Richard and Leonora Hill Lecture Series
The Hill Lecture Series was established by Dr. Richard and Mrs. Leonora Hill to sponsor an annual lecture in vision science and research. Dr. Hill was dean of the Ohio State College of Optometry from 1988 to 1995.
2025 Lecture by Dr. Harry A. Quigley, MD
“21st Century Glaucoma Care”
Dr. Harry A. Quigley
April 16, 2024 5:30 p.m. ET
In-Person: The Ohio State University College of Optometry, Hamilton Hall 080
About Harry A. Quigley
Dr. Quigley, the A. Edward Maumenee Professor, Wilmer Eye Institute, Johns Hopkins, has been CEO of ARVO and Editor-in-chief of IOVS. His 450 publications are the most cited in the ophthalmic literature with over 100,000 citations. He received the Friedenwald, Joanne Angle and Epstein Mentoring Awards by ARVO, Doyne Medal and multiple awards from RPB and Alcon, and the Lewis Rudin Prize. He is a Life Achievement Honor Awardee of AAO, having given 50 named lectures, including the AAO Jackson Lecture.
Dr. Quigley has trained 75 glaucoma clinician--scientists who lead glaucoma centers worldwide. His research improved glaucoma diagnosis of glaucoma, was first to report on success with laser iridotomy and his trabeculectomy suturing technique was widely adopted. He pioneered studies of glaucoma epidemiology, conceptualized the roles for iris and choroid in angle closure, performed the first neuroprotection gene therapy, and initiated scleral neuroprotection research and developed glaucoma models in monkeys, rats and mice.
2025 Hill Lecture by Dr. Harry A. Quigley
Video Transcript
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DR. WALLINE:
We'll start with a formal. It says Dr. Quigley, the A. Edward Maumenee Professor at Wilmer Eye Institute, Johns Hopkins has been CEO of ARVO and editor in chief of IOVS. His 450 publications are the most cited in the ophthalmic literature with over 100,000 citations. He received the Friedenwald, the Joanne Angle and Epstein Mentoring Awards by ARVO, uh Doyle, right? it is Doyne Doyne Medal and multiple awards from RPB and Alcon, as well as the Lewis Rudin Prize. He's a life achievement honor awardee of the Academy of Ophthalmology, having given 50 named lectures, including the American Academy of Ophthalmology Jackson lecture.So that's the formal introduction, just to give you an idea of some of the breadth of work that, that Dr. Quigley has has done over his career so far.
But I wanna talk a little bit about Dr. Quigley and sort of what I learned today. He is what I would call sort of the quintessential clinician scientist. So he's an excellent clinician, and you may or may not know that he's a glaucoma specialist. And that means that he treats everybody from adults to pediatrics. There aren't very many specialists who treat both adults and pediatrics, but he's one of them. So that tells us a little bit about the breadth of his clinical care. He also has a wide breadth in terms of his research. So if you know some of his papers, you know that he's done research in glaucoma all the way from sort of the mechanisms of glaucoma to the effects of glaucoma on the patients. And it's from these perspectives that he's gonna give us a wonderful lecture tonight. So if you would please join me in giving Dr. Harry Quigley a warm Buckeye welcome, I would appreciate it.
DR. QUIGLEY:
Well, thanks, I really appreciate being asked to be here. And first and most importantly, Dick Hill, who was your dean and somebody who contributed massively to the field relating to contact lens use. Now, if you're one of the younger people sitting toward the back there, you can say, well, how could somebody have time to be a scientist, a clinician, and a dean and all that. Well, it doesn't happen to you immediately. You build up to it over time. But he was asking some really fundamental questions about the cornea and whether a contact lens maybe cut down the oxygenation. How do you build a contact lens that better oxygenates the cornea. If you all are contact lens wearers, if there's any of you non-LASIK treated young people out there, you'd know that when you take them off at the idea of contact lens blur, and that's due to the anoxia caused by hard lenses of the time. And so Dr. Hill's contributions over time for 20 years worth of papers that I kind of reviewed to come here ahead of time, were special at the time because there weren't very many people doing work of that quality.Glaucoma is a major problem in ophthalmology and optometry. You will be seeing it in your clinics. And for the next few years, we have the opportunity to improve dramatically in how patients are cared for. So I'm gonna do a flyover tonight of a lot of things about glaucoma. That way, you can't get bored cause it'll change, the slides will change pretty quickly. when it comes up, I'm gonna tell you where any financial interactions that I have with companies may impact your listening to what I'm saying about the particular subject matter.
Very interestingly, you might say, well, you know, you're so you're an expert on glaucoma. What is glaucoma? How do we define it? And believe it or not, the most common definition in randomized clinical trials, very important, big time, randomized clinical trials is, cause I said so. Cause three guys sat down and looked at the picture of the optic nerve head and said, you know, we agree that's optic, that's characteristic glaucomaous optic neuropathy.
I call that the three guys in a smoke-filled room method for diagnosing glaucoma, and I'll tell you that it doesn't work. And the reason it doesn't work is Bal Shahan, a OD PhD from Dalhousie, has done a study at which I was a part. And they took 1,000 glaucoma patients, clinical photos, OCTs, and fields. And they asked 100 glaucoma specialists around the world online to look at these pictures and to rate the patient's chance of glaucoma from 0 to 100%. You will see that at the far end of this, way up at 100% of glaucoma, the, the spread in the assessments was pretty tight. And down here near zero doesn't have glaucoma. They agreed about that. Take a look at the vast majority in the middle here. There were patients being rated from 25% to 75% of having glaucoma.
So what we needed, what we need now and what we actually have in your hands is an objective definition of glaucoma that's based on OCT and field. And if you match up a quadrant of abnormal OCT in the case of this patient, it's the inferior quadrant, with a typical definable objective visual field test in the upper visual field. In other words, they match because the world's upside down, right? That gives you a chance that that patient would be agreed to by a large number of ophthalmologists and optometrists as having open-angle glaucoma, glaucomatous optic nerve damage. And the chance that it's not a glaucoma patient is under 1%. So if clinical studies that you see in the future, say we had a definition of glaucoma, it was the three guys in a room, you wouldn't be able to do a study to duplicate that study and be sure that you had the same crowd of people in your study that they had in theirs. But if they also said, oh, and by the way, we diagnosed the glaucoma dystopic neuropathy by this objective definition, then apples would be apples instead of something else.
Now we know that in Columbus and Baltimore and around the world in developed country cities, We miss half of the glaucoma patients. They're walking the street outside here, and you don't know who they are yet. So how do we stop diagnosing glaucoma outside. And the answer is in part because in our heads, we've been using a magic number that I'm not going to say it's on the slide. You should look at it and then you should please forget it. It has nothing whatever to do with your patient having open angle glaucoma, though it is true that the higher the pressure is, the more likely they are to have the disease. Stop thinking that you need to use that number to decide what else to do. You want to take a look at the optic nerve head and more importantly, do more visual field tests on people with a family history, on people who are myopic, people who have risk factors, including ocular hypertension. And if we do that, we're gonna find more patients with glaucoma.
But we still need, as I heard today from one of your investigators, better ways of screening for glaucoma, maybe with binocular field testing or other methods that will help us to identify it quickly and easily. I personally think that a system that our medical students are using in their screening program in Baltimore is a very good way to go, and that's to take an OCT instrument into the field and take OCT images of people. You can see AMD and diabetes and the RNFL and the optic disc features, all with an instrument that's portable. Not terribly portable, but you can take it apart and put it back together, and we've done it in screening programs every Saturday in Baltimore for a lot of times. AI, everybody's favorite word, don't get too used to it because Time Magazine will have a new special thing next year that's gonna solve all of our medical problems. But AI has had a lot of trouble diagnosing glaucoma, and the reason is cause there's no ground truth. They don't have 10,000 pictures of people where all 10,000 had somebody do an OCT in a field. But if you don't do that, you're stuck with comparing AI to three guys in a room. And that means that you're comparing it to a very wishy-washy kind of definition. It is a lot easier to diagnose diabetic retinopathy. That's already an FDA approved screening method in medical offices around the country, but little diabetic hemorrhages are easy to see. Figuring out if the disc is glaucoma from a color photograph is a lot harder.
