Lecture: How to Interpret OCT Findings in the Diagnostic Evaluation of Glaucoma

Lecturer: Dr. Chris Leung, Head of Dept., Clinical Professor, Dept. of Ophthalmology, The University of Hong Kong

Transcript

DR LEUNG: Good morning. Good afternoon. Good evening, Cybersight webinar audience. I’m Christopher Leung from the University of Hong Kong. In this webinar, I’m going to share with you some practical tips on how to interpret OCT findings in the diagnostic evaluation of glaucoma. OCT is the bread and butter technology in glaucoma care. But it’s also a very confusing technology to a lot of people, because we have so many different OCT models and different parameters and also different regions of interest. To be imaged. So in the diagnostic evaluation of glaucoma, sometimes it could be difficult. And I hope the tips and pointers I’m going to share with you tonight will be helpful and relevant to your practice. These are my disclosures. I work with a number of OCT industries. And I have some warm-up polling questions before we start. And I hope to get your response. You can key in your response after I read out the questions. Question number one: Which investigation would you perform to help establish a diagnosis of glaucoma? A, visual field, B, OCT, C, both. And here is our answer. So 86%, almost all of you, will use both OCT and visual field to establish a diagnosis of glaucoma. Very good. So question number two. Which investigation would you perform to monitor glaucoma progression? A, visual field, B, OCT, C, both. We have 75% of the audience that will use both technologies. Very good. So question three. Which region would you image for detection and monitoring of glaucoma? The optic disc region, the macula, or both? 15 seconds. We have actually about 40% of our participants who would scan the optic disc without imaging the macula. Very few of you would just image the macula. About 60% of you would scan both regions. Question four. For OCT imaging, which parameter would you measure for detection of glaucoma? You would image the retinal nerve fiber layer, the ganglion cell inner plexiform layer thickness, the neuroretinal rim width, or a combination of these parameters? 15 seconds. All right. So about 60% of you would image everything. The rim, the RNFL, the GCIPL, and then we have about 20% of our participants would use RNFL and GCIPL. Last question. Which OCT instrument do you use most often for detection and monitoring of glaucoma? We have different models from different OCT companies. 15 seconds. So 36% used Cirrus, Carl Zeiss platform. And then about 8% of you are not using OCT at all, having no access to OCT. The second most common OCT platform we have here is the Spectralis, with 21% of the audience using the Spectralis. So one important question we need to ask ourselves when we decide what parameter to measure in the diagnostic evaluation of glaucoma is about how to establish a diagnosis of glaucoma. Back in 2016, we had a group of glaucoma specialists from different parts of the world come together to discuss about how to diagnose glaucoma. It was the World Glaucoma Association Consensus Meeting. This was about diagnosis of primary open-angle glaucoma, and this is one of the consensus statements we made in that meeting. The clinical diagnosis of glaucoma is predicated on the detection of a thin retinal nerve fiber layer and narrowed neuroretinal rim. We have two parameters here. One is the RNFL and the other is neuroretinal rim. These are the two most important parameters in the diagnostic evaluation of glaucoma. The retinal nerve fiber layer is the most sensitive indicator of optic nerve damage in glaucoma. Whereas the neuroretinal rim is a more specific indicator of glaucoma. I’ll unpack that later on in the presentation. The role of visual field in the diagnosis of glaucoma and here we have this consensus statement, which says: We actually do not always need visual field diagnosis of glaucoma. It is important to recognize that glaucoma is a chronic, progressive optic neuropathy. And with OCT, we can image and measure the retinal nerve fiber layer and the GCIPL thickness, and these parameters are important, because these are the direct surrogate biomarkers of retinal ganglion cells. And for visual field, we use visual field basically to reflect the functional loss of the optic nerve, but there are other ocular conditions that can also end up with visual field abnormalities. So the presence of visual field defects is not the same as glaucoma. There are other ocular conditions — macular degeneration, cataract can give rise to visual field defects. So the diagnosis of glaucoma should be predicated on a structural evaluation of the optic disc or the optic nerve. But we use visual field most often for the evaluation of functional loss and also for monitoring disease progression over time. The question here is: When we apply OCT to get structural information of the optic nerve, there are at least three parameters we’re talking about here. The retinal nerve fiber layer, ganglion cell inner plexiform layer, neuroretinal rim. Which one should we rely on? The question we have here is about understanding the anatomy. For a cross section of the retina, here’s a histology cross section, we notice that we have different layers. The RNFL, the GCIPL, the IPL. They