Open-Angle Glaucoma: A Review of Treatment Strategies *ACPE-Accredited*

[MUSIC] Hello everybody, welcome back to another episode of the Core Consult Rx podcast. McCost, Cole, joining me is always, how's it going, man? >> I'm doing great, enjoying the cooler weather. >> Yes, definitely nice, nice type of cooler weather out here. Although I feel like the heat has been creeping back in the last few days. Not ideal, but it is what it is. >> We get false fall down here, but I thought we already had that, you know? >> You get second false fall. >> Yeah, second false fall. >> Yeah, but really you gotta move to somewhere with better weather, not so hot. >> I know. >> Keep saying I'm gonna do that every year, but never happens. >> Over the weekend, we went up to the mountains to go apple picking. It turns out you have to go all the way to the mountains to pick apples. >> Yeah, that's insane, yeah, it's a long way. >> And it was just packed, dude. There were just an immensity of people going apple picking on this random Sunday. >> Man, yeah, that is something that I too would be willing to do. The family was like, we have to go apple picking, but I'd have such a bad attitude in my head. I would just be so, so angry about having to go do that. But I would fake a smile for the kids' sake. >> Let's just say it wasn't my idea, but in the middle of it, Nathan's just so excited because he's just picking off apples and eating them. But then he goes, dad, thanks for taking me apple picking. I love my family. >> Man, that's the best. >> Maybe it was worth the two and a half hour drive up here to pick 20 apples. >> That's hilarious, those are the most expensive apples ever. >> I tell you what, they're good. >> They better have been good. Yeah, then you get this bushel of apples that you're never going to eat them all because nobody consumes that many apples, at least most people don't. >> We only were able to afford a peck, so we got a peck. You got to get a few pecks to get to a bushel, but we got a full peck. >> Oh, excuse me, sorry, I didn't mean to. To be totally honest, I didn't even realize that was an actual measurement for apples. >> Yeah, that sure is. >> I just use that because I've heard that phrase before. But I didn't even know there was a different smaller category. You've heard a bushel on a peck and a hug around the neck? >> Yeah, yeah, I just never knew it. I don't know what, I guess I thought a peck was like a peck on the cheek, like a kiss on the cheek maybe, I don't know. >> Unit of measure, unit of measure. It's like quarts to a gallon, pecks to a bushel, I think. >> There's so much gold on this podcast, I'll tell you what, you think you're coming here to learn about some kind of pharmacotherapy topic, and instead you're learning, well, hopefully not instead, but in addition to that, you're learning about Apple terminology, it's very important stuff. >> Gold and delicious, you might say. >> Yeah, something like that, but apples, vitamin A can help with the occurrence of what night blindness, if I remember correctly, that may not be true, but that's our segue into talking about ophthalmology, which tonight we're going to be discussing glaucoma and kind of the various maintenance treatments that are available currently. And this is an accredited episode, so this is a topic that we've definitely covered before, and has since expired as far as continuing education credit, so we're reviewing it again. And not a ton of new changes as far as the medication side of things go. We'll touch on some of the new or more popular procedures that are being done now towards the end, but that's definitely not our forte, so we'll limit how deep into that we go, but we'll give you at least a quick rundown just to make sure you've at least heard of it. But again, this is going to be a accredited episode, so for those of you who are members of FreeCE.com and have access to all of their content with an unlimited membership, this, along with all of our other accredited episodes, is available to get one hour of continuing education credit for pharmacists and nurses. And so for those of you who are members, listen closely. We'll give you a password at some point during the episode. Use that password on FreeCE's website to access the post-activity test, 10 question, multiple choice, and you will pass that, you get your one hour of continuing education credit. So definitely take advantage of that, and if you're not a member, definitely encourage you, as always, to go check out FreeCE is a plethora of great content and, you know, it's something for everybody in as far as the various styles of learning and all that. So definitely encourage you to check them out. They've been a great partner for us and really enjoyed all of our time and them giving us the opportunity for offering all these accredited episodes. So you can get probably four or five years worth of your CEs knocked out just by going through our podcast episodes, which is crazy to think about, but, you know, hopefully useful for at least some of you. So glaucoma, and we're going to be focusing, you know, on primary open-angle glaucoma tonight, but, Cole, you want to jump into some background information, get things rolling? Yeah, we'll start with some kind of general background information about glaucoma. And we'll just touch on angle closure glaucoma at the end to contrast some things. But yes, for the most part, open-angle is what we're going to be talking about. And the primary driver with glaucoma is intraocular pressure as far as the cause goes. It's -- there's many factors that contribute to the development and progression, but intraocular pressure certainly contributes and is what you'll hear about a lot. Some other mechanisms that could contribute a decreased or dysregulated blood flow, leading to ischemia affecting the optic nerve, autoimmune reactions can as well, excitotoxicity, those are some examples. Eventually what happens is the processes cause apoptosis of the retinal ganglion cells, and that leads to axonal degeneration, and the end result can be permanent vision loss. Yeah, it's definitely something that you do not want to leave untreated and hopefully get that intraocular pressure down. When we say intraocular pressure, the normal range is typically 12 to 21 millimeters of mercury. A high intraocular pressure does not always -- an automatic prediction of visual field loss. In fact, some patients don't really experience damage even, you know, at that above 21 millimeter mercury ocular hypertension. And some patients, you know, will have