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On June 12, 2020, Glaucoma Research Foundation presented an Innovations in Glaucoma Webinar, "What's New in Glaucoma Medications?"
The recorded webinar features a discussion with glaucoma specialist David Richardson, MD (San Marino Eye) and Thomas Brunner (President and CEO, Glaucoma Research Foundation).
"Excellent presentation giving patients an authoritative capsule review of glaucoma drugs often hard to find elsewhere."
- James Aylward
"I am newly diagnosed and was interested in various eye drop pros & cons as well as any common interactions with other prescriptions.
- Paula D.
Dr. Richardson discusses existing and new medications for treating glaucoma and provide answers to frequently asked questions about glaucoma eye drops. Learn how the new medications are different from existing treatments, and about their potential side effects in this recorded webinar.
Tom Brunner: Good afternoon. My name is Tom Brunner, and I am the president and CEO of Glaucoma Research Foundation. Welcome to our webinar: What's New in Glaucoma Medications? Today, we will learn about current and new medication options to treat glaucoma. Dr. David Richardson has very kindly agreed to join me today to talk about glaucoma treatment options, and we'll try to answer as many of your questions as possible.
David is a glaucoma specialist and medical director at San Marino Eye in Southern California. He went to Harvard Medical School in Boston and did his ophthalmology residency at University of Southern California, Doheny Eye Institute. David is also an attending ophthalmologist at the Veterans Health Administration in Los Angeles and one of our newest Ambassadors for Glaucoma Research Foundation. It is my honor to welcome Dr. David Richardson.
David Richardson, MD: Welcome everyone. And hopefully this will be an informative hour for you. So let's go ahead and get started. Now, before I go over the medical treatment of glaucoma, I think it's important to take a couple of minutes just to introduce intraocular pressure and aqueous fluid, because these are intimately related to what we're going to be talking about.
If we look at this schematic of an eye, we can see the front of the eye here with the cornea, the iris. Light is focused through the lens, back to the retina and the signal is then sent out to the brain through the optic nerve (#15 here). Now, the optic nerve is what's damaged in glaucoma, and that damage is often related to elevated pressure. So let's talk about pressure. The pressure in the eye is important in that you need some pressure to keep the eye round just like you need pressure to keep a ball round.
That pressure is produced by the balance between the production of fluid, what we call aqueous fluid, which bathes the internal structures of the eye, provides nutrients, and helps remove waste products. Now, this fluid is produced behind the iris in these little finger-like projections. These are called ciliary processes. They produce fluid, which then goes around within the eye, and then leaves the eye between the lens in the iris through the pupil and out the trabecular meshwork.
We could spend a lot of time talking about that, but just know that the trabecular meshwork is believed to be the primary source of resistance to fluid leaving the eye. There are other mechanisms by which fluid can leave the eye, including through what's called the uveoscleral pathway, which is basically between the iris and the trabecular meshwork. But for the most part, it's the trabecular meshwork that we're concerned about. So again, [fluid] production (here) flows through the eye and leaves through the trabecular meshwork.
Now, before we talk about new medications, let's first review what's old. It's worth knowing how the medications that have been around, and the meditations that most of you who are on this conference are likely taking, it's worth knowing a little bit more about these than you may have been told in the visit to the medical office.
We're going to start with one that's really old, pilocarpine. Very few of you are probably taking pilocarpine, and we'll talk about why. Pilocarpine is what we call a myotic, and myotic basically constricts the pupil. By constricting the pupil, it kind of tugs on the trabecular meshwork, stretching it open. By stretching it open, fluid can then leave through the trabecular meshwork and out the eye. The problem is that you have to take this drug four times a day.
Now, I doubt that most of us on this conference are organized enough or OCD enough to actually take something four times a day, regularly for a chronic period of time. So for that reason, it's not a drop that we see much. And also, because the side effects are quite severe: headaches, blurred, vision, other systemic side effects such gastrointestinal distress, diarrhea. So pretty unpleasant really. It used to be quite cheap, but as with many generics now, for reasons why I can't explain, it's now 10 times that expensive. So it's just not something that you're going to see prescribed very frequently.
