Lecture: Optimizing Glaucoma Treatment Factors to Consider in Selection of IOP-Lowering Therapy
In this presentation, Dr. Leung discusses the following topics:
• Do we need additional IOP lowering therapy?
• What IOP levels should the treatment target?
• What factors to consider for determination of the target IOP?
Dr. Leung also answers the questions from the participants at the end of the presentation.
Lecture location: on-board the Orbis Flying Eye Hospital in Binh Dinh, Vietnam.
Lecturer: Dr. Christopher Leung, The Chinese University of Hong Kong
(To translate please select your language to the right of this page)
DR LEUNG: And what I’m going to talk to you this morning is about how to manage glaucoma patients in your clinic, using medical therapy. So today, I would like to show you how we manage glaucoma patients, not just according to the intraocular pressure, but also according to the status of the optic nerve. Just to show you a patient here, we have a 53-year-old lady with primary open-angle glaucoma. So let’s just focus on her left eye. She had the visual acuity — normal visual acuity, and the cornea is a little bit thin, and she’s been put on a PGA. So I just wondered — the first line of medical therapy here in Vietnam — is it PGA, or is it beta blocker, or is it carbonic anhydrase inhibitor? How many of you would give PGA, prostaglandin analog, as your first line? Okay. Beta blocker? Okay. We have one. Two. Carbon anhydrase inhibitor. Okay. So you’d give carbonic anhydrase inhibitor? Like Trusopt, Azopt, acetazolamide, brinzolamide? Eye drops? Azopt? Okay, okay. How many of you also use Brimonidine? Alpha-2 agonists? Alpha-2 agonists? Alphagan? Alphagan? So that’s the first line? So most of you actually use the PGA as a first line, which is good. Because it’s a very effective first line medication. And you see this patient’s already put on a PGA. And this is her pressure. The baseline — 15. And you see the pressure was 15, the range between 12 and 14. Now, when we follow the patients over time, the question that we often ask is whether this patient would need additional IOP therapy. So just say here, in this case, we see these patients already on one medication, the IOP is in the profile of 12 to 14. How many of you would consider these levels of intraocular pressure would be good? Okay. Most of you. So some of you think — how many of you may think — well, 12 may not be enough. I want to have an even lower intraocular pressure? Now, let’s take a look. On the optic disc and the visual field, before we decide. Because very often the treatment approach very much depends on a number of factors. And obviously we are interested to know how severely damaged this optic disc is. And when we decide to have the IOP lowered further, the question is: What levels should we be aiming at? It doesn’t really apply for this patient only. But it applies to all glaucoma patients you manage in your clinic. You want to ask how low the pressure you should aim at. And then what factors should we consider to determine the target pressure? These are important questions. And it’s important questions, because we face patients with high pressure, with low pressure, all the time, and we know glaucoma is a chronic disease, and they come back for follow-up very often. And you are often, when you’re facing the question: Should I need to lower the pressure further for this patient? Now, the concept of target pressure has been proposed for a number of years. Just wanted to check: How many of you have heard about the concept of target pressure? Oh, wow. Many of you did. Very good. So basically, again, this is a consensus statement from the World Glaucoma Association Consensus Meeting, back in 2011. Again, we had a group of glaucoma specialists come together, and we talk about specific topics related to glaucoma, each year. And that year, we talked about intraocular pressure. And in this meeting, we talked about target pressure, which sets… Target pressure is an IOP range, at which the clinician judges that progressive disease is unlikely to affect the patient’s quality of life. And then the burdens and the risks of therapy should be balanced against the risk of disease progression. Now, notice as I highlight some keywords here, we have progressive disease, we have patient’s quality of life, we have the risk of disease progression. Now, I would talk about these individual terms, but I would like to highlight to you that sometimes, as a glaucoma surgeon, you can do more harm than good to your patients, if you treat your patient too aggressively. Medications have side effects. Surgery would have complications if you’re not careful. And there are also complications related to laser treatment. So all forms of therapy — medical, surgical, laser — carries inherent risk. And we have to be wise in deciding what patients would need additional IOP-lowering treatment. That’s why you have quality of life. Now, imagine how inconvenient a 70-year-old lady