In this lecture, Dr. Johnson reviews the pharmacological and medical therapies available for Glaucoma.
Lecture Location: on-board the Orbis Flying Eye Hospital, Kingston, Jamaica
Lecturer: Dr. Sandra Johnson, University of South Florida, USA
DR JOHNSON: Good morning to all the people here seated on the plane and all the people who are joining us via the Cybersight. Hopefully later we can find out where you all are. Kind of enjoy the global aspect of this program. We’re here on the plane with many people from all around the Caribbean, who are taking care of some tough glaucoma. My task this morning in Jamaica is to talk to you about pharmacology and medical therapies that we have for glaucoma. I know for many of you this will be review, but hopefully it will fill in any little blanks or gaps you’ve forgotten in your knowledge. All right, and that question, for any of you who don’t see it well, it’s which of the following is a topical selective beta blocker? And this is what our audience thought. Most of them picked betaxolol, and we will see at the end if the majority is correct. Next question: Which of the following uses an amidase — that’s a corneal enzyme — to cross the cornea? So we’ll see what kind of thing we’ve got. So pretty scattered. So which of the older glaucoma meds — so this would be pre-’90s — is still used often today? So we have — the majority landing on timolol. Some picked Latanoprost, which is interesting, because, you know, that’s not really an older med. Okay. And very good. No one picked propine, so that’s nice. We don’t use that anymore. I don’t even know if it’s made. So good. The audience knows that. Okay. So we’re gonna switch over now and talk about different classes of glaucoma drops, a little bit, and some of the pros and cons of them. And just have hopefully a solid review. So when we think about the miotics, the miotics are actually the oldest glaucoma medicines, right? They’re well over 100 years old. That was the first medicine ever found to be useful in glaucoma. And it’s an outflow medicine. So it works on the trabecular meshwork part of the eye, the outflow of aqueous. And it pulls on the scleral spur, and it increases outflow that way. So it literally opens up that TM that’s collapsed. It comes in a variety of percentages. Used to be 1/2% all the way up to 6%. I haven’t seen the 6% in a long time. They may only manufacture now 1%, 2%, and 4%. And the thing is… You have to use it every 8 to every 6 hours. Okay? It really is only a 6 to 8-hour drug. So most patients had to take it 4 times a day. There used to be a gel we don’t see much anymore that worked 18 hours, that people did at bedtime. Pilopine gel. And unfortunately they stopped making it. Only one company made it. And we had carbachol. Carbachol was twice a day, much easier to use. And we had echothiophate, which we don’t see much anymore either, and that was BID. They’re very inexpensive. It’s not one of the generics, where they’ve been making the price go up. So it’s still cheap to get, but when you do four times a day and three times a day, difficult compliance. It’s also difficult compliance because of the miosis. Right? So what happens when you put pilocarpine in the eye? Anybody know what happens to your vision? So you get a miosis. It might be a happy pinhole effect. Say, if you’re pseudophakic. But what if you’re phakic? What happens for 20 minutes or so, after you put in your pilocarpine? Does anybody know? What does it do to the lens-iris diaphragm? It pulls the lens-iris diaphragm forward. So you don’t want to use a high percent of pilocarpine when someone is in angle closure. You’ll make them worse. That’s why the teaching is don’t give them more than 2%. If you’re desperate and you want to give them some miotic. You’re gonna make it worse. Okay? And so when you pull the lens-iris diaphragm forward, your phakic patient is gonna be myopic for a little while. So all of a sudden they’ve got more myopia. They’re not gonna want to jump in the car and drive to work or something, because they’re blurry. So it’s difficult for a phakic eye, because of that shift. And just for your pharmacology, if you think of the red caps, you put some atropine in the eye, what happens? We use that in aqueous misdirection. We use it in choroidal effusions, we use it in shallow chambers. It pulls the lens-iris diaphragm back. So it helps to form the anterior chamber, when you give them things with the red cap. But the green caps make you shallower, and they make you myopic. Okay? You’ve got to be careful in high myopes, because back in the day, when this literature was being written, a lot of people think that science now started in the year 2000, when everything went onto the internet. And I go to meetings, and I see posters, and I go… Oh, this was done before. But that young person at the poster didn’t go back before 2000, because they don’t want to go to the library and find those dusty old volumes, right? So they think