represent different components of the cell. The retinal nerve fiber layer comprises axons of the cells. The ganglion cell layer is composed of the cell body of the retinal ganglion cells, whereas the IPL, the inner plexiform layer, is largely composed of the dendrites of retinal ganglion cells. To scan the retinal nerve fiber layer most often over the optic disc region, because most axons are retinal ganglion cells. They converge at the optic nerve head. That’s why the optic nerve region is particularly important for evaluation of retinal nerve fiber layer. The image, the GCIPL of the macula — because there are 5 to 6 layers of ganglion cells at the macula, which — we have a higher density of retinal ganglion cells over the macula, compared with the regions. The foci, the macula. And that’s why we measure GCIPL thickness over the macula. The RNFL over the macula is relatively thin. But it is also important to study RNFL over the macula. But for some OCT instruments, they just measure the GCIPL, and some instruments they include the RNFL together. It’s confusing, because we have different instruments, different models, and they basically measure the optic nerve head region, the macula, using different scan patterns. Or the Spectralis OCT, for example, it uses a retinal nerve fiber layer scan. It captures only the circumpapillary retinal nerve fiber layer thickness. And the way we determine whether the retinal nerve fiber layer measurements are normal or not is dependent on the diagnostic classification. When the retinal nerve fiber thickness is in green, we call this no abnormalities. When it is in yellow, we call this borderline. When it is in red, we call this abnormal retinal nerve fiber thickness. So it is the way we determine whether the measurements we get are normal or not. And it depends on the normative database of the instruments. So if it is in yellow, it means it’s below the 5th percentile of the normative values. And if it is in red, it is below the 1st percentile of the normative value. And it’s the approach we rely on for the OCT to determine retinal nerve fiber layer defects. The Optovue devises an image of the optic nerve head region using 12 radial scans and 6 concentric circles. So we can get a topographic representation of the retinal nerve fiber layer. Which you can see the retinal nerve fiber layer typically is thickest over the superotemporal and inferotemporal quadrants of the optic disc. But the analysis or the classification is still very much reliant on the circumpapillary or the circum scan measurements. So we do not get topographic representation of the classification. We only get the circumpapillary retinal nerve fiber layer thickness classified in these green, yellow, red categories. The Cirrus OCT is a little bit different. It images the optic nerve head region in a 6×6 millimeter area, and it also shows the RNFL deviation map, showing you where the abnormal retinal nerve fiber layer thickness is. In this case, we don’t see any pixels highlighted in red or yellow, indicating that this is a normal-looking retinal nerve fiber layer representation. The Triton OCT scan — an even wider area is scanned. The optic nerve head together with the macula, using a raster scan, 12×9 millimeter. But the classification of the retinal nerve fiber layer is still very much limited to a 6×6 millimeter square over the macula and a little bit smaller than 6×6 at the optic nerve head. So the classification in terms of the red and yellow representation of retinal nerve fiber layer abnormalities is smaller than the 12×9 millimeter region. So we can understand all OCT data basically presenting retinal nerve fiber layer measurements in a circular scan, but only a few of them present topographic measurements of the retinal nerve fiber layer. Topographic retinal nerve fiber thickness analysis is actually more informative and more sensitive than circumpapillary retinal nerve fiber thickness analysis to detect retinal nerve fiber layer defects in glaucoma. The reason is that a lot of times retinal nerve fiber defects, especially if they are early, if they are focal — circum papillary retinal nerve fiber layer measurements can miss these types of early defects. Here is an example demonstrating that we have a clear retinal nerve fiber layer defect. Inferotemporal sides of the optic disc. The quadrant measurements and the thickness profile — unfolding of the circular scan, as I said, retinal nerve fiber layer thickness is greatest over the superotemporal region, and also inferotemporal region. In this thickness profile, that is a hint that there appears to be a thinning of the retinal nerve fiber layer right over here. But if you’re able to get a topographic measurement, you’re getting much more information in terms of the retinal nerve fiber layer thickness distribution, and you get a high confidence deciding whether the retinal nerve fiber layer measurements are normal or not. So I would like to share with you five steps. Some practical tips. How to interpret OCT printouts. And the number one thing when you read an OCT analysis printout is to look at the signal strength. The signal to noise ratio, or image quality, is very important in the interpretation of the retinal nerve fiber layer thickness analysis. Because it’s directly related — the signal