needs to put eye drops three times a day, from one bottle, and then twice a day from another bottle, and then she has to do it every day. She might be forgetful. And she may not be compliant. And even when she is compliant, then sometimes she may actually develop itchy eyes, red eyes, that we often see in our clinic. So this greatly impairs the patient’s quality of life. The tricky thing about this statement here is: We really have to understand the risk of disease progression. Now, in the consensus statement, there are a number of items in the checklist that we listed, so that we all have a reference to decide how to determine the target IOP. That includes the amount of glaucoma damage, estimated damaging IOP, estimated patient’s life expectancy, estimated rate of progression, and consideration of other risk factors for progression. Now, we were very good at putting up these terms. We were good at putting up these terms, but we were not doing a good job in quantifying or being able to specifically tell you what amount that we should estimate for a patient, how severe an optic disc should be considered as severely damaged, what should be considered as the damaging IOP, and how are we going to estimate rates of progression? So we just listed these items. But we didn’t specify any details. Concepts appear a bit abstract. But I would like to tell you that the most important element for you to decide whether you need additional IOP-lowering treatment is that you need to have a very good follow-up of the optic nerve. You need to have OCT, retinal nerve fiber layer measurements, and you need to have regular visual field measurements. And in the consensus statement, basically what we mentioned here is that there is no validated algorithm for the determination of the target IOP. So it’s a very strange practice. Although we recommend, we suggest having a target IOP. But we really — it doesn’t say much about how to determine exactly the target IOP levels. This is from the consensus statement. Now, let’s take a look on the patient that I just showed you earlier on. So this is her visual field. We’re looking at the left eye. You see the damage is mild. And then the IOP levels was between the range of 12 to 15. And she is expected — I mean, the life expectancy for this lady, average life expectancy in Hong Kong for women is about 85, 86. For men, it’s about 83, 84. So we’re expecting this lady to have another 20-plus years. And then the rate of progression for this lady, which you can take a look at this visual field here… Now, I’m not sure whether you’re familiar with this display. This is actually what you can get from your visual field device. Those of you who have the Humphrey field analyzer would have this analysis software. This is called a GPA. So how many of you have seen similar printouts before? No, none of you? But how many of you have the Humphrey field analyzer in your clinic? Okay. So many of you have the Humphrey field analyzer. So I strongly encourage you to go back to your clinic and ask for a GPA, which is a software to analyze progression from your dealer. You can ask Carl Zeiss Meditec to send you the software. It can be installed in your Humphrey field analyzer. And it’s extremely useful. Extremely important. Because you really can’t judge visual field loss — you really can’t judge visual field progression — by your eyeballs. Now, you see, we have two analyses here, indicating whether there is visual field loss over time. Now, here we have this — called trend analysis of the visual field index. Now, visual field index, or VFI, is a very useful index to tell you the average loss of visual sensitivity. I don’t have time to talk to you, how VFI is calculated. Those of you who are interested can always search on the internet. But the key here is it’s an index between 0 and 100%. 100% means a normal visual field. 0% means a totally abnormal visual field. So you can take a look. This is the first visual field taken in 2007 for that lady. And the VFI is 95%. Now, all of you are familiar with this indicator, MD. Mean deviation. And it’s -1.77 decibels. Now, MD is an average number. It’s, again, an overall representation. The mean sensitivity of the visual field. The more negative the number is, the worse the visual field is. But the VFI, again, basically correlates very well — correlates very closely with MD. But it’s less affected by media opacities, like cataract. So for patients developing cataract over time, MD can also get worse over time. VFI is relatively — relatively — insensitive to the development of cataract. But I’m saying relative. Okay? Just listen carefully. It’s relative to MD. It’s less sensitive to the interference of media opacities, like cataract. Now, this is the visual field taken in 2008. You can see one was taken in December, and this one is about 4 months after. And you can see the VFI is 92. Now, MD changes from -1.7 to -3.7. The important thing I want you to remember is, although you see the