science started in the year 2000, and sometimes they confirm what your grandparents figured out. So there’s reports in the older literature that people got RDs, because it pulls on the pars plana also. Right? And so if you’re a high risk RD, so like a pigmentary patient, they’re myopic, you put this on them, some of them would get retinal detachments. And of course, if you were… When I used to use this more, because unfortunately I have gray hair, I used these drugs before the new drugs, and you would have people — you’d better do a really good retina exam, because you may never see the peripheral retina again. Right? So if you’ve got a person who you’re worried about diabetic retinopathy, sickle cell retinopathy, lattice out in the periphery, whatever, this was not a good drug. You can’t monitor that retina once they’ve been put on miotics, and it made cataract surgery difficult. In all of these drops, if you look at the studies, they’re a little bit cataractogenic, and then you put them on something like this, with a little pupil, the people who used to be on pilo, before we had all these fancy rings and hooks, you know, they had those little irises that kind of looked like a star. You know? Someone would have to make a bunch of little snips in the sphincter, so they could dilate the patient and take out the cataract. So pros and cons back then. We don’t use it too often. But it’s still available to us. Adrenergics. Okay? The FDA in the United States has kind of given all the drops colors. So the miotics are green. The dilating drops are red. The adrenergics tend to have a purple cap. So when we used to have propine, it was a purple cap. And the newer ones are a purple cap, that fall into those categories. So propine was our first prodrug. Right? We used to use epinephrine for glaucoma, back in the day, and people had a red eye. Right? And they got a little dilated, and it wasn’t good for your blood pressure, and things like that, to be putting epinephrine drops in all the time. So somebody figured out: Propine, which is a prodrug. So propine would use a corneal esterase to cleave a side chain and get into the eye and act as epinephrine and exert its uveoscleral outflow properties. And so things like epinephrine and propine help your uveoscleral outflow. Pilocarpine slows down your uveoscleral outflow. So the miotics do the opposite as the epinephrine class. So propine would increase uveoscleral outflow. It wasn’t really a strong drug. It just dropped the pressure a little bit. It didn’t combine well with the non-selective beta blockers. Okay? So the non-selective beta blockers are everything that’s related to timolol. Right? And then the selective of course was the betaxolol. And a lot of people had a red eye. Papillary conjunctivitis was super common. And then you would put your drop in, blanch all those conj vessels, and then two hours later, they all vasodilate, right? It was like using Visine every day. So you would have this rebound hyperemia. And like I said, it was not very potent. It was cheap in the day, but I don’t think it’s made anymore. Oral CAIs. You know, they’re still used in practice. We don’t use them much anymore for chronic therapy. Okay? And these suppress aqueous. They work on the production of aqueous in the ciliary body. And CAI stands for carbonic anhydrase inhibitor. So the enzyme it’s inhibiting is carbonic anhydrase. And we do have a little bit more of that in the eye. There’s some carbonic anhydrase in your endothelium. So sometimes cornea specialists worry about you putting sick corneas on CAIs, because you might affect the pump. You can get kidney stones. You can get fatigue. You can get nausea and vomiting. I’ve had people say… Oh, I’m on this Diamox. I lost 15 pounds. Food doesn’t taste good. They don’t feel very good. If they’ve got lung disease or something, you can get significant metabolic acidosis. If you use this in a newborn baby, you can write for Diamox elixir for babies. You’ve got to look up the dose. But you’ve got to tell the pediatrician, because sometimes they need bicarb supplementation when they’re on the oral CAI, until they get their surgery. The dreaded bone marrow suppression. You can take one dose and get aplastic anemia. It’s very rare, fortunately, and fortunately I’ve never seen it. I would just die. But it’s out there. You know? So that’s kind of idiopathic, and you don’t know when it might happen. So that’s why I don’t like to leave people on that for their life. So usually short-term IOP control. And if you have a real sulfa allergy, you can’t take it. Some people have like a fake sulfa allergy. They had some Bactrim-type antibiotic that’s got sulfa in it, and it made them feel bad, but they didn’t get a rash. They didn’t get anaphylaxis. They have an intolerance, and maybe they can take a few doses. So common uses for me, for these old drugs, I use pilocarpine before I do laser iridotomies. So you bring the pupil down nice. You put it on stretch. Much