pressures in the 20 to 30 range for years before the disease actually progresses to the point where they're actually starting to have that visual field loss. Like I mentioned, we're going to primarily focus on primary open angle glaucoma, or POA Gs, you'll see it abbreviated. But that is glaucoma in the presence of an open interior chamber angles. So increased intraocular pressure, like kind of like Cole was saying, can be due to aqueous production, aqueous outflow, or anatomic or physiologic features of the trabecular mesh work. And other outflow structures. Overall, primary open angle glaucoma is usually silent and progressive, which, you know, leads it to being worldwide anyway, one of the leading preventable causes of blindness. So not in the US necessarily, but I'm thinking about things worldwide. It is very much a serious thing that is preventable. So knowing that the treatment is an important thing for all of us, even if we're not working directly in ophthalmology. Yeah. And just to mention a few other types of glaucoma. Like we mentioned, there's primary angle closure glaucoma abbreviated as PACG. This happens when the channel that drains the aqueous humor is abruptly blocked, and that can lead to a sudden increase in intraocular pressure, notably very high intraocular pressure, for example over 60 millimeters of mercury, may result in permanent loss of visual field within a matter of hours to days. So it can happen very rapidly. Secondary glaucoma is another type. It's when the channel that drains the aqueous humor is blocked from inflammation that can originate from an injury or an infection. This is usually more of a gradual process and will slowly increase the intraocular pressure. There's also congenital glaucoma, where the channel that drains the aqueous humor is blocked due to some sort of genetic abnormality. The patients will typically present with a cloudy cornea, and they may also experience a sensitivity to light. And if we can get through all of our main content that we're going to try to review tonight, we'll maybe toss in a quick summary of at least a couple of options for primary angle closure glaucoma treatment, which is more of an emergency situation. So there's usually a protocol of various medications that you give in order. And so we'll touch on that towards the end if we have time. But focusing on open angle glaucoma primarily, we'll jump into some of the medication classes and things in just a second. But I do want to touch on some medications that you should kind of have your radar out for that can potentially increase intraocular pressure. So doing a med rec for a patient that is newly diagnosed and being started on treatment, it's a good idea to make sure that we're not causing worsening of that intraocular pressure by a medication that they maybe could do an alternative for. So obviously a big one, anything with an anticholinergic property, antihistamines are in various over-the-counter products, obviously, and lots of other medications, even if they're not something that we directly think of as being an anticholinergic, we'll have anticholinergic side effects. And so those should definitely be something that you are on the lookout for. And also reviewing the patients over the counter meds, not just necessarily what's on their prescribed medication list. Also looking into a recent history of any kind of ophthalmic or even systemic corticosteroids. And then one that I always tend to forget about until I review this topic, but topiramate also can increase intraocular pressure. Topiramate has obviously a wide variety of uses nowadays and migraine prophylaxis and weight loss and all kinds of stuff, so it may be something that a patient may be taking and not even realizing that that could be worsening their glaucoma. And then when we start a patient on actual treatment to maintain that intraocular pressure and hopefully maintain their vision as long as possible, that's ultimately our main goal of treatment is to keep that intraocular pressure down by either decreasing the aqueous humor production or increase in aqueous humor outflow. One of those two methods is how most of our medications ultimately work. They come about in different ways, but that's usually the two main categories of mechanism of action. Right. You're thinking of vision issues. I know we've talked about this, your terrible contact lens habits in the past. Do you still wear contact lenses? Yeah. Yeah, probably gotten, if anything to be just totally transparent, probably gotten worse about changing my contacts is now with the kids and everything, it's hard to get the eye doctor and so I'm just like, you know what, just keep those jokers in. Yeah. My literally like the last time I saw my doctor, he said a quote was, man, I cannot believe you hadn't gotten conjunctivitis yet. He said that? Yeah. That is hilarious. I've known the guy for ever. So he kind of drops professionalism a little bit, but he's like, man, he's like, your eyes are pretty good at not getting conjunctivitis. I said, thank you. I'm going to put that in my LinkedIn profile. I wonder if there's a Guinness Book of World Records for, you know, longest worn contact without it. I'm sure. I mean, I don't know, maybe, but I guarantee it's someone's done it longer than they. I'm actually there's no way. Do you have glasses if you needed to wear glasses? I couldn't tell you where they are or if I even act. I haven't seen them in so long. I don't even know if I actually still have them, but at one point I did have them. They just, they give me such a headache wearing regular glasses that I ended up just wearing them for two seconds and switching back to contacts. So when you were younger, what made you realize you needed, you needed glasses. I couldn't see anything. Like, I would, my dad or, you know, mom would point out a sign and I'd be like, I don't even see letters on that. How old? They were like, you can't read that. I was like 12. Wow. Okay. Yeah, I was super young. I'm just thinking about it because my, like one of my cousins, my aunt, she has the story about how he was doing very poorly in school and when he was younger, my guess was probably elementary school. And then they realized eventually that we couldn't see the board and all that, you know, because it was a glasses issue. Cause I, it's on my radar to be looking out for with my kids, but I just, I'm curious what ends up, how that realization happens. Cause I guess you had bad eyesight, what your whole life until then, but they didn't realize until you were like 12. Yeah, I get, I