This interactive webinar will cover the basics of glaucoma and the clinical examination, including gonioscopy, visual fields, and optic nerve assessment. Real-time questions and answers will be taken from audience members.
Lecturer: Dr. Louis Cantor
Introduction to Glaucoma 09/23/2016 from Cybersight on Vimeo
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DR LOUIS CANTOR: Great. It seems like we’re good. I’ve got a couple messages back from some of you. Welcome. I appreciate the opportunity. I appreciate the support of Orbis. Dr. Neely and the entire Orbis team. To cover this introduction to glaucoma that we’re going to discuss for the next few minutes. I’m going to go rather fast, perhaps, through some of this information, as I do want to leave time to get to some of the questions that some of you submitted in advance, or that you might have during the conference, video conference here. So it’s a great pleasure, and welcome to all of you, wherever you are. Good morning, good day, or good evening. Let’s talk about glaucoma. This is a group of diseases that really have in common several things. But the most important factor in glaucoma is that it’s a characteristic form of optic neuropathy. For which visual field loss and elevated pressure are really just risk factors. We can classify glaucoma in a number of different ways, and there are a number of different schemes for doing that. I like to think of glaucoma functionally, if you will. And whether the angle is open or closed, and then if it’s open, where is the obstruction to outflow? Is it pretrabecular, trabecular, or post-trabecular? We’ll talk about some of that. And angle closure — is it an anterior pulling mechanism that’s causing the glaucoma? Is it a posterior pushing mechanism? And then we have the broad category of childhood and developmental glaucoma. This is a very busy slide, and I apologize for that, but this goes through in a very quick fashion some of these functional classifications of glaucoma, and what falls under it. So what would be a pretrabecular type of open-angle glaucoma? Well, it would be something like a fibrovascular membrane over the angle. Endothelialization over the angle. Fibrous ingrowth. Inflammatory debris is common in uveitic glaucoma, for example. Trabecular is our more typical open-angle glaucoma, whether it’s an early onset or juvenile, but it can also be blockage of the meshwork for a number of reasons. Steroid-induced glaucoma would fall into this. Post-trabecular is generally something that affects the canal, or more commonly the episcleral venous pressure. And there’s a number of things that can contribute to that. In angle closure glaucoma, an anterior pulling mechanism is contraction of membranes — would be a classic example. Posterior pushing is pupillary block, or even a non-pupillary block angle closure, such as we might see when there’s ciliary body rotation, anteriorly, and plateau iris. And then there’s the whole category of developmental. So I encourage you to think of glaucoma, and when you see a glaucoma patient, think of the mechanism that’s contributing in that patient. We also know that there’s a number of genetic predispositions and factors and genes that have been associated with glaucoma. And I’m not gonna go through this in any significant detail. But leave it to say that there are now dozens and dozens of genes that have been found associated with glaucoma and various forms of glaucoma. All of these genes put together, however, still only account for a small percentage of the entire glaucoma population. So we are beginning to open the door on the genetic influences for glaucoma, but we have a long way to go to really understand the causes of glaucoma, genetically. And it also appears that there may be multiple genes involved in glaucoma in any one individual, or in conveying the severity, susceptibility, the risk of progression, even, for glaucoma, in a given individual. So let’s talk about primary open-angle glaucoma. And in primary open-angle glaucoma, I include the entire spectrum, beginning with normal pressure glaucoma — if you will, low tension glaucoma — through juvenile onset, if you will, relatively early onset, but not congenital, through the more typical — what we see — adult open-angle glaucoma. Again, it’s that characteristic optic neuropathy which is most typical. Elevated intraocular pressure is but a risk factor. And the anterior chamber angle appears open, of course, and we don’t see anything that might contribute to a secondary elevation of the intraocular pressure. In the US and Western world, this is our most common form of glaucoma. In other areas of the world, angle closure may be. And also in other areas of world and reasons, normal pressure end of the spectrum of primary open-angle glaucoma may be more common than the higher pressure end of the spectrum. It does account for a lot of disability. The incidence certainly increases with age. It’s a major cause of blindness in this country and others. We know that in different populations, such as African-Americans, it is more frequent, more refractory, results in damage at earlier ages, and higher rates of blindness. And there can be a lot of discussion — there’s a lot of literature about why some of this is, including access to health care and so forth. We know that elevated intraocular pressure is a risk factor. But we also know that the majority of individuals who have elevated intraocular pressure do not develop glaucoma. And conversely, we know that a number of — a significant percentage of individuals, again, depending upon the population, who develop open-angle glaucoma never have elevated pressure or have relatively low pressures. As we age, it’s more common. Again, the issues with African-American, Hispanic, and other populations are more at risk. And family history is a significant risk factor. There’s about a five-fold increased risk with first-degree relatives. We note these other possible factors that might contribute