strength is directly related to the thickness of the retinal nerve fiber layer. If the signal strength is not sufficient, you are more likely to get false positive measurements. In this case, you have a patch of red pixels over the inferotemporal sector. Although it appears to be a defect, but in fact, it’s related to a low signal strength. But if you are able to get — this is another scan done on the same day, but with a higher signal strength. The first scan, we have a signal strength of 5. The second scan, we have a signal strength of 9. So with a higher signal strength, you can see thicker retinal nerve fiber layer measurements, and then the false positive is gone. So different instruments, they have different criteria, different cutoff threshold for optimal signal strength or signal quality. The Cirrus OCT, for example, a minimum of more than 6 typically is required for a proper interpretation of the retinal nerve fiber layer thickness measurements. Sometimes when you look at the printouts, there is a lot of information. There are measurements, cup to disc ratio, thickness profile, as shown in this printout. But the two most important parts in the printout is actually the retinal nerve fiber layer thickness map and the retinal nerve fiber layer deviation or probability map. Typically, I only focus on these two maps to make a diagnosis of retinal nerve fiber layer defects. Step two — what you look for in a printout — is to look for correspondence between retinal nerve fiber layer thickness map and the retinal nerve fiber layer thickness deviation map. Now, notice that we have a deviation map showing in red over the inferotemporal sector, indicating that these pixels are below the first percentile of the normal values, suggesting that these are likely to be retinal nerve fiber layer defects. And you need to look for correspondence in the thickness map. So you see this region looks blue. This is the thickness map — indicated in false color codes, in red, indicating thick. In blue, indicating thin retinal nerve fiber layer. So this is the thickness map representation. And you do see here a correspondence between the loss of retinal nerve fiber layer in the thickness map and the normal pixels in red in the retinal nerve fiber layer thickness deviation map. It is important to look for correspondence, because a lot of times false positives can develop, or can be misdiagnosed as glaucoma or retinal nerve fiber layer defects, if you’re not studying the correspondence between the thickness map and deviation map correctly. Here is an eye with high myopia. The optic disc looks normal. The retinal nerve fiber layer looks normal. But we see these abnormal pixels happening, developing, over the inferotemporal and superotemporal sectors of the optic disc. Casually, you may recognize: Wow. That may suggest that there are retinal nerve fiber layer defects in this eye. But in fact, the correspondence is not apparent when comparing the thickness map and the deviation map. Because you do observe here very healthy-looking, thick retinal nerve fiber layers in the thickness map. Superotemporal, inferotemporal, retinal nerve fiber layer, they are intact. So these areas are false positives. And it happens very often in myopic eyes. Because in myopic eyes, the eyeball is elongated, the superotemporal, inferotemporal retinal nerve fiber layer tends to look a little bit converged over towards the macula, leaving the superior and inferior part of the optic disc relatively abnormal, compared with the normative database that is used in most OCT instruments, which they do not contain any — they do not contain eyes with high myopia. And this is a study that we did some years back, studying the performance of OCT normative databases here — we used the Cirrus OCT, and we checked the specificity and sensitivity of the built-in instruments, built-in normative database. And you can see the specificity is very bad. It’s lower than 40%. So more than 60% of eyes with myopia, when you scan these eyes, 60% of the time you get false positives. But when we use a myopic normative database, so basically we collected healthy eyes with no RNFL defects, from healthy individuals with high myopia, when we apply this myopic normative database, we’re able to get a much higher specificity. Here is an example demonstrating the difference between the instruments built into the normative database, where you get these false positives of the superior and inferior sectors of the optic disc, but when we apply a myopic normative database, we no longer see the red pixels in the probability or deviation map. So we need to be cognizant about the fact that when we image the retinal nerve fiber layer, we need to understand the refractive errors of our subjects, and we need to interpret OCT findings properly. Taking the thickness map and the deviation map into consideration. The first step when you look at OCT printouts is you need to study the area of abnormality to check whether the defects we’re looking at in this deviation map or probability map conform to the trajectories of the retinal nerve fiber layer. Now, here is an example we just saw. And you see a patch of abnormal areas. We already know this is a false positive. But what helps us to know this is a false positive detection is based on the fact that when we