don't really know when it started to be honest. I didn't notice it until I finally said something to my parents cause I, they just based on a couple, you know, like signs and stuff like that that I couldn't read, but it never was like anything that was super bothersome. Right. So I didn't really notice, but yeah, I would like to use that as my excuse for, you know, being a problem student, but I think I would more of just excessive hyperness and inability to focus. So just being a boy is what it was. Yeah. Yeah. There you go. Yeah. So with glaucoma, thinking of Mike's adherence to, you know, replacing his, his contacts, adherence can be a significant issue with glaucoma patient support, adherence or nonadherence occurs in 25 upwards of 60% of glaucoma patients. So highlighting that and addressing the fact that this is one of those diseases that, you know, it's not a disease that causes pain or inflammation or something that's the patients have kind of tangible changes when they take their medication, but highlighting the importance of the longterm. A large percent of patients fail to use the drugs correctly. So that would be an adherence issue as well. And so ensuring that they have proper technique is important. So we will highlight that for you now. They, the technique is called the eyelid closure and nasolacrimal occlusion technique. You want to tell them to wash and dry their hands, shake the bottle if there's a suspension in the bottle. And then with a forefinger, pull down the outer portion of the lower eyelid to form a pocket to receive the little drop, grasp the dropper bottle between the thumb and fingers with the hand braced against the cheek or nose, and the head needs to be held upward, kind of tilted back, place the dropper over the eye while looking at the tip of the bottle, then look up and place a single drop in the eye. The lid should be closed, but not squeezed or rubbed for five minutes after installation, which I've just, I know that that's not done very often. This increases the ocular availability of the drug and reduces systemic absorption. I got to say that staring that dropper in the face is not a pleasant sensation at all. Just looking right at the tip of it, you know what I mean? Yeah, I'm definitely not a huge fan of that myself. So highlighting this to patients that it is kind of unpleasant, but it's important is significant. And seeing is more important and more pleasurable than dealing with, you know, few drops in my opinion anyway, but yeah, maybe someone disagree with me. All right, so we talked about the proper, you know, administration of drops. Let's get into some of these bad boys and go through some of these classes of medications. We'll start things off with our first line therapy that most patients are started on, which is our Prostaglandin analogs. We have several options in this class. The Mataprost, we have LatanaProst, Travaprost, we have LatanaProstine, we have Talproprost, Ziopton being the brand name for that one. In fact, I think that one may still be brand name actually, but if not, it's gone generically, relatively recently comparatively to the others. And then that LatanaProstine I believe is the most recent one, so that wouldn't be brand name as well. But these are all working, you know, mechanistically by increasing the outflow of aqueous humor via the uveal scleropathway. As far as efficacy goes, the thought of as being somewhat, you know, similar, although the Mataprost tends to be, you know, considered slightly more effective overall. And, you know, that is in regards to lowering the intraocular pressure as well as getting a larger percentage of patients to lower intraocular pressures on average. And also for patients unresponsive to LatanaProst, but Mataprost has still been shown to be effective in one study. This, like I said, is usually a first line option for, you know, treatment if we're going to go that route versus some kind of a procedure. And, you know, it also has to take into account patients, you know, insurance coverage and all that, because a couple of these that are brand name only may be cost prohibitive if the insurance won't cover it. But prostagland analogs, you know, are thought to be the most effective agent overall in regards to ability to lower intraocular pressure. On average, they're going to lower the intraocular pressure from baseline. They're going to lower it about 25 to 35 percent. And although they are first line, and they are also, just before I forget to mention, they're also one drop, you know, at night versus the other options that we're going to go through are usually multiple time, at least twice a day if not more. So adherence is a little bit easier with these as well. But they are not without their potential problems. In fact, one warning on these in particular is prostagland and associated periorbitopathy. Periorbitopathy, if I can pronounce words. And this includes the darkening of the iris or the eyelid skin itself, and as well as increasing the length and number of eyelashes. You may recognize the, I think, which one is Lattice? Is it Latina Prost or Bama Prost? I thought it was Bama-doh. Bama-doh, yeah. So you may recognize that as a product for cosmetic purposes in most cases where it helps to grow the eyelashes longer and faster. But any of these prostagland analogs will potentially have that effect, you know, as far as the length and number of eyelashes. So it may be either a benefit or, you know, something not great for some of you. I don't think I'd want my eyelashes being super long, but that just may. Well, I'll have to get you one of those eyelash curlers. I remember my mom using that when I was a kid. Yeah, yeah, yeah. Look at it. I'm super handsome now with this, my new eyelashes. I haven't seen an eyelash curler in many years. I guess Anna does not, my wife does not curl her eyelashes. That was a throwback kind of memory from when I was a... Oh, dude, I have those things laying all over my house and definitely uses one. I've seen one earlier tonight, probably. They look kind of scary. Like, if you didn't know what they were and you just like found this thing, it's like, what kind of devil device is this thing? Yeah. I'm not putting my eyelid anywhere near this thing. The prostagland analogs, though, can not only just increase like, you know, eyelash and all that, but like we were saying can actually change the color, you know, and so, you know, it can increase the brown coloring of the iris and so patients who have naturally, you know, very light eyes that may be problematic in