to glaucoma. Myopia, diabetes, we talked about cardiovascular disease. A number of risk factors have been identified around vascular issues. Migraine, vasospasm, systemic hypertension, hypotension, perfusion pressure. But intraocular pressure is the one risk factor that we can most easily and obviously — that we direct our treatment at. As that is the most easily modifiable risk factor and the one that we know best today. Even if the pressure is not elevated to start with. We know this disease has an insidious onset. Slowly progressive, painless, and often asymptomatic, which is one of the problems. That’s why it’s often called the sneak thief of sight. Until central vision is really affected. It is bilateral, but can be very asymmetric. We also know that the risk of developing glaucoma — and a number of questions that were submitted beforehand were directed at the normal pressure glaucoma spectrum — and we know that there’s a certain risk, if the pressure’s high, and if we use 21 as an arbitrary cutoff — and that is very arbitrary — that a small percentage of those individuals per year will develop glaucoma. And that there’s a certain amount of risk for ocular hypertension. But, again, depending upon the studies we look at, 20%, 30% or more of glaucoma patients will not have consistently elevated pressure. However, we also know that lowering pressure in that situation is still of benefit for the majority of those individuals. When we discuss aqueous humor outflow, this is the classic diagram — or one similar to it — that help us understand what we are looking at when we talk about glaucoma. And also has important implications for how we look at our therapeutic options, which we’re not gonna spend a lot of time on today. Today we’re focusing more on the diagnosis and clinical examination. But we know that aqueous is produced in the ciliary body. Some of it never makes it out of the ciliary body, or there’s backflow through the tissue. The majority of it will enter the posterior chamber behind the iris. And then into the anterior chamber. And then exit the eye through the trabecular meshwork, or what we call the uveal-scleral outflow pathway. And there is resistance at various portions of that outflow pathway, primarily at the trabecular meshwork. That’s our most pressure-sensitive area to the aqueous outflow. We know that there’s a skew — and this is from the American population — this also can differ greatly in other populations. But the most important factor from this diagram is that individuals who have some elevated pressure and glaucomatous visual field loss — we can see that the visual field loss across the spectrum here can occur at any pressure. Even really low pressures. Very high pressures. The most common area where we see patients who have glaucomatous visual field loss is not at markedly elevated pressures in our population, but more in the mid-20s. Of course, in different populations, this can be quite different. When we measure pressure, we want to make sure that we’re doing so accurately. The most common way is with applanation tonometry, but there are a number of other methodologies that have been validated. But also which have factors that can cause artifact. The most common reason for seeing artifact or incorrect pressure measurements with applanation tonometry is just simply how much fluorescein is in the eye, and not having the correct alignment, so that the mires don’t have too much or too little fluorescein, so that we overestimate or underestimate the pressure. We call this the Goldilocks rule, where you want it just right. Gonioscopy is critical in glaucoma, and all patients with glaucoma should have gonioscopy performed, and even repeated periodically. Even open-angle glaucoma patients can develop angle closure over time from lens changes or other conditions that can predispose to angle closure. There have been studies done that, even in the US, have suggested that in a Medicare population, that maybe even up to half of patients who undergo glaucoma surgery have never had — at least on billing records — a gonioscopy performed. So this is probably something we don’t do enough. We don’t have great data on it. But it is critically important towards understanding glaucoma and getting back to that mechanism and understanding the glaucoma mechanism well. What are we trying to do in gonioscopy? Well, obviously we’re trying to understand what is the angle anatomy in an individual patient. And this is a schematic, of course, of — in detail, of the various layers of the angle. We’re not gonna see the deep layers on gonioscopy. But we will see the anterior chamber angle, look for the scleral spur, which is an important landmark, ciliary body, trabecular meshwork, and Schwalbe’s line is also a common landmark. But it’s something you have to do, you have to practice, and you have to get very comfortable with. I like to use the Spaeth gonioscopic grading system. I think it’s important to have systems so that you do these examinations in glaucoma patients in a systematic way, in a reproducible way. And I find this a very useful system. You may have your own system, which is fine. As long as you do it the same way every time. Obviously the goal is to distinguish what’s abnormal from what’s normal. Because normal covers a broad, broad range. We can certainly do simple tests, short of gonioscopy, such as shining a penlight across the anterior chamber, to assess where the shadow is and how shallow the angle is, but that’s obviously — while quick, it’s not very sensitive, and it doesn’t give you a lot of information or anything you can follow very easily. There are other systems, looking at the Van Herick system, where you look at the corneal light reflex through the cornea and compare it to the chamber depth. If the peripheral anterior chamber, which is PAC, is greater than the corneal thickness, that can be called grade 4, and then equal to half, quarter, less than a quarter would be progressively more