number change from -1 to -3, it’s about 2 decibel changes. But would you consider it as a visual field progression? Would you consider that as a progression of the visual field? Well, I mean, some of you… I mean, how many of you would consider — this should be considered as visual field progression? Right? We see actually a couple hands. But I would say never. Never interpret visual field by your own judgment. These numbers fluctuate. And you will not be able to get a reliable judgment of visual field changes, unless you have at least a number of tests. At least three to four visual field tests over time. And that’s why you need a software to help you. Now, notice — wow, this is 2 decibel change. It’s a lot of change over 4 months. The patient is progressing. But look at this plot over here. Now, this is the first visual field corresponding to this one. And the second one — you see the drop over here? Which is this one. And I hope you can see the third time — the visual field came back to normal. I mean came back to its original level. And you can see these squares can be up and down over time. And why does this happen? It’s because visual field is a subjective test. I really want you to remember: You really need to train your technician in order to take a good visual field. I heard the other day in the clinic that — I mean, there’s a patient shown to me, and I was told this patient cannot perform a visual field, because they’re too old. I can assure you that every single patient, when they can fixate, they always can have a visual field performed. You just need patience to teach the patient. And you need to instruct the patient carefully. So you see, this visual field can be — the measurements of the visual field can be up and down, because visual field is a subjective test. And that’s why you need multiple tests in order to determine whether change has occurred. Now, when we look back, this printout — what it shows here is a statistical analysis, what we call as a linear regression analysis. So you’re all familiar with linear regression analysis, right? So basically it’s an analysis between the VFI and time. And you can see the linear regression analysis — it gives us two informations. First, it shows us whether there is a significant negative trend over time. So if it has a significant negative trend, then it shows up here. It doesn’t really… Perhaps it doesn’t show a p-value. But it should have a p-value. So if you see a p less than 0.05, this is the statistical level that we look at, to determine whether there is a significant change or not. And then the second information you can get from the linear regression analysis is the rate of change. And here we are looking at the rate of change of VFI is -3.3% per year. And if you project the change over time, you can see this patient is going to go blind by the age of 72, perhaps. So this shows the patient has progressive loss of the visual field, over this — from 2007 to 2011. Over these four years. I find it to be a very useful tool for doctors and patients. Because glaucoma patients, they don’t know they have a problem, very often. The medication you give them or the surgery you do to them — basically it doesn’t really change the vision much. So for some time, the patient may think… Wow. What’s the point of taking medication? And then they do not take it anymore. When you show this to your patient, they will be aware that… Wow. You see? My visual field is getting from this to this, and I’m going to get blind in about ten years. They would be very… So I’m not trying to scare the patient. But at the same time, I don’t want them to be relaxed about their conditions. Ultimately, they need to follow our instruction. They need to take the medication regularly, in order to preserve their vision. So very often, I find this to be a very, very useful educational tool for my patients. And show them — wow. Your visual field is getting darker and darker over time. Even though they’re not aware of it. Now, another way of analyzing visual field progression is this. We call this event analysis. This is difficult to translate. This is trend analysis. And this is event analysis. So trend analysis makes use of all data collected for a patient. So you see each individual visual field measurements are plotted over here. And we perform the linear regression analysis using all these data points. For event analysis, basically we just compare the follow-up to the baseline. And for GPA, you need to have two baseline measurements. And when we have the follow-up measurements, when we have the difference between the follow-up measurements greater — once again — basically what GPA does is that it measures the difference in visual sensitivity between the follow-up and the baseline measurements. At individual locations of the visual field. At individual locations of the visual field. So it compares the follow-up to the baseline, and it measures the difference. When the difference is greater than the