something you want to warn them of. Also, you know, kind of keeping a look out for any type of like bacterial keratitis, you know, with especially the multi-dose solutions that could potentially become contaminated. Obviously, there are certain things that are done to hopefully prevent that, but that is something to at least be on the lookout for. And then the ones that are not -- or I'm sorry, the multi-dose vials that are available typically have a preservative called benzoclonium chloride or BAC. That's the very, very common preservative in a lot of ophthalmic solutions. And we've talked about it when we went over dry eye disease, not too terribly long ago, but these medications are going to be used long-term. And so the more kind of exposure to that preservative BAC, the more likelihood it can lead to like chronic inflammation and it also can be absorbed into contact lenses. So if a patient is someone like me who wears contacts, you should have them take out the contacts and administer the drops and then wait at least 15 minutes after it's applied before they put them back in, maybe even longer if you can. And then, you know, the patients who do have concomitant dry eye disease, obviously that BAC preservative can be problematic in those patients because it can worsen dry eyes over time if continued to be used. And so there are a few different options that either have alternative preservatives like the Travapros or Travitanzi being a brand name has a different alternative preservative in it that isn't as problematic long-term. And then one of the formulations of Latinaprost, I use a brand name also has a different preservative. And then the Zyoptan, the Tafloprost is a single use vial. So it looks more like the original, you know, rastasis cartons if you've ever seen that. But each drop you administer and then toss the whole little single use vial away and you can just get a new one each time so you don't have to worry about the preservative aspect. Yeah. Highlights some more adverse effects. They can cause blurred vision, topical irritation like a stinging sensation. They can cause a sensation of having like a foreign body in your eye and they can't increase the pigmentation of the iris. Like Mike mentioned, they're typically dosed one drop per eye at bedtime, which I imagine if you took it and then went straight to sleep, it might make it easier to keep your eye closed for five minutes like you're supposed to. But you know, who knows people like that. Life hack. Yeah. There you go. Mike mentioned the Lattice which is bimadaprost and is used for helping the eyelashes grow. Just a few points about that. You don't want to use it in patients that are already taking a different prostaglandin inhibitor for glaucoma. So you would think this is apparent, but there's all sorts of situations where we kind of accidentally have duplications of therapies. That's one to be on the lookout for. You apply the medication by drawing a line along the skin of the top of the eyelid only. So different application process than you would use bimadaprost for glaucoma. And you want to remove excess medication by blotting with the tissue or a cotton pad if you apply it to the skin on the top of the eyelid like that. Ma'am, when I was in pharmacy school, this just popped into my head when we were talking about Lattice, my now wife, who was a girlfriend at the time, we were both driving towards the College of Pharmacy. She was in front of me and I could see from, you know, from Ruvimir or whatever that she was applying makeup or messing with that while she's driving, which you know, super safe. But this was long enough ago that I can say this. And apparently she had tried to curl her eyelashes while she was driving. Slammed on brakes because she wasn't paying attention like she should have been driving and then like ripped all of her eyelashes out of one eye. So I didn't know what happened. I just, she got to, we got to school and she was like in the worst mood all of a sudden. And I was like, what happened? And she like wouldn't talk. And then I realized it's because she had like one crazy, I would know I was like, uh-oh. That is hilarious. Yeah. We horrible. I had to order some painful. Yeah. I don't think it felt great, but we had to order some Lattice to get them things to grow back. I thought you were going to say fake eyelashes. Yeah, not at the time we were too poor for all that. But yeah, now, now if anything, she's a big fan of those fake eyelashes now, but now back then. Yeah. I also have memories of my mom applying some makeup while driving or at red lights or whatever. So before there was texting and driving, there was makeup application and driving. Yeah. And because of all that, now we got this law in South Carolina where you can't even have your cell phone out at all or you get it pulled over immediately apparently. Yeah. That's been in Georgia for a long time, at least 10 years, if not more. Yeah. Well, I blame our parents' generation for it. Yeah. Unbelievable. Even though we were the ones with started the whole texting thing. Yeah. I tell you what, though, there's nothing more dangerous than driving your car, man, especially now that I'm kind of closer to the Atlanta area. It's just like, yeah, like traffic. There's so many traffic. There's so many traffic deaths. It's unbelievable. Yeah. That's so yeah. Definitely something. So if nothing else that you take away from this episode, don't apply makeup in the car. That's foolish. Yeah. Don't text and drive. Yes. Don't text or at least turn your auto, you know, autopilot on your Tesla if you have to. There you go. If that's an option for you, otherwise do not text and drive. Probably texting the probably Tesla folks. Yeah. All right. So just to mention as well that Latina Prostine medication, it's the newer prostaglandin analog, the one particular systemic literature review that was done that included 106 trials and over 18,000 patients. Basically the authors were investigating the efficacy of Latina Prostine versus other medications for overall ocular hypertension and open angle glaucoma. Latina Prostine was numerically better than Latina Proste and Tauphal Proste. It was similar to Bamanaproste and slightly worse than the higher concentration of Bamanaproste, the 0.03%. Then Latina Prostine also was significantly better than Beta Blockers that were studied. So, you know, again, Bamanaproste, that higher concentration still tends to be the considered the most effective when you're talking about intraocular pressure lowering, but this is another very