nicer to do your iridotomy or an iridoplasty, because of the miosis effect, and you get a little IOP effect, maybe. We didn’t talk about the newer adrenergics yet, but the adrenergics have a quick onset of action. Their peak is quicker than, say, timolol. So because of their quick peak, we like to use those also, prelasers. So you’re blunting the possible postop laser spike from whatever laser you’re doing in the anterior segment. So anybody with glaucoma that’s getting a laser — so I have a glaucoma eye, and I’m doing a YAG cap, I give it to them. I’m gonna do an ALT or SLT, I’m gonna do an iridotomy or iridoplasty. They all get some adrenergic. Whichever one I’ve got. And then the oral CAIs is a temporary drug for me. So you come in, and your pressure’s 50. And I’m gonna start you on some drops, but you know what? The pressure gradient is so high — to me, they don’t penetrate the cornea very well. So I’ll put them on Diamox for a couple days, try to drop the pressure from the inside, get them going on their topicals, and then they can have a nice drop in pressure. And actually, I learned that from going to Africa, because so many people present with very high pressures, and it’s a very nice way to get that pressure to start going down, and it works in other people. You know, a steroid responder comes in with their PK, and their pressure is really high, and I put them on a little Diamox and get the drops going in. I use pilocarpine in those PKIs. So those, if they have secondary open-angle, it’s from collapse of the limbal tissue, and so pilocarpine actually does have some use in cornea transplant in aphakic eyes, where part of the pathology is collapse of the trabecular meshwork from their other anterior segment surgeries. But oral CAIs are good in the short term. And I usually write it to them as four pills a day. 250 QID. And then I say: Okay. If you’re feeling sick, maybe you can take two a day. And I have the patient titrate it. It avoids phone calls back. They know they might feel bad on the medicine. And they can taper themselves. So at least they’re getting some in the system. Because some can’t take four times a day. And I usually find that people can take Diamox for about two weeks, most of them, before they’re feeling sick. So I’ll try to book their surgery within two weeks. So I’ve got the Diamox working, getting their pressure down, I’m gonna bring them back for their tube or their trab, and I’ll have a safer surgery, as the pressure is coming down, and I’ve usually got a two-week window before they start telling me like they feel — I can’t stand these pills anymore. Feel free, anybody, to ask questions or tell Shearer what your practices are. Okay. We’re gonna go to beta blockers. All right. So timolol is really the generic that’s known throughout the world. That was the original beta blocker, back whenever. I forgot when it came out. I think it’s the 1970s. And it’s still very commonly used today. It’s not off the market, thank God. You can get them really cheap in the United States. You can get them from $4 for a 5CC bottle. And there’s been different brands over the years. But they haven’t really taken the market, because when they go off-patent and stuff, everybody is still making timolol. So we had Istalol, which instead of being a timolol maleate is a timolol phosphate, and it’s supposed to last for 24 hours. It tends to sting. It’s still marketed. You can still have patients buy it, if you want to use that. We have betimol, which I hardly ever see anymore. That was another type of timolol. Carteolol was special, because carteolol had this intrinsic ISA. So beta blockers tend to vasoconstrict. And so carteolol, the idea for that was so you would have less vasoconstriction around the nerve. You know? And I used to use it in the low tension patients. Because it had a theoretical advantage. Optipranolol was another one. Metipranolol. Betagan. Sometimes we still see that. Levobunolol. So we have all of these. They all had yellow caps, designated by the FDA. It’s a little confusing now, because in the United States we used to make the 0.25% timolol come with the blue cap, and now it has a yellow cap. So a lot of people that you intend to put on 0.25%, because you’re worried about them for some reason, they’re a little old lady, and you just don’t know if they’re gonna tolerate a beta blocker, the pharmacist will give them 0.5% sometimes. And then you don’t know by the color cap which thing they got. So you’ve got to try to tell them to bring it with you, if you want it to be on a 0.25%. Sometimes they come back, and the pharmacist gave them 0.5%. And you’re like… Oh, okay. We jumped right to it. Are you okay? Because sometimes you want to just step it up and make sure they tolerate it, but we do have a problem now, because you don’t know if the pharmacist switched it on you. And then XE, the generic is gel forming, this was a great thing invented by Merck, where you had a gel in the