variability of that location, variability, then it will show up in a triangle over that location. So we need the difference to be greater than the test-retest variability. Because all these numbers just keep changing all the time during follow-up. So you have to exceed certain levels or a threshold before you consider this difference is a meaningful difference. So when you have the second follow-up, having the same difference, exceeding the test-retest variability, then you would see this half-filled triangle. And then when you have the third follow-up, showing the exact degree of difference greater than the test-retest variability, then you have a full-field black triangle. And then when you have three black triangles, then you will see this likely progression. I can understand, actually, it’s a very robust algorithm, to tell you whether progression has occurred or not. So just one triangle, white triangle, two white triangles — is not sufficient for you to say there is a visual field progression. So that means you need to have at least five visual field tests before you will see likely progression. Two baseline, and three follow-up exams. And this is the nature of visual field examination. Loss of variability over time. That’s why, again, don’t judge progression based on your eyes. Don’t judge progression based on one, two, three visual fields. So you need to have a series of visual field tests before you can tell whether visual field progression has occurred. So let’s continue for one more slide, and then we can circle around. Okay? So this is… I spent a lot of time on the visual field, because I think it’s extremely important for you to understand visual field and understand visual field progression. And you need this information to know whether you need additional treatment for your patients. And then I will talk about some treatment options in the second half of the lecture. Before I finish, I just want to tell you: In this case, you see clear evidence of visual field progression. You have progressive loss of the VFI, 3.3% per year, and then you see likely progression. Over these areas, for that patient. So that means, even though she had pressure levels between 12 and 15, that means these levels of pressure are not safe for her. And she’s progressing. And with this information, we know she needs additional treatment. So don’t think a pressure of 14 or below 14 is safe. It’s safe, perhaps, for most of the patients. But it’s not safe for all patients. And there are patients who would progress at a level of pressure between 12 and 14. And likewise, we always see patients with high levels of pressure, with high levels of intraocular pressure, for a long time, but they may not show any signs of visual field loss. They may not show any signs of progressive retinal nerve fiber layer thinning. So those patients may not need additional treatment. So we just mentioned, for the lady we just discussed earlier in the morning, with progressive loss of the visual field, then this patient would need additional IOP-lowering treatment. The lady next to me — I don’t know your name. But she asked a very interesting question. She asked — now, we talk about OCT, and I’ve shown you OCT is useful to detect glaucoma. I haven’t talked about how to use OCT to measure progression. But with OCT, why do we bother to use visual field anymore? It’s actually a very important question. Now, the current standard of practice that we need to measure, both the visual field and the OCT measurements. We need to obtain both the visual field and the OCT retinal nerve fiber layer, and optic disc measurements. For detection and monitoring of glaucoma. So the reason is that OCT gives us a structural perspective of the optic nerve. Whereas visual field provides us a functional perspective of the optic nerve. So we need to use both structure and function to monitor glaucoma progression. I think there are still a lot of investigations and studies ongoing to identify the best approach to monitor glaucoma progression. So imagine — I mean, five, ten years ago, we are still using very much the old technology. OHRT you may be familiar with, to measure the rim, and we use the time domain OCT to measure the circumpapillary retinal nerve fiber layer thickness. So back in those days, five, ten years ago, when the technologies were not very good, people did not have confidence in reading the OHRT or the OCT printouts. And they relied more on the visual field to diagnose glaucoma. In fact, when I was a medical student, I was told, when you diagnose glaucoma, you need to have a visual field defect. But with more and more studies, we now know that actually we can detect glaucoma much earlier. Earlier than before. Now, we see macular abnormalities in the OCT. We see retinal nerve fiber layer thinning in the OCT, before we see visual field loss. So we can see the trend now is actually shifting more and more to using the OCT to detect glaucoma. So this is for detection of