Mayo Clinic Ophthalmology glaucoma surgeons discuss updates on glaucoma therapies, including medications, minimally invasive surgery and management of the ocular surface.
Speakers:
Syril K. Dorairaj, M.B.B.S., M.D., Ophthalmologist, Mayo ClinicCheryl L. Khanna, M.D., Ophthalmologist, Mayo ClinicDave R. Patel, M.D., Ophthalmologist, Mayo ClinicGavin W. Roddy, M.D., Ph.D., Ophthalmologist, Mayo Clinic
Good afternoon and welcome. Thank you for joining us today for the update on glaucoma therapies webinar. I'm Doctor Cheryl Conor, an ophthalmologist and glaucoma and cataract surgeon at Mayo Clinic in Rochester, Minnesota. And I will be your moderator and one of the presenter for today's discussion. We are also very glad to have you with us today. During today's presentation, you will hear from myself and three other board certified fellowship trained glaucoma surgeons from our Mayo clinic locations in Arizona, Florida and Minnesota. Each speaker will present for about 10 minutes. We will then have time for a Q and A session at the end. With that, I'm glad to introduce our first speaker today. Doctor Cyril, um Do Ray Raj. Doctor Dray Raj is an ophthalmologist and glaucoma and cataract surgeon at Mayo Clinic in Jacksonville Florida. Doctor Doray Raj is speaking to us today about minimally invasive glaucoma surgery in the supor space. Welcome, Doctor Dray Raj. Thank you, Cheryl. Thank you for the introduction and, and thank you for monitoring this session. Well, uh to start off. Uh I would say that we are in one of our best times in our career, especially while taking care of our glaucoma patients. I haven't experienced little more than 30 years. I've been taking care of glaucoma patients. I have more opportunities and more options to treat our glaucoma patients and give them opportunity to choose more than what I had started initially. 30 years back. So 30 years back, probably like in 1997 this is what I used to do. I used to do just Trabeculectomy. This is towards the left side is my dissertation comparing P fluoro and Mytton Mycin C while doing trabeculectomy. So for mild, moderate severe glaucoma stand alone or along with cataract, this is the only surgery that I would do in 1997 trabeculectomy, trabeculectomy, trabeculectomy. But, but it is by far one of the most successful surgery. It's by efficiency. It is one of the most successful surgery that I have seen in my entire career. But unfortunately, like when I came here, there was a balance of safety and efficacy. And so a lot of new surgeries were introduced, something called mps that's called minimally invasive blood based surgery. There are two new devices were introduced, something like Zen and pressure flow, pressure flow is not approved in FDA by FDA. But these two surgeries try to mimic trabeculectomy and glaucoma its device. But again, the problem is it had the same complications as if like you are doing a trabeculectomy. Almost 9% of these patients in their lifetime would have vision threatening complications. It would go to a to an extent, like within days they will lose everything what we worked for in our entire lifetime. So that's where the concept of mix. That's the minimally in meso glaucoma surgeries came into picture. The first is the angle based surgery. This was introduced, it's called the trom in 2008 and from 2008 until now, then 15 years, there is a lot more options that's available for now. This angle based surgeries, it can be cutting the angle or exci excising a piece of trabecular meshwork or having a trabecular meshwork bypass devices itself. So basically what it does is it uses the conventional pathway, conventional pathways. We think that the major point of resistance is that the trabecular meshwork and once we bypass the trabecular meshwork, we have access to the shes canal and then from that chems canal, we go to the distal collector channels. So that is the conventional pathway where 40 to 60% I would say the outflow pathway is dependent on. But if you look at what the angle based surgeries, a internal, this is my office. I took picture just to show there is so many new devices that's been coming out in since last two years. If you have to do a goat toy, you have like five or six of them. Unfortunately, we don't know which one works. How, where and which one where exactly the resistance is what is that we need to do for to make the outflow of channels work better in these patients. But if you actually look at this diagram where if you see from this orange di picture to this to this, from, from ST to Schwalbe lane, it's like around 500 microns. The entire all these devices that I showed you kind of like clumps together in this 500 microns. You have to be extremely precise if you want to have a predictable outcome. If you are doing a surgery, say if you are doing a trabecular bypass stenting, you need to focus on going into the shams canal and placing that device exactly in the shams canal to have the right outcome. But unfortunately, if you look at the safety and efficacy, it has become more safer. But unfortunately, it's the efficacy is kind of like compromised, basically because we don't know where exactly the resistance is. And also we don't know whether the procedures that we are doing is doing the exact thing. Like if you are trying to place the device in the sham scanner, we are not accurately sure or that we are placing it in the shams canal. So that is the problem. And also all this angle based surgeries, which depends on opening the shams canal and the other roots is dependent on the epistle of venous pressure. So in severe glaucoma where the pressures have to come down in almost like less than 8 to 10, something like that. It's very hard for us to like go to that point. So in our updates on glaucoma therapy, this is where I want to like go and touch base on. Probably we know the mix in the sci region. A any mix that's placed in the sci region doesn't conform to the limitation of being. You are limited by the eral venous pressure. But you have to understand this surgery that's creating a psychosis cleft was like actually was done in 19 hundreds. Previously, it was tried, but basically because it causes fibrosis, it didn't come into picture. So it has other advantages, especially when you are considering s coral space, the supra space itself has a negative pressure gradient. So it is like around four millimeters less than the anterior chamber. So that any