eye. So just like the Istalol with the different side chains, you’ve got a long acting effect from the drop, because it was a gel forming. And it actually was a very nice drop. Very well tolerated. But it got kind of pushed off the market by the generic gel forming, which is very sticky. You’ve really got to tell them to store it upside down, because they’ll think the bottle is empty, because as they go through the bottle, they can’t get the stuff out in the morning. So I tell them: Get a shot glass. Keep that gel forming upside down. It’s hard to get. Same thing. If I write gel forming, the pharmacist substitutes solution. So it’s hard to get people in my country now to be on anything but generic timolol. That’s all the plans and the pharmacist and everything — they probably get it for 2 cents and then they sell it for $4, and they’re making a good profit on the generic. So that’s what’s out there. But it’s just kind of nice to know what other innovations have been there, and sometimes they are great, but the marketplace doesn’t keep them for us. Let me go back one minute. Betoptic, which is on this slide, which I probably have another slide about, this is our selective beta blocker. So theoretically, if you have asthma or something, you can take Betoptic. Betaxolol is cardioselective. Okay? So it’s a selective beta blocker. It will slow your pulse, but it’s gonna have less airway interaction, because of the receptors that it hits. Okay. So when we do beta blockers, some people are deathly afraid of prescribing them now, patients will come in, and they’re on everything else, but I’m like: Have you ever been on timolol? I notice some people just don’t even go there. And it actually can be a very good drug, if you take the time to screen your patients’ health history. And most people can take a beta blocker. You’ve got some out there that cannot. But many, many patients can take them. But it’s the heart disease patients, for one, you’ve got to worry about. Right? Because the receptors are in the heart. We do slow down the pulse. And we can’t use it in airway disease. So if people have got reactive airway disease — and that’s a little different than fibrotic airway disease, right? So you can have rheumatoid arthritis and have fibrosis in your lungs. That’s not the same as reactive airway disease. So sometimes people are afraid of any kind of lung disease. But it’s mostly the reactive, where they get wheezy and bronchospasms and these things. It’s very cheap. Like I already expressed. It’s cheap all over the world, as far as I know. It’s great dosing. Because it doesn’t work that well at bedtime. Because we make less aqueous at night. So aqueous suppressants generally don’t work as well at night. And there’s a whole study by — I think the person’s name was Orlisi from Italy, where they looked at different drugs and what happened at night. And then the beta blockers don’t have much effect. The CAIs had more effect. If they’re on a prostaglandin, it has more effect. So a lot of doctors just use it in the morning. Right? And that could be very nice for the patients. Very potent. Used to be the most potent drug, ’til we had the prostaglandins. So it’s still like number two in potency, more or less. We have a few new ones on the block. So beta blockers — those are things to watch out on. I use it in people who have a good working pacemaker. They tell me they used to be bradycardic. If they get a pacemaker in there now, I don’t worry about it. And to tell you the truth, even the asthmatics in the United States — you don’t know how many of those are on metoprolol. I go… Your internist has put you on metoprolol? Because they really like that for the blood pressure. So they don’t care about the airway. They’re on metoprolol and three inhalers. So if I put them on timolol every morning, that’s a drop in the bucket. They’re getting 100 milligrams of metoprolol every day. So what’s my little Timoptic doing in the equation? Now, if I notice they had to go off their metoprolol, when they come back, a year later, whatever, then I’ll take it away from the eye. But if they’re on a whole bunch systemically and their internist is happy with that, my little drop of beta blocker is doing nothing. Okay. The non-selective. So this is our betaxolol, and it’s marketed as Betoptic, if you get it as a name brand. And this is all what I’ve told you already, except it has less potency. Right? So it’s not blocking as many receptors, so it doesn’t aqueous suppress as well as the non-selective beta blocker. And then it’s got the blue cap, like the branded Timoptic used to have. So your patients can know it’s a light blue cap, when the nurses talk to them or the assistants, or you, to figure out: What are they doing? Are they taking their medications? That has a distinctive cap color. Any questions on beta blockers? Any questions from across the globe? Okay. All right. A little more about it. I told you about the gel forming. There was a study