shallow. And here’s an example of that. This is a Van Herick estimation of the peripheral anterior chamber depth. And we can see the light reflex through the cornea here, and then we see the gap, which is the anterior chamber depth, before the light hits the iris. And maybe we’re at certainly half or more, close to a full light reflex thickness in the anterior chamber. Whereas in this situation, we’re looking at, we see the light reflex in the cornea, but no gap. So this anterior chamber is flat in the periphery. So Spaeth proposed a system, now going back many years, that really looks at different aspects of the anterior chamber angle. And the three most important aspects are where does the iris insert, where does it actually contact and insert the anterior lining of the eye, what is the angular approach that the iris overall takes to that angle, and what does the peripheral iris specifically look like? And there’s also other things that we can note — probably most importantly would be pigmentation, PAS, and so forth. So iris insertion. So we grade the iris insertion by A, B, C, D, and E. A is anterior, where all you see is Schwalbe’s line, B is behind Schwalbe’s, C is scleral spur, D is where you’re seeing some ciliary body, and E, where you’re seeing a lot of ciliary body. And this is a schematic, showing the various levels where the iris can insert, both normally and pathologically. And we’ll look at some examples in a second here. Obviously A and B angles, where the iris insertion is anterior to Schwalbe’s line or into meshwork, are abnormal. That would always be an abnormal circumstance. C, D, and E angles can be normal or abnormal, depending on where you started at. And just here again — here are some schematic examples of what an A, B, C, D, or E iris insertion might look like. Now, the angular approach is typically what we think of when we just look in the anterior chamber and we see — what does that angle look like? And it’s defined by doing two tangents. One through the meshwork and one through the middle of the iris, the middle third of the iris. So it’s just drawing that angle. And we do this in our head all the time. It’s pretty subjective. It’s not based on what you actually see, but what you think it is. But I think we can get pretty accurate with that. Is this a 10-degree chamber that’s very shallow? Or is it more normal in the 30, 40-degree? Or is it really deep? Like a 50-degree angular approach on gonioscopy? And then the last part of the system is really understanding the peripheral iris configuration. Is it flat? That would be the normal — flat, or with a very mildly anterior bowing, curve to it, that’s typical. Is it concave or bowing posteriorly, such as we might see in pigmentary? Is it bowed anteriorly, like we might see with pupillary block? Or is it just bowed in the periphery, with that peripheral iris hump, but then fairly flat after that, as would be typical in plateau iris? You can miss these various nuances of the angle and misdiagnose someone, particularly with angle closure. You can miss and probably very frequently miss this plateau iris. It’s probably our most commonly missed diagnosis in glaucoma today that I see. So here would be sort of — this is an ultrasonic view, an anterior segment ultrasound — that just shows the normal mild anterior bowing of the iris. We can also do indentation gonioscopy as part of the system, because the angle, while it may look like the iris is inserting anteriorly, it may not be scarred in. There may not be synechiae where it’s permanently stuck there. It may just be optically closed. So what we do with that is the optical insertion, where what it looks like without depression — we put in parentheses. Because that’s not the real insertion. It’s just what it looks like. The actual would be put afterwards. So I’ll show you some examples of that. So here’s an angle where it first looked completely closed. And then we push on it, do indentation gonioscopy, and we see part of it stays closed as A, and part of it we start to see the meshwork. That’s B. So we can distinguish what areas of the angle are open or closed. And in this case, where it’s B, we would put the A, if we’re writing this down in parentheses, but the real insertion is B. This is another gonioscopic picture of similar findings, where the angle looked completely closed, and looked to be A, all the way around, but when we pushed and indented and pushed the peripheral iris back, part of the angle opens up. And here’s another example, similarly, where the angle was completely closed. We apply some indentation gonioscopy technique, and it opens up. And then pigmentation can be graded, and the amount of iris bowing can be graded. Here’s just a couple more ultrasound biomicroscopy examples. If you look at this angle, if you just look at the anterior chamber portion of it, it looks rather deep, centrally, away from the angle. But as you get closer to the angle, it looks like it’s not so deep, and that maybe the angle is sort of hidden in that recess. So if you were looking at this with gonioscopy, you wouldn’t see any of the angle detailed. This is actually a case of plateau iris. A peripheral iridectomy was performed, and the angle didn’t really change. It stayed very narrow. But if we do peripheral iridoplasty in an eye such as this, and thin out the iris peripherally and get rid of that hump that’s out there, that’s caused by the ciliary body behind it being anteriorly rotated and forward, we can then open up the angle. So appreciating that plateau iris configuration really is important towards doing the proper treatment and considering iridoplasty. This is just a gonioscopic view of an eye that has pigmentary glaucoma. The angle is wide open, and we see that dense pigment band in the trabecular meshwork. This is an eye that’s had trauma, with angle recession. We see ciliary body, and then there’s even more behind it. So there’s a deep ciliary body insertion. Switching gears now to the optic