Lecture: Glaucoma: A 2020 Update

DR SRINIVAS: Thank you. Hello, everyone. Thank you so much for joining me today. The title of today’s talk is: Glaucoma, a 2020 Update. My name is Dr. Sowmya Srinivas. I practice at Dartmouth Hitchcock Medical Center in Lebanon, New Hampshire. I have no disclosures. So the outline of today’s talk will include an introduction and an overview of glaucoma. We’ll review some landmark clinical trials, and what we’ve learned from them. We’ll go over diagnosis and management of glaucoma. We’ll discuss therapeutics. And finally, close with some cases based on what we’ve learned this morning. So why is glaucoma important to identify? And what tools and knowledge, old and new, do we have to diagnose or treat or manage glaucoma? So from this picture, you can see that the number of people over 65 years of age is steadily increasing. And people are living longer. So this is a graph of the aging population in the world, compared to the United States. And it’s showing that life expectancy has steadily increased. And here’s a picture representing that life expectancy is increasing all over the world. And people are living much longer. Generally beyond 65 years of age, as you can see in this diagram. In many parts of the world. So the projections for glaucoma, from 2010 to 2050 are shown here. And you can see that among all ethnicities, the incidence of glaucoma is expected to more than double from 2.7 million to about 6.3 million. What does this mean for eyecare professionals? We have a responsibility to provide good quality of life for all our patients, so it’s important to identify and treat glaucoma early on, so we can have our patients enjoy a good quality of life as life expectancy is increasing. So here’s our first polling question, which is: What is the definition of glaucoma? Is it, one, retinal ganglion cell loss? Is it, two, optic nerve damage with corresponding visual field defects? Three, increased IOP is a modifiable risk factor? Or all of the above? Before we delve into more of the specifics, please choose the definition of glaucoma. You did a great job. All of the above is correct. This indeed is the definition of glaucoma. Excellent start. So now we’ll step back and review some of the landmark glaucoma studies, and how they affect our management strategies today. So the first major study was in 1998. And this was a collaborative normal tension glaucoma study. There were a few key points to take away from this study. And those were: The risk of progression, including higher in females more than males, and if a disc hemorrhage reoccurred on your clinical exam, they had a higher risk of progression. And any patient with a migraine history also had a higher risk of progression to glaucoma. And so this was the first study to clearly demonstrate that lowering IOP is an effective treatment for glaucoma. And in 2000, there was an advanced glaucoma intervention study. And the main takeaway points from this study included: Higher IOP fluctuation was associated with visual field progression. There was reduced risk of progression with consistently 18 millimeters of mercury or below of IOP. And this study also showed that African Americans had less progression with initial laser treatment, while Caucasians had better outcomes with trabeculectomy. And a year after that, another study, the collaborative initial glaucoma treatment study, which showed that quality of life and blindness from glaucoma are a concern. So IOP lowering is beneficial in glaucoma in all clinical situations. So the mean deviation, if the patient’s mean deviation is -10 or worse on visual field, they have a more likely visual field progression, with either medical versus surgical treatment. But if their MD, or mean deviation, was -2 or better, there was no difference, if a patient was treated surgically or medically. So, in other words, consider surgery in advanced glaucoma. So filtering surgery is easier, before eye drops are used. And major surgical complications are few. The main point is to keep IOP steady and evaluate and reevaluate the IOP, because every 1 millimeter of IOP matters when you’re treating glaucoma. And the next large scale study that came out was the ocular hypertension study in 2002. So this study showed that risk factors for primary open-angle glaucoma development are the following. Advancing age, increased IOP, a greater pattern standard deviation on a visual field test, thin pachymetry, in other words, central corneal thickness, and vertically elongated or increased cup to disc ratio. And the European glaucoma protection study, which came a few years after this study, in 2005, showed the same risk factors for progression as the ocular hypertension study in 2002. So this is a representation of ocular hypertension study. So observe that if a patient’s pachymetry reading is less than 555 micrometers — about 550 is average — in other words, if they have thin pachymetry, and their IOP is greater than 25 millimeters of mercury, they have a 36% chance of progression to glaucoma. Whereas if their IOP is thick, anywhere above 588 thickness, they have just about a 6% progression to glaucoma. So in the early manifest glaucoma trial, which came in 2002, it showed that baseline risk factors included increased IOP, again, advancing age, presence of exfoliation, bilateral disease, and worsening deviation on visual field, and also disc hemorrhage recurrence. So this study showed that more or less the risk of progression is less with the larger IOP drop. So the sooner we catch and identify glaucoma and treat glaucoma, the patient’s risk of progression is less. As you can see here, based on control versus treated groups. So the main clinical pearl from the landmark studies of glaucoma showed the evidence that lowering IOP reduces risk of further progression, and this must be regarded now as very strong. So the main takeaway from all these studies is diagnose and treat early. So as you all know, some of the diagnostic procedures for glaucoma include measuring