fluid in the anterior chamber just gets sucked in into the supra space. The interstitium of the ciliary body is kind of like a sponge. It absorbs the aqueous and then pushes into the supra and then it goes into the supra coral space. So the actual dimension, it's like if you look at the trabecular mesh work, if you're taking a kelly punch and just punching one or two, and then when you compare it to the surface area, it's almost like 100 and 60 times more area where the fluid can drain out and more volume it can accommodate. And we also have evidence from pro evidence before that prostate lining analogs, which depends on the outflow system with the U sterile outflow is one of the most effective therapies that we have currently available. So based on this, so you know, we need some device or some procedure in the superciliary space where it is not blab dependent because blob is like a ticking time bomb, anything can go wrong, it might not work. You need to keep doing some work to keep it working. And we also know it has an hypertensive potential. There is compared to traditional filtering surgery it might have, but like it's not proven with any ran randomized control trial that it might be much more safer. But the other major point is there is no blood. So the surface of the eye is far more comfortable. The quality of life for the patients is better. Dave is going to touch base on that. So based on this in 2016 CIA was introduced by the FDA. So I'm going to uh show you a case that I did in 2016, I had a uh opportunity to treat on a patient. 80 year old I CD 10 classification, moderate glaucoma pressures of like around 22 in uh two medications. I went ahead and did a ac ipass placed the IPASS in both eyes, took out the cataract and you can see the ipass was placed exactly where it needs to be. There were two rings, the one of the rings has to be at this little spur and then it uh it should not be pro protruding into the ante chamber. And if you see the other pictures like here, I, I most of the uh surgeries that I do, I take some pictures. This is the transverse c towards the left side to show where exactly the rings are. And then the sci space where the fluid is collected. But if you notice any, if you make a clap, if a cyclo iss is clap, even if it's one clock hour, the fluid goes 360 degrees everywhere you can see fluid are off. So unfortunately, what happened? This is the uh email that I got it from FDA 2018, it was withdrawn. So the device that we are thinking that we are looking as a possible potential to be used in the future. We tried it, we had to, we tried C I pass and then they withdrew because of endothelial cell. Last. This is my patient. After 2017, the patient came back last week, two weeks back, the patient came and I took the endothelial cell count and compared from the pre op to the post op. And as you can see, there's not much of changes according to FDA, the endothelial cell loss should be more than 30% to say that this is not good for our patients. But remember any procedure, any make some scan are based any kind of device that you do. If it's done accurately, you won't see that kind of side effect, but it will also have the best benefit. That's what like I'm trying to reach. I, I, so we learned quite a bit from CIA, what's the problems? It should not protrude, we needed something which is much more softer, which can avoid endothelial cell loss and also prevent fibrosis. And currently, there are three devices being evaluated from the FDA. The one of the device that probably you might be seeing in next few years, 2 to 3 years is mini jack. So this is a uh a device that's been like approved in 2017 and they got to see mark. And this is basically a medical grade silicon where they used pores, they create pores so that there is a fluid flow unidirectional from the chamber into the proce space. It's almost like five millimeters in length. It's like around one millimeter wide and then around 0.6 millimeters like around uh in the eye. So it can be used as a stand alone. And so there's quite a bit of data available over that. And you can see this is these are some trials that's been done. Star one star two star three, they had like around 66 patients and almost 77%. They looked into almost three or four years and they looked at the efficacy, the pressure drop from around like 23 to like around 15, it's almost like 35% per pressure drop. And the most important towards your right side, you will see medication free patients. We forget when we are like thinking of just reducing the intraocular pressure, we also have to think how many of these patients can go off medication and can they be stable? This is one of the very important part, medication associated with glaucoma treatment can cause a lot of problems. And so these are the other uh trials that's been conducted and they have little more than 3 to 5 years of data. And most important point is to compare the endothelial cell loss. And what we notice compared to other devices like the zen pressure flow, even the Trabeculectomy, it's like around 6 to 9% which is almost the same. What is the difference? The difference is the material itself instead of having a tube where the fluid drains continuously and it can't suck these cells around this device, which has a like a micro pores can help prevent the loss of endothelial cell in the long run. The other thing is it can also prevent fibrosis because it's, it's kind of like bio integrates with the eye. So like it's, it's better to like use a device which can cause less fibrosis because in our glaucoma surgery, say for trap or any surgery that we do for trap. I mean glaucoma fibrosis is one of the biggest problems that we face. So having said that where does it fit in? Because when CIA was introduced, they gave it to cataract surgeons. So now they are thinking probably as a stand alone from moderate to severe where you want to avoid blood based surgeries, uh where you want to have less complications or keep uh the trabecular mesh for later, probably you can try something like ab internal like this. But still now, you know, there's a lot of studies being going on FDA is trying to get around 350 patients safety data for 3 to 5 years, looking at the endothelial cell laws and also to prevent fibrosis. So I think probably if you are thinking of an update in glaucoma therapies, we have a lot of mix that's already there for a little more than 15 years