressing adherence with low risk options. It’s about using novel devices and drainage devices that we have out there, continue to evolve and I think we’re only on the first or second level of intervention, by the way. Cataract is afforded a reasonable approach in combining procedures in a safe manner and I think the ability, again, like I said, the synergy with sustained release, whatever drug it is, whether it’s IOP-lowering, neuroprotection or wound healing facility, to synergize to address adherence are all factors.
We’re still going to have challenges and I hope that I challenge you, I hope that many of you have disagreed with my approach, that is what this is about, but I think that the interventional glaucoma train has left the station. I think that we’ve already changed the mindset of our patients, we’ve changed the mindset of our industry partners, we’ve changed the mindset of the financial world, we’ve changed the mindset of each other. And we see this, even, I look at the uptick in glaucoma fellowships. When I applied, there was about 20 vacancies out there, in my year. Now I think it’s hard to come by and I think that alone shows you the advantages. Refractive and retina and cataract was sexy when I applied. Obviously, I’m not into that so I went into the other side, but I think we’re starting to see glaucoma become hotter, becoming sexy.
Every patient with glaucoma deserves the right to see to live and live to see. We need to develop a long-term strategy that’s sustained to prevent blindness prevention, assessing quality of life and I do think that one of those aspects is lowering IOP to the low end of normal safely, addressing adherence with low-risk, long-term procedures and I think MIGS and drug delivery and elution, I think are some of the answers. And you know, as of course many of your read Jeffrey Moore’s book, Crossing the Chasm, of course we’ve seen innovation in this field for many years and of course, when you’re at the cutting edge, you get cut and I’ve certainly been cut in many different ways but we’re seeing now early adopters really thrusting forward and that’s really the cross - what Crossing the Chasm is about, it’s about getting that momentum for early adoption to really push the field forward. So interventional glaucoma or IG, the future is now, the future is present, I look forward to the rest of the great presentations today. Thank you so much for the invitation again and it was a pleasure to be here. Thank you
Last reviewed on March 13, 2020