the IOP, or intraocular pressure, pachymetry, gonioscopy, clinical exam — in other words, evaluation of the optic nerve — and diagnostic imaging is used. The OCT, GDx, HRT, and of course, visual field. So when we took a step back and learned about clinical studies and how we can — each millimeters of mercury matters when we’re treating glaucoma. Some of the newer parameters for earlier diagnosis and management include the following. Over the past few years, we learned that corneal hysteresis, the shock absorbing properties of the cornea — it’s the cornea’s ability, in other words, to absorb and dissipate energy. So corneal hysteresis measurement, if high, confers a protective factor for glaucoma. Less risk of progression, versus a lower corneal hysteresis measurement. Ganglion cell complex analysis tests the macular area. And we’ll go over how we can use this to diagnose glaucoma early on. HVF 10-2 is another newer parameter used in diagnosis and treatment, because recall that in 24-2, only 4 test points are tested in the macular region, and these test points are spaced about 6 degrees apart. And OCT angiography has been used in more recent days to observe blood flow, to evaluate the health of the ganglion cells. So we see loss of ganglion cells early on — we can diagnose and treat glaucoma early. And some of the newer visual field strategies include adding central points to the standard 24-2, so this is the 24-2C. And this test adds about 10 additional points in the central 10 degrees, so what this does is: We can detect glaucoma, or central scotomas early on, and recent studies have shown that central 10 degrees were undertested, relying on the older 24-2 visual field. So now we’ll get into the concept of structure and functioning glaucoma. So diagnosis of glaucoma can be made based on your clinical exam, and imaging, like we discussed. So we correlate what we see on the optical coherence tomography, which is the structural aspect, and functional, which is the visual field abnormality. So we used these tests to identify glaucoma. And earlier identification of glaucoma, the strategic use of both of these devices, may result in an opportunity to intervene as early as possible in the glaucoma disease course, and we avoid preventable and progressive vision loss. So you may have heard about glaucoma red and green disease. So when we find the OCT color pattern is all green, we cannot assume that everything is normal. So, in other words, ophthalmic imaging is an important clinical adjunct to your clinical exam. And we use these imaging devices in conjunction with our exam. But do remember that there are artifacts in imaging, and there are limitations in technology, because certain normative databases are used. So we’ll go over some examples here next. So, as you know, OCT has become an integral component of modern glaucoma practice. It’s important to recognize that green disease, or when you see a color pattern which is green, we cannot assume that everything is normal. It should prompt you to do a good clinical exam. It should prompt you to explore the structure-function component. So, in other words, if you’re seeing a structural damage, does this match up functionally on a visual field test? And this way you can avoid missing glaucoma treatment, if it’s necessary. So here’s an example of red disease. So the thinner retinal nerve fiber layer of the high myope does not conform to the normative database, and is colored red. So if you observe on the optic nerve scan — there is a large amount of peripapillary atrophy. So what the OCT below is showing is: There are a lot of red areas on the OCT nerve fiber layer scan. But this does not mean that the nerve fiber layer layers are damaged. So this happens when you see red. You cannot misinterpret and say that this patient definitely has glaucoma. Because of their high myopia, the OCT is showing a lot of red areas. But we have to take into consideration other factors. So here is an example of, quote-unquote, green disease. So here the OCT appears green. As shaded in both left and right eyes. But if you notice on the left eye, the retinal nerve fiber layer measurement is labeled normal. But if you look at the small red arrow, it points to a focal loss, inferotemporally, in the left eye. But if you look at the corresponding OCT, it’s highlighted green. So this is easily detectable on the posterior pole, and retinal thickness map, and hemisphere asymmetry analysis, which is on your right, so if you were going based just on the color patterns, you would have potentially missed the small focal defects that are shown on the right lower part of your screen. So again, it’s very important to use imaging in conjunction with your physical exam, as opposed to looking at color patterns and saying: Red is definitely glaucoma or green is definitely normal. So it’s important to correlate structure and function. So here are visual field defects we expect in glaucoma, including nasal step, arcuate defect, and others, as noted below. So it’s important to grade the severity of glaucoma, because it can help you tailor the treatment for each individual patient. So mild is characteristic optic nerve abnormalities or consistent with glaucoma, but there’s a normal visual field. Moderate glaucoma means visual field abnormalities, or one hemifield, and not within 5 degrees of fixation. Severe glaucoma is when visual field abnormalities are in both hemifields. And the loss is within 5 degrees of fixation. Glaucoma can also be staged on mean deviation patterns. Mild, moderate, and severe. You can see the 30-2 SITA cutoff points on your left hand side. So we talked about ganglion cell layer analysis, and how it’s important to use that aspect in management and diagnosis of glaucoma. So A, which is the top left hand portion of your screen, shows the ganglion cell layer. Image of the patient’s left eye. In the middle is a retinal nerve fiber layer map. And on the right hand side is a visual field. So ganglion cell layer, if it’s shaded red, is