If you were to prescribe a glaucoma eye drop, what's the chance that the patient is actually taking their eye drops? Now I think we know that it's probably not ideal. I didn't know it was this bad until we electronically monitored a crowd of patients, and we actually knew how many how many drops per week they were taking of a prostaglandin eye drop. And the answer is that patients who were in a study, signed a consent form knowing they were going to be monitored electronically, were given free eye drops that they didn't have to go to the drugstore to take. We're on average taking 73% of the drops per month. And noticed that there were people down there at the 20% and 30% range. Were you to ask these patients, are you taking all of your eye drops? Most of them would have said yes. Doctor, I'm religious with my eyedrops, and they're not lying to you, they actually believe that. They think they're taking their eyedrop, cause they're looking at a bottle and they can't see they have leftover pills at the end of the week, cause they need a pill. So we've begun asking a question that it turns out in our electronic monitoring, has identified the patient you need to worry about with regard to adherence with eyedrop therapy. And that question starts with saying to the patient, you know, I know how hard it is to take eye drops. You know, I'm supposed to be taking a pill every day, and I, every so often, I notice I've got too many pills and I must be forgetting them, you know, it happens to all of us. What are you doing? You're opening the door. You're saying, even though I'm in an optometric office and I look like I had all these fancy instruments and stuff, I'm human and so are you. Do you think in the last two weeks, maybe you missed your drop once or twice? If they answer that question, yes, I think I might have missed some. Their average in this testing that you're looking at was 50%. They were taking half of their drops or fewer. If they say, doctor, I never miss. I know I took all of them, you have no idea what they're doing. But if they admit it, that's the patient who needs to help you by working, you work with them on electronic monitoring.
Now, the reason why eye pressure in the clinic is poor is shown on this slide. This is what the adherence was with patients who were electronically being monitored. And if you look here, the, the, the visit that they had was over here, and the next visit was over here. And these folks are the worst adherent patients, and notice what happens right before the visit. They start taking their drops again. How many of you fail to floss before you see the dentist? How many of you fail to floss the other six days of the week or month or year? It's, it's human. That's, that's fine. But that means that their pressure looks great, but their glaucoma is being poorly controlled. And it's the single biggest cause of gee whiz, the pressure is being treated, but glaucoma patients still lose some vision. It must be something else other than the eye pressure. It might be, but that's the biggest cause of the pressure looks good, and the patient's getting worse.
We used electronically bugging people on their cell phone or their computer. To juice them into taking their drops, and that works. And more and more of us are walking around. How many of you people don't have an iPhone on you at the moment or a Samsung phone, right? And believe it or not, 70 year old patients of ours, 75% of them. Look at email or a text every day. So all you gotta do is send them the text or call their phone at 9 p.m. It's time for your prostag gland and eye drop. Did you take your drop? Press 1. Did you have to go back to the the bathroom and find it and take it and press 2, right? That improved adherence very significantly in a large number of patients that we were doing.
The ultimate answer for the next 10 years is finally to develop sustained delivery, and I don't mean Durysta. That's the one that's injected into the anterior chamber because that's completely impractical and somewhat dangerous. Perhaps sustained delivery of subconjunctival delivery, which might be actually very practical for technical staff to do. If you had a sustained delivery drug that was only half as good as an eye drop. It would be there all the time and it would be as good as the eye drops for the patients taking 50% of their drops. And they wouldn't have to go to the drugstore, etc. etc. So I'm very hopeful that we can finally convince a drug company or two. We know what agents will work. Dorzolamide works, subconscious subcons delivery, nanoparticleized, so it's sustained delivers over an extended period of time.
We were part of the Durysta study. This was approved by the FDA for one injection into the eye. The Durysta implant damaged the cornea in some patients in the study. One of our patients suffered significant corneal damage from only the 2nd injection. In that study, there were multiple injections. And Ophthalmologists are not going to be injecting patients bilaterally. On a multiple basis every 3 months. It's just not gonna happen.
So this is not going to be the solution for us, subconscious type of delivery work, it was done by Ian Pitha, now at the University of Utah, and showed that in a rat model, we could lower the eye pressure in a long sustained fashion, but it hasn't yet been tested in humans, hasn't been because drug companies don't necessarily want to pick this up. Why? They're gonna lose their eyedrop market. It's a $2 billion a year for Latana Prost alone. What if this works, and they don't have to take drops. So we may have to have a different model for this, or later I'll tell you about stem cell work. We may have to have a different model outside the capitalist system, uh, whereby a nonprofit corporation starts doing this kind of thing.
What we'd like to have, and we were very close, is to have something where when the patient is taking their drop, we would know whether they were adhering with therapy or not electronically. And the device that you see on the right, the Calicare drop, unfortunately, this company has presently been bought and probably killed by a larger corporation. That's a buy it to kill it phenomenon in our system. Another of the wonderful things about systems. This thing, when the patient takes the drop, it records the time and date, and when it's placed into its dock, it sends it to our office. So we're sitting there watching the patient's adherence with therapy. And one of the things that we were first told when we did electronic adherence treatment therapy monitoring was, yeah, but you didn't prove that it actually benefited the patient to take those drops. You didn't prove that their field didn't get so worse when they were better adherent compared to worse adherent, you don't have an outcome measure of actual proof.
So we began doing a variety of things, one of which was monitoring people at home with the home eye care pressuring device. And if you've seen this one, the newer version lets the patient see what their pressure is, and once again it sends it to us. So, within the time period of your optometric practice, I will predict that you will have on the patient's eye drop bottle. And the patient ability to monitor their pressure at home, the ability to see are they taking it? And is it lowering their pressure? You'll have software which says, oh, Mrs. Jones hasn't taken a drop in 4 days. Send her the call, or better yet have a human call her from your office. Mrs. Jones, are you OK? We noticed that you, oh yeah, you're off at vacation and you left your bottle at home. OK, we'll get to the pharmacy. Mrs. Jones, we noticed that you're taking your drop dutifully, but your eye pressure is not going down. Are you sure you're getting it in your eye? Did you look at that chapter in Quigley's book on how to put drops in your eye? Or if you are sure and your husband swears that he watches that drop hit your eye, that drop's not working, and I don't want you to wait 6 months till the next visit. We need to see you next week. Imagine the effect that those simple measures, which are presently technologically feasible, are gonna have on glaucoma care, it'll be as good as measuring your blood pressure at home. Except even better, cause the internists don't know if you're taking your pills.
We are very close to being able to put a device through the sclera. implanting it in an office or in an operating room. And the device, the one that's in the lower picture here, is a company that I work with at no charge. I'm a I'm an unpaid consultant to this company. In an attempt, we've seen it now in rabbits, and the device can measure the eye pressure inside the eye and telemeter that to something that's say, on the eyeglasses. And from there to our software in the research zone. It works in rabbits. They need to continue working on it to get an FDA approval. And the first series of these are gonna go in when people have cataract surgery who have glaucoma. Cause you're in the operating room anyway, you're already sterile, you're already instrumenting the eye, and you leave behind the ability to have a battery operated tenometer that's rechargeable. But it's in the eye. So you know that it's actually accurately measuring eye pressure. There's another company, the EyeMate, it's a German company. They're also attempting to produce something like this. it's gonna have to be small, and the one by EyeMate is a quite large device into the super coroidal space, and I'm quite worried about putting things in the super coroidal space.
Bob Derek and I were just talking about the vascular causes of glaucoma and the mechanical causes. We'll get to the mechanical causes in a minute. But if blood flow is important in glaucoma, blood flow to the optic nerve head, and we know that it is, there's epidemiologic evidence, there's clinical evidence for that. What can you do as a clinician to improve the blood flow to the optic nerve head? Well, first, we know that blood pressure falls at night, and so people who take their blood pressure pills should take them and have its maximum effect in the morning. So if your patient is taking blood pressure pills at night, you want them to take it in the morning only. You want them to take Timolol in the morning, because Timolol doesn't work very well during the night. So why take that second drop? And an investigator and I, a woman who's done orthokeratology on herself for many years, she's a space engineer who's involved in some of the telescope things that you read about. She and I use the triggerfish device, which is a contact lens that instruments the limble flexibility. It's an interpretation of what the eye pressure is, and you can wear it 24 hours. What we did was have people sleep. Laying down, your pressure goes up. But if you bury your face in your pillow and your eyelid is pressing on the eye, the trigger fish alerted us that the pressure goes up and it went up more in glaucoma patients than it did in controls. That's a biomechanical effect. Dr. Luke can tell you about that. That means that their eye potentially in the front of the eye, where the trigger fish is, might be stiffer. We're gonna find out that glaucoma patients' eyes, in fact, are more compliant, not stiffer.
So what can you do for blood flow? Well, if you get somebody to take 5000 steps a day or more, Their glaucoma does better and my colleagues, including Dr. Priti Bramalou, who's our head of glaucoma, has demonstrated this and there's a randomized clinical trial beginning now where patients are going to be given an exercise bike and the control group doesn't get an exercise bike, except the exercise bike is instrumented so we know if they freaking used it. And will then follow their visual field tests and show whether more exercise actually improves visual fields.
But you gotta get people up off the couch. It's better for their glaucoma, we suspect, and we'll hopefully still prove, but it's also better for their general health and other things.