nerve. As we said, what really defines glaucoma — and this ties into our diagnosis and decision-making processes more than anything else, or should — you know, I was asked to give a talk once at our Fellows Society, for the Spaeth Fellows Society, and I decided to have the title of: If glaucoma is an optic neuropathy, why is the optic nerve so unimportant? Because we tend to ignore the optic nerve a lot, and look and rely more on our visual fields or just the pressure, when really what defines glaucoma is the optic nerve, and we need to look at it, examine it, and understand it. And we know that glaucoma is this progressive damage to retinal ganglion cells and their axons. And it’s that progression. We can have a lot of eyes that we might consider having funny-looking nerves, or they might look suspicious for glaucoma, and we can’t really tell from their visual field, and maybe their pressure is okay, so they’re a glaucoma suspect. How do we determine if that’s a patient that we should be treating? The most important way is something will change over time. It will progress. What comes first? Structural damage or functional damage? There’s a lot of debate over this in the literature, and it’s really limited by what our tools are for measuring. We have… We know that we can detect retinal nerve fiber layer damage even before typical white on white visual field defects, by certain psychophysical tests such as frequency doubling perimetry or short wavelength automated perimetry, SWAP the blue-yellow perimetry, but we don’t use those tests commonly, because there are a lot of false positives. But we think that functional change should happen first. The problem is our tests are not very sensitive in early disease, so what we often rely on and what’s important is looking for the optic nerve changes. Here is an eye that has glaucoma, in a patient, and this was actually significant cupping in that patient, with a normal visual field over time. But that same patient looked abnormal on SWAP and FDT. Again, the problem with these tests is they’re not universally available, and you will get a lot of false positive tests, or little ditzels on these fields, quite frequently. Because they’re not easy for patients to perform well on. So also, by the time we detect visual field loss with our standard perimetry, such as a Humphrey visual field or whatever white on white-type visual field you use, by that time, the disease is pretty advanced. A third to half of the optic nerve may be gone or more. So we do have to be looking at the nerve, I believe, particularly in early disease, to ensure that our patients are not progressing, and are being treated adequately. And this is often how we schematically sort of look at the various parameters in structure and function. But this is highly dependent on what tools we have to measure the optic nerve, the retinal nerve fiber layer, the visual field. And as our technology improves, these curves shift over time, and as they should. A lot of patients don’t get their optic nerves looked at. This was a study that was done in the US, looking at nearly 400 patients, and about half of them — half of these patients with glaucoma did not have documentation of their optic nerve findings on their initial exam. So what do we look at? We’re gonna march through the cardinal signs of glaucomatous optic neuropathy. First of all, a disc evaluation cannot be — a good proper thorough disc evaluation is incredibly important, and it can be the most sensitive and specific way we have for diagnosing glaucoma. Again, our functional testing is not great. And pressures do not define who has glaucoma either. And we need to document it. Either photographically or imaging if we can, or if not, draw it and be a very keen observer. There are a lot of generalized signs. Just a large cup. Even some asymmetry of the cup may not be very diagnostic. But progressive enlargement is. We look at all these different things — and we’re gonna march through some of these focal signs here. And there’s also less specific signs relating to the lamina, the blood vessels, peripapillary crescents, and so forth. Our main goal here is to understand also the nerve fiber layer, which we look at with our imaging technologies that are evolving today, such as OCT. So what are the rules? Number one, estimate the optic disc size. It’s hard to place the cupping in context unless you know the disc size. It would be like measuring pressure and not having any idea what the corneal thickness is, for example, which we didn’t talk about, but we know that in eyes with very thin corneas, we may be underestimating the pressure, and very thick corneas, overestimating the pressure. The same sort of context applies to the nerve. If you’ve got a very small nerve, for example, as we’ll look at, a moderate-sized cup could be very significant. You know, here’s an eye with a small cup. Where you have to find where the rim is in the scleral canal. And then estimate the vertical and horizontal disc diameter. The 5-degree spot — just on our standard direct ophthalmoscope — that little 5-degree small aperture spot, for most eyes, that should be approximately the size of the optic disc. That’s one very simple way to just estimate. If the nerve extends well beyond that, then we have a large nerve. If the spot is well larger than the optic nerve, then we know we have a fairly small optic nerve. We can also look at it and measure it with a lens, with an indirect. But depending upon the magnification of the lens or what lens we use, we might have to apply different correction factors. The average vertical diameter is about 1.8 millimeters, and horizontally about 1.7 millimeters. As I mentioned, the cup sizes can vary quite a bit. These are all eyes that do not have glaucoma. But they have different sized optic nerves, and they’re from very different-looking cups. We consider small generally anything under 1.5, and large generally anything over 2.2 in vertical diameter. I said small