So let's move to another older drop, the beta-blocker class of medications. This class has been around for half a century. It's very effective. The most commonly prescribed one is Timolol. Although I have been of late prescribing an older one, betaxolol, which we may get into why that one would be worth prescribing, at some point. The method is by decreasing production of aqueous fluid. So it doesn't actually work at the level of the resistance. It reduces the amount of fluid. It's just like you've got the sink, you've got the faucet, you've got the sink and you've got the drain. The problem is with the drain. But many of the treatments are not working at the drain, they're working at the faucet. This basically decreases the flow of fluid, production of fluid. The nice thing about beta-blockers is that they can be taken once a day in the morning or twice a day. And we may discuss at some point why once a day may actually be preferred. Side effects: low blood pressure, low heart rate, difficulty breathing.
This is one of the few medications that, although it's working out the level of the eye, can actually cause systemic issues. And so we need to be very careful about that in certain people. There are methods to decrease the systemic effects, and we may get into that during the Q&A portion of this talk. Cost: This is one of the least expensive drops out there. You should be able to get this for, it used to be as cheap as $3 at Walmart. I think they might've upped it to about $5. If you're paying more than $20 - $25 a month, you're getting ripped off -- if it's generic. Now, it can be much more expensive if it's a branded one. And we'll also talk about combination medications. Many of these medications are in what are called fixed combinations. So you're getting not just one class of medication, but two classes. And so Timolol in the beta-blocker class is available in Cosopt and Combigan are the brand names for the fixed combinations that have beta-blockers.
Now, I just mentioned Cosopt. Cosopt just Timolol plus a carbonic anhydrase inhibitor. So the carbonic anhydrase inhibitors, commonly branded here in the U.S. as Azopt and Trusopt are newer than the beta-blockers and pilocarpine. They work also by reducing production of aqueous fluid. Unfortunately, it needs to be taken multiple times a day, at least twice, ideally really three times a day to get the best effect, which is very difficult for most people to get that middle of the day dose in. Side effects are pretty much limited to stinging. So you wouldn't think that would be a big issue, but I've had patients say that it stings more than they can tolerate. Cost: Generics can be inexpensive. Branded ones can be quite expensive. This may be one of the classes of medications where the brand actually does work better than the generic. There have been some issues with some of the generic carbonic anhydrase inhibitors, dorzolamide. And it is available in combination. So, combined with Timolol, a beta-blocker, in Cosopt, and combined with the next class I'm going to talk about, the alpha-agonists, in Simbrinza.
So let's talk about the alpha-agonist class. Brimonidine is the generic name for the most commonly prescribed. The brand name is Alphagan P. How it works: This one also works by decreasing the [intraocular fluid] production. But, it does have the benefit of increasing outflow as well, but not through the trabecular meshwork. It increases the outflow through the uveoscleral pathway, which I briefly mentioned earlier. This one, unfortunately, also has to be taken at least twice, but ideally three times a day. And there's mounting evidence that it really does need to be taken three times a day for the best effect, which limits its usefulness.
The side effects are pretty much limited to red eye and allergy. The allergy can be pretty significant with this class. Somewhere between 10% and 15% of people who take this will eventually develop an allergy and have to stop it. The cost: the generic 0.2% is inexpensive and covered by most insurances, but is the one that's most likely to result in allergy. The 0.1% is the brand. The 0.15% is available generically. Oddly, whether it's generic 0.15% or branded, they're both kind of expensive. And it is available in two combinations: one with Timolol, Combigan, and one with the carbonic anhydrase inhibitor, Simbrinza.
Now, one of the newer medications. This came out during my residency, so about 20 - 25 years ago, in that range: the prostaglandin analog class of medications. This revolutionized the treatment of glaucoma. We see this in multiple brands, Xalatan, Lumigan, Travatan-Z, Zioptan. There's another one, Xelpros, that just came out. How it works: This actually works by increasing the outflow. So from helping fluid leave the eye through the uveoscleral pathway. So again, not through the trabecular meshwork, which is the primary point of resistance. It's taken only once, in the evening. It can actually be taken any time, but we generally recommend it in the evening, because one of the side effects is [eye] redness. And it's thought that if you take it in the evening, some of that redness will be resolved by morning.
