Cynthia Steel:
Hello everyone. My name is Cynthia Steel and I am the Chief Scientific Officer here at Glaucoma Research Foundation. I am so excited to be doing this wonderful interview today with someone who’s really an expert in this field and also a GRF ambassador. Barb, could you introduce yourself please?
Barbara Wirostko :
Yes. Thank you, Cynthia. So Barbara Wirostko, I am a glaucoma clinician scientist. I’m also the professor of ophthalmology and biomedical engineering at the University of Utah, and an entrepreneur, chief medical officer of MyEyes and also of Qlaris.
Cynthia Steel:
So Barb today we’re going to be talking about intraocular pressure, or IOP. Can you remind us what is IOP and why is it important?
Barbara Wirostko :
So IOP or intraocular pressure, is really the only risk factor that we can actually modify for glaucoma. And we think of glaucoma as a pressure-related disease, but in fact it’s a slowly progressive optic neuropathy. I think more and more we’re realizing that there’s other risk factors, but up ’til now we can only modify intraocular pressure. And as I often tell patients, we talk about high IOP or low IOP, but a lot of it is really patient-dependent. It’s also a factor that is affected by other comorbidities, and it’s a physiologic parameter that varies.
Cynthia Steel:
And does IOP remain steady throughout the day, or does it naturally change?
Barbara Wirostko :
That’s a great question. So all of our prospective studies and something you alluded to before, is why do we reduce intraocular pressure or IOP? And it really is all the progressive studies that we’ve done over the years to show that if you reduce IOP, you can actually slow down damage to the optic nerve and to vision. So basically slow down visual field loss or impacts on your vision.
And we’ve always known that pressure is highest in the morning. We would bring patients in our studies at 8:00 AM, and then over the course of the day, the pressure would go down. I’ve also always been taught and told patients that a patient with glaucoma, their IOP can actually fluctuate, sometimes up to eight or 10 points during the course of the day. And again what we’re realizing now is that that is just a small snapshot of what is really happening over time. So no, IOP is not steady.
Cynthia Steel:
Let’s talk more about IOP fluctuations. Do you consider it to be a fluctuation if it’s eight to 10 millimeters of mercury, or can it be more? What causes that?
Barbara Wirostko :
So from all the work that we’ve been doing, so right now at Moran and Wilmer, we have an open MTA and we’re studying upwards of 400, 500 patients, with looking at home tonometry and looking at IOP fluctuation. And we’ve been finding that a lot of patients actually their peak IOP or spike is in the early waking hours. Thomas Johnson actually ended up publishing a paper a few years ago showing that those IOP spikes are occurring early waking hours between 4:00 AM and 6:00 AM.
So if you take a step back and you say, “Okay, so what’s happening during those early waking hours?” Well, your body is waking up. So you’ve got the sympathetic innervation, you’ve got cortisol, you’ve got heart rate going up. We’re also finding that other vascular parameters could affect IOP and even sleep apnea. So a lot of it is coming out of REM sleep. We know that cortisol actually increases IOP, nitric oxide, positioning, your IOP is going to be higher if you’re laying flat than if you’re standing up. So yeah, there’s a lot that’s still not known about intraocular pressure and the amount of fluctuation.
And I think what’s fascinating too is we are seeing that it can actually be different between eyes. So if a patient’s got advanced glaucoma in one eye and perhaps not as much glaucoma damage in the contralateral eye, that eye with the more advanced glaucoma actually will be having much bigger fluctuations and/or spikes. So there’s something that’s going on that’s systemically driven, but then there’s also a intraocular or ocular component to it as well.
Cynthia Steel:
Awesome. So this is a really important topic in glaucoma research right now, it sounds like.
Barbara Wirostko :
Yes.
Cynthia Steel:
So interesting. So then is that why fluctuations are so important? How does fluctuating IOP potentially lead to worse glaucoma?
Barbara Wirostko :
So if you look back in the literature, the AGIS study, the CIGTS, there was a post-hoc analysis on the OHTS study as well. So these are all studies that were done over six, seven, eight, nine years. CIGTS in particular looked at visual field progression over time and they found that if a IOP in the clinic fluctuated more than 8.5 Millimeters, actually that was linked to visual field progression and/or loss of visual field over time independent of what the mean IOP was.
So again, when a patient comes in and we’re looking at a mean IOP or an average IOP at one visit that is really a very inaccurate or insufficient, that’s the better word, insufficient way to evaluate what is really going on with an intraocular pressure.