glaucoma. So for monitoring of glaucoma, we would need, in my opinion, both the OCT and visual field. Which I explained to you earlier. Because they provide us different information. Structure and function. Structural tests is good, because it’s objective. It’s less variable. Although visual field is not very good in the sense that it is more variable and it’s subjective, it provides us a perspective about how the patients see. You can understand better from the patient’s perspective which part of their visual field is abnormal. And if time allows, I would love to talk to you more about the structure-function relationship. Before going to that, I would like to focus the lecture first. So we just talk about the options we have here to consider, when we need to lower the intraocular pressure further. So, again, you’re all familiar with this. We have medication, laser, and surgery. So we mentioned all these already. Laser we haven’t talked about yet. I just wonder whether you have these laser instruments in your clinics. Do you have SLT? Selective laser trabeculoplasty in your clinic? Okay. We have one doctor having an SLT in your clinic. PLT and MLT perhaps you may not have. They are newer devices for laser treatment. Generally, they can lower intraocular pressure at a similar level. The beauty or the advantage of laser, or SLT, is that it’s a very safe procedure. It’s quick. It takes about 10 minutes. And then you usually would get about a 20% drop in IOP. The side effects would be mostly anterior chamber inflammation in the first or second day after the laser. But they generally subside in a few days. So it’s a very safe procedure. The shortcoming is that about 20% to 30% of patients do not show a response. And the 20% of intraocular pressure lowering is an average number. Some patients may have more. Some patients may have less. So there is still a little bit of unpredictability, in terms of the treatment outcome of SLT. And we know from the literature the most important predictive factor for a successful outcome is the pre-op IOP level. The higher the baseline, the more likely you’ll get a good effect. Now, for surgery, basically we now have two main forms of surgery. The conventional filtration surgery, comprising tubes and trab, and you also may have heard about MIGS. Minimally invasive glaucoma surgery. So how many of you have heard of MIGS before? MIGS? Okay. So I do not have time to talk about MIGS today, but I hope I can share with you on some other time. But MIGS… As its name implies, minimally invasive. We now have different forms of MIGS available. But some people often make fun about MIGS. Make fun. Make jokes. They call this procedure — for MIGS, they call this procedure MEGS. MEGS. Which stands for minimally effective glaucoma surgery. The English is minimally invasive — turns into the minimally effective. So… Well, obviously we know the IOP-lowering effect of MIGS is lower than conventional filtration surgery. So since most of you would be treating patients with medications, I would like to talk a little bit more about medications today. Now, most of you would consider PGA as your first line, but I would also like to highlight to you some other factors you would like to consider, before you decide which medication to give. So to prescribe medication, you want to know how effective this medication is in lowering the IOP. And from studies, we know these medications have been shown to lower intraocular pressure to a various degree. But perhaps you know less about whether the medication you’re using can lower intraocular pressure, whether it can lower the pressure during the daytime and nighttime. So I would like to show you the data we have from the literature — which medication can lower the IOP not just during the daytime, but also at night. Dr. Ting the other day asked me about Alphagan. And Alphagan is currently the only drug that’s been shown to have a neuroprotective effect, independent of IOP. So I will share with you these medications. Now, we know there are 24 variations of IOP. So the diurnal variation means the variation in IOP during the day. And the variation could be up to 5 millimeters of mercury. So if you have a patient coming to your clinic in the morning, having a pressure of 25 millimeters of mercury, when you measure the same patient in the afternoon, the pressure may drop to 20. It’s just a physiological variation. So another point I want you to remember is that nighttime intraocular pressure generally is higher than the daytime intraocular pressure. So when you’re lying supine, the pressure generally goes up. And the second point I want to share with you is that intraocular pressure, generally, is highest in the early morning. It generally peaks at about 5 to 6 a.m. Obviously we do see variations among individuals. Now, this is data collected from a sleep lab at UCSD, at University of California San Diego. So you can see the IOP changes at daytime and at nighttime, and at different