There are other largely cosmetic side effects associated with [prostaglandin analogs]. Iris color change. If you've got hazel eyes, they can come out brown. Brown eyes stay brown. Blue eyes without any pigment or brown spots in them, pretty much stay the same. But if you're in that [eye color range of] blue with pigment or hazel, your iris will get darker and it's a permanent change. Long lashes. A temporary change, appreciated by some, not by others. And then there's eyelid tissue changes in the Prostaglandin Associated Periorbitopathy we speak of now. We may get into that in the Q&A. Cost: It really depends on which one you're getting. If it's the generic latanoprost, it should be very inexpensive, between $10 and $20 a bottle. The brands are more expensive. The good news is that the generic latanoprost seems to work just about as well as most of the brands. There are some reasons to consider the brands, which we may get into later. It is available in combination, the combination with the newest class of medications, which I will be talking about, and that's Rocklatan, which is latanoprost plus netarsudil, a ROCK inhibitor.
So that's the old. Now let's get into what's new, because there are some really exciting things in the treatment of glaucoma here. So the first one is nitric oxide donators. The brand name of this is VYZULTA. So what is a nitric oxide donator? Well, nitric oxide is a molecule that when released in the eye can do a number of interesting things. It potentially increases blood supply. Now, whether it increases blood supply to the optic nerve itself is not entirely known. But we do know now that glaucoma is not as just a pressure-related disease, but there's probably a perfusion aspect to it. So it's exciting to think that there might be something that could actually treat glaucoma through a mechanism other than just intraocular pressure. So this exciting for that reason.
But the other thing is that nitric oxide actually kind of relaxes the trabecular meshwork and the canal, Schlemm's canal, behind the trabecular meshwork. So this medication, this class actually works at the point of resistance. And so it's exciting when we've got something that's working where the problem is. Now, VYZULTA is not just a nitric oxide donator. It's what I call latanoprost plus. It's a prostaglandin analog plus a nitric oxide donator. So as I mentioned, it works by increasing aqueous outflow, but it does so through both the uveoscleral pathway, which the prostaglandin portion does, and the trabecular meshwork, the nitric oxide portion. It's taken once nightly. So it's nice and convenient. The side effects are identical to the prostaglandin analog class because it is a prostaglandin plus the nitric oxide donated component.
So there really does not seem to be any specific side effect related to the nitric oxide portion of this. Cost: This is going to depend on insurance coverage. Since this is a new medication, there's no generic available. If your insurance does not cover it, it will be very expensive, in the hundreds of dollars per month range. It is not available in combination, but I pretty much view this as a combination drop, a combination of a prostaglandin analog and a nitric oxide donator.
Now, another really exciting development is the class of rho-kinase inhibitors, or ROCK inhibitors. Essentially, you have to understand that from the turn of the millennium to just a couple of years ago, 2017, we had no updates in glaucoma therapy. There was nothing new. And then both VYZULTA and Rhopressa were FDA approved in 2017. Rhopressa, or netarsudil is the generic name, is very interesting, because this works at the level of the trabecular meshwork, and it does so by actually changing the structure of it. So if you can think of it in terms of a meshwork, in patients with glaucoma, the trabecular meshwork gets stiff and does not allow fluid through it as easily. Rhopressa actually works over time to make the trabecular meshwork more flexible and essentially allow the fluid through the trabecular meshwork into the Schlemm's canal.
This doesn't work right away. It takes many weeks to actually make this change, which is an interesting element of this medication. But there are other things that it seems to do as well. Rhopressa also lowers the episcleral venous pressure. That's the pressure of the vessels into which aqueous fluid flows. Fluid tends to flow down a pressure gradient. So if you can lower the pressure of the destination of the fluid, in this case the episcleral venous pressure, then you can potentially bring the pressure down even lower. There may also be other benefits of this class, including improved blood supply. So it's a very interesting class of medications. We don't know everything about it yet. But what we do know about it is very exciting.