with data, variable data, especially saying it's much more safer but efficacy wise like we always compare with Trabeculectomy, which is yeah, with, with nothing can bring down the pressures to single digits. So this can be comparable to Trabeculectomy because it's not confined to limitations of eral venous pressure. And also the main advantage is the surface there. You don't have a blab and you don't have, you don't have to worry about long term and doth mitis and other problems related to blood. So this is some potential and currently we are doing a lot of studies on it. Probably you might see in your practice in the next few years. CPAs might come in a different way. Thank you. Thank you, sir. Thank you so much. Next, I will be presenting um about when MS is uh not enough. So as Cyril mentioned, minimally invasive glaucoma surgery has many advantages. They're less invasive, uh potentially lower risk profile and many patients have a faster visual recovery. I want to point out a few scenarios when *** may not be appropriate. However, they may be less effective for a shorter period of time and nicks may not treat the specific glaucoma diagnosis at hand. In addition, in patients with advanced disease makes may not um lower the pressure adequately across the male enterprise. Our glaucoma subspecialists offer many mix currently including selected laser trabeculoplasty, EENT, Kook hydrous kalop, Plasty Zen. And in the past, the serial mentioned Trebec Home and Cath. Today, I want to point out a few scenarios when mixed may not be appropriate. For example, I saw a 40 year old woman who was referred with elevated intra pressure after having a selective laser trabeculoplasty in the right eye. Unfortunately, after the selective laser trabeculoplasty, she had a dramatic rise in her in her intraocular pressure and on exam on goos copy, she was noted to have peripheral anterior sneaky and many iris nodules in the periphery. She had a diagnosis called Ice or Coogan Ree syndrome um which was not amendable to an SLT. Fortunately, she went on to have a bear belt and did very well. So selective laser trabeculoplasty, which is a very common mix that many of us use is appropriate in patients with opening of glaucoma, secondary opening of glaucoma such as exfoliation and pigmentary glaucoma. And we really use it for any stage of the glaucoma including as an initial therapy. SLT is also very effective for patients with steroid induced glaucoma. I tend to avoid SLT. However, in patients with neovascular glaucoma ice as in the example that I provided in my patient with Kogan Reefs syndrome, inflammatory glaucomas in patients after trauma, patients with a fake glaucoma and patients with Anglos glaucoma. So I wanna encourage everyone to treat the specific diagnosis and think about whether N is appropriate. For example, this is a second case of a 58 year old woman who was referred for elevated pressure as a 27 in the right eye and 40 in the left eye and maximal medications topically. Of note, she had a history of high myopia in both eyes. You can see on these slip lamp photos that she had a peripheral eid and there are peripheral ey in both eyes. This patient did have cupping in her left eye as well as retinal nerve fiber layer thinning in the left eye. Of note, her specular microscopy revealed a normal endothelial cell count as well as normal endothelial morphology. She did have a mild glaucoma uh glaucoma visual field deficit in the left eye and so upon presentation, I thought was this patient a mixed candidate. But first why did she have a peripheral iridotomy in both eyes? The answer um was really in a test called ultrasound biomicroscopy. I obtained this after I looked at her angles on colonoscopy and her angles were open and because it wasn't clear why she had these performed and she was a high my open and really should have uh open angles. It was noted that she had a FAK IOL which wasn't actually evident on her slit lamp exam due to poor dilation. So she had her natural lens as well as a FIC IOL with elevated pressures that were uncontrolled on Maxwell medications. As we know, there's many mechanisms um for glaucoma in patients with fake IOL. In our patient, the mechanism was U Vitis glaucoma hyphema syndrome. The FIOL was rubbing against the posterior pigmented epithelium of the iris, releasing pigment and causing inflammation and elevated pressures which were uncontrolled. Th eye wells may also uh result in angle closure, inflammation, pigmentary glaucoma or steroid induced glaucoma. Since many of these patients have chronic inflammation, necessitating steroid use chronically. So, in this patient, um I offered cataract extraction, I removed the FIC IOL and also placed an eye stent at the same time in both eyes. And fortunately, when the mechanism of the glaucoma was addressed, she had 2020 vision and normal pressures without glaucoma medications. So I encourage you to treat the mechanism of glaucoma and sometimes N does not allow us to do that. Another example when mixed was not quite enough is the 63 year old woman who has open angle glaucoma. And I did place a Zen in this patient. Unfortunately, despite lowering the pressure from the mid twenties to the teens, she continued to progress by visual fields after Zen needling, which was unsuccessful, I decided to remove the zen and perform a tuberculum with mitoMYcin C which fortunately was successful in lowering her pressure into the low teens and her glaucoma stabilized. Similarly, I saw an 85 year old woman with severe opening of glaucoma who had pressures of 33 and 35 on presentation. She was on five topical medications and her visual field um revealed severe glaucoma nose, visual field loss. So in this patient, really performing migs would only delay definitive treatment and she did well with Trabeculectomy in both eyes. Finally, I saw Sturge Weber uh patient who was a child, 14 year old international patient and she had received a bear belt locally. Unfortunately, upon presentation, it was noted that her bear belt tube was anteriorly positioned and she had decreasing endothelial cell counts with an anterior located tube in the anterior chamber. The pressure was also uncontrolled. You can see on the foot lamp photo that her tube was anteriorly displaced and this is a poor uh photo of her uh optic nerve photo of her optic disappearance, but she was quite cuffed in the involved eye. And this is specular microscopy