discs may have small cups. Is this a normal optic nerve? It actually isn’t. There is thinning of that superior rim. And this is an eye from a patient who had glaucoma. Next we want to look at the rim itself. And the rule that we use is the ISNT rule. And the ISNT rule is the distance between the disc border and where the edge of the cup is, or where the blood vessel’s been can often give us an idea of where that is. And the ISNT rule merely states that the normal retinal nerve fiber layer, in the vast majority of patients — I won’t say there aren’t some exceptions normally — but the inferior rim is thicker than the superior, which is thicker than the nasal, which is — last, the temporal. So it should go in that order. So ISNT. Just remember the ISNT rule. Here’s an eye where the inferior rim is obviously very thin and notched out. It doesn’t adhere to the ISNT rule. We have to be careful of pallor and that we don’t misinterpret where the disc margins are. This is an optic nerve with pallor that’s actually a small cup. But it’s easy to misinterpret these as having some rim thinning somewhere, if we’re not careful. And we have to think about other things, other than glaucoma. Next, it’s easy just on clinical examination to get an estimate of the retinal nerve fiber layer and what it looks like, just by looking at it. We know the retinal nerve fiber layer has a definite pattern to it and has a certain light reflex to it, when we examine it clinically. Here’s an example of two different patients. The one on the left obviously is a normal retinal nerve fiber layer. Deep cup. It even looks like there’s (inaudible) glaucoma, but look at that very robust light reflex off the retinal nerve fiber layer. And when we compare that to the other example, where the cupping may not be in general that different — it looks qualitatively different — but there’s really no light reflex, and there’s a lot of thinning of the retinal nerve fiber layer. And we can get a sense of that just from our clinical exam. Again, other examples of that. And where we can even see localized areas of loss of retinal nerve fiber layer or striations and gaps in the nerve fiber layer. And this can be appreciated clinically. And many of our eyes with glaucoma also have peripapillary atrophy. And there’s two zones here. There’s what’s typically called the alpha and beta zone, and it’s that beta zone, which is more adjacent to the optic nerve, where there’s atrophy of the RPE and choriocapillaris, that is more commonly associated with glaucoma. This is not a typical myopic crescent. And this can progress over time, and it often is greatest in the area of greatest rim thinning in the optic nerve. So you can get a hint as to whether or not this may be a glaucomatous optic nerve by looking for this peripapillary atrophy. Disc hemorrhages. An important sign in glaucoma. Many patients don’t develop disc hemorrhages, but when they do, it is a red flag. And it can be a tipoff. And can be very easily overlooked. And these are various examples of photographs. There are small little disc hemorrhages. Here’s normal nerves. But they can be hidden, and easily overlooked. There’s a lot of interest and talk about imaging in glaucoma, and certainly our imaging technology has progressed tremendously, and is very, very beneficial today. We have a number of technologies I’m just showing here. What I would say about imaging technology — if you have it, it’s great. It’s a useful adjunct. And I would encourage you to use it. But you don’t have to have it. And I wouldn’t rely on it totally. I still like to obtain a photographic documentation on every patient that I can, because that’s durable. A lot of our imaging technologies are like computers. They will change over time. And then our new scan 5 years from now may be not able to be compared to our old scan. But a picture can always be compared. There’s areas where imaging is especially helpful. And that’s in some of these glaucoma suspects, such as this patient. Where there was significant asymmetry in the cupping that was very suspicious on this Heidelberg exam, but when we looked at it, the nerves are very different sizes. And the rim area is actually the same. So the classification here is normal. So it can really help sort out some of these funny-looking nerves in glaucoma suspects to see who’s normal and who’s not. I’m not gonna go through a lot of the basics of OCT. It uses an interferometer and low coherence light to create an image, and there’s a lot of technology behind this, and you can all look this up and read this elsewhere. But it can be very useful clinically, and it does correlate well with what we see. Here’s an eye where there’s glaucoma. Worse in the right eye, obviously, than in the left eye, with essentially an inferior altitudinal defect in that left eye. And there’s good correlations, with loss of the retinal nerve fiber layer, especially superiorly, that correlates well — and with a lot of our imaging technologies, one of the keys is to make sure that we have correlations between our discs and our field imaging and assessment. And that’s one of the keys in glaucoma diagnosis also. It’s difficult to rely on any one technology for making a diagnosis of glaucoma, whether that’s pressure, field, or optic nerve assessment, and it’s also true for trying to determine glaucoma progression. It really has to all fit. We want our clinical examination, patient complaints and all, to all fit into a package that suggests whether a patient has glaucoma or whether their glaucoma is progressing. Visual field assessment I alluded to a little bit before, but what we’re really trying to assess is where is there loss of what is typically determined — that Traquair’s island, that island of vision in the sea of darkness. We know what the normal visual field looks like. We typically do not test the entire field in glaucoma. We’ve learned to hone down to where most of the glaucoma visual field defects develop. Some of them will