positions. So what we can see here is that, when you lie down, when you lie supine, the pressure generally is higher. So we have a term we call normal-tension glaucoma. But we often actually only measure intraocular pressure at daytime. So those patients — what we don’t know about is their pressure at nighttime. So some patients may have a normal pressure during the office hour, but they may have high pressure at nighttime. So you can see for the patient, a pressure of 15, 16… The pressure can be up to 22 at night. This is the missing information that we don’t get from our patients. So we have to be careful about how we determine IOP measurements. So this graph just shows you a comparison between the beta blocker and the PGA. For the IOP-lowering effects during daytime and at night. So what you can see here is the circle represents patients without any treatment. Triangles are patients put on a beta blocker. And square, put on a PGA. So we can see here, number one — you see PGA generally is more effective to lower the pressure than beta blocker. But one important fact that you can see from this graph is that only PGA can lower the pressure at night. But not beta blocker. So that’s why PGA… We use PGA as a first line treatment. Because it can… It’s very effective. And it’s effective not only during the day, but also at night. And then this is, again, a complicated graph that I would like to show you here. We have three groups of patients: One group with PGA, which is the circle, and the triangle represents a combination treatment. PGA together with a CAI. Azopt. Again, square, we have PGA with a beta blocker. And what we can see here is that when we compare the triangles and the squares, you see a nighttime IOP-lowering effect can only be found for patients taking CAI. But not patients taking a beta blocker. So for selection of medication, we now know PGA is a very effective at lowering IOP, and it can lower IOP during daytime and nighttime. And when you add on top of a PGA, you get additional IOP-lowering effect. For both a beta blocker and a CAI. But if you’re adding a CAI instead of a beta blocker, you see an additional IOP-lowering effect at night. So if you want to have very good control of eye pressure, for patients who have been put on a PGA, then you might want to actually consider adding a CAI instead of a beta blocker. Because CAI provides an additional IOP-lowering effect at night. Now, how about Alphagan? Now, how often you usually prescribe Alphagan? Twice a day or three times a day? How many of you are prescribing three times a day? Okay. Many of you. How many of you are prescribing Alphagan twice a day? Three times a day? Twice a day? So we have a few hands over there. So what we show here is that, first, you see Alphagan does not have a nocturnal IOP-lowering effect. It doesn’t lower IOP at night. It only lowers IOP during the daytime. And then you would consider actually prescribing Alphagan twice a day, instead of three times a day. Because when you add Alphagan three times a day, the nighttime dosage is unlikely to give you any benefits, in terms of IOP-lowering. So this is some data that you can consider, when you are prescribing glaucoma medications. Because we know some patients may develop an allergic response, particularly to Alphagan. So the more eye drops you put into the patient’s eyes, the more uncomfortable they become. So how about SLT? So laser trabeculoplasty. You see, laser procedure can lower the pressure at both daytime and nighttime. Although the effect, sometimes, may not be as good as medication. During the daytime. But, you see, the nighttime effects are actually pretty good. But obviously this is an average response. The response to treatment actually varies among patients. Now, we talk about neuroprotection. We talk about Alphagan. Although Alphagan cannot lower intraocular pressure at night, what you can see here is a study, called low pressure glaucoma treatment study. What this study shows is that they compared the intraocular pressure-lowering effect between the beta blocker and an alpha-2 agonist. And we are looking at here the Y axis, the proportion of patients developing visual field progression, and the X axis is the follow-up time. And what you see here is, of two, three, four years, you see more patients developing visual field progression when they were put on a beta blocker, compared with patients taking an alpha-2 agonist. So more patients get worse when they were put on timolol, despite the fact that they actually have similar levels of intraocular pressure control, throughout the follow-up period. So that means that, although the IOP levels are similar, we’re seeing an additional neuroprotective effect for Alphagan. And this study was done in patients with low pressure glaucoma. So for patients — I’m sure you have this kind of patients in your clinic — then you might actually consider using Alphagan for this group of patients. Because it’s shown to have a neuroprotective