understand retinal nerve fiber layer defects, when they develop over the superotemporal and inferotemporal sectors, they often assume a wedge-shaped configuration. Because it is the configuration, it is the trajectories of the retinal nerve fiber layer, like over the superotemporal and inferotemporal bundles. And here is a technology we develop. We call this ROTA, or retinal nerve fiber layer optical texture analysis, which provides us a visualization of the individual axonal fiber bundle trajectories. Here we are able to see the temporal raphe. We can see the individual axonal fiber bundles over the temporal raphe on the macula, and here is the superior arcuate bundles. And this is the inferior arcuate bundle. Now, when you understand the anatomy of the distribution of these axonal fiber bundles, you are now able to appreciate retinal nerve fiber layer defects when they are there. They will take up a wedge-shaped configuration. Wedge-shaped means that the area of abnormality expands from the optic disc margin towards the macula and the peripheral retina. So you can see I have a triangular shape, pointing towards the optic nerve head. For all these examples. Before we had OCT, we relied on raphe photography to image the retinal nerve fiber layer. But this technology, because ROTA gives us a better ability to appreciate retinal nerve fiber layer defects in glaucoma, and also in non-glaucomatous optic neuropathies — so notice the wedge-shaped configuration of retinal nerve fiber layer defects in this example. Those of you who are interested to know more about this technology, you can look up the reference here, which was recently published in Nature Biomedical Engineering just a month ago. Now, when we look at this area, if it is a genuine defect, we expect the defect would be bigger when it moves away from the optic nerve head region. But in this case, we don’t see any abnormality beyond the optic disc margin. So it is an odd indication, suggesting this is an artifact. Now, notice that we also have a little bit too small patches over the nasal side. But retinal nerve fiber layer defects are quite uncommonly developed over this area. So these two patches are also artifacts, which — we don’t see these two patches, where we have a higher signal strength in this scan. So noticing that the previous area of abnormality is a false positive, I would like to ask you in this example: I show a bigger view here. You notice that there’s also a patch of abnormal pixels indicated in red. The question for you is: Is this a retinal nerve fiber layer defect? Yes or no? Can we have the poll? 15 seconds. So here are our polling results. Very interesting. 50% of you say yes. 50% of you say no. So basically it’s a very difficult question. Now… In order to determine whether the abnormalities showing up in the deviation map is genuine, a pointer is to look at the symmetry of the retinal nerve fiber layer. We notice that the superior part of the retinal nerve fiber layer here is thinner than the inferior part, based on the thickness map information. We then study symmetry between eyes, right and left, and also between quadrants. The superior and inferior quadrant. So notice that not only do we have a thinner retinal nerve fiber layer on the superotemporal side, compared with the inferotemporal side for the left eye, but when we compare the left and right, you can also appreciate the superotemporal retinal nerve fiber layer over the left is thinner, compared to the right. Yes, it is difficult. But it is a useful hint for us to determine whether there’s something abnormal here. Now, obviously with ROTA you can see pretty clear that is a definite retinal nerve fiber layer defect over the superotemporal part of this eye. The reason why we don’t see kind of like a wedge-shaped pattern is because this is a very early focal defect. Look at that. Look at the expansion. Look at the wedge shape of the defects. At the ROTA map. The triangular part, the tip of the defect, close to the optic disc margin, is actually very small. It means that the region of the retinal nerve fiber layer close to the optic disc margin — the loss of RNFL thinning, the loss of retinal nerve fiber thickness, is actually very small. And because the loss is so small that it doesn’t show up as being abnormal in the deviation map… So that’s why sometimes it’s actually quite challenging and difficult to determine retinal nerve fiber layer defects, especially when the defects are early. I hope the comparison between the superior part and the inferior part, the right and left, comparing the symmetry distribution of the retinal nerve fiber layer will give you a useful idea whether the abnormality we’re looking at here is genuine or not. Now, notice that we also have here a circumpapillary retinal nerve fiber layer scan, as mentioned. If we’re just looking at the quadrant measurement or even thickness measurement, we’re not able to detect any abnormalities. So that’s why the important take-home message for you is that we need to move away from the circumpapillary scan to topographic analysis. We need a wide field assessment of the retinal nerve fiber layer. Because when we are looking very close to the optic disc, we tend to miss information. Step five. Final step. Which is also very important. We always need to examine the