which demonstrated um abnormal morphology of the cells as well as a decreased endothelial cell count in the involved left eye. As we know, there's a high bleeding risk with migs and Sturge Weber patients. And I also wanted to avoid um repeat general anesthesia in a child. So I went to a more definitive solution and I pursued psycho photo coagulation as well as placing the tube in the sulcus to protect the cornea and hopefully delay or even avoid a corneal graft on the road. So in summary, the treatment for glaucoma should be based on the specific diagnosis and at times, nicks may not be appropriate or um or address the specific diagnosis, goos copy and ultrasound biomicroscopy may be key to diagnosis and surgical planning ns at times, however, can be combined with other procedures for better intraocular pressure lowering in cases of advanced glaucoma. Consider non mixed interventions such as trabeculectomy and glaucoma drainage devices. Thank you. So next, I'm very happy to introduce Doctor Gavin Roddy. Doctor Roddy is an ophthalmologist who performs cataract and glaucoma surgery at Mayo Clinic, Rochester. And today, Doctor Roddy is discussing sustained release drug delivery or glaucoma. Welcome, Doctor Roddy. Thank you, Doctor Conan. So as already has been discussed today, um different treatment algorithms for glaucoma have been laid out from drop therapy to laser intervention to migs to to incisional glaucoma surgery. Well, we still have many patients that progress in spite of these multiple therapeutic options. So, what is the state of, um, the current state of pharmacological treatment for glaucoma? Less than half of patients take all medications as prescribed. And this may be due to, uh, voluntary compliance issues such as managing the, um, various dosing regimens of, of the prescribed medications. Um, to in involuntary compliance issues in that up to a third of our patients for an atomic reasons aren't able to adequately instill medications from things like manual dexterity issues to cervical spine issues. Furthermore, fluctuation and pressure also contributes to glaucomas topic, neuropathy. Um as an independent predictor, our current approaches, um we might give a drop once a day up to four times a day with a single bols of medication. And so there is certainly a waning of drug dose. Furthermore, missed doses um contribute to fluctuation. And as well, none of our current pharmacological classes are able to really reduce di di diurnal curves which um contribute to fluctuation and progression. And finally, as will be discussed in the next talk in much greater detail. Over half of patients taking glaucoma medications have ocular surface disease. And so when defining successful drop installation as not touching the tip to the ocular surface instilling one drop, um and having the drop actually reach the ocular surface anywhere from one quarter to one third of patients are able to successfully instill a medication I, in my practice, if I have a patient that is unresponsive to two or more different classes in a row, I'll actually ask the patient to, to demonstrate installation of a medication and clinic. And it's, it's often a very sobering experience in that we assume when we write the Rx that, that the drug will actually reach the patient's circular surface. But um many times that is an assumption that it is not valid. And so I do believe that the medical management of glaucoma is headed toward this goal of sustained release of sustained IOP reduction with minimal therapeutic um treatments in order to improve compliance, reduce fluctuation and ultimately decrease progression, decrease decreased blindness and and perhaps decrease need for surgery. And so anatomically, there are some different options um that, that allow potentially a provider to um to provide a therapeutic that can be eluded in a sustained fashion. And so, um with, with contact lens approaches, um and most of these are still uh in experimental phases. But as as one might imagine, when a, when a topical drop is instilled, the contact time on the ocular surfaces is minimal, such that less than 5% of the drug is bailable. A contact lens approach. If a drug can be um placed and then slowly eluded, can increase contact time and the viability can by availability can increase 10 fold up to 50% problems. Um With contact lens delivery has been drug loading into the platform as well as ocular uh optical clarity. And then um of course, other issues inherent with contact lens use including infectious keratitis and dry eye. Uh punctual delivery systems have also been approached uh scientifically um and are not quite ready for prime time. But um one of the reasons for this is that in current systems, only low drug doses um can be can be um loaded into the punctal delivery systems making at least at the current time prostate analogs. But perhaps um the more useful medication class and like other uh punctual occlusion approaches, side effects could include discomfort and epiphora. Um perhaps a a quite hot topic moving forward are uh periocular delivery systems that might include subconscious tal approaches using various implant systems. Um microspheres or even liposomes as various delivery vehicles um to, to slowly release drug. And perhaps the really the two prototypes I'd like to discuss this in a little bit more detail. Uh that have more data behind them are approaches using the chin of Forni um with the man post ring in particular. And then um the intersegment approaches with the intra came injection of up to us. So we'll talk about those in a little bit more detail. So the Bama arose ring is available in different sizes from 24 to 29 millimeters in diameter. The cross sectional thickness is one millimeter and there is a polypropylene center support structure surrounded by a silicone um and uh ma matrix that is that is loaded with the matta prost and this can provide um IOP reduction for up to six months uh per application. And you can see down at the bottom um the the schematic of, of inserting this um such that when the device is fully inserted, um it's really only visible to a small degree at the medial canthus. Um One great advantage of, of this type of approach um is that it's preservative free. And so our patients that are limited in their topical um medication usage due to uh preservative allergies, um might uh might benefit greatly from a from an approach like this. There has