Now, how it works. We just talked about that. How it's taken, once nightly. So, wonderfully convenient. Side effects: red eye and achy eye. And the redness can be pretty severe. The achiness tends to be temporary, but it can last for a few days to a week. Most people that can push through it get used to it. The redness gets better and the pressure goes down. How effective is it? Well, it's interesting because it seems to bring the pressure down by between four to six millimeters of mercury (mmHg), regardless of the starting pressure, which is unusual. Most drops are bringing pressure down, let's say 20%, 30%. So if you start with a higher pressure, you get a larger millimeter mercury difference, which means most medications don't work all that well for what we call low-tension glaucoma, because the pressure is already so low.
Netarsudil actually seems to work well even with low or normal tension glaucoma. And that may have to do with the episceral venous pressure lowering that I just discussed. Cost: This is a new medication and no generic available. If it's not covered by insurance, it's probably going to be on the order of $300 a month, meaning it's not going to be affordable. It is now available in a combination, Rocklatan, which is latanoprost plus netarsudil. So you're actually getting both class benefits in a once nightly drop.
And then the last thing I want to talk about in terms of what's new is really interesting, and something that a year or so ago had you asked me about this, I would have thought that there was no need for this. This is DURYSTA (bimatoprost). It's actually an implant. It's not a drop. This is a prostaglandin analog that is injected into the front of the eye, between the cornea and the iris. A couple of years ago, I thought this would be unnecessary, because the prostaglandin analog class [as an eyedrop] is for the most part well tolerated. It's once nightly. It's available generically, and it works well. Even if you miss a drop periodically, it seems to be strong enough to carry over. So why in the world would anybody actually go into an office every four months to have something injected into their eye? I just didn't think there was a lot of need for that.
But here's the interesting thing: the initial studies looking at bimatoprost, in which people had this injected in their eye three times. So what we call point zero, four months later and eight months later. One would think that by 12 months out, the effect would have been lost. So it was only supposed to last about four months. The study looked at people who had only those three implants and many of these people two years out, from the initial injection, a full year from their last injection, still had pressure control. And so this really has us rethinking the benefit of placing implants with medications in the eye, in high concentration, rather than on the surface of the eye, where you can get into all of these other side effects that I mentioned, both surface side effects as well as systemic. None of those should be an issue in an implant. So anyway, we have much I'm sure to talk about still with the Q&A, but that is what's new.
And everything I've talked about today has been FDA approved. There are other things that are interesting, that are in the works. But all of this is now available. The question for the newer stuff, as I've already alluded to, is cost. We don't know how much, for example, DURYSTA is going to cost and which insurances, if any, will actually cover it, assuming that it is affordable. This is a very exciting time. Are we ready for questions?
Tom Brunner: Yes.
David Richardson, MD: Okay.
Tom Brunner: Thank you very much, David. That was an incredible presentation. I learned a lot and I'm sure our participants did. So our first question is about dry eye and what can be done about that, and the fact that many glaucoma patients feel that the [glaucoma medication] eye drops may be contributing. So would you care to comment on that?
David Richardson, MD: Absolutely. Before I get to the issue of ‘why do most glaucoma eyedrops cause dry eye,’ I first want to pull back to recognize that the glaucoma drops may not be causing the dry eye. Many people who have dry eye already are not necessarily symptomatic. And then when you add the glaucoma drops, many people with dry eye will then become symptomatic. And this is because both dry eye and glaucoma are more common as we get older.
Most people with a mild amount of dry eye aren't necessarily bothered by it. But when you add something to the surface of the eye, whether it's an eye drop or a contact lens, or other activities or things, it can push the dry eye to the point where you start to notice it. And what is it about glaucoma drops that worsen dry eye? Because again, it doesn't generally cause [dry eye] on its own, but it tends to worsen it to the point where it's symptomatic or more symptomatic.
Most glaucoma drops have a preservative in them called benzalkonium chloride. Benzalkonium chloride, or BAK for short, has been shown to actually damage some of the cells on the surface of the eye that are very necessary for proper lubrication and protection with a good quality tear film. And somebody who is taking especially multiple glaucoma drops a day, that building up of the BAK frequently over time can actually worsen dry eye.
As far as what can be done to alleviate it, one of the things to consider would be switching from BAK [preservative] to preservative-free drops or drops that have a preservative that is a non-BAK preservative. So for example, Alphagan P, the branded brimonidine, has a preservative called Purite in it, which essentially disappears on contact with the surface of the eye. So those are two things that I will often recommend as methods to alleviate the dry eye exacerbation from BAK.