effect, independent of IOP. So for efficacy, as I said, when we consider how to select glaucoma medications, we often need to consider efficacy and safety. Just to recap, PGA and CAI and SLT — they have a nighttime IOP-lowering effect, in addition to day time IOP-lowering. And you can consider using Alphagan or alpha-2 agonists in patients with normal pressure. So usually my strategy of stepping up glaucoma medication is that I would put the patient on PGA as a first line. If they require additional medication — say if I see progressive retinal nerve fiber layer thinning — if I see progressive visual field loss — I need to add another drop, then I would choose CAI. If additional medication would be needed, then I would consider adding a beta blocker, basically with a combo, which you have in your clinic, which is Azarga. Which is a combination of timolol and Azopt. So if additional medication is needed, then I would add the third medication — would be alpha-2 agonist. Alpha-2 agonist. Alphagan. So this is for patients with progressive nerve fiber layer or visual field loss, for patients with high pressure. And for patients with normal-tension glaucoma, I would still use PGA as the first line, because PGA is very effective to lower the IOP. But I would consider using Alphagan earlier. If I see progressive loss of the visual field and the retinal nerve fiber layer. So another factor we want to consider — again, I mentioned — is safety. Tolerability and adherence. All glaucoma medications we are giving to our patients contain BAK. BAK is a form of preservative. It’s benzalkonium chloride. And we know patients develop red eyes. Patients develop itchy eyes, painful eyes. It’s because they are using many, many bottles of glaucoma medication, and they are putting on a lot of BAK onto their eyes. And BAK, generally, basically, is a detergent. It’s used to digest, to melt the membrane of bacteria. But it also damages the conjunctival epithelial cells and the corneal epithelial cells. So you see patients developing corneal erosion, and you see the conjunctiva becomes red, and you see patients complaining of dry eyes, itchy eyes. It’s all the effects secondary to BAK. So try to minimize the number of bottles of medication you’re giving to your patients. The more drops you prescribe to your patient, the more likely that this patient would develop some kind of discomfort. We call this OSD. Ocular surface disease. Ocular surface disease. So this is the patient that I showed you earlier. What you see here is: We detected progressive visual field loss. At this time point, 57 years of age, so we followed this patient for up to 4 years, and you remember we see the loss of VFI is about 3%. So at this point, we added a CAI, and then we also performed SLT. And you can see the rate of visual field loss decreased from -3.3% per year to 1.1% per year. This is over about 10 years of follow-up. 10 years of follow-up. Now, the point I wanted to mention here — you see that glaucoma is a chronic disease. It’s a chronic disease. And it really takes a long time to progress. And if you manage it properly, many glaucoma patients do very well. But if you’re not careful, some of them can progress quite rapidly. And don’t get yourself a forced reassurance, when you see a pressure of 12 or 14. You need to check the visual field and the retinal nerve fiber layer regularly. So this is the last slide. It’s summary. So I would not repeat this. You can take your notes. You can have your handouts later on. And I would like to take some questions from you, if you have any. Great. The most common side effects of PGA would be hyperemia, patient developing very red eyes, they may have skin pigmentation. So the patient may not feel good about using PGA. If patients — long lectures! So if patients cannot tolerate PGA, then you would go for second line. Which I would choose generally as CAI or beta blocker. Some patients may be actually very sensitive to any kind of medications. Then SLT, laser, would be a good option. And then if SLT cannot provide you a sufficient IOP-lowering effect, then I would perhaps consider a mix. And then if further IOP-lowering is required, obviously you would consider a filtration surgery. We see this as a step-up approach that you can consider. But I would be very carefully examining the optic disc, I would be very carefully examining the change of the field, the change of the retinal nerve fiber layer over time, before I decide whether additional treatment is needed. Remember, glaucoma, as I said again, it’s a chronic disease. Glaucoma patients are unlikely to progress in a few months. And the key here is that you would need to get sufficient numbers of visual fields and OCT examination in order to get better information about how to manage the patients. All right. So we have a couple of questions from the online audience. Here the question is: How to improve compliance with patients to glaucoma medication? Some very good questions. I