develop outside our standard central 24 or 30-degree visual fields that we typically perform. But in order to test the full field, it would take too long, and the variability in the peripheral field is high. So while we’re going to miss maybe some early visual field defects that may occur out at 50 degrees, we can’t detect those reliably anyway with our current technology, so we focus — we go for where the real payoff is, and that’s in that more central 24 to 30-degree field. Typically we do a 24-2 test for visual field assessment. That still goes out 30 degrees nasally, but doesn’t test as much in the other areas of the field. The goals of perimetry are, again, to identify what’s abnormal and to monitor for progression. We typically look for these nerve fiber bundle type of defects. Paracentral scotomas, arcuate scotomas, nasal steps, wedges. Or it can just be generalized constriction, or a generalized decrease in sensitivity can also be a very early and not atypical defect in glaucoma, but it’s non-specific. It can also be caused by cataract, for example. Here’s a typical nasal step, also showing the area of the retina and the ganglion cells that are damaged, that would typically lead to that type of defect. Similarly, with a paracentral scotoma, the damage is more centrally, for a superior paracentral defect on the visual field, with some superonasal loss, the area is shown where the damage might exist — is illustrated. And similarly, for a more arcuate or Bjerrum scotoma. Similarly, temporal wedge defects, and where the damage might exist. We can look at a single field interpretation. One of the things we want to look at, when you look at a visual field test, an automated test, is you want to first assess the reliability and quality of the test. False positives, false negatives, fixation losses, how much fluctuation there is. We do expect that areas where there are some defects they would be more variable than other areas. So false negatives may be higher in areas of glaucoma damage. And that’s okay. So we can’t always take exactly what the machine tells us. We also have to look at that in the context of the visual field. So if you have a number of false negatives, but in an otherwise normal field, without defects, that may be an indication that the test is not very reliable. But if you have some false negatives in an eye that tests with a lot of visual field defects, those false negatives might be just because there’s glaucoma damage, and that’s okay. It doesn’t mean it’s unreliable. How do you determine what’s a significant defect? What’s abnormal? Well, clusters of points. Two or more points that are depressed by more than 5 decibels, compared to surrounding points. Single points that are very depressed can be significant. Above and below the horizontal midline can be important. But also one of the key things is that if you think there might be a significant defect, it’s gotta be reproducible. So repeating visual fields is a critical component. And it requires a reliable baseline. You probably need at least two fields. Some studies suggest that in order to really diagnose progression, two fields is not enough. Three fields may not be enough. The AGIS study, the Advanced Glaucoma Intervention Study, suggests that in some patients, it could require 5 to 7 fields to really confirm definite progression. So fields can vary quite a bit. Make sure that you reconfirm the visual field defects when there’s any question, and make sure that they correlate. Again, it’s getting back to that correlation with the optic nerve, with the pressure, what’s going on with the patient, what they say, and put it all into a consistent pattern that really helps you define what this patient has and whether or not they’re progressing and whether or not they need greater intervention. So… With that, I have the great fortune of being here in Indianapolis, at the Eugene and Marilyn Glick Eye Institute, and I wanted to leave a few minutes at the end here to address some of the questions. Some of you may also submit questions online, which we’ll try to get to, and our moderator will help us with that. But several of you — and I thank you for submitting some questions in advance — I would like to maybe address some of those and go from there. Several of the questions were around what is the best way to handle the glaucoma suspect. And as I’ve been talking about, the clinical examination is critical here. Careful examination. And I think the most important thing in a glaucoma suspect is to make sure that everything fits. Just because someone may have elevated pressure doesn’t mean they have glaucoma. Just because they have an optic nerve that looks suspicious doesn’t mean they have glaucoma. Just because they have a visual field defect that may be suspicious doesn’t mean they have glaucoma. But put all that together. If they have elevated pressure, if they have a suspicious-looking optic nerve and visual field and they have a family history of glaucoma, and so forth, then that might give you enough to really consider if this patient is really no longer a suspect, but has glaucoma. One of my things I harp on with our residents, when we talk about this issue, is somewhat philosophic, but the point is that diagnosing someone with glaucoma is a major step. It is committing them to a course of therapy that could be for a lifetime. And what we tend to do is we tend to overdiagnose glaucoma suspects, but undertreat real glaucoma. So my approach to the glaucoma suspect is to be very conservative about making the diagnosis. If you don’t make the diagnosis before they’ve lost their first 10% of ganglion cell axons, that’s okay. These patients do not have — and they have a window of time where you can sort things out, and that could be over weeks, months, it could even be following them for a year or two, and seeing if something progresses and changes. And once you’re convinced they have glaucoma, then treat them aggressively. What we tend to do is treat