actually normal. So if you look in A, the ganglion cell layer is actually quite robust and normal. So red is normal. And you can see that this patient has a very strong robust and normal ganglion cell layer in A. The retinal nerve fiber layer also looks excellent in this patient’s eye. And therefore the visual field is normal. These are correlating and corresponding with each other, showing that this patient has normal ganglion cell retinal nerve fiber layer and functionally has a normal visual field test. If you look in B, you’ll see that the ganglion cell layer is damaged. Damaged inferotemporally here. And the retinal nerve fiber layer also shows some thinning on the inferior portions. And therefore the visual field matches with the early superior loss. So this is corresponding with each other. This is how you use the testing. So again, structure and function, which is a visual field. In C, you can see there’s absolutely no red. So the ganglion cell layer is very thin. And the retinal nerve fiber layer also shows a thinning pattern, especially inferiorly. You can see that the ganglion cell layer — you don’t see any evidence of any ganglion cell layer, and the superior field loss is corresponding to both of these images. So again, this is a great way to use ganglion cell thinning and the retinal nerve fiber layer to correspond your visual field defects, to help identify glaucoma, early on. So now we step into the management of glaucoma. So here glaucoma suspects or glaucoma diagnosis. So again, if present, we stage their disease, as we learned. Mild, moderate, or severe. And then we assess the risk. We look at age, we look at patient’s IOP, we look at pachymetry, severity of damage, whether glaucoma is unilateral or bilateral, we look at the presence of disc hemorrhages, and family history. It’s important to note that the risk of glaucoma is higher if a sibling has glaucoma. And then we come up with our treatment plan. And surveillance. So we establish baseline with OCT and visual fields. And photographs. And then monitor based on the severity of diagnosis. So we discussed how the risk of glaucoma is higher if a sibling has glaucoma. So this study by Sung et al. showed that siblings of glaucoma patients have a higher increased risk of developing glaucoma, and the risk increases with age. So the way I use this in my clinical practice is to ask patients if they have siblings with glaucoma. And in that case, I can monitor them closely and start treating early on, if I see any signs of glaucoma. You can also urge patients, if you see glaucoma in an individual’s eyes, you ask if their family members — especially siblings — have been tested for glaucoma. And so this may — we can catch and identify and treat glaucoma early on, knowing that siblings have a higher risk — siblings of glaucoma patients have a higher increased risk of developing glaucoma. So here is your next polling question. What is the best type of imaging to use to detect progression in mild to moderate stages of glaucoma? OCT, HVF, both, or none of the above? So we’ll go over this next. So it’s very important to remember that the best method to detect progression varies depending on the stage of the disease. So you’re right. We use both tests. But remember that in mild to moderate glaucoma an OCT is more effective, but there’s a concept called floor effect. So about 55 or 60 micrometers — the OCT starts to bottom out. Which is why in moderate to advanced glaucoma, we would use a visual field test. So going back to this question, what is the best type of imaging to detect in mild to moderate glaucoma? The answer is actually A, OCT. And we’ll go over this concept on the next slide. So this concept is important to remember. This is the floor effect on the OCT devices. The floor effect happens at approximately 50 to 60 micrometers. It varies on each OCT device. And this happens because the average retinal nerve fiber layer measurement never goes to zero with advancing damage. So you’re bottoming out at 55 or 60, and it does not go any lower, because in addition to the nerve fiber layers, the optic nerve is comprised of glial and other structural tissue, which accounts for 40% of its makeup. So for that reason, we’ll see in the case example that there’s a floor effect on OCT, and we can only use OCT effectively in mild to moderate stages of glaucoma, and then when the moderate to advanced stages of glaucoma — we rely on visual fields. So there are a couple of ways to measure progression. The first one is trend analysis. So trend means rate of change. So this is a regression line, drawn to determine the rate of change for data collected over time. So here we can use visual field index or mean deviation or retinal nerve fiber layer thickness to monitor trend analysis. And the slope or percentage of rate of change is calculated. And this is most valuable when multiple visual field tests have been performed. And this trend analysis, which is a measure of progression, is good for identifying fast progressors and generalized or large visual field defects. So here’s an example of trend analysis. So on your y axis is the visual field index. On the x axis is the rate of progression. So in this particular patient, we have several visual fields that have been performed, and we can see that with good confidence they are remaining essentially close to 100%, which means if their therapy is — IOP therapy is stable, then this patient has a very high likelihood of maintaining good vision for many years. So the second way to measure progression is event analysis. Event analysis means: Has this changed, compared to baseline or consecutive tests. And this is a point by point basis. Look at the testing. So this is mostly used in the early follow-up time period. But it’s also helpful in middle and late stages of the disease. So here what you would like for are shaded triangles, indicated by a single point, which is worsening over consecutive tests. And the event analysis is good for identifying slow progression and