macula. We always need to have a wide view. Now, notice that this eye — we have a definite abnormality in the thickness map and deviation map. You see correspondence over here. In the deviation map, we typically don’t get this beautiful wedge-shaped pattern. Because there’s annotation — it’s not perfect. But the idea here is: We get a bigger area of abnormality when we move away from the disc margin. So imagine when we move further away towards the macula, we are actually able to see bigger areas of defects. So using a macular scan is helpful to confirm any suspicious defects in the optic disc region. Because we’ve got a bigger representation. And in the left eye, you can see the deviation map doesn’t have any pixels indicated in red. So when you look at the thickness map, it’s also quite okay. It’s quite normal. It’s quite thick over the superotemporal, inferotemporal sides of the optic disc. But when you study the macula, here is the measurement of the GCIPL — you can see there’s actually a wedge-shaped defect over the inferotemporal sector. So if you’re not studying the macula, you’re going to miss a big defect of the left eye. So I hope I can point out the abnormal areas for you here. Not only just limiting on the inferior side, but also you can see some normal areas here. The upper right corner here, the temporal, the nasal side, is an artifact. Because this is a signal-void region. But for the arrows over here, and here, are these genuine retinal nerve fiber defects. So the deviation map over the GCIPL, the essential abnormalities… But when we use wide field scan here, the 12×9 OCT scan imaging the retinal nerve fiber layer, you might actually get a better idea. Now you can see the wedge-shaped retinal nerve fiber layer defects on the inferotemporal side, for both the right and the left eye. But it’s still a little bit confusing to decide whether there are genuine retinal nerve fiber layer defects over the superotemporal sides of these eyes. Because the thickness map suggests that is the case. But it’s not that apparent over the deviation map of the RNFL or the GCIPL measurements. The probability map, deviation map, doesn’t show abnormal superior loss of the RNFL and GCIPL. It’s only when we use ROTA you can appreciate that actually we have both the superotemporal and inferotemporal retinal nerve fiber layer loss. The loss is obvious and definite. But it is so hard to determine using the conventional RNFL and GCIPL analysis. So we need to recognize the limitations of OCT, especially for defects at the very early stage. But I hope that the notion when we’re able to see a wide area, when we’re able to form wide field scan, we can actually get a better understanding of what’s going on. The challenge we have here when we image the macula is that for patients with macular pathologies, it can give rise to false positive or false negative findings. So always look for macular pathologies. The normal distribution of the GCIPL thickness — the fovea is very thin because it has no ganglion cells, and the thickest ganglion cell layers is around the fovea. We have about five to six layers of retinal ganglion cells. So we have a higher density of retinal ganglion cells on the macula. That’s why we have this doughnut shape. But when we see this very atypical configuration of the thickness distribution, we always need to study the cross section of the B scan to exclude here in this case — a case of epiretinal membrane. So much about retinal nerve fiber layer and GCIPL. What is the role of neuroretinal rim assessment? We typically study the cup to disc ratio. We know cup to disc ratio is not a sensitive biomarker for glaucoma. We’re not using it in our diagnostic evaluations. But with OCT, we can quantify the rim width, with reference to the Bruch’s membrane opening. This is the standard approach. We measure the rim dimension. Now, as I mentioned before, rim assessment is a relatively specific sign for glaucoma, compared with retinal nerve fiber layer. Here is an example demonstrating why it is the case. As I mentioned, because for eyes with early glaucomatous damage for focal retinal nerve fiber layer defects, the loss is actually very difficult to detect at the rim. Because it’s so small that it’s really hard. Here the upper left panel showed the BMO minimal rim width analysis. They’re all normal. So nothing is flagged up as abnormal here in the BMO-MRW analysis. But with OCT retinal nerve fiber layer analysis, we’re able to see a pretty definite clear retinal nerve fiber layer defect in this case. So for nerve damage assessment, retinal nerve fiber layer is more sensitive than neuroretinal rim. But we still need to rely on the neuroretinal rim. We need to evaluate the optic disc clinically, in a diagnostic evaluation of glaucoma. It is important, because we need to exclude other causes of optic neuropathies. All forms of optic neuropathies would have thinning of the retinal nerve fiber layer. All forms of optic neuropathies would have loss of retinal ganglion cells. Glaucoma is characterized by not just loss of the retinal nerve fiber layer, but also loss of the neuroretinal rim. So that’s why examination of the rim is important. By contrast, non-glaucomatous optic neuropathies, they often have intact neuroretinal rim. And (audio drop) glaucomatous optic neuropathy is