been a phase two study uh completed and um the results are promising with IOP reduction, all of the metrics did not fully meet non inferiority compared to timol, but it was suspected that this may have been a sample size issue. And um another quite positive set of data from this round of experiments uh compared to prior approaches of drug looting devices in the Forex. Uh there was much greater retention rates of this device um in the 90% range. Um even um at six months, the Beatris implant also known as DeRita is FDA approved and um a single use 28 gauge applicator. Um You can see the size of the implant um in reference to a coin um is used to inject this um biodegradable implant into the anterior chamber typically on goos copy, these are visible in the um inferior angle and after injection, the the device does tend to swell before it, it slowly completely breaks down and it is biodegradable and does actually break down into co two and water phase three data has has been published and this did show non inferiority to timolol through week 12. Of, of particular note, an advantage um is that both periorbital side effects and ocular surface side effects that had been previously observed with topical prostaglandin analogs were not seen with this approach that places the implant directly into the anterior chamber. I should note. However, as was mentioned with CIA, you know, in this post IAS era, I think we were all, we were all quite concerned with cordon solos and in the mats implant group um that was seen um in a higher proportion compared to the topical timol group. Furthermore, being a pro analog, um higher rates of UBI itis was seen as well. And so sustained release approaches to peer reduction certainly have the potential to reduce disease progression by minimizing IOP fluctuation by improving patient compliance and the leading candidates to date. Um both elude a Prostaglandin analog using a scaffold one in the contra type of forex and one in the interior chamber. And I think these approaches are very promising whether, whether these, these two in particular are sort of proof of principle and there might be newer um approaches including types of scaffolds locations or even drug eluded. Um But certainly it's a very encouraging proof of principle um for our patients that we might be able to minimize disease progression by improving compliance and reducing fluctuation. Thank you. Thank you, Doctor Rody. I'm happy to present our last speaker this afternoon that is Doctor Dave Patel. Doctor Patel is an ophthalmologist and performs cataracts and glaucoma surgery as well as corneal transplants at Mayo Clinic in Phoenix, Arizona. Doctor Patel is discussing the management of ocular surface in glaucoma patients. Welcome, Doctor Patel. Thank you, Cheryl. Uh very much honored to be here with uh my colleagues and uh learning a little bit as we go along. Uh I'm the cleanup hitter as they call it. And I have the driest topic. Um but it is a passion of mine, you know, dealing with enter segment and certainly some of the, the uh renaissance and glaucoma that we're happy to be part of as Cyril has pointed out and just as sort of a background. Uh I finished training when uh Xalatan hit the market. So it's sort of long ways back. But uh we were so excited, we had a, a new class of drugs, uh highly potent, uh you know, in different mechanism of action. And I thought that was a game changer that everybody should be first line on Xalatan. Uh fast forward. Now, uh we're talking megs and uh we're seeing some of the detriment uh over the years, uh you know, decades, I would call it uh of the side effects that we weren't aware of in the beginning on the onset. So we'll talk a little bit about uh the issues that we're experiencing. So as we know that dry eyes uh aging process, uh we deal with it commonly with our non glaucoma patients. Uh but add to that, the concept of glaucoma, uh which is also an aging uh prevalence and you combine the two. So it's a sort of a bad mix, having dry eye and glaucoma. And in, in essence, there's a higher prevalence. But when you look at studies uh university, they show that the uh the glaucoma, the dry eye situation is exacerbated uh with glaucoma and glaucoma treatments. So, the conclusion is that the treatment of glaucoma induces or uh exa exacerbates dry disease. Um And looking at that, um some of the highlights of the pertinent studies show that there's uh increase in corneal staining, which is the uh risk factor and certainly a marker that we use in the clinical setting. But in addition to that, uh you know, identifying the, the causative agent, uh most notoriously the toxicity from preservatives and the topical medications that the patients are uh subjected to uh bak being the, the, the primary culprit uh which has led to the development and advancement of preservative free formulation. Uh the injectable medications that uh Gavin has mentioned uh and slow release formulations that are, you know, at least investigated. But I, you know, I wanna highlight some of the direct and indirect mechanisms that contribute to the unstable ocular tear film. Uh So let me just show you a cartoon here. Uh biochemistry of til. So we we kind of know uh the the uh three layers of triple layer sandwich, we call it uh we have the lipid layer, the aqueous and the mucin. Now, what glaucoma treatment, topical glaucoma treatment does is it affects all three layers, uh sometimes directly, but mostly I'll talk a little bit about the indirect mechanism. So the lipid layer uh predominantly from my bomia glands. Uh when you have prostaglandin use uh inflammatory disease leading to dysfunction, mimo gland uh deficiency. So you lose a lipid layer. Chronic bak has been shown to cause uh goblet cell density loss, uh which is the primary uh component to elicit the mucin layer. So you lose that and then aqueous layer is typically the detriment with chronic uh uh lacrimal uh gland dysfunction or inflammation within the lacrimal gland, which is a precursor to aqueous deficiency. So you've got sort of all three hits uh in one way or another with topical medications, we have some tools at our disposal quite commonly. And if, if you're not uh try or utilizing it, I highly recommend just looking at the surface of the eye and having the patient blink and you'll see tear breakup time. In addition, uh uh again, aging myself. Uh we had to carry a bottle of uh rose Bengal during