focal defects. Here is an example of event analysis. So on the top visual field, this is from August 2017, there are shaded triangles in the inferior portion of the visual field. And this indicates a single point, which is changing over consecutive tests. This particular patient happened to improve in the follow-up testing. But if things were worsening, you would look for the shaded triangles to identify a slow progression or focal defects to appreciate the change for event analysis. So this brings us to visual testing. How many visual field tests are needed to detect change? Many studies have shown that insufficient testing can fail to detect glaucoma progression. So based on this particular study, by Chauhan in 2008, it showed approximately 6 visual field tests over 2 years, or approximately 1 visual field test every 4 months is needed for a patient who is progressing at -2 decibels per year. So in other words, if we do insufficient testing, we can fail to detect glaucoma progression. Which brings us to our next point. So I have many patients in my clinic who have a hard time doing visual field tests, because if you look at the SITA standard 24-2, the approximate time to takes to run a SITA standard 24-2 is a little over 7 minutes. SITA Faster is up to 50% faster. And this study, by Heijl et al., showed that all three tests, the Faster 24-2, SITA Fast, and SITA Standard had variability over an entire range of threshold values. So in other words, if a patient has a hard time focusing or concentrating on SITA Standard, you could consider doing a SITA Faster or SITA Fast 24-2 and still be able to manage their glaucoma appropriately. So this brings us to treatment. So as we discussed, it’s important to slow the progression of disease or blindness, as patients are living longer, and we have to give them a good quality of life. And prevent progressive vision loss. The goal here is to lower IOP medically or surgically. But when we do that, we have to consider burden of treatment and the cost of treatment. And compliance becomes a huge issue. So this is one study which showed the total non-compliance was about 15%, 16%. And full compliance was only 50%. So it’s really important to remember compliance when it comes to treating glaucoma patients. So next we’ll talk about advances in therapeutics. There are a new class of prostaglandin analogs, which were introduced in 1996, and this set high standards, due to effectiveness, dosing frequency, and minimal side effects. This is dosed once at night. Several combination drops have been approved in recent years, and there have also been advances in surgical techniques, such as SLT and MIGS. So the mechanism of medications — so prostaglandin analogs — were by increasing uveoscleral outflow. Beta blockers decrease aqueous production. Alpha adrenergic agonists decrease aqueous production and increase uveoscleral outflow. Miotics increase trabecular outflow, and carbonic anhydrase inhibitors decrease aqueous production. This is a quick overview of mechanism of medications used in glaucoma therapy. And here are specific medications. The drugs that work by trabecular meshwork, uveoscleral pathway, and aqueous humor. So latanoprostene bunod works using two pathways. The aqueous humor outflow, and the mechanism of latanoprostene bunod is depicted in this diagram. The green arrow demonstrates conventional outflow through the trabecular meshwork and Schlemm’s canal. The yellow arrow designates the unconventional pathway out into the ciliary muscle and suprachoroidal space, and both of these pathways are used and are increased by latanoprostene bunod. So the pharmaceutical landscape over the following years have included the following. The prostaglandin analogs in 2017/2018, Vyzulta, as we learned in the previous slide, increases uveoscleral outflow and relaxes TM. This was shown in the APOLLO and LUNAR phase 3 studies, and showed lower IOP compared to timolol alone. Monotherapy. Latanoprost emulsion or Xelpros has no BAK, it has a different preservative, and the rho kinase inhibitors enhance trabecular meshwork outflow and reduce episcleral venous pressure. And the ROCKET 1 and 2 studies showed it was non-inferior to timolol. The MERCURY 1 and 2 studies showed that Rhopressa and latanoprost had a greater reduction in IOP compared to monotherapy alone. Here’s a quick overview of ROCKET and MERCURY trials with Rhopressa and latanoprost. So fixed dose combination of both of these medications were superior in decreasing IOP at all time points over a span of three months. Patients achieved at least a 30% reduction from baseline IOP. So this was in comparison to the monotherapy. So either Rhopressa or latanoprost monotherapy. So some clinical pearls, based on what we’ve used so far. So progression detected using clinical exam, photographs, imaging, and visual field are extremely important in diagnosing and managing glaucoma. So it’s important to be vigilant and detect change early on. And it’s important to remember that we have to perform enough tests to establish baseline and be able to monitor and detect change. And over time, with stability, we can reduce the interval for testing, but if change is detected, we need to modify the exam and testing interval. So the main concept, the huge clinical pearl here, is diagnose and treat early. For glaucoma. So next we’ll jump into some cases. And here’s a case of a 78-year-old Caucasian female. She has 0.8 cup to disc ratio in both eyes. As you can see on the fundus photos. The IOP is low to mid-teens. Angles are open on gonioscopy. There’s no pigment dispersion syndrome. No pseudoexfoliation. Average pachy is about 560 microns. There’s no family history for this patient. And the optic nerve cup to disc ratio has been noted to be this way since 2011. Here are her OCT and rate of progression on her visual field. And her visual field index has been about 100% in both of her eyes. So we come to our next polling question here. What is your diagnosis for this particular patient? Do they have mild