SLT laser therapy, that's gotten a lot of press recently. There's a study by Dr. Gazzard and colleagues that suggested that it's as good as eye drops, and it may very well lower it certainly lowers the eye pressure in early glaucoma. It is ineffective in moderate or severe glaucoma. It often requires not one session of laser treatment, but two And unfortunately, while some, a large number of eyes are drop free, they don't need eye drops, they achieve the target pressure with the SLT alone. Patients have two eyes. And if one eye is drop free, but the other one isn't, the patient's still going to the drugstore or getting a mailed in prescription every month. And so while we offer SLT now as initial therapy, As an alternative to or in addition to eye drops, patients don't choose it. And the reason is, patients don't trust procedures, and they do trust eye drops, even though, as I just told you, they're not taking them as much as we'd like. They think they are, and a procedure could hurt me, whereas just taking an eye drop, that can't hurt me. Well, yeah, it can cause it has side effects. Most of them are mild. But the interesting thing is in this SLT study, the study was called the light study L I G H T right? They for three years had patients take the eye drops or have the laser treatment. At the end of three years, they concluded SLT was pretty good and they said to the eye drop treated patients, Wouldn't you like to have an SLT now? 2/3 of those patients who were in the study, they'd agreed to be randomized. They were told the SLT was really good and they ought to think about it. 2/3 of them said, no thanks, I'm continuing my drops. Why? Because people would rather do a non-procedural thing. So, whether SLT is going to have a huge effect or not, it's not quite strong enough, still leaves some patients taking eye drops, but it's a great thing for the non-adherent patient. Or for patients who don't respond to eye drops initially and have relatively early disease.
Now, surgery in glaucoma is changing fairly rapidly, although probably not permanently. An awful lot of what you're hearing about that are new procedures are not very effective, and we're dispensing with them. There are 2 or 3 that are really relatively good. One of the things we'd like for the more advanced glaucoma patient, the one who didn't respond to medicine, who has significant damage, is a better tube shunt. The tube shunt is a good procedure. But it has some difficulties. And as first surgery, in other words, for the patient who's going to have an operation, the tube shunt surgery against tuberculectomy came out pretty well. Except for those glaucoma patients who needed a very low eye pressure, and there the tuberculectomy won, but tuberculectomy had more side effects of too low in eye pressure, requiring a revision to bring it back up again. The tube shunts, on the other hand, uh, did well at lowering patients who had a high pressure. But had double vision With a fairly high rate, and had a problem that the tube shunt can extrude, can come out through the surface over a period of years afterward. And while that number is relatively low, it's about 7 or 8%. If you're the 7 or 8%, doesn't go any good to tell you, oh gee, that doesn't doesn't happen very often. Yeah, but doctor, it happened to me.
We've been working and I am a paid consultant for the company Gore. How many of you have Gore-Tex on a running suit or some kind of equipment, right? OK. Gore also makes stints for cardiac use. When somebody says, oh yeah, I had a, I had a car and Catherine and I had a stint. That was a Gore-Tex stent. The Gore-Tex folks came to us and said, we think we can build a better reservoir at the end of the tube, and we're gonna make it out of Gore-Tex material that's water permeable. But not permeable to cells. Except on its one surface, so it'll adhere to the sclera. But otherwise, the water will just percolate through it. They now have 20 patients who've been treated in a phase one clinical trial. The complication rate is as low or lower than a standard tube shunt, and the pressures are doing reasonably well in the majority of the patients. But there's a way to go. I think this is one of a number of potential improvements, including an adjustable tube shunt where even after surgery, you could use a magnet to open or close the flow. Right up next to the patient's eye. They may have to worry about getting an MRI to change their flow through their tube shunt, but we can deal with that if we had an actual adjustment that was possible.
There are quite a number of new glaucoma surgeries. They are referred to generically as MIGS surgeries, minimally invasive glaucoma surgery. They are not minimally invasive, they are invasive of the eye. Overall, none of them has as yet in any randomized true clinical trial been as good as tuberculectomy or tube shunt surgery. They are, however, lower in terms of side effects. So if you need not that much pressure lowering, And you want something that's low risk. You can do it, and it's very often that this is being done combined with cataract surgery. There's unfortunately many more of them being done with cataract surgery than are actually justified. In terms of the patient requiring something to be done and achieving a useful and beneficial effect. That's my opinion, I can back it up with data. Early glaucoma cases are by and large the ones that are being treated. And the cost to Medicare and other insurers of these surgeries is a dramatic improvement in the overall cost of glaucoma care, and our country has what's called a zero-sum game for medical care. There's a certain amount of dollars that Medicare is going to put out there, and it's not gonna go up. It's very likely even the present situation, it's gonna go down. And if we're taking up a lot of that cost with procedures that don't do a lot for the patient, then we're doing the wrong thing. In fact, the newest best surgery that lowers eye pressure in glaucoma patients is cataract surgery alone.
In every one of the randomized clinical trials where cataract surgery was compared to cataract surgery plus a new procedure. The major effect on lowering eye pressure was in the cataract only group. And a slight improvement with one of the procedures called Hydrus, which is a stent that's put in. It's a titanium metal-based stent. But we now know that cataract surgery alone can help the glaucoma patient. We can't promise, we don't tell them you'll be off eye drops, but it's, it's something that can be beneficial. You all test visual fields in the clinic.
How often should you be doing that on a patient with glaucoma? We did a medical chart review of large insurance database work, and we showed that in Medicare patients, and the patients in our clinic, it was on average about once a year. So what is best though, to detect if the patient's doing well, is once a year OK?
Here's a a graph. It shows whether glaucoma patients were progressing or not. If you were not, if you were not progressing, You were over here at 0. And if you were progressing and getting worse, you're over here. If you were getting better, you're over here. Now, unfortunately, glaucoma patients don't get better. So, measurement of getting better means that's a false positive rate. So, pretend that's a Gaussian curve. What you've got is these folks over here were the ones who were getting worse under treatment by Canadian glaucoma specialists. And some of them were getting worse catastrophically. And that was under careful observation. They weren't lost to follow up, they were in care. And so what we need to do is be able to identify. The glaucoma patient who's gonna be getting worse dramatically, they're about 10 or 15% of the patients. And you can find out in the 1st 18 months that you see them. By doing 5 visual field tests. You might say, oh my God, the patient's gonna hate me.
Patients hate doing visual field tests. But Bal Shahan from Dalhousie University in Canada, and Andrew Hale did a study that showed that if you only do a field test every year, You're gonna take about 5 or 6 years to be able to detect the rapidly progressing patient. By then, they've already lost 10 dB in their field, and they're functionally severely impacted in one eye. Whereas if you've done those 5 fields in the 1st 18 months, on everybody who's new, most of them wouldn't have to do another field except a year from now, and a year after that, cause you've already proven that they're not rapid progressors. And then you've found the rapid progressors and those need more aggressive treatment, they need more frequent visits, they may need multiple drops or laser or surgery.
So the real field new patient, do more field tests. Now, we definitely need better biomarkers for whose gonna get worse faster. There's a lot of research in that field, and I'm gonna show you some pictures of one method. there's a, there are 2 or 3 randomized trials right now going on, giving vitamin B3 in massive doses to see if you can get a reversal of some of the visual field loss. We'll, we'll see if that's gonna work out. We can hope that there is some DNA that identifies the rapid progressor floating through the blood. I know a young man named David Quigley, who's done a liquid biopsy showing metastatic prostate cancer patients and what's wrong in their cancer. So it's not unreasonable to think that we might be able to do that. Measuring the susceptibility to biomechanical stress is another thing that Dr Lu and our lab are working on in terms of identifying what's going on.
This is a picture of the optic nerve head, the lamina fibrosa. It's a scanning EM picture here on the upper left, and you can see that there's an area of the optic nerve, it's the inferior part of the optic nerve head, where there's less supportive connective tissue. This is a 30 year old picture. Since then, we were able, due to Vicky Nguyen, my colleague, and Dan Midget, a doctoral student, able to show and measure how the optic nerve in a dead eye, a postmortem eye from the eye bank, how it flexes when you raise and lower the eye pressure. And what we found was that it flexes more in the areas with less connective tissue. If you were to look at an optic nerve from a glaucoma patient, you'd find that that area has lost the myelinated nerves from that zone much earlier or more. And if you looked at the visual field, you would find that area corresponds to the area that we know is the very typical early or moderate glaucoma visual field damage. So, the biomechanical endowment. And its behavior are very likely to predict for us if we could measure that in some useful way.
So what Dr. Nguyen and we have done is to take OCT images with Heidelberg Spectralis. They loan us the instrument. I don't get any money from Spectralis for doing this research. And what you see are pictures of what's called biomechanical strain. These are eyes of people where we change their eye pressure. In the case of these people, we did suture lysis after tuberculectomy. We, the pressure was too high and we cut a suture and lowered it. We've done it also with starting an eyedrop to lower their eye pressure. So, if you were to start a patient on an eye drop, you could take an image of the patient, start the drop, bring them back in 3 weeks, measure them again with Spectralis at the lower eye pressure, and generate these images of what the biomechanical strain was in the lamina cribrosa This is the lamina right here.