Tom Brunner: Our next question is about eyedrops that are preservative-free, and what are the benefits of preservative-free medications?
David Richardson, MD: This is a nice segue from what we were just talking about, for those who do have irritation from the BAK [preservative]. Moving to preservative-free eyedrops eliminates the BAK. And so in theory, it should not exacerbate or worsen dry eye. As far as the brands that are preservative free, in the beta-blocker class, Timolol is available in a brand Timoptic in Ocudose. The fixed combination Timolol and carbonic anhydrase inhibitor is available preservative-free in Cosopt PF (PF for preservative free). There's also a prostaglandin analog, Zioptan, which is preservative-free. And then Xelpros is one of these that has kind of a disappearing preservative. These are all brands. And as brands, they can be quite expensive. Although oddly enough, I find that many insurances will cover Zioptan as a prostaglandin analog.
There are other options as well. There are pharmacies in the U.S. that compound glaucoma medications. Imprimis [Pharmaceuticals] is one of the more common ones that will provide combination drops in a preservative-free form. And so that's what I would consider as one of those options for somebody who does have a significant amount of symptomatic dry eye and needs to take glaucoma medications.
Tom Brunner: And our third question is about side effects. You talked a lot about that during your excellent presentation, but I wonder if you can comment about when should a patient actually be concerned about side effects or when should they contact their doctor?
David Richardson, MD: Yes. Let's take it by class [of medication]. With the beta blocker class, if there are going to be side effects, they tend to occur right away. Low heart rate, difficulty breathing, low blood pressure. For those who need to take the beta-blocker class, there are a couple of things that can be done. For example, you can perform what's called digital punctal occlusion, which is essentially pressing one's fingers or a balled-up tissue in the corner of the eye, near the nose, because that's where the drainage system is.
When you put any kind of drop on the surface of the eye, there tends to be more volume in that drop than is going to remain on the surface. Some of that drains into the nose. The nose, the sinuses, are very vascular. Anything that goes into the nasal sinus tissue is going to be absorbed into the bloodstream. So that's one way to do it [minimize side effects].
I've mentioned that the drops tend to be too big. Another way [to minimize side effects] is to use a drop applicator such as the SimplyTouch. It's a silicone applicator that's available online (Amazon.com has it for about $15) that allows you to actually place the drop on the surface of this tiny little silicon spoon, and then place the spoon up against the eye. And by doing so, less drop gets into the eye, so then there's less of an issue with that [excess medication] getting into the sinuses and absorbing into the bloodstream. There's also the option to switch to eye drops that may have less systemic side effects.
I mentioned betaxolol earlier. Betaxolol tends not to give people problems with low blood pressure and low heart rate, things like that, but it stings. So there's always some kind of a ‘payment,’ one way or the other.
Now, in terms of the darkening of the eyelids skin, same kind of issue. If you're dropping one or two drops on the surface of the eye and not blocking it off, if a prostaglandin analog gets onto the skin, it will worsen the darkening of the skin. So, using as little as you possibly can, making sure that you're getting a tissue to remove [excess], that can help with that. Many of the other side effects are unfortunately just related to the local interaction of that medication with the surface of the eye or the eyelid. And so it's not always possible to eliminate the side effects. But there are some things, as I said, to reduce some of them.
Tom Brunner: I guess if a patient has a concern, it really is important to discuss that with your doctor. And I guess potentially, there might be changes to medication that could minimize [side effects]. Is that a fair statement?
David Richardson, MD: Absolutely. Any types of difficulty that you're having with the medication should be mentioned to your physician. And then together you can work on either alleviating those issues, switching to something else, or finding other ways to deal with them. There will be certain things [side effects] that are serious enough that you will need to move on to another medication. Then again, sometimes we get into a situation where the glaucoma is so severe and the pressure is so high that the only option to eye drops is really to consider surgery, which has risks associated with it.