open-angle glaucoma, moderate open-angle glaucoma, severe open-angle glaucoma, angle closure glaucoma, or physiological cupping? Correct. So the majority of you chose physiological cupping, which is correct. So if we look back as a quick review, her nerves are large. But her testing has been stable over many years. And so therefore physiological cupping is the right answer for that particular patient. So here is our next case. So this is a 45-year-old Caucasian female. As you can see in the nerve photos, she has tilted nerves. Peripapillary atrophy. And borderline cup to disc ratio. Her IOP, mid teens. There is no pigment dispersion. Pseudoexfoliation. She has average pachymetry. Angles are open to ciliary body band. So open angles on gonioscopy. Normal OCT. Normal 24-2. And no family history of glaucoma. So here is this patient’s optical coherence tomography, retinal nerve fiber layer scan. And her visual field tests in both her left and right eyes. So this brings us to our next polling question. What is your diagnosis for this patient? Mild, moderate, severe glaucoma. Or would you watch this patient as a glaucoma suspect? Exactly. We’re watching this patient as glaucoma suspect. She is myopic, and there’s a high risk in myopic patients. I would definitely watch this particular patient as a glaucoma suspect. So here’s another case of a 67-year-old Caucasian female. She’s been diagnosed with mixed mechanism glaucoma and pseudoexfoliation in her right eye. So she’s had PIs in both eyes and cataract surgeries in both eyes. And her baseline IOP was 23. Her pachy was 560, and her recent IOPs have been within target. So less than 18 OU on timolol, which she reports good compliance with, and she uses every morning in both eyes. So here is the optic retinal nerve fiber layer scan on the left hand side, and on the right hand side, the ganglion cell layer is robust in both her left and right eyes. And here are her visual fields. So based on these tests, it tells me that her IOP is managed very well, and we’re using all of the imaging modalities here, to make sure that this patient is compliant with therapy. And we’re using optic nerve scans, the ganglion cell layer, and visual field, to make sure her IOPs are within 18, as this shows the glaucoma has been managed well in this patient’s case. So here’s a 75-year-old Caucasian female. Chronic open-angle glaucoma. She’s had history of ALT and SLT in both eyes. Her pachys are then, her target should be less than 20 on latanoprost and timolol. So here is her right eye. So the retinal nerve fiber layer, the ganglion cell, and the visual field of her right eye. So notice how the ganglion cell layer is essentially gone temporally. And because of that reason, you’re seeing nasal defects in the right eye. So again, matching structure, retinal nerve fiber layer, ganglion cell, and function, so because of the thinning of the temporal aspect, you can see some nasal defects on her visual field in the right eye. Here is the left eye. Some thinning of the ganglion cell. Here’s the retinal nerve fiber layer scan, as well as visual field in her left eye. And because of the thinning of both the ganglion cell layer and the retinal nerve fiber layer, the functional component of the visual field is being picked up… Inferonasally in her left eye. So again, another example demonstrating how we used retinal nerve fiber layer, ganglion cell, and visual field to monitor and manage glaucoma. So here is a 54-year-old Caucasian male, chronic open-angle glaucoma, left more than the right eye. IOP on the date of the exam was 18 in the right, 26, and if you notice, his T maximum was 25 and 34. The pressure in his left eye is approaching Tmax. There’s a family history. His pachys are very thin. 506 in the right, 509 in the left. Angles open on gonioscopy, he’s on Trav Z, and Alphagan was added twice a day OS. Latan/Lumigan/timolol was ineffective and he hasn’t had any surgery. Here are his visual fields for his left and right eye, starting from 2017. There’s one in 2018 and 2019. And the rate of progression for both his right eye on top, left eye on the bottom. So for this patient, what is the next best course of action? Would you, A, add another drop? B, would you refer this patient to a glaucoma specialist, considering surgical options, or would you continue to monitor this patient? Exactly. So the majority of you said refer to glaucoma specialist for surgical options, which I agree with. Again, he’s young. He’s 54. His IOP at the most recent exam was 26. Remember, Tmax was 34. Thin pachy. Family history. And poor response to three different drops. So this is someone who would definitely refer for surgical options. Next case. 69. Caucasian male. And on his most recent exam, sectoral thinning, inferotemporal, was seen. His eye pressure was 17/18 during this exam. His Tmax was 18 in the right. 22 in the left. Pachy about average. Angles were open on gonioscopy. And there was no family history of glaucoma. And the OCT on the left hand side was the baseline OCT. The follow-up, which we did on the date of the exam, showed that the inferotemporal thinning I had noted in his optic nerve on the clinical exam. So this is the area of concern, inferotemporal thinning. And the follow-up OCT did show that particular area of thinning. On his left eye. And so the visual field of the left eye is on your left hand side. Right eye is on your right hand side. So there are functional defects here. As seen in the visual field of his left eye. This brings us to our next polling question. So for this patient, would you start treatment? A, yes. Because of the early superonasal defects corresponding to inferotemporal borderline thinning, would you repeat visual field testing, or would you continue to monitor this patient? Correct. A and B are both very reasonable responses. If we step back. I went with A. But B is also… If you wanted to repeat the visual field testing one more time, to see if the defects are repeatable, that would have also been a reasonable approach