And interestingly, what we have found is that persons with glaucoma, if you lower their eye pressure, Their lamina cribrosa goes from a tuna fish can to a tomato juice can. It gets narrower and higher. And there's also an effect of, if you imagine taking the Tomato juice can and tilting it's called shear. The world literature says that glaucoma patients have stiffer eyes, and that's why they get damage from glaucoma. Every bit of evidence we have so far, and it's been corroborated by another group, so we may be right. Glaucoma patients have a more compliant eye at the time that you evaluate them with their glaucoma. That doesn't mean they had a more compliant eye at the start. But it does mean it's more compliant now. So the disease process itself is unlikely to be causing the eye to get stiffer, it's more likely to be causing it to try to accommodate the effect of pressure on it, and I didn't say high pressure. Half of the patients we study have glaucoma at baseline untreated at normal pressure. So their eyes are not tolerating normal pressure. That's why you can't use that magic number that we're not gonna talk about.
If you were doing a clinical exam, and you wanted to identify an angle closure patient, You might try to use something called the Van Herick test, which means a diagonal slit beam is coming from the outside, and you're trying to judge how close is the iris to the back of the cornea. We did what we thought was a pretty definitive study comparing faculty gonioscopy, faculty Van Herick test, resident ophthalmologist, gonioscopy, and Van Herick test. The residents and the and the faculty agreed really well. The problem was that the Van Heerrick test didn't identify the angle closure patients. It missed 30% of those who had true angle closure by gonanoscopy. And only 1 in 15 of the positives by Van Herick actually had primary angle closure disease. So I'm not telling you don't do it. I'm just saying please do more gonanoscopy.
There have been some recent studies that suggest that we're doing a lot too many laser iridotomies. The study called the ZAP study, you have to have a cutesy acronym for any study, right? This study was done in Zhongqiong, South China, so that's where the Z comes from. And I was part of designing some of the study, but Heming Wang and Dave Friedman and others deserve credit. They followed 900 Chinese persons from this area. Many of them were selected from the population previously untreated. So this means that they were actually representative of the population. That's the way to do a study. And when I got a laser iridotomy and the other one didn't, was left untreated, even though they all had gonanoscopy that showed the iris against the trabecular meshwork throughout 270 degrees of the angle. You would have said that's an an eye in a positional closure. And in the United States right now, that person would be told you're gonna go blind tomorrow from angle closure, you have to have youridotomy immediately, don't even wait till next week. So the zap study didn't wait till next week. It waited now for 14 years. In the initial report of the study, fewer than 1% of those suspects who were untreated had anything bad happen. And mostly what happened was they developed one clock hour of PAS. They did not. There were 2 or 3 acute attacks of ankle closure glaucoma. They were in part induced by the exam that was done because we dilated everybody once a year. Just to prove that we couldn't make their pressure go up. And during the course of those exams, there were 2 or 3 people who had pressures go up, and they of course got an immediate iridotomy. We've now done the 14 year follow up, and that finding hasn't changed a wit. So you can tell someone who has oppositional angle closure that I can follow you without sending you to somebody to do a laser iridotomy, or if you all will begin, but who knows what the future is gonna hold to get the capability of doing laser irididotomy, please do it only on people who are, who has a family history of angle closure glaucoma. Or present to them the low chance that they need this treatment, but if they're gonna go home tonight, unable to sleep cause they think it's always me, I'm always gonna be the one who has something happen. Fine, the iridotomy was quite benign, it speeds the development of cataract. Not a lot, but enough that it was statistically significant. But it's a pretty benign treatment. It's, it's not that hard to go through. So doing it though to 900 people instead of a few people, is not what we should have been doing.
The 14 year follow-up also showed something that was interesting that the irises of people who develop acute attacks and ankle closure glaucoma. are sponges that don't dump fluid off into the anterior chamber. And we found this by measuring iris area change with pupil dilation. And it's a pretty good biomarker for who's going to develop angle closure. There was a study called the Eagleri. It also deals in angle closure. The eagle trial did the following. They took a bunch of people who had real angle closure disease. Their pressure was above 30, or they had field loss and angle closure. And they were offered cataract surgery. Or laser iridotomy. Now, the study conclusion, which was in The Lancet, big journal, right? Remember, even the Lancet has to retract things once in a while. The, the, the study, I'm not asking that the legal study be retracted. I'm suggesting they had the wrong endpoint. They ask patients. Do you think you're you're better off now? It was a quality of life measure. If you take a + 3 hypero. And you make them plaino. Are they gonna be happy? Yeah, I've had to wear glasses all my life, and now I just have to put on some reading glasses and I can drive and do everything. That wasn't the question. The question should be, how did their glaucoma do? And while doing cataract surgery does definitively treat pupillary block, so does laser eridotomy, and it's safer and cheaper. And so We don't wanna be doing cataract surgery on people who don't need cataract surgery just because it might help their Angle closure disease.
So as I mentioned, the iris is a sponge. You probably know that if you look at the slit lamp, you can see all the holes in the surface of most irises, not thick dark brown irises, which don't have crypts, but most irises do have crypts. And when we measured the area of the iris from position of light with a small pupil to positioned in the dark with a large pupil, and then you measure the area of this portion. You'd say what's the iris, it doesn't change, does it? Yeah, it loses 50% of its area going from small people to big people. What do you mean area? Well, it's a sponge, it's full of water. Where did the water go? Went into the anterior chamber. And then when the pupil comes down small again, the water goes back in again. You've seen the holes. I just showed them to you. It's going in and out of the holes. But if the iris can hold on to that water and the angle happens to be narrow, when the pupil dilates, it's gonna be much more likely to occlude either chronically, much more commonly, and PAS develop, and asymptomatic primary angle closure disease starts or an acute attack happens. And now, 3 different groups on 3 different continents have shown that that phenomenon is important. Uh, unfortunately, Viante, which one of your investigators and I talked about today, uh, has been largely killed by the company, and we need to be able to make this measurement effectively with an an segment OCT like device.
So, iris area loss per millimeter of pupil enlargement is less than those. Who have an attack. Their their iris doesn't dump off water. And when we looked at the zap study, this is the study I mentioned, laser rootomy in one eye, no no treatment in the other eye, and you look and see who developed PAS or the few who developed an attack. The loss of iris area was lower in the ones who developed the disease. So this is the prospect of proof that that was an important phenomenon.
We're gonna talk about positive pressure. Positive pressure means that when you operate on somebody, Let's say you're doing, one is doing cataract surgery. The lens of the eye all seems to want to come forward and shallow the anterior chamber quite dramatically. And that's been a bit of a puzzle over the years as to why was that happening. And these are people, many of them who already had an iridotomy. They weren't having angle closure due to pupillary block, cause they had a hole in their iris. What they have is choroidal expansion. They have an expansion of the extracellular space of the choroid. It happens when somebody pokes a hole in the cornea and produces atmospheric pressure in the anterior chamber, and the choroid in these people is hyper responsive to the pressure difference in the back of the eye to the front of the eye, and the choroid starts to expand, and that brings the lens forward, that brings the iris forward, gives the surgeon a bit of a pain in the. Backside, trying to do the cataract surgery. And in fact, opening through the sclera, to let some of that fluid leak out to orbital pressure is the way that we treat this when it's happening in the operating room. But it turns out that persons with primary angle closure disease, typical ankle closure patient, Have expanded choroids on a regular basis, and this was one of the couple of the papers that show that that phenomenon is actually very operative in potentially the majority of persons with primary angle closure disease. So we need more work on what causes the choroid to expand. I'm gonna propose to you that it's a breakdown in the blood choroid barrier at the choreo capillaries. It's probably related to something called emmatropization. Oh yeah. Anybody get myopia in your practice around here? Any of your faculty studying myopia? Well, myops have a poor development of the back of the eye because blurred retinal images signal to the choroid. To tell the sclera to change its development, so the eye gets too big. That's at least one hypothesis, it's the dominant hypothesis for what's going on. They have some kind of, what if you had that mechanism? That became deranged in adulthood, and the choroid for no reason that it should, decides to expand or on being stimulated by lowering the front of the II pressure, the choroid hyper responses. So if we were to understand that phenomenon better, We not only work on myopia, we could work on angle closure glaucoma, even though one of them has big eyes and the other one has small eyes. There's probably a similar mechanism in each.
Getting to, we're gonna talk about something called malignant glaucoma, that may or may not be something that each of you has seen. It's a situation where the anterior chamber goes flat, and it is said to be due to aqueous misdirection. That means that the aqueous humor sometime, somehow goes to the back of the eye, can't get back to the front of the eye, and because aqueous is misdirected, the chain, the pressure is very high. And the patient has to have surgery to get out of it. The surgery is to remove the vitreous gel. It turns out that vitreous abnormality combined with choroidal expansion is the cause of this disorder. If fluid could go from the front of the eye and get misdirected to the back, it could come back forward again. Where's the one-way valve? The pressure elevation is coming from choroidal expansion. And in these people, the fluid can't transmit across the vitreous gel, which is why vatrectomy removal of the vitreous works.