Cynthia Steel:
You and I are both researchers, but for those who aren’t, you were talking about some of the landmark clinical trials right there, right? AGIS, Advanced Glaucoma Intervention Study?
Barbara Wirostko :
Yep, exactly. CIGTS, Collaborative Interventional Glaucoma Study, and OHTS, Ocular Hypertensive Treatment Study.
Cynthia Steel:
And these are landmarks because they were so large and comprehensive.
Barbara Wirostko :
Yeah.
Cynthia Steel:
That’s like the gold-standard in our field, right?
Barbara Wirostko :
They’re the gold-standard. And basically what they looked at was different stages of glaucoma. So AGIS was advanced. They actually looked at surgical intervention trabs. They also looked at lasers. CIGTS was medical therapy collaborative, and then ocular hypertensive was asking the question if a patient has a higher IOP but is not yet have glaucoma, should we actually treat them and lower their IOP? And all of these studies showed that yes if you lower IOP you slow down progression.
But you know what’s interesting as I think about it too, and this is just a hypothesis. In all of these studies and especially OHTS, despite treatment, patients still progressed. And I wonder if it’s because they didn’t know about that fluctuation piece. So in the office the IOP looked okay, but perhaps it was actually fluctuating. I mean, we’ve got some patients that could be in the teens in their office and yet they’re going into 20s, high 20s, even 30s in the early waking hours. That’s crazy. That’s far above 8.5 millimeters that CIGTS showed that was important or critical.
Cynthia Steel:
Wow. You are part of a company called MyEyes, and you help provide home tonometers to patients so they can monitor their pressure at home.
Barbara Wirostko :
Yes.
Cynthia Steel:
If a patient receives a home tonometer or they rent a home tonometer, how should they be thinking about that as part of their overall glaucoma care?
Barbara Wirostko :
And that’s a great question because it’s not an independent diagnostic. It’s used in collaboration. As I always say to patients, it’s the totality of the data. The risk factor, the amount of damage. For someone, a small fluctuation could be much more detrimental than for someone else. And the iCare HOME is a prescription device. Currently, it’s the only available device that patients can get and use at home.
And generally the way I recommend it is they should be taking their pressure several times during the day, most importantly in those early waking hours. So set your alarm for a few hours before you normally wake up. You can take your pressure either lying flat or sitting up, and then take it again a few hours after you wake up, maybe noon, 4:00 PM, 8:00 PM before you go to bed.
And then we’ve had a lot of interesting patients too, that have asked the question, “So what does my IOP do after I’m running or diving?” Or we’ve had some patients that were actually mountain climbers and wanted to know what happened with their IOP when they were at different altitudes.
The other thing that was really neat too is I had a patient who ended up undergoing surgery. She had a shunt procedure and she lived in Arizona part of the time. So it was really nice because we were able to manage her IOP and her postoperative period virtually. She also has asthma. She’ll go on steroids. We always worried about steroids increasing her IOP, but she was able to tell us if her IOP was going up on the steroids. And then again, we could manage that without sending her back and forth to the office.
Cynthia Steel:
So it’s like you are your own research subject, but your doctor definitely should be the one guiding your treatments.
Barbara Wirostko :
Yes. You always want to be in communication with your doctor. And again, it’s been that real time collaborative learning experience, both I have found for myself and for my patients. I had another patient that was really interesting where he was actually going to undergo surgery because his fluctuation was too much for the health of his optic nerve. And again, that’s a really important thing to consider the amount of fluctuation, the delta, the numbers, it’s really getting down to personalized medicine. But it was fascinating because he was then diagnosed with sleep apnea, and it turns out that those fluctuations actually decreased once he stopped having so many apneic events.
Cynthia Steel:
Wow, that’s interesting. So if a patient has their iCare HOME and they’re using it and it’s picking up fluctuations, how can their doctor help them with that? Is there anything that a doctor can do about that?
Barbara Wirostko :
It’s a great, great question. So if you look at the literature, we talk a lot about now the light study. So this was the study that was done out of Moorfields and they asked the question, “What is a preferred first-line treatment? Is it an SLT, selective laser trabeculoplasty, or is it topical eyedrops?” And they then followed these patients out to six years. And it was really interesting because I’m going to say roughly 700 patients, but half of them received SLT first-line, the other half received topical eyedrops. And even though the IOPs in the office were essentially the same, over those six years, the patients who received the SLT had less visual field loss and less progression.