pale. In fact, there are studies demonstrating that neuroretinal rim color was 94% specific for non-glaucomatous optic neuropathy. So that’s why it is very important to not just rely on OCT, but also you need to study, you need to look at the optic disc configuration in particular. You need to study the color of the neuroretinal rim. Here is a patient. The right eye, left eye, you can see the left neuroretinal rim is intact. As normal as the right, in terms of the rim dimensions. But the color of the rim definitely is abnormal on the left side. But if you look at the OCT retinal nerve fiber layer thickness, it’s difficult for you to differentiate based on this presentation whether it is glaucoma or not. Because it also has pretty extensive thinning of the retinal nerve fiber layer, more over the superotemporal side than the inferotemporal side. So studying the optic disc is important. Glaucoma is very common. Actually the most common form of optic neuropathy. It’s characterized by cupping, loss of the rim, loss of the retinal nerve fiber layer, but the residual rim — look at the residual rim in this advanced glaucomatous eye. Remains pink. That’s why studying the rim color is important. The disc looks pale, because the rim is very thin. But the residual rim remains pink. So I have five quizzes for you. And I think it’s a good time for us to take some exercise to know whether you’re able to master some tips and tricks for interpretation of OCT. So quiz number one. We have this OCT printout. The question for you is: We have retinal nerve fiber layer or GCIPL defects in this eye. A, yes. B, no. Polling time! 15 seconds. So 82% of you say it is A, retinal nerve fiber layer/GCIPL defects. And 15% say no. So let’s take a look. The manufacturer says that more than 40 signal quality is acceptable. We have 62 signal quality. We do see correspondence in the thickness map and the deviation map. So we have a wedge-shaped, triangular-shaped retinal nerve fiber layer defects in the thickness map, and we also have correspondence. Meaning that the deviation map or probability map shows up in red, corresponding to the abnormal thickness in the thickness map. And we do have a certain degree of asymmetry. The superior retinal nerve fiber layer is thicker than the inferior retinal nerve fiber layer, and when we look at the macula, here is the macular GCIPL analysis. We see bigger defects because of the wedge-shaped panel. So here is an eye with the clear retinal nerve fiber layer/GCIPL defect. Quiz two. We have a second case. We have retinal nerve fiber layer/GCIPL defects in this eye. 15 seconds. So 61% say yes. 40% of you say no. Okay. Let’s go through this once again. Now, when we look at the signal strength, we have pretty good signal strength of 7. But when we study the correspondence, again, I think this is a very important example we need to be aware of. Here is an eye with high myopia. And for eyes with high myopia, the retinal nerve fiber layer thickness is superotemporal and inferotemporal axonal fiber bundles. They tend to converge a little bit towards the macula, because of the axial elongation of the eye. So this OCT, it doesn’t have a myopic normative database. So that’s why it leaves the superior and inferior part of the optic disc here relatively abnormal, relative to the normative database it has. So given the fact that we’re able to see pretty good looking thick retinal in the thickness map, here we have pretty red signals. Red means thick. We have thick retinal nerve fiber layer over the superotemporal, inferotemporal side. For both the right and left. So these abnormalities showing up in the deviation maps are likely to be false positives. Likewise for the GCIPL, these measurements are false positives. Just because the GCIPL in myopic eyes basically is also thinner, compared with normal, healthy eyes. So the normative database in the system’s instruments are not able to account for these myopic differences. So we have retinal nerve fiber layer artifact defects in this case. Quiz three. Now, let’s study the left eye first. Do we have RNFL/GCIPL defects for the left eye? Polling time. 15 seconds. We’re asking about the left. Polling time, please. Do we have RNFL/GCIPL defects over the left eye? Okay. Most of you say yes. It’s quite definite that we have retinal nerve fiber layer and GCIPL defects. We can go through this again. We have relatively good signal strength of 7. And then we do see correspondence between the thickness map and the deviation map. You see lots of red in the thickness map, and the appearance of red in the deviation map. So there is a good correspondence. And then the shape of the defects is almost wedge-shaped. Meaning that the area of abnormality is bigger when it gets away from the optic disc margin. And we do see asymmetry. The superior retinal nerve fiber layer is thicker than the inferior. It’s pretty obvious. And then when we study the GCIPL — again, you see much bigger defects over here, compared with the RNFL analysis. Because of the wedge-shaped pattern that expands towards the macula. That’s why we see bigger defects here. So very clearly, we have a definite retinal nerve fiber layer/GCIPL defect. Quiz four. Now, let’s look at the right eye. Do we have RNFL/GCIPL defects of the right eye? Polling time. 15 seconds. Okay. Most of you say no. 70% of you say no. Let’s go through this again. Good signal strength. 