think the number one rule of thumb would be to have good communication for your patients. Patients don’t take medication, because they don’t understand these medications are important to them. Because, for glaucoma patients in particular, they have — most of them have good central vision. So it’s just like a patient with hypertension. If you give an antihypertensive medication to them, they won’t feel they get better. And after some time, they just stop taking it. So why bother to take medications that do not improve my vision? So it would be difficult to convince the patient to take medication, if they do not understand the problems. So they need to understand glaucoma is a progressive disease. And they need to understand the importance of follow-up and taking the medication on a daily basis. And this is our duty, to spend time with our patients. And then the second trick I would use is that I would show them their visual field. I show the results. I show them the OCT results. I show them the visual field results. And the visual field printouts I showed you early on. Actually, as I said, it’s very educational. You need to inform the patient that he or she is likely to progress. The visual field is going to get lost. The central vision is going to be affected, if the intraocular pressure is not under control. If you’re not taking the medication on a daily basis. So, in essence, what you need to do is that you need to develop a good rapport with your patients. You need to earn their trust. If they trust you, they will do anything you ask. So you need to have some charm. You need to be charming. Okay? To engage with your patient. So we have a second question. Any role for pilocarpine, nowadays? Very good question. So… In the US or in Europe, I don’t think they’re using pilocarpine anymore. As a routine medication for glaucoma management. But there are some patients that I think would be very good or pilocarpine. So in Asia, in China, and I’m sure in Vietnam, you also have quite a significant proportion of patients with angle closure. So some of these patients, they have narrow angle or angle closure and high intraocular pressure. And obviously you would consider performing laser iridotomy on these cases. But some of them may still have residual angle closure on their angle, even after an LI. So those patients may show an IOP-lowering effect after you put them on pilocarpine. But obviously they would also… They would also need other glaucoma medications, including PGA and CAI, to lower the intraocular pressure. But this group of patients is particularly responsive to pilocarpine. Pilocarpine, now, is not a very fashionable medication. It’s all because of the side effects. It constricts the pupils, so it gives you dim vision. At night particularly, for glaucoma patients, that’s not very good. And it gives you a headache. Headache. And it particularly often is commonly seen in young adults. So patients who can tolerate pilocarpine, actually, are not that common. Two more questions to go. Why beta blockers have no or less alternate effect? Now, this is, again, a very good question. Now, beta blockers, we know, is a medication — the mechanism is to reduce the aqueous outflow. Increase the aqueous production, sorry. It decreases aqueous production from the ciliary body by dampening the sympathetic nerve. And it’s been proposed that, at night, we have a lower sympathetic tone. And this is why adding a beta blocker may not be particularly useful, when you already have a low sympathetic tone at the ciliary body. So the final question is: Is IOP reduction an ultimate goal of glaucoma management? Again, this is a very, very pointed question. And the answer is not. IOP reduction is not the ultimate goal of glaucoma management. The ultimate goal would be to preserve the quality of vision and the quality of life of our patients. You would do more harm than good to your patients, if you lowered the IOP excessively. So we have to be wise. Our patients, each one of them, would need different treatments. Depending on the degree of the optic nerve damage. And also depending on how fast is the optic nerve… Is deteriorating. For an optic nerve with advanced damage, for an optic nerve with rapid deterioration, we need to have aggressive lowering of intraocular pressure. For optic nerve with mild or early damage, and for optic nerve without showing any evidence of progression, very often we can observe for some time before we decide what kind of management would be appropriate. Very good. So when we add a medication, how long should we wait until we ask the patient to come back for follow-up and check the effect? Well, I don’t have a rough number four, but generally, for me, I would check the pressure in about 2 to 4 weeks. And remember, a single office measurement is not particularly informative. It’s useful. But you really need to have a series of IOP measurements, in order to see the general pattern of IOP levels. All right. Very good.