our cornea fellowship and staining every cornea and these patients left the office just beat up red. So, uh that's all passed now. Uh Nice thing is that listening green is a very well tolerated uh stain. Uh It's uh you know, just I, I put a little anesthetic on this paper strip, dip it into the eye and uh it, it washes away pretty readily, but you do see enhanced congenital disease as well in addition to the corneal uh staining. So my preference is listening green. Uh of course, you if you have none and you can look at fluoresce staining that typically will be uh more evident in severe dry cases. Uh If it's mild, you may not pick up the staining with fluoresce. And then quite commonly, if you just watch the patient in consultation and look at their blink rate, you'll notice that some patients will have a poor blink rate and that's, you know, e exacerbating their underlying condition. Uh objectively, we do Shermer testing, which is quite uh time consuming. But uh that is an objective needs, especially for research protocol that we can analyze the Shermer testing and of course osmo osmolarity and MMM MP testing is also uh a very good objective means of isolating the severity or at least the stage of dryness in a patient, especially with glaucoma treatment. Uh One of the questionnaires that uh was popularized and, and still in use, but we've moved to the speed uh score is the ocular surface disease index OS D I as we call it, it looks at uh 12 questions. Uh They're div uh divided into three sections. One is based on symptoms, the other is vision and, and vision function. And the last is the environmental triggers causing their symptoms. So it's a subjective test. Patients are asked to fill out the questionnaire and they will give you a score rela and uh uh cla categorize them as a low dry eye or severe dry eye patient according to their test results, uh that is uh objective means or at least subjectively to uh identify if their treatment or progression is uh uh identified. Um I wanna focus the tail end of it uh to, to the mechanism of glaucoma which is still evolving in my mindset. But I've really grown into understanding a lot more in depth being a, a primary surgeon now for glaucoma. And even when my glaucoma surgeries failed, I question, you know, what is it, what, what can we do and what better and how can we get ahead of the game. But we have to kind of think about our, our uh understanding of glaucoma and dry eye and the the common variable is inflammation. So if you buy into the theory of inflammation leading to detriment of collector channels uh to regular meshwork dysfunction, uh obviously conjunctival uh uh fibrosis, uh that in itself can be exacerbating, the treatment itself can be exacerbating the disease. So, topical medications with their preservatives over a prolonged period. Again, it's not seen uh in the initial stages. But I think long term, you're talking about patients who have been on drugs 5, 1015, 20 years, uh even from the Pilocarpine and Timolol days, uh, we still see them in their eighties and nineties now. But the inflammatory effects of prostaglandin I think has, has accelerated or at least increased that propensity, uh which is resulting in a lot of dysfunction in the myeloma gland and leading to the evaporative dry eye state that we see on a clinical basis. But the poor teofil uh induces the optical disturbance and that leads obviously to patients having more uh difficulties with their day to day functioning and OS D I worsening. Um This is a very complicated uh tree, but I want, I want everybody to sort of see where I see it from and why I have a bias for intervention or surgery uh potentially moving up to the scale of first line uh as in the SYT study, if you will recall. So as you see at the, the top of the, the spiral, uh it's the initial stages where there's very little inflammation and patients are um um given uh trabecular mesh work and high IOP, you introduce IOP lowering agents. Well, that triggers an inflammatory response. VA K FX long term therapy. Now you got ocular surface disease which induces more inflammation. So, not only is the drug treatment, but now the reaction from the drug, the chronicity of use induces ocular surface disease, creating more inflammation. So now you've got this downward spiral. As you can see, uh this leads to progressive toxicity. TM changes and TM damages and inflammation further increases in the deeper tissues of the eye. Now you induce resistance to outflow, you, you're forced to add more medication to offset the rise in the pressure. Again, it feeds into the inflammatory cascade and creates more progression of glaucoma. And then you get uncontrolled IOP or very little, um, uh benefit with drugs and you've, you're forced to, at least at this point offer surgery. Now, as we've talked about migs and the traditional surgery as Cyril started the conversation with five fu and my mycin. Well, we still, you know, resort to that because unfortunately, that's the last resort. And the challenges are these patients who have been prolonged or treated for long periods of time with these, uh, topical medications do poorly with surgery versus a virgin eye, uh, initial surgery. So that's where my bifurcation is, is the, the failure rates that we're starting to see with some of the therapies, uh, in patients who have a, you know, prolonged use of topical medication. And in doing so, it really highlights some of the biomicroscopy. Uh a a very good uh illustration of uh inflammation uh as you can see in the stating there, there's a top left eight panel which has dendritic cells or fibrotic skulls within the cornea with topical treatment and chronicity. And you'll get the staining pattern. Similarly in the slide B where ventin is the identified uh agent uh seen in uh histologic tissues. And you see that in the cornea uh which is commonly seen uh in vivo. But you can also see it in, in histologic slides involving the trabecular meshwork, which is panel c where you get inflammation within the trabecular meshwork. Now, these are patients who are treated long term and you know, you can see these inflammatory markers lighting up in the beginning or at least uh uh drug therapy stages and it kind of leads to the spectrum. Um you know, we have the spectrum of glaucoma, early, mild, moderate and severe. Well, this is a spectrum of inflammation if you wanna call it and it's to overlap with the propensity of