8. And do we have correspondence? I believe we have. Here we have relatively blue superotemporal retinal nerve fiber layer, although the patch next to it is red. So it’s really hard to tell. But there is a correspondence over here. So we have deviation map showing up in red and the thickness map in blue. Wedge shaped — probably not that wedge shaped. It’s a linear type of streak we’re looking at here. It’s hard to tell. Asymmetry. Again, it’s difficult. When we look at the superior and inferior, it looks like they are having more or less the same thickness of the retinal nerve fiber layer. And then when we compare the rise in the left — the left obviously looks normal, especially over the inferior side. So when we look at the macula, here again is a tiny kind of rim of abnormality. It’s really borderline, really hard, very difficult for the right eye. Let’s look at the wide field. When we look at the 12×9 scan, you can now appreciate there is a more wedge shaped appearance of the defects detected over the superotemporal side. And it corresponds pretty well to the deviation map or probability map. Here the red pixels indicating that these are abnormal, below normal, retinal nerve fiber layer thickness measurements. So we do believe that this is a genuine superotemporal retinal nerve fiber layer defect. So again, it’s hard. And that’s why sometimes in these cases, to get a wide field examination and then also in this case, you may also get a visual field to confirm whether there is a correspondence between structural change in OCT and functional loss in visual field. Visual field is not always required in the diagnosis of glaucoma. But for these cases, when you have suspicion, there is a defect there. It’s helpful to have a visual field to confirm the abnormality. Last case, quiz number 5. A 50-year-old lady with long axial length. We do observe here an optic disc, pretty much glaucomatous-looking. We have apparently loss of the rim of the inferotemporal side. Question for you: Is it glaucoma or not? Polling time. 15 seconds. Half of you say yes. Half of you say no. It’s difficult, again, because of the very glaucomatous-looking feature of the optic disc in the fundus photograph here. But when we study, the signal strength is okay, but when we study the correspondence, again, it’s a very typical example where we have pretty normal-looking retinal nerve fiber layer in the thickness map. The deviation map obviously is not normal. We have superotemporal, inferotemporal patch of red pixels, showing up in the deviation map. But again, the fact is: This eye is a high myopic eye. And the normative database would not be appropriate here to indicate abnormalities. So again, I think we need to train ourselves more often to study these maps and to study correspondence. The shape of abnormality to get a better sense how to determine whether it is normal or not. The idea here that this eye is likely to be normal can be echoed with a ROTA map. Here we have pretty good-looking trajectories of the axonal fiber bundles. They’re intact. You see the raphe over here, and you see the axonal fiber bundles that run along with the retinal vessels. So we don’t see any abnormal loss of the retinal nerve fiber layer in this case. So there is no evidence of glaucoma. Despite the fact that the neuroretinal rim looks quite abnormal. But the retinal nerve fiber layer assessment is by far a more sensitive way to determine the presence of optic nerve damage. In this case, we don’t have any evidence of optic nerve damage. So here is the last slide, just to outline some take-home principles for diagnostic evaluation of glaucoma using OCT. We need to rely on the map or topographic assessments of the RNFL and GCIPL, because it is by far more informative and sensitive, compared with circumpapillary retinal nerve fiber layer thickness analysis. To detect optic nerve damage in glaucoma. I’m sure a lot of us tend to rely on the thickness plots or the clock hours or quadrant representations. Because it’s easy. But I hope to encourage you to study more often the distribution of the retinal nerve fiber layer of the map, because we don’t need to limit ourselves to the circum scan. The reason why we use the circum scan is because before we had Fourier domain OCT, time domain OCT is very slow. That’s why we only got a circum scan measurement. With the faster Fourier, spectral scan OCT, the scan is in a wide field. So it’s important for us to get more information from this wide field analysis. So point number two: Wide field OCT imaging, including both the optic disc region and the macula, is important. The retinal nerve fiber layer developing superotemporal, inferotemporal — they are often wedge-shaped. So wedge-shaped means the area of abnormality expands towards the macula. And that’s why it is easier to detect abnormality over the macula than over the optic disc region. Especially for early defects. But we need to look for macular pathologies to avoid false positive or false negative diagnoses. Finally, point number three: Retinal nerve fiber layer assessment is more sensitive than rim assessment for detection of optic nerve damage in glaucoma. But we need to evaluate the optic disc. We need to evaluate the rim basically