in managing this patient. But I went with A. So I did start with patient on treatment, based on the early defects corresponding to the structure and functional tests, as well as my clinical exam. So here is your next case. 60-year-old Caucasian female. You can see nerve photos of right eye above, left eye below. Observe in both eyes the peripapillary atrophy. So the disc shows diffuse thinning on clinical exam, and it is also seen on the retinal nerve fiber layer scan. Her cup to disc ratio was 0.85 in both eyes. She had trab surgery about 10 years ago. Her IOPs have been stable at less than 12 in both eyes. And her global thickness was 62 for her right eye and 76 for her left eye. So the reason why I had this case up was: We talked about why it’s important to manage glaucoma looking at your clinical exam and your testing. But it’s important to notice that in her left eye, even though the retinal nerve fiber layer scan is showing on the screen, it’s important to take into consideration your clinical exam. So her cup to disc ratio was 0.85 in both eyes. She was not treated in one eye, but rather both eyes, with surgery, trab surgery, ten years ago, and it was important not to ignore the left eye showing green, that things were normal. So again, it’s important to go based on your clinical exam, imaging, and not just based on the color pattern of your testing. So here is another case, chronic open-angle glaucoma, left more than the right eye. 57-year-old Caucasian female. Family history of glaucoma in her father. Had a history of ALT and trabeculectomy in both eyes. She was lost to follow-up for more than a year. Her most recent IOP was 14 in the right and 20 in the left. Recall that her left eye has more disease than her right eye. And this patient self-discontinued latanoprost in both eyes. So here is an image of her right eye and left eye on retinal nerve fiber layer scan and nerve photos. So the global thickness was 76 in the right eye and 50 in the left eye. So remember how we talked about the floor effect on OCT? So in mild to moderate cases of glaucoma, we can use OCT to manage, but her OCT is bottoming out at about 50 in her left eye. So here is a visual field of her right eye. And left eye. So there’s an inferonasal step to even inferior early arcuate, and recall that her eye pressure was 20. Here we have a patient, 57, poor compliance, she’s not following up as advised, and she has self-discontinued latanoprost. So for this particular patient, it’s really important to be aggressive with therapy, and hone in on the importance of compliance with therapy. Again, she is young. Poorly responsive to follow-ups and medications. So this is a 77 Caucasian male. He was monitored as glaucoma suspect, seen in 2015 for a second opinion, as to whether he had visual field loss and if so whether this patient had glaucoma. Severely tilted optic nerves with peripapillary atrophy. No family history. IOP was in the mid to upper teens for many years. Tmax was 18. His angles were open on gonio. Mild hyperopia, astigmatism, and here is what you see when this patient presents to you for clinical exam. So this fundus photo shows a Drance hemorrhage. In his right eye inferiorly. Note the Drance hemorrhage inferiorly. We step ahead. We get the optic nerve scan. But notice how the quality of the optic nerve scan is poor. Especially in the right versus left eye. So we can not meaningfully use the optic nerve scan for this particular patient. Because of the artifacts to the large amount of PPA or peripapillary atrophy, and the tilted nerves. So here are his visual fields for both the right and left eyes. And the rate of progression for his visual field, the right eye above and left eye below. So for this particular patient, it’s important to — I brought him back in 1 to 2 months to check on his Drance hemorrhage, and kept a very close watch on his glaucoma progression, because of the presence of Drance hemorrhage. And again, important to use your clinical judgment and not just rely on the imaging for this particular case. And finally, monitoring progression using OCT and visual field. So this is an example of a 63-year-old Caucasian male. He had severe pigment dispersion glaucoma. He was on latanoprost nightly and brimonidine twice a day in both eyes. Pachymetry was thin, 527/537. His eye pressure had been stable at less than 11 in both eyes. And here are his retinal nerve fiber layer scans. And the global thinning — I know it’s hard to see on your slide. His global thinning was 54 and 55 in his right eye and 47/45, baseline follow-up scans. Remember how we talked about the floor effect on OCT. So his OCT is not meaningful, because it’s starting to bottom out at about 40s or 50s, so it’s important to rely on his visual fields at this point, due to severity of glaucoma, instead of — it’s still important to get an OCT, but rely on visual field, due to severity of glaucoma. So I wanted to emphasize that point. Beyond global thickness of 40 to 50, the OCT bottoms out. So it’s important to use your visual fields for managing. So fortunately, this patient has been stable. As you can see on his visual field test. And the rate of progression is holding in a stable pattern. As evidenced by this graph here. So to wrap up, it’s very important to use good clinical judgment in glaucoma. It’s important to carefully observe and document the appearance of the optic nerve. On clinical exam. You must obtain baseline imaging. And you should utilize diagnostic testing. But please remember that: Do not let the testing make the diagnosis for you. Be aware of red and green disease on OCT. Never ever diagnose red disease as glaucoma and green disease as normal. It’s really important to put your imaging and your clinical exam together, to treat and manage glaucoma. And the most important thing is diagnose and treat early. Because every 1 millimeters of mercury of eye pressure matters in glaucoma. Thank you so much for your attention this morning. And I’m happy to answer any questions you may have.