So then we asked the question at Moran, “Is an SLT lowering those spikes and reducing the amount of fluctuation?” And sure enough, and we’re going to be publishing this data, we had over 50 patients now followed out to 18 months. And yes, SLT does a really good job of reducing that early morning pressure spike.
So we’re rethinking our choices. I think too, what we’ve found and my colleagues have now thought about is if you’re having a lot of fluctuation and you’re spiking into the 20s, your next steps in terms of interventions could be very different if you’re progressing and you’re not spiking. So maybe we just need to do a surgery and get you to 15. But if you’re not having a lot of fluctuation, maybe you need to trab and you need to get to 10 all the time.
Cynthia Steel:
I see.
Barbara Wirostko :
That’s how we’re starting to think about it. So again, it is much more personalized.
Cynthia Steel:
Interesting. Interesting. So going back to glaucoma in general, what do you tell a patient who has a new glaucoma diagnosis and is nervous about it?
Barbara Wirostko :
So it’s again, the totality of the information. IOP is the risk factor we treat, but very often we are now sending patients for sleep apnea testing. We’re also doing 24-hour blood pressure studies. We’re also doing blood pressure monitoring. So again if someone is having a lot of blood pressure variability, that actually also can impact perfusion to the optic nerve.
There’s a lot of research coming out of Bascom Palmer. They just published on that. Sleep patterns and sleep disturbances just came out of UCLA with Anne Coleman. So we’re learning more and more about what is impacting IOP and hence what is impacting glaucoma. I still scratch my head because I have patients who sit in the mid 20s and never progress, never develop damage. But then why do I have a patient with a pressure of 10 that is slowly losing vision?
The other thing that’s really exciting is polygenic risk scores. That’s another thing that we’re hoping to offer actually through MyEyes. Because there are so many genes, I want to say 300 to 400 genes, that interact that perhaps play, or actually not perhaps, but do play a role in developing glaucoma, there are now a test available that looks at not specific genes, but looks at a risk score. So it’s a polygenic risk score and it gives you a printout and tells you if you’re mild, moderate, or severe.
And I could see myself, to your question, if someone is having a certain amount of fluctuation, which maybe is not a lot, but if their risk score is great or severe for progressing, maybe we would be more aggressive early on. So maybe we would do that SLT earlier than just following the patient, or think about a MIGS procedure.
Cynthia Steel:
Obviously glaucoma is a very rapidly changing field. I mean, even just in this conversation in the last 15 minutes, we have learned about so many papers. There’s so much new data that’s coming out. And obviously that’s one of the reasons why I love talking to you.
But I would imagine that the flip side of that is that there can be a lot of misinformation and a lot of information out there that’s not accurate. So if a patient wants to get the most accurate information or at least get some very well-thought-out information on glaucoma, besides talking to their doctor, where could they go?
Barbara Wirostko :
It’s a great question. And I’ve always had your brochures. I think the Glaucoma Research Foundation does such a top-notch job providing up-to-date information. But keeping it simple, there is a lot of misinformation out there. I was actually reviewing a paper and I found it fascinating on how many websites actually do have misinformation. So who is checking that data? AAO, obviously. We have the Wikipedia eye page through the American Academy of Ophthalmology is excellent optometry. But if it’s a organization that is focused in ophthalmology and then obviously like GRF focused on glaucoma, that’s where patients are going to get the most accurate and up-to-date information.
Thank you for doing what you do.
Cynthia Steel:
You’ve reviewed some of the articles on glaucoma.org and I review or write a lot of the research articles. So yes, in a very biased opinion, glaucoma.org is an excellent place to get some good information.
Barbara Wirostko :
And you know what, Cynthia, too, I get asked a lot and we hear from a lot of patients who struggle to get information from their doctors and/or even get a script for the iCare HOME. And I equate IOP fluctuation like any physiologic parameter blood pressure. If you’re having fluctuating blood pressure, you want to know because you’re at risk of a stroke. If you’ve got diabetes, you want to know what your glucose is doing, highs and lows. Studies have shown that if you can reduce the fluctuations, you’ve got better outcomes, less risk of end organ damage, whether it’s kidney disease, peripheral neuropathies, vasculopathies.
And glaucoma is not that different. Again, you want to control the fluctuation, you want to understand the IOP. And I think patients deserve to have physicians that will discuss this with them. At the end of the day, the physician, it is your body, it is your vision, and I think they need to seek out the information they need.
Cynthia Steel:
100%. I agree with that 100%. Thank you. Thank you, Barb.
End Transcript.