because glaucoma diagnosis requires loss of the retinal nerve fiber layer and narrowing of the neuroretinal rim. And then we also need to exclude non-glaucomatous optic neuropathies by studying the color of the rim. A pale-looking neuroretinal rim is indicative of non-glaucomatous optic neuropathy. So thank you very much. I hope my lecture is practical. I understand a lot of you may not have gotten the correct answer. It’s not easy. But I hope you can get more time to practice reading OCT. To practice reading the printouts. And I’m sure you’ll get more confident when you use OCT more often. I would like to take the last five to ten minutes to answer some questions posted in the Q and A. The first question is: Is there any method quantifying ocular nerve damage into mild, moderate, severe, and end stage? It’s a good question. For visual field, we typically use mean deviation, MD, to classify mild, moderate, and severe. -6, better than -6, is classified as mild. Between -6 to -12 is moderate. Worse than -12 is severe. But unfortunately, we don’t yet have these figures for OCT. In fact, OCT measurements of the retinal nerve fiber layer thickness — the measurements, the numbers themselves, cannot be used interchangeably between different models of OCT. So it’s actually pretty hard to get a threshold. And so we don’t have that. But for structural assessment, using OCT, I think, is always helpful to get an idea about the location of abnormality, and also in terms of the staging, the disease, we actually more often rely on visual field assessment. We can relate the regional changes in OCT to the regional changes in the visual field to get a better assessment of glaucoma overall. Question number two. Considering the fact that there’s no normative data for OCT in those younger than 18, can we make a diagnosis of glaucoma using OCT in younger individuals? We cannot make a diagnosis of glaucoma using OCT alone. Now, imagine, as I said before, if you just look at OCT without studying the optic disc, here is an example I just showed to you earlier. If you just look at the OCT, without looking at the optic disc, you would misdiagnose glaucoma in this case. Because this is not a case of glaucoma. This is a case of non-glaucomatous optic neuropathy. So you need to look at the optic disc. You cannot just rely on OCT alone for all ages. For younger individuals, it is also a problem. We don’t have a normative database for young individuals. So it is quite difficult to make a diagnosis of retinal nerve fiber layer defects in young individuals at this stage. Question three. How can we drive adoption of universal normative… It’s a good suggestion. But I think the challenge here is we have so many different OCT models, different countries, different cities, different clinics, they may use different OCT instruments. And it’s really hard to standardize a normative database. And a normative database is also problematic in myopic eyes. So it’s not easy to get the job done. Question number four. What is your comment on the (inaudible) analysis? GCIPL or GCC? They’re basically the same thing. GCC includes RNFL and GCIPL. GCIPL includes just the GCIPL, excluding RNFL. But in terms of the diagnostic performance, they’re pretty much comparable. Question five: What happens in a situation where a patient is both high myopic and glaucomatous? How would they present? Very good question. We have a lot of difficulties in determining glaucoma in eyes with high myopia. Because of the disc configuration, because of the abnormal or unusual configuration of the rim. OCT, extremely useful. But the normative database is not that helpful. So I would typically study the pattern of the distribution of the retinal nerve fiber layer thickness in the thickness map. The deviation map is not that useful. So relying on the thickness map representation is hard. It’s not easy. Because it’s not a quantifiable — it’s a qualitative assessment. But if you read these maps enough, I’m sure you would get a better sense of whether it is glaucomatous or not. So relating the disc configuration with the retinal nerve fiber layer thickness map, I think, is an important approach in the diagnostic evaluation of glaucoma. ROTA, or retinal nerve fiber layer optical topographic analysis, the technology I just mentioned, is also extremely helpful in the diagnostic evaluation of myopic optic disc for detection of retinal nerve fiber layer defects in glaucoma. So a couple of questions asking what OCT instruments I would recommend… I would recommend any instruments that can provide you a topographic wide field analysis of the retinal nerve fiber layer and GCIPL. So there are many OCT models on the market that only show the circum scan. Although some models, they perform raster scan or clip scan or the optic nerve head or the macula, but they don’t have this probability map or deviation map. So what I would recommend is that you can use any models that show both the thickness measurements in the wide field and the probability classification in the wide field. That would be ideal. Thank you very much for your attendance. I hope I can share with you some time in the future about interpretation of diagnostic evaluation of glaucoma progression. Thank you very much. Have a good day.

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