solid option. Again, assuming that insurance companies and all that are going to cover it. Sure. All right. Moving on and actually before we go to the next class, did you want to just go ahead and do the password since what kind of yeah, yeah, let's do it. So today's password is going to be PAOG25, PAOG all capital letters and then the number 25. So if those of you who are members, you'll take that password, go on to freesea.com under the different podcast episodes that are on there and available. Click this one in particular to ask for that password and then you will get immediate access to the post activity test. So guys, I'm sure we'll all do wonderful. Get your one hour training education credit and be that much closer to being able to renew your license at some point, whatever that's due. And being a rock star pharmacist. Yeah, something like that. All right. So the next class medications, there's just one medication in this class, but it's a prostaglandin EP2 receptor agonist. So a slightly modified mechanism. But the drug's brand name is omlonti. And it's omidinepag, omidinepag, isopropyl solution, approved a few years ago, 2022. And it's a selective E prostanoid subtype 2 receptor agonist EP2. It decreases intracular pressure in this way, though the exact mechanism of how it does that isn't entirely understood. But this is the receptor that it acts on. It's also administered once a day in the evening and has a similar effect on low ring pressure compared to the other prostaglandin analogs. And has been shown to be effective in patients that were either non responders or poor responders, specifically to Latina post. It's only been studied in combination with Timolol. So hasn't been studied as a as a monotherapy. It does contain benzalconium chloride as a preservative, notably, and has adverse effects such as conjugal hyperemia, corneal thickening, macular edema, or cystoid macular edema, as well as ocular inflammation. And this is one that price could definitely be a factor on in insurance coverage and all that. Maybe a little bit harder to get approved than some of these others that had generics available for quite a while. Right. So always take that into consideration even when you get the cool new, you know, kid on the block as far as the new drugs out there. Price always needs to be something that is kind of at the forefront of your decision making. All right, so we'll jump into our next, you know, group of medications and you know, the prostaglandin along as we said are typically first line. These are oftentimes considered, you know, our second line agents and that would be the beta blockers, the ophthalmic beta blockers, not not just any beta blocker. So we have our Timolol, which is in different concentrations. There's a 0.25, 0.5 under the brain named Tomopic. There is also a betaxolol in the LiVo-Bunolol is another option out there. The LiVo-Bunolol has additional properties, not just the beta blocking properties, but it also has some alpha androgenic effects. And does it seem to be the most effective beta blocker, you know, comparing that class of agents together, still not as effective as something like Bematoprost, but of the beta blockers, the LiVo-Bunol is considered to be the most effective or, you know, has the best intraocular pressure lowering ability. Mechanistically, these are working to reduce the production of aqueous humor outflow and I'm sorry, not outflow, but the actual reduce the actual production of aqueous humor to begin with. And on average, we would expect around a 22% drop in intraocular pressure from baseline with these. So not quite the same extent as the prostagland analogs and you do oftentimes have to dose these twice a day, which, you know, make them a good candidate for a second tier option to add to a patient's regimen, but usually the prostagland analogs are one of those newer drugs we talked about are going to be first line. Beta blockers do have some contraindications. For example, sinus bradycardia, second and third degree heart block, unless the patient has a pacemaker, interestingly. Some adverse effects, burning, stinging, bradycardia, bronchospasm. All of these are nonselective beta blockers, except for butaxolol, which is branded as Batopic S, it is less likely to cause worsening of COPD, asthma, chronic bronchitis and emphysema. These are dosed twice daily, notably different from the prostagland and analogs, except for Timoptic XE and Timolol GFS, the gel forming solution. Those are both dosed once per day. A lot of times people just assume you're administering a drop ophthalmically that you're not going to get much systemic effects from it necessarily, but the ophthalmic beta blockers in particular can definitely have a pretty substantial effect on blood pressure and heart rate overall. In fact, some people will even talk about being able to taste the medication when they put the eye drops in. So definitely some systemic side effects to consider even though we're administering them ophthalmically. All right, let's move on to our alpha 2 agonists. A couple different options in here. We have Bramonidine, which is the most prevalent medication in this class. There's also Apraclonidine as well. In fact, the Bramonidine is also available over the counter under the brand name Lumify. It's indicated for ocular redness, but the Alpha GANP, the prescription version is still available as well and is a potential option for glaucoma, usually more of a third line option. Once you've gone through the prostagland analogs and the beta blockers, this could be a potential third line option that's added on. Mechanistically, these are increasing aqueous outflow as well as reducing aqueous humor production. Just one of the warnings that are associated with this particular class is that it can cause CNS depression. Just like with the beta blockers, we still have some systemic effects even though it's an ophthalmic solution. Other more common side effects are going to be more localized, so burning, maybe dry mouth, drying up of the sinuses as well, maybe a little bit of sedation, which kind of goes along with that CNS depression, but it can definitely cause some burning in the eyes, so warning patients about that. Giving them kind of a heads up may help to increase adherence because a lot of times you have to take these multiple times a day. Yeah, there does three times a day, the alpha 2 aqueous R, which is more than the other two we've talked about. The older versions contained benzylconium chloride as a preservative, the newer ones have some different