glaucoma and severity of disease. So you'll see on the top bottom left, you'll have uh microscopic or histologic inflammation. And these patients are asymptomatic, they're doing their drops, they're on target pressure. Their glaucoma is sort of uh on a plateau. We're not seeing any progress. Then you get the turbulence where the inflammation is uh beyond the scope of containment, you'll get mild symptoms, you'll get uh S the clinical signs of surface disease with corneal stating conjunctival staining. So now you're already behind the curve. That's what I think. I think that this, this reaction that we see in a clinical level is uh beyond uh our understanding because it's happening at the cellular level further on. Uh as this develops, patients will be more symptomatic, we initiate treatment. Uh of course, uh you know, multitudes, uh you know, a whole hour can be spent on management uh and treating dry eye disease uh with various modalities. But again, preservatives are gonna be involved. Artificial tears are preservers unless you're specifically doing preservation. So you may be enhancing this cascade and of course, as it develops and worsens and ages again, fighting against this because now these patients are 1020 years older, you get severity of disease. So now you've got a, a really inflamed eye and you have to entertain surgical treatments which obviously uh create more risk given that they've had chronic inflammation for prolonged years of, of use of topical treatment. So it kind of loops us back to what, what do we consider? How do we sort of evaluate managing a glaucoma patient who we already know are gonna, we're gonna create dry eye. And so my considerations and food for thought and, and I know we're doing a Q and A after this, but these are sort of possible scenarios where I would introduce the, I think uh overall acceptance at SLT before meds. Uh, they've had robust safety data. Uh, well, you know, efficacy data. And, uh, it's not uncommon that most patients are offered laser prior to meds. At least that's what I've been implementing. Uh, of course, there's a discussion with the patient and their, their risk tolerance, but I do think that laser therapy would be a, a very good first line treatment before drugs are introduced. Having said that, uh, when and if these things evolve, uh, do we use meds as a bridge to surgery? Say, well, ultimately, surgery might be the best option, uh especially in an early stage or virgin eye versus a eye that's had chronic treatment and it's progressive. Uh So that's a debate that I think in the glaucoma world it's ongoing, but that's certainly something to consider is un until we can get the patient to a safe place or surgical stage. Uh, meds could be used as a bridge with the ultimate end point of surgery. The nice thing is that the migs are demonstrating at least a relatively good duration. Uh Cheryl's pointed out some of the limitations even despite uh the excitement that we're having that they, they are always there are nothing's 100% of course, but are, are there options unique to the patient to the eyeball, to their disease state, to their, their stage in life uh that can uh alleviate the drop burden and the side effects in the in the uh uh issues that dry eyes brings along with it. Uh demonstrating that mix could be a therapeutic intervention early on. And I think lastly, and certainly something that we tend to do a lot more is, uh just like glaucoma is a very difficult uh I uh condition to explain or at least have patients. You know, you don't feel it but dry eyes, you feel people experience that and it's symptomatic. So they don't equate the severity of glaucoma with severity of dry eyes uh readily. But you have to partner with the patients to understand that their treatment may be exacerbating the dry eyes. And we need to focus on both arms of uh treatments to alleviate their day to day. Uh visual needs. Um importance of ocular health uh may be uh omega fatty acids, uh hot compresses, lid hygiene, uh topical steroids uh to quiet down uh inflammatory markers. Uh So those are I think, ongoing ideas and areas of investigation uh and to better manage some of the dry eyes that we're creating um using topical medication. So I leave that uh to the Q and A but I appreciate the time and uh thank you for your attention. Thank you very much, Doctor Patel. So at this time, we have um a few moments for questions and feel free to submit any questions that you may have. Um Maybe I'll ask doctor um Duray Raj about uh sidal space devices. We certainly have many comprehensive ophthalmologists who are interested in performing megs and maybe considering different devices. How would you advise them um about sidal devices? Um Do you think that should be in the skill set of comprehensive ophthalmologists? You have um special words of wisdom or advice or comprehensive ophthalmologist who may be considering these um sidal devices that are, that are soon to be on the market. Um That's a very good question. Uh Cheryl, you know, because everybody has a different way of learning things. Some people just like during the residency might have done a few cases here and there. And then once they come into practice, they can start doing their stuff on their own just because some industry is coming there. And then they're asking, let's do a new mix device and they will say let's do 10 devices and then uh go ahead and let's uh start doing it. People who stand on the podium and then they speak about their experience are extraordinary surgeons. But I'm an average surgeon. If you ask me a question regarding Super Coral device itself, we learned something from our previous experience with the CIA. When Cyprus was introduced, it was like graded for mild glaucoma along with cataract surgery. So what happened? People who used to do cataract surgery, we had no evidence of, you know, dealing with the angle or dealing, dealing with any problems related to the supra oral hemorrhage or fluid hyperten related problems they had no clue about it. It's not only just doing the surgery, it's most easy. Like doing a surgery is like most easy. But dealing with the complications, dealing with the, what it comes after having some problems is more important for us. This is where we need that support CIA. In a matter of like two years, people started putting so many and it started, they started noticing changes in the endothelial cells because most of