And we now have, thanks to Coroidal thickness measurements on OCT direct evidence that eyes with malignant glaucoma have choroidal expansion. Before they get the disease in their fellow eye of the eye that had malignant glaucoma in the right eye, these are pictures of the left eye. So an expanded extracellular space of the choroid perhaps breakdown of the blood choroid barrier is not only in general angle closure important, it's probably one of the primary causes of malignant glaucoma.
So how close are we to neuroprotection? We're lowering the eye pressure. We ought to keep doing that. That works. But we still would like to also protect retinal ganglion cells. I mentioned the vitamin B3 clinical trials, and by the way, don't go out and tell your patients to take these doses of vitamin nicotinamide pyrovate there are two patients so far who have developed liver failure, neither died, fortunately. But that the dose of vitamin B3 that's in these trials, they now have to monitor very carefully the liver function studies. And I think there's some possibility that it maybe might improve things a little bit, and of course it'd be wonderful because the stuff's cheap. It's not an expensive drug.
We've done work that gets back to that biomechanical thing. Remember the biomechanical thing? And what we did was to study agents that would change the biomechanics of mouse eyes that were given experimental glaucoma. We raised the eye pressure in the mouse by putting beads in the front of the mouse eye, the pressure goes up, and in some of the mice, we treated them with an agent that blocks transforming growth factor beta. If you've studied the physiology of connective tissues. You know the TGF beta can cause lots of change in connective tissues and losartan, a well-known blood pressure medicine effects as an inhibitor of a particular receptor infected by transforming growth factor beta, and it was neuroprotective in mice. Well, that's mice. So who cares? You know, there have been lots and lots of experiments of neuroprotection that was supposedly helpful in mice, and it never turned anything in humans. So, Pappelis and Jansonius in Europe, looked at a group of patients they'd followed for 13 years in excruciating detail, visual fields, OCTs, and at every visit, they logged what blood pressure medicine the patient was taking. Not a single blood pressure medicine was associated with either better development of glaucoma. In other words, they didn't develop glaucoma. Except one. The same one that was neuroprotective in the mice, Losartan. Once again, I'm not telling you to go tell your patients until there's a randomized clinical trial that Losartan is what they ought to be taking for their blood pressure, but I always smile when one of my patients is on it because I kind of suspect that it's going to turn out to be beneficial. We need a randomized trial.
At the present time, there are two ways of doing neuroprotection by delivering something called a neurotrophin, brain-derived neurotrophic factor or ciliary derived neurotrophic factor. These, these are agents that ganglion cells eat up, they love it. Pumps up your ganglion cell, but to deliver it, Keith Martin working with us and now in Australia. Took a viral vector, the AAV2 vector, and tagged it with BDNF or CNTF, and in a rat glaucoma model similar to the mouse one I mentioned, it was beneficial to protect ganglion cells from dying at the same pressure elevation that the non-treated. Control animals did. This can now be done in humans. It's being done by a Japanese company in what's called phase one, which means they're testing to be sure it's safe. This viral vector is the one that is FDA approved for the treatment of labor's disease. So we know that humans can have this done. We know it's already benefited somebody with an eye disease. And this vector continues delivering the neurotrophic agent for years. That's also now known. So it's not, oh, didn't he tell me at the start of this talk, he didn't want to inject the eye in the office? Yeah, but what if I only had to do it once? Like once when they were having a cataract or glaucoma operation. Or just one time.
In addition to this way of doing it, there is a capsule that's already been in human eye that has cells in it that deliver this chemical, CNTF and and an incision is made in the sclera. This is sewn to the sclera, the capsules inside the eye. The patient can't see it. And these have been in human eyes for 3 years so far, and continue to deliver the same chemicals, CNTF. Didn't benefit retinal disease, that's what they tested first. It is now about to be tested further in glaucoma eyes. Hasn't been in enough eyes to tell us for sure that it actually works. But Jeff Goldberg has a paper in Ophthalmology Science in 2023 that shows that at least it didn't hurt anybody to put the thing in.
Our colleague David Derrick Wellesley has nanoparticleized an inhibitor that blocks one of the chemicals that kills ganglion cells, it's called DLKinase, dual lucy zipper kinase. It's the injury signal that when an axon and the optic nerve head gets squished or runs out of nutrition, the signal goes up to the cell body to say you've been injured. You better set off your survival mechanisms or you're gonna die. What Derek gave to animals in the studies was an inhibitor of that injury signal. And it was dramatically effective, whether you crushed the optic nerve or produced experimental glaucoma. he and my colleague Don Zack now have a company that is working on the initial human trials of a sustained delivery effect using tozasertib or sunnitinib, which are actually cancer drugs. If you gave it to persons as a pill, they get terribly sick. You just put it in the eye. If you had a long prolonged effect, you might very well block their glaucoma.
The final step in the future, of course, is to restore vision. You're going to get very tired of telling glaucoma patients, Mrs. Jones, I'm really sorry that we can't do anything to restore your vision. We can block it from getting worse. But we can't put it back. So my colleague Tom Johnson is one of the leaders in the field of putting it back. We aren't close. But we've taken the 1st 5 steps in having stem cells to replace vision. Let me tell you where Tom is at the moment. The cells will be gotten from one of 3 sources. There are retinoids, that's growing an eyeball from a stem cell. They might be generated from fibroblasts in the skin, turned into retinal ganglion cells. What Tom has been working with are embryonic stem cells from those embryonic lines that were just barely saved from being killed off during the Bush administration. And Don Zack figured out how to take embryonic cells from, let's say an 8-cell embryo and turn them into a retinal ganglion cell-like cell, producing everything that a ganglion cell produces, 8 major chemicals. You put them in culture, they grow dendrites and an axon. However, they are from somebody else. So when you put these into an eye, there may very well be a need to block immune rejection. They wouldn't be from the patient themselves, but you can get a ton of them. We can make thousands and thousands. The second is Tom and I worked on transplanting these cells into the eyes of mice. We put them in the vitreous, and they wouldn't go into the retina. They don't get in the retina, they're not gonna work. The blockade was the internal ending membrane. So we digested the internal membrane, the cells went into the mouse retina. Integrated into the retina. And grew dendrites in an axon.
This is how Don Zack developed those cells. We don't need to look at that. Here's where we disrupted the internal limiting membrane, and the, the, the maroon color that you see here are the injected cells growing into the retina, and interestingly, they know where they ought to go. They go to the ganglion cell layer, and they don't go further than that. If you put them in the vitreous. Interestingly as well, these cells now have incorporated enough. With bipolars and amacrines. Such that when you flash a light on one of the injected stem cells that has been given a calcium signal indicator. That when you, when a light is shined, a neuron has a calcium internal signal that says, oh, I saw a light. So Watch what happens in the mouse eye. When the light goes off. That would not just happen from the intrinsic ganglion cells that we talked about a little bit earlier with one of your investigators that are intrinsically sensitive to light. These guys are not, they don't have the molecules of an intrinsically sensitive ganglion cell, so they have to be connected. In the retina. So OK, so now we've got the cells. We've got them into the retina. We know there's synapsing in the retina. Tom has some additional evidence that shows they actually are making immunofluorescently identifiable synapses. Now we got to get them to grow an axon.
So here they are in a monkey eye, we've moved moved, now we need to work in bigger eyes. So we now have worked in monkeys, and what you're looking at is a monkey eye in which the membrane, the internal limiting membrane was peeled surgically, retina surgeons do this all the time. It's a little trickier in a monkey, it turns out, but our premier retinal surgeon figured out, they peeled the internal membrane, Tom put a bunch of the stem cells, like I just showed you, they're red. And you can see them In the retina and growing axons and very interestingly, look where the optic nerve head is on that arrow. The axons seem to know that's where they want to go. They're not just going randomly all over the retina, like spaghetti. So we may get saved in the stem cell work by the fact that the internal program of the cell, once it becomes like a ganglion cell, is gonna recapitulate what happened in embryologic development. That's the only way we're ever gonna get there. But the problem now is those axons aren't going through the nerve head out of the eye. So we're gonna have to figure out how to induce them to do that, and that's the next step.
Tom has a consortium of 130 scientists around the world, all of whom are pooling information on the stem cell work. And it's a unique academic interaction because they're telling each other what they know. The usual deal is you don't tell anybody. So you publish it, cause I gotta publish it first. And this time, everybody's saying, look, for us to get anywhere, we have to share every bit of information that we can. And so that group is doing that.
Through the talk, I happen to mention the book about how to take an eye drop. If you happen to want to be interested, we have a website called diagnosisglaucoma.com. It has 45 podcasts for patients. It has this book which Mona Kaleem, who, uh, Christina Mona had the baby yesterday. My colleague, uh, Mona Kaleem had her second child yesterday, and she and I, she helped me edit the second edition. There'll soon be a 3rd edition. Of this book, we find that patients really benefit after you've spent time with them in the clinic, talking about why are you taking eye drops and how do I, they want to read stuff. And all of this is free. We don't benefit financially from any of it. And there's an audio version, if somebody wants to listen to the book, we actually dictated the book. So if, if that's you we can also buy it as a book on Amazon if you want. It's like $35.