a lot of glaucoma suspects just because we don’t know, and we throw a little medicine at them, and then our real glaucoma patients we don’t treat aggressively enough. I think that should be reversed. We should be conservative about diagnosing glaucoma, but then aggressive in treatment, when we do know that we have real glaucoma and we’re convinced of that. We talked a bit about visual field assessment. There’s a lot of different ways to assess visual field. And what we use most commonly is the standard Humphrey visual field 24-2. We use the SITA program, if you have that available. It’s very well validated. It’s a relatively quick test that you can get through in an efficient period of time, without wearing patients out. As you know, a big problem with fields is our patients get very fatigued during the test, and often don’t perform reliably. There were some questions, again, about normal tension glaucoma, which we spoke about, again. That’s similar to the whole discussion around glaucoma suspects. Normal tension glaucoma patients — again, we should be conservative about making the diagnosis. But once we’re convinced that there’s a diagnosis, we should treat them. And the goal is usually a 30% reduction from their baseline. That’s from the normal tension glaucoma study. It did show that it greatly reduces the rate of progression. But we also have to understand that in these normal tension glaucoma patients, a lot of them don’t progress, or if they do so, they do very quickly. The goal is to try to determine who are the rapid progressers and who aren’t. There were a couple of questions about surgical and other approaches. I hope through the graces of Orbis, if we can get back together to maybe delve into more of the medical laser and surgical management of glaucoma, and how we handle those patients, and there’s a lot of — a lot that can go into that discussion. We typically do try to start with medications, but that’s changing. It depends on your location and what’s available. Prostaglandin analogs are the typical first line therapy in the US, and our most effective agents, but we fortunately have other classes of agents available. The key is to have a goal. And that’s usually to obtain at least a 30% reduction in pressure over time, and we can talk more about goal setting when we talk about therapy in a future talk. There were other questions here. Again, going back to pressure: How do you diagnose glaucoma in LASIK patients? Interesting question. Well, we know that there’s a lot of corneal issues that can cause artifact in our tonometry, and LASIK not only thins the cornea, but flattens it. So we know that after refractive surgery, the pressure is gonna be lower than what it truly is. There is no good algorithm for correcting for that. Probably the best way to do that, if it’s at all feasible, is to have several pressure checks on a patient before they had their refractive surgery, and then hopefully they have some pressure checks afterwards, and we can see what the difference is, and maybe add that back, so it’s individualized. But in general, we really do not know, and we have to rely on other factors, such as the field and the optic nerve, more than the pressure. There was a question about neuroprotective approaches in glaucoma? There’s a lot of excitement in this area, but it still looks like that’s a ways off. But there are things that we can take into account, such as in the — what we call vasoprotective and neuroprotective world that, again, I hope we can get to in the future. So in our last five, couple minutes here, I just want to look and see if there are any questions online that were proposed. I’m just checking out here to see what questions we might have. There was a question I see here about IOP phasing procedure. I’m not sure exactly what that is. Is it still relevant? I think the most important thing about IOP is to get multiple measurements, to try to get it — to also try to assess the pressure at different time points. And to have different assessments of the pressure over time. And during the day, if you’re unsure. Because patients may have their — they may look low tension, when you check them, but if you check them always at 10:00 a.m., and don’t check them at 3:00 or 4:00 p.m. in the afternoon, you may get a very different sense of that patient. So I think it is important, with patients, to really assess their pressure at different time points during the day. There was a question about what test to start with, if there’s a suspicious disc with abnormal visual — with a normal IOP. And again, the key to the suspicious disc in glaucoma suspect is correlation. What else is going — if a patient only has a suspicious disc, but has a normal field, normal IOP, no other risk factors, no family history, for example, we’re generally very comfortable following that patient to look and see if there’s any progression over time. There was a question about nasal step. Nasal step just refers to that area of the arcuate visual field defect that we say that’s clustered in the nasal peripheral field. It can be a superior nasal step or inferior nasal step, but it should respect the horizontal meridian in the nasal portion of the field. Again, there was a question about central corneal thickness. To correct IOP. And again, I don’t think that any of the conversion tables that I’ve seen have been validated and are accurate. Because there’s more to it. There’s more to the cornea than just the thickness. Corneas with very similar thickness can have different degrees of stiffness, based on their collagen makeup and how they are. You know, some of us have thick hair, thin hair. Some have thick skin, some have thinner skin. We’re all built a little bit different. So it’s not just the corneal thickness, but it’s how rigid is an individual’s cornea to begin with. So all that we can say is that someone’s cornea is significantly thinner — and by thinner in the ocular hypertension study, we’re talking about less than 550. But