them, they didn't get a proper training. They had some people have a different learning curve compared to other people who are already working in the angle base. People like some people who are working in the angle, who knows about the SRO space, who know, who knows how to deal with the clysis cleft and if you give it to them, they will handle it. So my point now is I would give it, I would give a training to someone who's comfortable with the angle based surgery and who knows how to deal with complicated lock em up. Like, you know, blood based, we do have sup coral hemorrhage or supor fluid. They should know how to deal with hypo. For me, believe me, it's easier to deal with higher pressures. I can deal with higher pressures. But hypo me, I'm kind of like I'm one step behind. So like I'm, I'm kind of, oh, what should I do? How should I deal with this? So that is what like I would recommend for a comprehensive surgeon who's thinking of starting a little bit of a longer, you know, learning curve might be needed. But this device might be a little more forgiving compared to CIA. But exact placement, the outcomes depends on the exact placements. The complications depends on the exact placement of the right an article place. So we need a little more annual day this time and giving it to the people who have a little bit of experience in angle based surgeries. That's what I would say. Instead of like opening up the market to mild, moderate everyone to do. Like I would give this device which is like a little more in my hands. I would say it's in my hands is a little more tricky. I need a little more experience doing this and of course, dealing with the I partner dealing with the Super Coral Pro problems, I should know how to deal with and then I will give it to them because ultimately, what matters is our patients, the what we recommend, what we promise our patients and my patient like you know who's undergoing a cataract. Yeah. So that's, that's what happens over time. If this procedure are not properly learned, you don't prop have proper support and see them over time. We might lose that opportunity to learn from what we didn't learn from CIA. That's what I would say. Thank you so much, Doctor Roti. You mentioned uh several alternatives to drops, many of our patients are on multiple drops. Um Do you know of any technologies coming that would introduce multiple agents? Um and uh intra camera um device or um conjunct device to deliver drugs. Yeah, they're in the experimental phases. Um But combination drop therapy folks have talked about maybe two or even three meds. Um I think that would be great for our patients. Um But you know, my guess is those are probably a couple of years down the line. Um For now, as I kind of alluded to most of the approaches have, have used single use, single agent uh using a Prostaglandin. But I think that would be, that would be wonderful moving forward. All right. Thank you so much, Doctor Patel. Um You mentioned that for many patients with dry eye, you would recommend starting uh with an SLT selective laser trabeculoplasty if a patient does not have adequate control with SLT, what is your algorithm for next steps? Well, it's a tough one. I, I think it's open. Uh it's a discussion with the patient but depending on their severity of disease, uh if they've got field loss, uh and we have a, a tight target that we need to hit. Uh I actually entertain uh the option of surgery, uh a mix based procedure if possible uh if they're fake it or pseudo fake. So there's a lot of variables. Uh So I can't umbrella the answer, but I do think that uh we are in Arizona so dry, environmentally is a bigger uh ordeal. But that's not to say it's not elsewhere, but II, I experienced a lot more of that here. And so I, I have to sort of weigh the option of topical treatment. Uh Fortunately, we have preservative free formulations. The process, the lands have been uh uh my first line uh minus SLT uh and to back on uh Gavin's Point, uh we use a compounding pharmacy to sort of integrate the agents into one bottle. So uh we have uh commonly patients who have uh uh surface disease and they're not, they have a drop burden that's excessive. So we try to minimize that by formulating or having the compounding pharmacy put the beta blocker, the ca I uh the alpha agonous all in one bottle and 11 drop in the morning, one drop at night. So it tends to, you know, just uh sort of dissipate some of the bak effects. So, you know, there, there little strategies there. Uh if we can optimize your dry eye, I think that's uh uh avenue to pursue uh maybe, you know, cyclosporin or stasis punctal plugs, uh better lit hygiene, uh more uh you know, surface lubrication to optimize their surface and then sort of uh challenge them with uh topical treatment if surgery is not on the table. But, you know, I, I think that's something that uh I, I actually you know, uh have an open dialogue with my colleagues and yourself. Like, where would you, where do you stand on this? It's, it's almost like a uh a variable that are walking the line because uh as serial is spread out that there are risks to everything. And it's just, do you want 1000 cuts, uh you know, uh over time and that's the way I feel about it is that the dry eye is not something that's uh we don't have a cure for dry eye. Uh but we have very good therapies for glaucoma and I think some of it unfortunately is surgical. Uh of course, that's a bias. Uh I'm a surgeon, so I, I have that lean uh and pat uh doctors who don't have that experience uh will tend to lean towards the conservative measures at least, uh depending on their setting and, and their practice. But yeah, I would optimize the surface challenge them with preservative free medications or combined medications to start. Uh and then sort of uh elevate after that. Wonderful. Thank you. Any final questions from our presenters? Ok. Well, on behalf of all the presenters and myself, thank you um for participating today with over 250,000 outpatient visits for eye care each year across all of our sites in Minnesota, Arizona and Florida Mayo Clinic. Welcomes patient referrals for rare serious and complex eye conditions to discuss a patient or learn more about referring a patient to Mayo clinic. Please contact our referring physician services at one of the numbers on your screen or by visiting Mayo clinic.org/medical dash professionals. Thank you again and have a great day.