preservatives. For example, branded alpha-GNP has a preservative called purite that has very broad antimicrobial activity even at very low concentrations, and that replaced the benzylconium chloride. The generic version, Bermontadine, has the preservative polyquad. It's a detergent type preservative derived from benzylconium chloride. It's much less harmful, but can potentially reduce the density of conjunctival goblet cells, and that can decrease aqueous tear film production, which I presume would maybe cause a dry eye type side effect. It's one of the only medications that I can think of where there is a true clinically different reason to prescribe the brand name over the generic because of that preservative change that happens, but you will definitely run to every once in a while ophthalmologist that will write specifically for alpha-GNP, brand name only, and that's the reasoning behind it. Although I will say, obviously, it's a different preservative, but that polyquad, when they call it a detergent type, man, that sounds like not good to put in the eyes. It's a detergent type preservative, so go ahead and pop a few drops of those in. Is this a natural preservative? No, no, it's a detergent type preservative. It's more natural in the laundry care section. It's more like Tide Pod type preservative. Yeah, you've had a Tide Pod in your eye before, right? It's like that, very similar. We're not suggesting these are the same. These are all jokes people. We're making jokes. Yeah. We have to put that disclaimer in there. Get very angry emails from the makers of the generic alpha-GNP. Could you imagine? That would be so funny. We're on there, Radar. We finally made it. Yeah. All right, let's talk about another class that is not as high up on the hierarchy of preferred agents. That is our carbonic and hydrase inhibitors. Oftentimes, these would be considered more of a fourth line agent. There are several options here, including some combo products as well, but the dorsolamide is one option, and then there's the brinsolamide. Dorsolamide is also available in combination with Timolol under the brand name COSOPT for convenience sake and all that. If the patient's insurance will cover a combo like that, it's generic now, so it's definitely more affordable and all that than it once was. Then there's also the cimbrinza, which is the brinsolamide in combination with brmonodine. If you have a patient that's on four different medications for their glaucoma, then maybe pulling out some of these combo options can be good as far as just cutting down the number of drops needing to be administered every day. These carbonic and hydrase inhibitors are also going to work by reducing the aqueous humor production, and a few things to keep in mind. One, they can cause some systemic exposure that can have some effects systemically in blood pressure and things, but also if a patient has a true sulfonamide allergy, then you want to use some caution with these because they do have a sulfonamide moiety at their center of their chemical structure, so it can definitely trigger that allergy if that's present. Always checking for that on the patient's chart as well is an important thing with this particular class. They have some other adverse effects, burning and blurred vision, dry eyes they can cause. Interestingly, dorsolamide can't be used in patients with a creatinine clearance less than 30, so you wouldn't usually think to look out for kidney dysfunction with an eyedrop, but here you do. The oral agent diamox acidosolamide is another option. It's typically saved for acute closed-angle glaucoma, IV, or oral, and it also contains a sulfonamide group. Good old acidosolamide. What's the, is altitude sickness? Is that the, that's what you'll see that you can use for? I feel like that's the only thing I ever think of with acidosolamide, at least that I ever see. I would see it in neurology for, what's it called? It's like, it's pressure on the brain. I can't remember what the term is, but yeah, I would see it there. People who have to intracranial, it might be intracranial pressure. Intracranial. Yeah. That seems right. It seems like a good term. It sounds right. Yeah. It sounds like a medical term. It sounds like a medical term. You think that that one would have been easier to remember? I know. I know. But yeah, so another option or a class that we have out there is the, although, you know, this is even further down the treatment algorithm, just because of side effects and whatnot, we have our cholinergics, also known as our myotics. And there's a couple in this class. There's the pilocarpine, and then there's also the carbacol. These work by increasing the aqueous humor outflow. And from an adverse effects standpoint, they can cause corneal clouding. They can cause pupil constriction, which can lead to poor night vision. They also can lead to like systemic hypotension, can cause bronchospasms, and even abdominal cramping, interestingly enough. But these should not be used in patients who have a history of any kind of retinal detachment or corneal abrasion. So making sure you're getting a good history on a patient before starting one of these, but usually this would be considered more fifth line option, just because of the side effect profile. And the last class we'll talk about before we kind of summarize some things in algorithmic form are the rokinase inhibitors. This would be ropreza is the brand name for one, Natarsadil. And then it also comes combined with Latana Prost, and that's branded as roclatan, which sounds pretty awesome on. I wasn't saying I love that brand name. It's like, okay, you guys nailed it. Good job. It's good. But the rokinase inhibitors increase aqueous humor outflow. So that's what that's what they are doing. The initial studies suggested that Natarsadil is non inferior to Timalol. A 2022 systemic review showed that it's probably inferior to Latana Prost and potentially slightly inferior to Timalol. So that's not great. Has adverse effects like burning, eye pain, conjunctival hemorrhage, excess blood vessels, which would be the conjunctival hyperemia we mentioned before. And it does contain benzoconium chloride. So yeah, probably not the first agent that you're going to you're going to go for. Yeah, I would think of this one, you know, maybe maybe being second line if the patient's on something like Latana Prost, but they have like a contraindication for some reason to a beta blocker. And then all these cost is an issue with these because they are on the more expensive side comparatively to, right, you