I work with a lot of people, a lot of what I've talked to you about, um, is done by somebody other than me. This is the team, Vicky Nguyen, helping me presently doing the work on biomechanics. Tom Johnson is the tallest guy in the back there doing the stem cell work, I think that the future for you all is that we're going to be doing a lot better with glaucoma therapy. We're probably, I don't wanna finish my career still prescribing eye drops, but it's looking tough at the moment. We may get there. And finally, we'll open it to questions and see if there are anything that any of you want to ask about uh um a few things that we talked about about glaucoma. Thank you.
DR. WALLINE:
Right, so people have joined us online. If you have any questions, you can put your questions in the Q&A and we will try to um get to those as they come through. But now we're gonna open up to the audience here for any questions that they might have for Doctor Quigley.DR. QUIGLEY:
Don't be shy, sir.ATTENDEE 1:
So you mentioned the uh the vitamin B3 studies being beneficial, but there seems to be some momentum in the other direction. The calcium channel blockers are particularly bad for patients with glaucoma in an IOP independent fashion. What's your thoughts on your patients with calcium channel blockers?DR. QUIGLEY:
Yeah, I think, uh, in general, some of the cal especially the short acting calcium channel blockers were originally touted as being neuroprotective for those with the lowest pressures. And the side effects of calcium channel blockers are now kind of coming to the fore. If it's the only medicine that helps the person's high blood pressure, or if they're not a glaucoma patient, they have no risk for glaucoma, then there's certainly nothing wrong with taking amlodipine or other things. Could two members of my family take the that that agent uh itself, right? Um, and on the other hand, without any question, it's not beneficial for glaucoma. And I can think of several reasons why it's actually not beneficial, and that deals in lowering the diastolic blood pressure, which it's very effective at doing. But unfortunately, Could have been, you know, not beneficial effect. So, we often see glaucoma patients who come in and you look at their med list, and there's four blood pressure medicines there. How did those patients get on four blood pressure medicines? Now, some of us need more than one But what if the patient takes the first, gets the prescription for the first one? Comes back, first blood pressure medicine looks great. OK, keep taking that. A year and a half later, they come back and they weren't adhering with their pill. Did the doctor identify poor adherences, work on that, and find out that if she just took the blood pressure pill, she'd be fine. No, what's the standard behavior? You had the 2nd pill. And that's why a lot of people wind up on 3 or 4 blood pressure medicines. So in addition to suggesting to the internal medicine doctor, maybe somebody ought to look into taking all these in the morning. Maybe the internal medicine doctor ought to look into a trial, especially with a home blood pressure monitor, of stopping one or more of those. And if I were gonna say which one to stop first in a glaucoma patient. be the calcium channel blocker. June. So amazing. Yeah, I know, but what was wrong with it? This is, this is the US of A, and if I give a lecture in Japan and I say to people, what did you think was weak about your talk? Oh, it was perfect. Everything was fine. That doesn't help me. She's gonna ask a tough question.ATTENDEE 2:
Yeah, I think it's amazing of everything you're doing here, but of course my focus is more related to the biomechanics, and I'm extremely interested in your work in Losar. Um, and the biomechanical, um, implications of that. I, know in your class one paper, and you guys did test, the sclera properties. And if I remember correctly, it does affect the sclera properties in those experimental models of mouse glaucoma or rat glaucoma, I forgot.DR. QUIGLEY:
At the time, we did not have the technology to measure. The effect on the astrocytic laminocribrosa of the mouse. Some of you may know that mice, the eye is not only really small, it's 3 millimeters, but there's no connective tissue in their optic nerve head. The astrocytes function as the, the thing that holds the optic nerve head from just blowing out the back of the eye. We didn't have a chance to measure astrocytic compliance, but we did measure whether axonal transport was affected. Now that's a surrogate measure for the biomechanical effect on axons, and losartan affected the axon beneficially affected axonal transport.ATTENDEE 2:
Yes, I, I wanted to get your comments on your, this study. I'm thinking about the, the sclera, you know, also the laminar part. So, so in that study, I believe that the sclera was um stiffened or more compliant after losartan.DR. QUIGLEY:
you may be thinking of another experiment that's very similarly related. It was the prior experiment. We, we thought, well, gee, if you want to block the effect of intraocular pressure in the eye, why don't you just keep the eye from expanding. Make it rigid. So we looked into chemicals that do that safely without killing nerve cells, and the chemical we used is glyceraldehyde. If you had a Prepared food today of any kind, it probably had glyceraldehyde in it. It's a well-known chemical. It's not a fixative like glutteraldehyde, which is really, really a potent turns eye tissue into concrete. But glyceraldehyde stiffened the sclera, and we proved that it stiffened the sclera. And then we stiffen the sclera by injecting it around the eye of mice with experimental glaucoma and injected saline in other mouse eyes. And instead of protecting the eye, it made the glaucoma worse. And I was so startled by that result that I did the whole experiment again. Because sometimes, you know, you do something and it doesn't come out the way you thought, but it was just a fluke, you know, let's do it again. I'm sure it's gonna work the second time, and it was even worse the second time. Both times significant. And what we think is going on is you make the sclera rigid, so you're intensifying the translaminar pressure gradient, which any good engineer could have told me ahead of time, and I would have spared myself a year and a half years of work, right? Except you got to do the experiment, and otherwise you won't know what's actually going on. So I would not, for any reason, want to treat the eye for a permanent stiffening one-time treatment, even though Bryce Chang, who's working with me right now, is doing exactly that. In a pig explant model, where we have a laminar cribroso, and like your human work, the pigs are cheaper, somebody was gonna have bacon anyway, so why don't we just take the eyes. I know, get a bag full of them and then we've proven that you can actually do axonal transport studies in the pig explant model that's gonna be published quite soon. So, what I wanna do though is to establish and maintain the equilibrium behavior of the peripapillary sclera and lamina cribrosa in the face of change and pressure. That doesn't mean make it stiff, and it doesn't mean blow it out, so it is totally elastic. Cause neither of those is physiologic. I wanted to simply respond to the eye pressure and stay there. Until the axon everything is fine, and we think that the systemic treatment with losartan. Did that closer to the ideal, because it was blocking the effect of transforming growth factor beta, which itself is producing changes in the nerve head, which probably in the human, and now I'm really speculating that that are Causing the eye to become more compliant. Both peripapillary sclera and the lamina corros, but definitely the lamina corrosa, uh, in glaucoma patients. We have the sclera papers coming out, human sclera, living human eye sclera, and we can measure that just barely now.ATTENDEE 2:
Yeah, I was just thinking how do we reconcile that, right? Losartan's effect of making it more compliant, which is, Well,DR. QUIGLEY:
I don't know that it made it more compliant. I, I just know that it blocked axonal transport. So we could do the losartan experiment again in the mice with fluorescent astrocytes and measure. The compliance of those astrocytes. Um, I don't think that, I don't think that it's actually measuring astrocytic behavior though. It's measuring an effect in the peripapillary sclera in the mouse, but it's why we're going to pig and it's why your human work is so much more valuable right now. We can do, we can do, you know, large scale drug treatment stuff first in a mouse, but it doesn't have an optic nerve head that's close enough to the human. Hi.ATTENDEE 3:
So it seems to me like you know there's quite a bit of evidence about BDNF being helpful. And I, I noted your um treadmill study. I'm curious, are you going to be measuring, we know that exercise actually increases the amount of BDNF. Yes, it does. Yeah. And I don't know, treadmill versus I know lifting weights in particular does, but I'm curious, are you going to also be measuring something quantifiable in the blood, something like a.DR. QUIGLEY:
It was part of the trial. Yeah, they're, they're gonna be looking at a whole bunch of things in the blood, um. the neurotrophins are certainly one. Whether the level in the blood is going to be highly relevant is a pretty, that's it's a speculative leap, isn't it? I just reviewed a paper where somebody studied skin fibroblasts of glaucoma patients. And said, oh gee, there's all kinds of gene expression in these skin fibroblasts that are different from controls. And they were talking about oxidative damage. In a fibroblast from the skin. How's that related to the eyeball? Where the cells in the eyeball that are being damaged by oxidative damage, the neurons, are they fibroblasts? How similar are those? And there's a couple of studies that show that Circulating white blood cells, which have been studied as a surrogate for brain tissues and eye tissues in terms of gene expression and methylation, which is one way of studying, you know, the gene expression. That what you get from the white blood cells is absolutely unrelated to the same degree of methylation in the in the eye tissue. So, we gotta try to hope that we can maybe measure something in eye tissue as well. But it's, it's a good first step and you can do it. So, you know, why not do it to find out.DR. WALLINE:
OK one question, online and two comments. I'll just go through those real quick and we got another question here.First, the question from online is from one of our colleagues at the University of Houston, and she asks, have the results of the life trial changed your recommendations for initial therapy for light therapy?