Tom Brunner: And we will talk more about surgical options in our next webinar. But we do have some more questions here, and one of them is an interesting one about -- ophthalmologists being reluctant to prescribe generics. Are there reasons for that, from your impressions, of wanting to stick with the brand names, even though there may be a less expensive generic?
David Richardson, MD: There are. What we need to understand with generics is that the only thing that needs to be equivalent in a generic is the active ingredient. That may not be as much of an issue when you're taking something by mouth [because] it's generally absorbed. And if you've got so many milligrams of an active ingredient in a generic versus a brand, once it's absorbed, it should be the same amount that gets into the body. The problem with eyedrops is that there's the active ingredient and then there's what we call the vehicle. It turns out that many of the ingredients in eyedrops, the absorption rate will change according to the vehicle. The vehicle can also impact the surface of the eye. So some vehicles with a different pH may be far more irritating than the brand name.
We know as physicians that if we prescribe something that's really irritating, it's less likely that our patients are going to take it. And we've also had experiences with some brands that just don't seem to work as well. I mentioned earlier the carbonic anhydrase inhibitor. I tend to avoid generic dorzolamide, because I found that depending on the generic brand that my patients are using, their pressure will end up being higher or lower. The problem is that pharmacies can substitute a generic. So you can have one brand of generic, and then one day the pharmacy just substitutes it for a different brand of generic, without necessarily telling the patient or the doctor. And so then that makes it difficult to figure out, well, is it the medication that's a problem? Is it an issue with compliance? Is the glaucoma just getting worse?
So I'm not, and many ophthalmologists are not a big fan of a certain generics. That being said, there are some generics that seem to work just as well as the brands and are much less expensive. The beta-blocker Timolol, for example, I've never seen much of a difference between brand and generic. The difference in price is significant. So almost all of my patients on Timolol are on generic Timolol.
There are some advantages to a couple of the branded Timolols. And so I will customize that treatment to the needs of my individual patients. And then the prostaglandin analogs, it turns out that [generic] latanoprost is just as effective or just about as effective, within a millimeter of mercury or so, as almost all of the brands. And so I'm very comfortable, as are most ophthalmologists, with prescribing branded or generic prostaglandin analogs. But as I said, the carbonic anhydrase inhibitors, not so much.
And then I spoke briefly about the alpha agonist class or brimonidine. The issue there is that the generics 0.2% is far less expensive than the brand, but has a higher likelihood to develop an allergy and also tends to cause more irritation and redness than the branded, which also has Purite. So branded Alphagan P 0.1% uses Purite, which is the disappearing preservatives versus the generic, which tends to have BAK in it. So those are the reasons why we in general will as ophthalmologists prefer a brand over a
Tom Brunner: So that raises the interesting question with this new long-term injected treatment, the DURYSTA that you spoke about at the end of your presentation. The question is, does that have any preservative? And are there any benefits for patients that have, say, a lot of reaction or discomfort from the eyedrops with something like an injected treatment?
David Richardson, MD: Absolutely. And again, I have turned 180 degrees in my opinion of the value of DURYSTA. Like I said, three years ago, I just thought this is ridiculous. Who's going to be paying what I'm sure is going to be hundreds, if not over a thousand dollars, for a treatment for this, whether it's patients or insurance, for a class of medications that overall is pretty well tolerated? But that being said, the ability to put something in the eye which, again, there's no preservative in it. It's an implant that dissolves over time, which has a high concentration of a prostaglandin analog. And in theory, once it's in the eye, there should be no side effects, other than there will be still the iris color change.
But there should not be any of the other issues [with side effects] that are associated with the prostaglandin analogs such as the Prostaglandin Associated Periorbitopathy, which for those who are not familiar with it, that is a loss of connective tissue around the eye, which at first can be cosmetically quite nice because it's like having kind of a laser resurfacing. But the problem is that, if it continues, it can actually make people look quite gaunt and you can start to see the bony structure around your eyes. And from a clinical perspective, not just a cosmetic perspective, if the tissue shrinks so much that it actually applies some pressure of the eyelids on the eye, it can be difficult to get an accurate pressure measurement in the office on someone with Prostaglandin Associated Periorbitopathy.