we generally sort of break it into those that are in the low 500s or maybe under 500. Those that are in the mid-500s, and those that are close to 600 or above. And all that we need to do, I think, and the best that we can do in those patients without locking ourselves in, is saying that we know that if your cornea is 620 that your pressure is probably significantly lower than what we’re measuring. We don’t know how much. Is it 2, 3, or 4 points? And does that really matter? We don’t know. But we just want to think of them as that. Likewise, if they have a very thin cornea, let’s say someone has a cornea of 490, and we’re getting pressures of 16, then we might have said our target was 16 for their pressure, but they’re really not 16. They’re probably running several points higher than that. How much higher? We don’t know. Again, 2, 3, 4 points higher, maybe? Yes. So we have to think about our target pressure differently, when someone has a very thin versus a very thick cornea. Now, there’s a question about how much of the nerve fiber layer can be damaged before it’s evident on OCT. And that’s a great question, and I don’t think it’s very well known. There haven’t been great cadaver studies done on others, in patients who’ve had defects. We know that in the optic nerve, from studies that were done at Johns Hopkins and by Quigley and colleagues, that maybe 30% to 50% of the optic nerve could be lost before anything shows up on visual field testing. We suspect that there can be significant thinning of the nerve fiber layer before it shows up in our standard OCT or other imaging technologies. What that percentage is I don’t think we really know. But is it 10%? 20%? 25%? I would think we would probably be in that range, based on the sensitivity of the test. As technologies improve, hopefully that’ll come down. But I don’t think we’re at the point yet where we can detect, say, a 5% change in retinal nerve fiber layer thickness reliably. That just doesn’t exist. And the technology is not that assessment today. There was a question also about visual field defects in normal tension glaucoma. First of all, normal tension glaucoma — and as I said, it’s a spectrum of primary open-angle glaucoma. It’s probably not a separate disease. Although the way we think of glaucoma, I think, is somewhat interesting as well. We typically, as I said, glaucoma is this typical optic neuropathy, but obviously there’s a lot of different things that fall under glaucomatous optic neuropathy that we just don’t understand. So maybe we will separate these diseases out. But right now, we really consider it a spectrum. It is said in many studies — it is evident that in normal tension glaucoma, the earliest visual field defects oftentimes tend to be more central or paracentral than the typical peripheral nasal step or peripheral arcuate defects that we see in the higher pressure spectrum of the disease. But there’s a lot of overlap. Different studies with different populations have shown differences or no differences, so I think it’s all possible with normal tension glaucoma that you can get any type of visual field defect. But in my personal experience, they do tend to be often more paracentral or central, earlier on in the disease, for reasons that aren’t really well understood. There’s more questions, and I’m glad. There are a lot of questions about corneal thickness. I think we’ve addressed that. And the biomechanics. Patients with normal visual field, normal retinal nerve fiber, normal IOP, but a positive family history — what I do in those patients, quite honestly, is if everything looks fine, and their only risk factor is the family history, I’ll just — depending upon their age, but I’ll suggest that they have a repeat eye exam in 1 to 2 years. As they get older, I lean more towards annual. If they’re younger, 30s or 40s, and nothing evident, then maybe 1 to 2 years. There’s a question about features of the normal tension disc. Some have suggested that there’s more earlier notching in those discs. Maybe more disc hemorrhages in normal tension glaucoma. But otherwise, again, it’s a spectrum. And anything is possible with normal tension glaucoma that we see in high pressure glaucoma. They are not, at least clinically, by what we can assess today, separate entities. What about tonometry in the edematous or scarred corneas? And that is problematic in those eyes. That we often go to different types of devices, such as Tono-Pen, Mackay-Mark, pneumotonometry — there’s a variety of different techniques, but it does become challenging. Most commonly, what we have available and use is the Tono-Pen. Looking at the questions here — OCT or HRT? Which one is better? Quite honestly, they’re both very good. The studies of correlations between all the different OCT devices and HRT — if you look at their sensitivity and specificity that’s been demonstrated in different studies, they all look very similar. So I don’t think we have to be, at least at this point, locked into any perfect technology out there, because the technology is still evolving. As I said, I think of these technologies as technologies. So how long do you keep your computer for? You know, how long is it good for? 4 or 5 years, maybe. 6 if you’re lucky. And then you often have to replace it. We are getting towards the end of our time. I see it’s 10:00. And in respect for everyone’s time, and sorry if I cannot get to all the questions. But I want to thank all of you for being on the call. I hope this was useful for you. We look forward to your feedback. And I look forward to having the opportunity to delve further into glaucoma, particularly on the treatment side, and having discussions about goal setting and how we might achieve that in different types of glaucoma with medical, laser, surgical therapy. Thank you all very much, and I hope you have a great day or — I know for some of you it’s early morning, and I apologize. But thank you very much for being on the call. Thank you.
September 23, 2016