DR. QUIGLEY:
No, we were, we were recommending SLT or ALT, um. But recommending SLT now, cause that's what everybody has in the office as a, as a laser. We were recommending SLT or drops to every new patient. 85% of them or more pick drops. Even though I think we're presenting a, an, uh, a balanced viewpoint of the two things, and the usual statement is, well, but you're not guaranteeing me with the SLT that I'll be off drops, right? I said, no, I can't guarantee you that. Well, OK, well, let's start the drops. But I think it's a reasonable first treatment. A couple of comments online and we'll get to aDR. WALLINE:
A question right over here. one comment is from an alumnus of ours who's now with Wilmer, Bryce Sinclair sends his regards, and he asks.DR. QUIGLEY:
One of our favorite colleagues, yeah, he actually asked aDR. WALLINE:
question too, if you could just spend just a moment with it, he asks about the evolution of the ODMD relationship and, and how you see that.DR. QUIGLEY:
Yeah, when you look at the next edition of the book that I wrote for patients. 15 years ago, I wrote a chapter, and then the chapter was titled "Who Should Care For Your Glaucoma?" This was in an era where not the majority of states in the United States had a drug capability for optometrists. And the new chapter is going to say glaucoma care at the Wilmer Institute is a team approach of optometric and ophthalmological colleagues. That uh your care will be done by people who are specifically trained about glaucoma and all of us uh feel that that's the best way for us to manage your disease. And my Every week colleague who is uh in the room next to me, seeing my patients and her patients with glaucoma, and I interact all the time, and Corinne Casey, that faculty member, uh helped me rewrite that chapter. And she's She's an optometrist.DR. WALLINE:
And then uh one comment comes from Cindy Hill, and she says, thank you, uh, for an informative and enjoyable lecture. My father, Richard Hill would have very much enjoyed it. Yeah.DR. QUIGLEY:
Thank you, Cindy. OK, um, so there's been a lot of talk aboutATTENDEE 5:
OCPA, and I thought I saw a quick sentence. About like monitoring the progression of glaucoma, even like a rotation. What is the like, will OCTA be used in honoring for progressive glaucoma?DR. QUIGLEY:
Can I make money if I give the right answer? No, it was, it was just a handshake. Oh, OK. Well, that's, that's fair. Right. So when OCTA, when David Wong first brought out OCTA, he had a flow index on it. And they were claiming that OCTA was measuring blood flow. It does not. It measures the presence of capillaries, and it does it beautifully. For if you wanna see whether capillaries are physically present or not in the retina. It's an incredible technique. He deserves all the kudos for for developing the methodology, and we find it to be fun and useful. There is a paper that's either in press or about to appear. It's from the Diggs study, which is a longitudinal study at University of California San Diego. Linda Zangel, and a junior colleague of hers named Bob Weinreb, um. And they have done OCT and show that it tracks very well with the degree of injury and with the degree of progressive injury. What hasn't been shown, and Bob Derek and I were just talking about this earlier, is the prospective, did the OCTA change in capillaries occur before there was the visual field loss? Did it predict it, or was it an effect? Now, bear in mind we're talking about the retina. We're not talking about the optic nerve head. The damage starts at the optic nerve head. There is damage in the retina and retinal capillaries. Auto regulate away as the ganglion cell there disappears. You don't need as much oxygen, you don't need as much glucose. There's an auto regulatory system and they involute. And I showed that in the optic nerve head like quite a number of years ago, same phenomenon. So we know that they're disappearing. But we don't know if it's cause or effect. That doesn't mean it's not a decent biomarker for what's going on. And what they did in this most recent study was try to say which is better, counting nerve fibers in the RNFL or doing OCTA. At the present time, we don't have anything like decent software for measuring OCTA effect. It's gonna be complex, because now you're out in the retina, looking at the variation with myopic eyes are bigger and smaller eyes are smaller. Um, you don't often know what the baseline state is. There's a vascular index of the number per unit area that's out there. I think it's gonna be interesting to watch what value OCTA has, but the purpose of what I put on that slide was, you're not measuring nutritional blood flow. And frankly, also you're not measuring it in the lamina quadrosa, because the capillaries in the lamina are completely encased in collagen. And I doubt that what we're seeing in OCT of the optic nervehead is actually laminar corrosive blood vessels. I think they are more superficial, and they may be a good surrogate. So it's worth very worthwhile research, not presently clinically useful in my opinion.
2024 Lecture by Dr. Loretta Szczotka-Flynn
“Clinical and research interests on the corneal endothelium: from swelling to surgery and back again”
Dr. Loretta Szczotka-Flynn
February 27, 2024 6:00 p.m. ET
The Ohio State University College of Optometry, Hamilton Hall, Rm 80
About Dr. Loretta Szczotka-Flynn
Loretta Szczotka-Flynn OD, PhD is the Philip F. and Elizabeth G Searle - Suber Huang Professor in the Department of Ophthalmology & Visual Sciences at Case Western Reserve University (CWRU) with a secondary appointment in the Department of Population & Quantitative Health Sciences. She is also the Director of the Vision Research Coordinating Center and the Contact Lens Service at the University Hospitals Eye Institute at University Hospitals of Cleveland and CWRU. She received her Doctorate of Optometry and Masters of Physiological Optics from The Ohio State University and her PhD in Epidemiology from CWRU. She is a Fellow in the American Academy of Optometry and Diplomate in the Academy’s Section on Cornea, Contact Lenses and Refractive Technologies where she is Past Chair of the Section. She is a Vice-President in the International Society for Contact Lens Research; Treasurer of the American Academy of Optometry Foundation, serves on the Board of International Keratoconus Academy and the Eye and Contact Lens Association; and is an Associate Editor for Eye & Contact Lens Journal. Her clinical and research interests include contact lens associated corneal inflammation and infection, keratoconus, and corneal transplantation which have been funded by the National Eye Institute (NEI). She was/is Director of the Coordinating Center for two large multicenter NEI funded trials in corneal transplantation; the Cornea Preservation Time Study from 2011-2017 and since 2021, the Diabetes Endothelial Keratoplasty Study (DEKS). She was also funded by NEI to study the genetic susceptibility to contact lens associated microbial keratitis.
2023 Lecture by Dr. Frank Schaeffel
"Functional changes in the myopic retina interfere with emmetropization"
Dr. Frank Schaeffel
March 21, 2023 5:30 p.m. ET
The Ohio State University College of Optometry, Fry Hall - Room 33
About Dr. Frank Schaeffel
Dr. Frank Schaeffel is a prolific contributor to the research field of refractive development, myopia, and ocular growth. His 1988 paper in Vision Research with co-authors Glasser and Howland was the first to report refractive error development of the chick could be altered by imposed defocus from spectacle lenses. Lens-induced myopia was a true paradigm shift away from previous experimental models using deprivation of form vision, one that has led to countless experiments on the visual control of eye growth and that has a direct connection to today’s optical myopia control treatments for children. Currently, he is the leader of the Section of Neurobiology of the Eye at the Institute of Ophthalmic Research, Centre for Ophthalmology, University Clinics Tuebingen, Germany. Since 1985, Dr. Schaeffel has published more than 100 original research articles (mostly on myopia), and has secured one patent on photorefraction. His PowerRefractor technology is in use in clinical instruments around the world. His research has attracted grants totaling more than four million euros, most recently a Research Training Network grant on myopia, funded by the European Community (together with six European partners).
2022 Lecture by Dr. Fiona Stapleton
"How to make contact lens wear safer"
Fiona Stapleton, PhD
March 8, 2022 5:30 p.m. ET
via Zoom
About Dr. Stapleton
Fiona was awarded her PhD from City University and Moorfields Eye Hospital in London and undertook a postdoctoral fellowship at University College London. She moved to Australia and was the first female Head of School of Optometry and Vision Science in Australia and New Zealand (2007-2019). She is a Scientia Professor and recently Associate Dean (Enterprise) in the Faculty of Science (2018-2021) at UNSW Sydney.
She is currently President of the International Society for Contact Lens Research, the 2018 recipient of the American Academy of Optometry Glen A Fry Award, 2018 Don Korb Award from the American Optometric Association and 2018 Barry Collin Medal from the Australian Optometric Association. She presented the Geoff Woodward Memorial Award Lecture at the UK Hospital Optometry meeting in 2019. She was nominated to the Australian Academy of Science, Technology and Engineering in 2018, to Life Fellowship of the British College of Optometrists in 2019 and became a Diplomate in the Cornea, Contact Lens and Refractive Technologies Section of the American Academy of Optometry in 2015. She has published more than 280 peer reviewed papers and is part of the editorial boards of 6 international journals.
Fiona is a clinical scientist with expertise in basic and translational research in the fields of corneal infection, ocular microbiology, dry eye and contact lens related disease. Her research has improved understanding of the epidemiology and pathophysiology of sight-threatening ocular diseases.