>> Thank you so much. We have a few questions, if you want to stop your screen, and open up the Q and A, and just answer as many as you have time for.

DR SRINIVAS: So medical management of uveitic glaucoma is very similar. We have our drops. So it’s important — uveitic glaucoma can be aggressive. So it’s important to manage IOP using the testing. And managing because of the aggressive nature of uveitic glaucoma. So in the ocular hypertension study, corneal thickness, if high, confers a protective factor for glaucoma. So if a patient has thick pachymetry readings, they have a protective factor for glaucoma. So it is based on pachymetry and IOP reading. Thick — corneal thicknesses is protective for glaucoma. So low tension glaucoma is… When there is damage to the optic nerve, but the eye pressure measurements are still within normal range, and the best management options are medical and surgical, for low tension glaucoma, and the reason being… It’s important to lower the IOP more than their baseline, just because the optic nerve does show damage. So you would use the same medications and surgical options for lower tension glaucoma. So the goal is to lower their eye pressure more than the baseline. So recall that OCT angiography shows the health of the ganglion cells. If there was loss of the ganglion cells early on, this was a good way to detect and treat glaucoma, using the newer imaging modalities. So it is important… Structural loss is… There’s not always a clear cut correlation between structural and functional loss. So it’s important to remember that… Not all cases of glaucoma have a very clear pattern of structural and functional loss, which is easy to pick up on the exam. So sometimes you may need some more testing. There are some gray areas. But it does make our diagnosis and treatment easier, if there is a strong correlation between structural and functional loss. So optometric management of glaucoma does include eye drops. So we would use the variety of drops that we have in managing cases of glaucoma. Besides the use of drugs such as latanoprost, what are the other treatments? So there are many classes of medications. Ocular hypertensives. Which we can use in glaucoma. And surgical options are also other treatments for glaucoma. So can SLT be used as a first line treatment of POAG? It certainly could be, but it’s important to try medical treatment first, prior to surgical treatment. But it could be the first line treatment of glaucoma if medications may have failed in the past. So the question is: Start with one drug. After initial finding, what would you start for treatment? Generally I start with prostaglandin analogs, and then I would consider beta blockers, but of course with beta blockers, you have to consider any medical history of heart or lung issues. Because beta blockers may be contraindicated if someone has heart or lung — COPD or other heart problems, so generally we start with prostaglandin analogs. The advantage with prostaglandin analogs is the dosing. So the compliance can be high. Because the medication is dosed once at night. But if they need additional therapy, beta blockers would be the second line of treatment. So how effective is the combination of latanoprost and timolol? In absence of OCT and HVF, what can be done in glaucoma? So I think the combination of latanoprost and timolol are very effective. Again, latanoprost or prostaglandin analogs are generally a good first line treatment for glaucoma. And we can then add beta blockers or timolol, based on their eye pressures and the amount of damage. And in the absence of OCT and VF, what can be done in the diagnosis of glaucoma? Fortunately I’ve had access to the imaging at the clinic I work at. So I’ve always used my clinical exam, as well as OCT and HVF to make diagnoses. But certainly in more severe cases of glaucoma, it’s very easy to pick up optic nerve damage. But there are many cases where the damage is subtle. So we would have to rely on imaging when it comes to managing glaucoma. So normal tension glaucoma means there is damage to the optic nerve. But the eye pressure is usually within normal range. So it’s important to use good judgment in identifying normal tension glaucoma and treating, lowering their eye pressure even further, to present visual field and vision loss. So the question is about compliance to glaucoma. Whether it’s in certain cultures, if this could be increased. Compliance I think is an issue pretty much across the board. And the reason I think compliance is an issue when it comes to glaucoma is… You know, especially Primary Open Angle Glaucoma does not have any symptoms. A patient may feel that since they’re not having any symptoms, it may be okay to ignore the therapy that has been advised that they be on. However, it’s important, as health care professionals, from our part, to emphasize that even though glaucoma has no symptoms early on, vision loss is significant in later stages of glaucoma. So I think it’s really important to hone in on that particular aspect, and have the patient be compliant with