So for those reasons, DURYSTA becomes very interesting. But again, the surprise in all of this, and what convinced me that this is something that I will be offering my patients once it's available, assuming that it is affordable, is that this could potentially be something that does not require every form of implantation, but rather implantation for a number of times and then just monitoring. So if you can get two years of pressure lowering off of three implantations, then this really starts to be something that could make patient's lives much easier, decrease the stress associated with, "oh, now did I forget to take my drop last night?" And completely eliminate the issue of adherence to a regular schedule. I would still like to see one of the other classes of medications developed as an implant.
So for example, if we could get the alpha agonist class, which is a three time a day dosing. If we could get that in an implant, that would be truly wonderful. But I think that this is just the beginning of what we're going to see over the next decade or so. I think we're going to see a number of different types of medicated implants coming out.
Tom Brunner: What about scarring when you make the injection? It's a very fine needle, I believe. But is that a problem when you're making these injections? They're through the cornea, I assume.
David Richardson, MD: Exactly. This goes through the cornea, the clear part of the eye. And it would be a very, very small incision. And because it's such a small incision, as long as it's done under sterile conditions, using some Betadine on the surface of the eye, whether it's in the office or the minor procedure room or the OR, the risk of scarring from such a small incision or the risk of infection is really quite small.
But there are some risks associated with putting something in the eye. Inflammation is a risk, infection is a risk, cataract formation is a risk. So these aren't necessarily things that I'm going to be recommending for my younger patients who are still what we call phakic, [meaning they] have a natural lens. But for somebody who's already had cataract surgery, this would be I think a very good option.
Tom Brunner: Another question, shifting gears a little bit here, and a practical question with the COVID-19, a lot of patients have stocked up on their medications, which is a wise thing to do. And the question is really about storage and temperature and the importance of keeping the bottles at a particular temperature. How critical is this for glaucoma medications?
David Richardson, MD: The answer is: it depends. I like to use the analogy that glaucoma medications are a bit like buying foods at the grocery store. You can have certain foods, let's say pasta, for example. There are certain pastas that you can stick on the shelf for years and years and years and at room temperature and they will be just fine. There are other pastas that are fresh that need to be refrigerated. And if you stuck them in the cupboard, they'd be ruined in a week or so. The same thing is true with glaucoma medications. You really need to look. And I know those inserts in those bottles, in the boxes, the package inserts are something that both patients and doctors hate. Incredibly small print, difficult to read. But there is one thing on the insert that I find actually useful, and that is the part where it tells you what the recommended temperature for storage is.
And it is different for different classes of medications and even different medications within the same class. So for example, the prostaglandin analogs, some of them need to be refrigerated until you open them, and others, not so much. In general, you don't want to freeze your drops and you don't want to leave them in the car on a hot summer day. So, extremes are bad for all drops. But in terms of what the ideal temperature is, the next time you get your eyedrops delivered to you by the pharmacy, pull out the insert and take a look at what the recommended storage temperature is.
Tom Brunner: And what about oral medications? A question on methazolamide.
David Richardson, MD: Yes. I did not discuss the oral medications. There's essentially only one class in oral medications, which is the carbonic anhydrase inhibitor class. And the interesting thing is that as an eye drop, it's the least effective class of medications. As a pill, it can be the most effective. So for example, the branded name Diamox, which is acetazolamide, is the most effective IOP (intraocular pressure) lowering medication that we have. The problem with acetazolamide is that in the 250 milligram dose, it has to be taken four times a day. And there is an extended release version, which can be taken twice a day at 500 milligrams, but it's more expensive. And Diamox has a number of potentially life-threatening side effects associated with it. An annoying side effect is it's a diuretic and so you have to drink more fluids. So that's just annoying, not life-threatening. But it's also associated with the development of kidney stones and the development of reduced potassium. So that needs to be followed, because if your potassium is too low, that can affect your cardiac status. It's also associated with a rare but life-threatening condition, aplastic anemia, where the blood count basically drops. So it's not a medication to be taken lightly.
We do tend to use the oral Diamox or IV around the time of surgery if we're worried about the pressure being too high for a period of time. But we tend not to leave people on it chronically, although I do have a handful of patients who, we don't have any other option because, for whatever reason, surgery is not an option and they're tolerating it. So it can be done, but you just need to be extra careful. With regard to methazolamide, the brand named Neptazane, it's got fewer side effects, but it also just doesn't work as well as acetazolamide. So I have no one currently on that. But I will on a rare day, maybe twice a decade, prescribe methazolamide.