2021 Lecture by Dr. Maureen Maguire
"Conducting Clinical Trials When Industry Is Not on Your Side"
Maureen Maguire, PhD FARVO
March 10, 2021 5:30 p.m. ET
via Zoom
About Dr. Maguire
Maureen G. Maguire, PhD, is Professor of Ophthalmology, University of Pennsylvania, with a secondary appointment in the Department of Biostatistics, Epidemiology and Informatics. She received her doctoral degree from the Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health.
Dr. Maguire is an internationally known expert in the design and conduct of multicenter clinical research in ophthalmology and has directed coordinating centers for several national trials. Dr. Maguire’s work has concentrated in the prevention and treatment of age-related macular degeneration, the leading cause of blindness in the United States. Other areas of research include preschool vision screening, dry eye disease, corneal transplantation, and diabetic retinopathy. She directed the Penn Vision Clinician Scientist Program (K12) for 15 years. She has served on and chaired many data and safety monitoring committees for clinical trials sponsored by NIH and industry.
Dr. Maguire is a Gold Fellow and President-Elect of the Association for Research in Vision and Ophthalmology (ARVO) and has received the Senior Achievement Award for distinguished service from the American Academy of Ophthalmology, the Singerman Award for Clinical Trials from the Macula Society, and the JDM Gass Award from the Retina Society. She has served as a member of the editorial board of Ophthalmology, IOVS, and four other journals. She has more than 300 peer-reviewed publications.
2020 Lecture by Dr. Austin Roorda
"Hacking the Human Visual System"
Dr. Austin Roorda
February 26, 2020 5:30 p.m.
Fry Hall - Room 33
The Ohio State University College of Optometry
About Dr. Roorda
Austin Roorda received his Ph.D. from the University of Waterloo in 1996 with joint degrees in Vision Science & Physics. Since that time, Dr. Roorda has been pioneering applications of adaptive optics and ophthalmoscopy, including mapping of the human trichromatic cone mosaic while a postdoc at the University of Rochester, designing and building the first adaptive optics scanning laser ophthalmoscope (AOSLO) at the University of Houston, tracking and targeting light delivery to individual cones in the human eye at UC Berkeley, and being part of the first team to use AO imaging to monitor efficacy of a treatment to slow retinal degeneration. Since 2005, he’s been at UC Berkeley where he is a member of the Vision Science, Bioengineering and Neuroscience graduate programs. He is a Fellow of the Optical Society of America, the Association for Research in Vision and Ophthalmology and the American Academy of Optometry. Notable awards are the Distinguished Alumni Award from the University of Waterloo School of Optometry (2007), the Glenn A. Fry Award from the American Academy of Optometry (2009), a John S. Guggenheim Fellowship (2014) and an Alcon Research Institute Award (2016). He is currently on sabbatical as a Leverhulme Visiting Professor at the University of Oxford.
2019 Lecture by Dr. Donald C. Hood
"Understanding Glaucomatous Damage: An OCT approach"
Dr. Donald C. Hood
March 5, 2019 5:30 p.m.
Fry Hall - Room 33
The Ohio State University College of Optometry
About Dr. Hood
Donald C. Hood, the James F. Bender Professor of Psychology and Professor of Ophthalmic Science (in Ophthalmology), has been a member of the Columbia faculty since 1969. He holds M.Sc. and Ph.D. (1970) degrees from Brown University and honorary degrees from Smith College (2000) and Brown University (2017). He is an elected Fellow of the American Academy of Arts and Sciences and a recipient of an Alcon Research Institute Award (2014). He currently serves as Editor-in-Chief of IOVS and is on the editorial boards of IOVS (since 1992), Documenta Ophthalmologica (since 2004), and J. of Glaucoma (since 2016); and he previously served on the boards of Translational Vision Science & Technology (2011-2017), Progress in Retinal and Eye Research (2016-2018), and J. of Vision (2004-2012). While some of his over 300 publications deal with issues of the basic neuroscience of vision, most of his work over the last 25 years has concerned research on diseases of the retina and optic nerve. He has had continuous grant support from NIH/NEI for over 45 years.
2018 Lecture by Dr. Eli Peli
"In- and On-the-Eye Low Vision Telescopes: A Critical Evaluation"
Dr. Eli Peli
April 4, 2018 5:30 p.m.
Fry Hall - Room 33
The Ohio State University College of Optometry
About Dr. Peli
Dr. Eli Peli is the Moakley Scholar in Aging Eye Research at Schepens Eye Research Institute and Professor of Ophthalmology at Harvard Medical School. He is also the director of the Vision Rehabilitation Service at the Tufts Medical Center in Boston. Dr. Peli is a Fellow of the American Academy of Optometry, the Optical Society of America, the Society for Information Display, and the International Society of Optical Engineering. He has published more than 200 peer reviewed scientific journal papers and has been awarded 10 US patents. Among numerous other awards, Dr. Peli received the Glenn A. Fry Lecture Award, the William Feinbloom Award, and the Charles F Prentice Medal from the American Academy of Optometry. Dr. Peli's principal research interests are image processing in relation to visual function as well as clinical psychophysics in low vision rehabilitation, image understanding, and display-vision interaction.
2017 Lecture by Dr. Chris A. Johnson
"Tablet-Based Visual Field Screening – There Really is an App for That"
Chris A. Johnson, PhD, DSc
Professor
Department of Ophthalmology and Visual Sciences
University of Iowa Hospitals and Clinics March 21, 2017 5:30 p.m.
Fry Hall - Room 33
The Ohio State University College of Optometry
About Dr. Johnson
Chris A. Johnson is a Professor in the Department of Ophthalmology and Visual Sciences at the University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA. His primary research interests are related to the development and evaluation of non-invasive diagnostic test procedures (perimetry, photography, imaging) for glaucoma and other ocular and neurologic disorders, with secondary interests in occupational vision requirements, vision and transportation safety, and oculomotor adjustments. He has also been involved in many multicenter clinical trials and the development and maintenance of visual field reading centers for quality control, evaluation and interpretation of perimetric outcome measures. Dr. Johnson has received many honors from Ophthalmologic, Optometric and institutional sources, has received a considerable amount of research funding, and has authored more than 425 journal publications and book chapters throughout his career.
2016 Lecture by Dr. Barbara Klein
"Biomarkers for Microvascular Complications of Diabetes"
Dr. Barbara Klein
University of Wisconsin School of Medicine and Public Health
June 9, 2016 5:30 p.m.
Room 33
The Ohio State University College of Optometry
About Dr. Klein
Dr. Barbara E. K. Klein is an experienced ophthalmologist and epidemiologist, and has dedicated more than 30 years to investigating age-related eye diseases. She is coprincipal investigator of the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR), a study of retinopathy and other ocular and systemic complications of diabetes. She collaborated with Dr. Ronald Klein on the study design and logistics of the first and all subsequent examinations, and has been an author or co-author on the vast majority of reports and manuscripts originating from the study. She is also coprincipal investigator of the Beaver Dam Eye Study (BDES), a study of ocular diseases of aging. The BDES has identified and quantified important risk factors for age-related macular degeneration and other eye diseases in older persons. Its findings have been instrumental in furthering understanding of the etiology of these diseases and focusing approaches to preventive interventions. She has been involved in developing and implementing protocols for grading eye disease, analyzing data, and collaborating on papers for the National Health and Nutrition Survey (NHANES), Atherosclerosis Risk in Communities (ARIC) study, Multi-Ethnic Study of Atherosclerosis (MESA), Los Angeles Latino Eye Study (LALES) and other population-based studies. She has also collaborated with numerous investigators around the world to study the epidemiology and genetics of diabetic and hypertensive retinopathy, diabetic nephropathy, chronic kidney disease, and age-related eye diseases.
2015 Lecture by Dr. David R. Williams
"Functional Imaging of Single Cells in the Living Eye"
David R. Williams, PhD
Dean for Research in Arts, Science, and Engineering
Director, Center for Visual Science
William G. Allyn Professor of Medical Optics
March 10, 2015 5:30 p.m.
Room 33
The Ohio State University College of Optometry
Dr. Williams Lecture Overview
The correction of the eye’s aberrations with adaptive optics (AO) has made it possible to image the normal and diseased retina of the living eye at microscopic resolution. Recent developments in the deployment of this technology, many of which combine AO and other imaging modalities with the goal of obtaining not only structural but also functional information at a cellular and sometimes subcellular spatial scale, will be described. The value of this approach with examples including single and two-photon fluorescence imaging of individual retinal cells will be illustrated, which allows us to optically probe the electrical signals the retina sends to the brain as well as molecular events in photoreceptors that would otherwise be invisible. It may be that these high resolution imaging tools, combined with recent advances in our ability to record from and control neurons with light, will eventually help complete our understanding of the computations the retina performs that allow us to see and also help to restore vision in the blind.