therapy. Otherwise, as we discussed before, life expectancy is increasing, and our goal is to make sure that our patients have a good quality of life, and prevent progressive vision loss that can happen from glaucoma. So I don’t think compliance is cultural — due to cultures. I think it’s pretty much across the board. And I think as health care professionals, it’s important to address that, and say: Even though there are no symptoms when it comes to early stages of glaucoma, it’s highly important to be on therapy. So what is the best management for angle closure glaucoma and low tension glaucoma? So recall that angle closure — usually the treatment would be surgical. Peripheral iridotomy is recommended for angle closure glaucoma. And then when they develop open-angle glaucoma later on, that is called mixed mechanism. So mixed mechanism glaucoma essentially means that they had — a patient had angle closure glaucoma in the past. For which peripheral iridotomy surgery can be done. And then if the optic nerves get damaged, then that would be open-angle glaucoma after. And so this particular type of glaucoma is called mixed mechanism glaucoma. And low tension glaucoma, again, is when their pressures are normotensive, but there is optic nerve damage, so this is the… For low tension glaucoma, best management includes eye pressure lowering drops, as well as surgical options. So what is the average of thin and thick pachy limits? So average is about 550 microns for pachymetry. And so thin I would generally consider 530, 540, and thick, 560, 570 would be about thick… So 550 is about average for pachymetry. When there is a defect on the temporal side of the ganglion cell, visual field will show a nasal defect, so I think the question was to explain this point. So remember that there is retinal nerve fiber layer loss inferiorly on the OCT. It will show up as superior visual field defect. So that is why the pattern is seen in that way. So the question is: When there is no OCT and visual field, and patient has cupping and high eye pressure, what is the best line of treatment? So if you don’t have access to imaging, and the patient clearly has a large cup to disc ratio, and high eye pressures, I would say treat the patient, and you can then refer to a clinic that may have some imaging, where they can monitor glaucoma. But if there is high IOP, and increased cupping, there are many studies, as we reviewed here, that have shown that high IOP is a risk factor for glaucoma. So it’s important especially with cupping, large cup to disc ratio, to treat the patient first, and then refer for effect. So what is the OCT floor effect? Can you please explain? OCT floor effect is when you obtain OCT imaging, and in the center of the optic nerve scan, you’ll see what they call global thickness. And this starts to bottom out at about 50. And just because there are other components of the optic nerve — it’ll never go to zero. So if you have an advanced, moderate to advanced glaucoma patient, it’ll start to bottom out at about 50, and so that is why it’s important to remember that in mild to moderate cases of glaucoma, you can use OCT meaningfully. But in moderate to advanced stages of glaucoma, when the OCT, particularly when the OCT reaches that floor effect, in other words, a global thickness of 50 or less, it won’t go to zero. So you can not rely on OCT for the moderate to advanced stages of glaucoma. So this is a good question. How do you define the IOP target? It’s important to define the IOP target based on the risk factors. So here we consider the corneal pachymetry, family history, and their age. So generally remember that prostaglandin analogs reduce the eye pressure by… You can expect 25%, 30% best decrease. And so it’s important to set that IOP target based on risk factors. So again, we use risk factors to identify how to target the IOP drop in glaucoma patients. So is MD more important or PSD? I look at all of these on visual field analysis. It’s important to look at both MV and PSD in glaucoma visual field analysis. The other question was significance of mean deviation, of pattern standard deviation. Again, important to look at both of these criteria. It’s also important to consider cataracts. Because if a patient has dense cataracts, you’ll see a generalized depression, but on the pattern deviation, you can see any specific glaucoma loss. I believe we answered that average pachy was about 515. Anything less than that is considered thin and anything more than that is generally considered thick. So management of normal tension glaucoma — basically based on management of thinning of the optic nerve. So the question is: How do you choose glaucoma medication as guidelines? So again, prostaglandin analogs are a good first baseline treatment for glaucoma. And then start with beta blockers as the second line, or depending on the severity, you can also consider other classes of medications, add or subtract. So thank you all so much again for attending my lecture today. And thank you for your questions. I really appreciate you all joining me.

>> Thank you.