Tom Brunner: What about missing drops, maybe for just a few hours, or forgetting a day? What do you recommend that patients do?
David Richardson, MD: It depends on the class. The prostaglandin analog class is very forgiving. Many times you can skip a dose and the pressure is still under good control, even next morning through the next day. I have a number of patients who are able to check their pressures at home. Either they have a Reichert or 7CR unit or the Icare HOME. I also provide for my patients the option of, we have Icare HOME's in the office that patients can take home for a week and check their pressure if they want.
So I do have patients who have monitored their pressure. And under these controlled conditions, I will allow them to use prostaglandin analogs every other night instead of every night, let's say, if they're having a lot of the side effects we talked about with prostaglandin analogs. But I limit that for those patients who have the ability to confirm that they're not spiking.
I also allow my patients to come into the office at any time and just get their pressure checked. They don't need an appointment with me. I wish that this was more common, because what I don't like about glaucoma is the fact they we're making these decisions [based] on pressure measurements that are done once every three or four months. Now, I would like to have pressure measurements every day. And I'm hoping we can get to a point where monitoring glaucoma is more like monitoring diabetes, where patients can check their blood sugar at home. They should be checking their eye pressure as well. So, with the case of the prostaglandin analogs, not so much an issue.
On the other hand, with the carbonic anhydrase inhibitors, Azopt, and Trusopt, or the alpha agonist class, Alphagan P, it's very critical that a minimum twice a day dosing be used on those. I mean, really they should be used three times a day. It's just so incredibly difficult to get consistently that middle of the day dosing in. But if someone is taking an alpha agonist or a carbonic anhydrase inhibitor in the morning and forgetting the nighttime dose, then they've lost the effect. It will not last more than eight hours. It really only lasts about six.
On the other hand, Timolol, a beta blocker. I have most of my patients now on Timolol [take it] just once a day in the morning. If they do take it twice a day, I recommend that they take the second dose in the early afternoon, because the beta blocker class does not work in the evening. There's no effect in the evening, but there can be an effect on the blood pressure. And so timing is important. There are many nuances that don't get discussed in a typical short visit in the office. So I'm glad that we're doing this.
Tom Brunner: That's a good transition comment, David. Unfortunately, we don't really have time for more questions right now. But to your point, when there are more questions or when patients think of a question after they've left the office, we really encourage them to visit our website, glaucoma.org, for more answers and for the latest information about new treatments, and also to learn about our research and the things happening at Glaucoma Research Foundation.
Also, we're now on Instagram ("@glaucomaresearch": https://www.instagram.com/glaucomaresearch/). And again, there are videos and articles and updates there. And so I encourage you to follow us. Glaucoma Research Foundation also just completely updated our booklet, Understanding and Living With Glaucoma. And the new one is now in print. You can order a print copy on our website, or you can "download it free from our website": https://www.glaucoma.org/treatment/literature.php. And again, you'll find lots of information about medications, about side effects and just about glaucoma, as well as how to live with glaucoma, in our new booklet.
We also want to, again, thank David for making time with us today, and for his dedication to helping with glaucoma. I also want to invite you to our second annual Glaucoma Patient Summit, November 7th, in Oak Brook, Illinois. And we're making special arrangements to be sure that this will be a safe and effective meeting for attendees. We will be videotaping the sessions so that the meeting will be available for those unable to attend. We also are already planning our next Patient Summit in Long Beach, California, in spring of 2021. And so, keep that on your calendar as well.
At Glaucoma Research Foundation, we are as committed as ever, especially in this uncertain time, to our mission to cure glaucoma and restore vision, and provide important information for patients and caregivers. And I want to encourage you to take your vision seriously and work with your doctors to help maintain your vision.
We want to thank Aerie Pharmaceuticals for their support of the meeting. And thank you all for joining us today. And again, thank you, Dr. Richardson.
David Richardson, MD: Thank you.
Last reviewed on June 29, 2020