know, other available options. But, you know, you could add this in even as early as second line if the being in a perfect world with patients insurance covers everything. But a lot of times, you know, because of the potential, you know, either same efficacy, or maybe even a little bit less to something like Timalol, probably not going to be, you know, the go to option, especially if a patient's got limited insurance coverage. Now, I know we keep saying like fourth and fifth line agents, and you may be thinking that sounds like a ton of medications for one disease state, which, you know, or maybe not if you've dealt with patients with glaucoma before, but there are definitely, you know, patients that will get started off and can do fine for a while on one agent or so. However, typically speaking, over time, patients will need to go on to a multi drug regiment. And in fact, there was one study called the ocular hypertension treatment study. And this looked at over 1600 patients. Basically, what they found is that by year five, around 40% of patients needed at least two drugs or more to actually reach the goal and trochial pressure that the study used for 24 millimeters of mercury or less. And then there was another one called the collaborative initial glaucoma treatment study that included over 600 patients. And those patients were followed and by year two, approximately 70% of the patients that were included in that study needed at least two drugs or more to reach the targeted intracular pressure that was set for that study. So, definitely, you know, even if they're starting off on one agent, kind of giving patients maybe an idea of the trajectory of the course of the disease and all that and kind of letting them know ahead of time that they will probably need to be on multiple eye drops at some point. But, you know, it's kind of up to your own personal preference as far as, you know, that rapport with the patient and all that. But I tend to kind of give them want to give them a heads up as far as as years down the road, we, you know, may see more drugs added to your regimen, hopefully not, but no, that's a possibility. Right. So kind of summing it up. As far as what you might want to start with and where you would go in certain instances, kind of in an algorithmic way, I'll, I'll start it and I'll let Mike, Mike finish. But we mentioned starting with a prostaglandin analog is probably your best bet, possibly a beta blocker. If they have contraindications to this, an alternative first line agent would be Bramona Dean. If contraindicated to these other first line agents, you may use a topical carbonic and hydrase inhibitor. And you would assess response pretty quickly. Two to four weeks, you would want to reassess. And if the patient's had an inadequate response, you certainly want to ensure that they're compliant, both they're taking it and they're using it completely correctly. Instruct the patient on nasal lacrimal occlusion. If they're not currently doing that, you may potentially increase the concentration if possible or increase the dosing frequency if it's indicated with that medication. Switch an alternative first line agent if the patient hasn't had a therapeutic response or consider adding a second first line agent if there's been some sort of response, but maybe it's not as much as you'd want to see. If the patient had had an intolerance to the medication, then if it's possible, you could reduce the concentration or change the formulation or switch to an alternative class or switch to an alternative first line agent if that is possible with the medication you're using. So do one of these things and then you can assess it again in two to four weeks and then move on from there. Yeah. And basically just kind of continue to add classes as you go. And previously, some of the surgical procedures or laser therapies and things would be held off until some of these other medications could be utilized. But I will say there is a push now and some of the ophthalmology folks that maybe for some patients, some of the more minimally invasive procedures and whatnot should be actually moved to closer towards the first line therapy options. And so just to kind of give you a little bit of an idea, kind of what the guideline focused on, there was one, I believe it was 2025. It was actually, it may have been initially published 2024, but available for everyone in 2025. But the focus was shifting laser treatments to first line therapy for at least some patients. There's also recommendations that are starting to emerge as far as specifically selective laser, trabeculoplasty, or SLT, as a first line treatment. Definitely in ocular hypertension or mild to moderate glaucoma, which may reduce the need for ophthalmic medications. There is also something called minimally invasive glaucoma surgery or MIGS, which is less invasive surgical option that includes improved stinting and micro shunts that more effectively and safely reduce the intracular pressure than some of our previous options and is often performed concurrently if the patient has cataracts as well. Then there's some newer sustained drug delivery systems. So there's like a thing called the Todd device, TODD device, and it basically offers a sustained release of medication, which again can potentially reduce the frequency of the daily eye drops and improve overall patient adherence because they're not as much to, not as many doses to keep up with. There's also like nerve stimulation therapy, which is another newer, noninvasive nerve stimulating device therapy that is something like similar to the eutronic therapy. There's various clinical trials that are looking at this as far as a way to halt vision loss, as well as potentially reverse damage by stimulating the optic nerve directly. Then as far as emerging technology as well, just to kind of keep an eye out for big advancements with AI, and AI in particular when it comes to glaucoma is starting to play a big role, at least in the clinical trial space, of playing a role in diagnosis and definitely may have applications for future screening processes and things, and it can help to identify the most effective surgical treatments for a specific patient. So it'd be very interesting to see how that starts to unfold over the next few years. There's also various gene therapies that are being looked at, and there's some even include approaches that target enzymes like MMP3, which should promise in early studies as far as protecting and potentially regenerating optic nerve cells, and then overall vision restoration. So there's some initiatives out there that are focusing on regenerating retinal ganglion cells and axions to potentially reverse vision loss, and that's kind of a shift, obviously, from managing intracular pressure to actually repairing that optic nerve damage and getting the vision back if they've previously lost it, or at least had a decrease in that. So kind of, again, way above our pay grade, but just to kind of throw some of those new things out there, and definitely encourage you to take a look at some of the newest guidelines because they go into a lot more detail if that's something that is of interest to you. Yeah. All right. So we will finish up just touching on primary angle closure glaucoma and just giving a very brief overview of what you might be looking at in this instance and a few medications that are given, are possible regimen to be given. But like Mike said before, it's a medical emergency. So patients, if this is the case, they need to be evaluated by an ophthalmologist within an hour of an acute attack. If longer than an hour, you would want to go ahead and start empiric treatment. If the vision is normal, but other symptoms and signs suggest an acute angle closure attack, empiric treatment should only be given if the intracular pressure is greater than 40. So one possible regimen, there could be one drop each of these medications given one minute apart. Timolol, 0.5%, apriclonidine, 1%, pilocarpine, 2%, and like we mentioned earlier, also giving acetylzolamide, 500 milligrams, orally, or IV. This would be an acute situation. Patients can also have chronic angle closure glaucoma. In this instance, they might need laser peripheral urodotomy or other surgeries and procedures to prevent that from happening long term. And that regimen that Cole listed is just one example. There are some potential options out there, but just one example. I believe that one came from the up-to-date authors that wrote the section on managing angle closure glaucoma. But there are others as well, so it probably would come down to protocol at whatever hospital system, whatever that you're working at, or outpatient clinic if you're just trying to stabilize them. But yeah, we'll maybe dive into that a little bit deeper later on, but I wanted to at least give you a quick idea of a possible regimen that may be utilized in that more emergency situation. Yeah. Alright, anything else we got to cover Cole? I think we're about almost out of time. No, just to say that yeah, I see a lot of patients who certainly are taking multiple of these. I think a lot of times it ends up being that the one medication is not enough. Yeah. I had a patient today that was on four, which is not an uncommon classification of four or more agents that you'll see patients on, but we were discussing possibly switching to some combos and things like that to make things easier because they were not thrilled about four different drops in the eye every day. No, if you think of adherence issues with one, then you've got to do four and some of them are more than one. I can't even remember to change my contacts. I can't imagine thinking about putting 17 drops in my eye every day. I'd be a terrible glaucoma patient. Right. I'm sure that as the vision issues worsened, they would be more likely to take those measures. Which is the wrong time to start taking measures after the vision's going. It would probably be more motivating for some. I would probably very likely be the same way when you don't have something acutely that is motivating you to do that, then it is difficult to go through that. Very much so. And remember to every day. Yeah. I'll be a terrible patient for most things. All right, so we got that summary kind of laid out for you. But like I said, I definitely encourage you to check out some of the guidelines that have been released over the last few years to get more in-depth with us, especially if the procedures and things are of interest to you. But if you do have any other questions or concerns or anything like that around this material, make sure you send us an email. We will do our best to answer it in a somewhat timely manner because I would be lying probably if I said a timely manner. But we'll do our best to get back to you as quick as we can. And for those of you who are not free CE members, and don't take advantage of the continuing ed credit and all that, I definitely encourage you to check them out. Even if your continuing education credit is good to go, you don't need any additional, they got all kinds of different content and different learning opportunities on the website. So if nothing else, you can expand your own knowledge at all under the free CE umbrella. So definitely encourage you to check them out. Make sure you go take that post activity test, get your one hour continuing education credit for those of you who are already members thanks to free CE for continuing to partner with us. And if you want more like lecture style PowerPoint slidesets and all that, you know, lectures, you know, deal with various pharmacotherapy topics and disease states, definitely check out our Patreon. So it's patreon.com/coreconsultrx. And you can get access to all of the content for it ends up being, I think, what $5 a month, $3 a month, something like that, $3 a month I guess, or you can pay upfront and get like a free month. So it's like $33 and you get access to everything, including, you know, all the video lectures as well as the slides, PowerPoint slidesets you can download. And if you do subscribe to an annual membership on Patreon, you'll also get a digital copy of the landmark trial or landmark clinical trials review book by Dr. Alex Poppin. It's a digital copy of his third edition, which includes over 175 landmark clinical trial summaries and reviews. So for those of you who are evidence based medicine nerds and want to familiarize yourself with some of the very important trials that have come out over the years, it is a great resource as well. And so all of that available on patreon.com/coreconsultrx. Cole, you want to tell them about your plugin for looking for drug info? Sure, it's called Med Search Chrome Extension on the Chrome Web Store. Check it out. It might help you search something faster. Cole programmed and designed it himself. So definitely check that out. And it can be another very useful tool. But without further ado, we will let you all go enjoy the rest of your day or night whenever you listen to it. Thank you all for the support and we'll see you guys in the next episode. Have a good one.