in Norway when this first came out, where they measured everybody’s pulse as a marker for how much systemic absorption people got. So people on the non-selective generic, just regular old timolol, they had effects on pulse. The ones who were taking the gel forming, which in those days was the XE, they were having no real effect on pulse. So that made me feel good. I used it a lot as my preferred beta blocker. Because if you’re worried about their exercise, if you’re worried a little bit about breathing, and then you get a long duration of action — so it was a nice drug, and it did have some proven safety. Punctal occlusion. That’s what we have instead of gels now. You make sure, if you’re worried about the systemic, to do punctal occlusion for a minute. And even lid closure helps with the sympathetic absorption. When you close your eyes, you kind of close your punctum. So you will not get as much systemic absorption, because where it gets in our system is all those blood vessels in our nose. Our nose — inside our nose is very vascular. And so when the drops get in there, it gets into the system. And that’s where people can have some systemic side effects from eye drops. And so when you do punctal occlusion, or even lid closure, you’re getting less into your nose, and you also get less in your nasopharynx. So if they complain about tasting the drops — some people have a really good sense of taste. We all have a different combination of taste buds, and some people really get a taste out of their drops. And then you do punctal occlusion. Less goes from your eye into your nasopharynx. And then they don’t taste it in the throat. So punctal occlusion is a good habit. And then if they’re doing it between different medicines, also make sure they’re not piling them all in together. Put a drop in. Take a little relaxation. Close your eyes. Cover your punctums. Say your morning prayers. Whatever. And then a few minutes later, ten minutes later, start again with your next drop. Okay? So here’s when, like I was saying, some of these new drugs came. So we had the alpha agonists. These were the new ones, that class of kind of adrenergic, like propine, and they do have a little bit of an effect on uveoscleral outflow, but the main effect is at the trabecular meshwork. So first we had Iopidine. It was like liquid platinum. It came in these little vials. It was 1%. And we would use it just for special occasions, like when somebody was having a laser or something, because it was kind of expensive and it worked really well, and what-not. And then it became available in 0.5%, in a reusable bottle. And then the Alphagan came a few years later, because it was tachyphylaxis with Iopidine/apraclonidine. So then — and we’ll talk a little bit more about the differences — but Alphagan, which is brimonidine, came on the heels of apraclonidine as something that you didn’t get tachyphylaxis with. And then they figured out the topical carbonic anhydrase. That’s like a 20-year project. To try to figure out: How do you get to… You have to inhibit like 99% of the enzyme. You’ve got to have a really high inhibition of the CAI to get the pressure to go down. And so somebody — I think it was Tom Zimmerman, who also worked on launching timolol — he was a pharmacologist glaucoma specialist who worked a lot on this with the Merck company, and they had the first one, which was Trusopt, and they figured out how to get the molecule into the eye, and suppress a lot of the enzyme, and they’re, like, 85% equivalent to the orals in general. Sometimes they are equivalent. So that’s a good thing. And then Alcon came out with brinzolamide after that, and they, instead of having it in a solution, theirs is a suspension. So patients have to shake it a little bit, and it’s particulate. When you have a suspension medicine, they’ve got more particles in a solution. And then in ’96, we’ve got all these… We start getting all the prostaglandins, right? So we’ve got Xalatan, which was a huge blockbuster. Rescula came out in Japan. It later got launched in the United States. But it’s very weak. It’s a BID one, and it does not work well, like the Latanoprost. So it never went too far. I don’t even think we have it anymore. I don’t even know if it’s sold in the globe. But it was very popular in Japan for a little while. Then we had the Lumigan come out, which was a little different Latanoprost, and then we had the Travatan. So the Lumigan is the one that’s an amide. It uses an amidase to get across the cornea. And if you look at the percentage, it’s got a lot higher percent of the prodrug, compared to Travatan and Latanoprost. Because you’ve got a low — a tear film with more drug to get it to go across the cornea. We must have less amidase. And so what happens is you get more of the side effects of the hyperemia and the lashes and all that. Because the percent of the prodrug is so high. So that happens when you kind of load the medicine in the tear film. Okay. So the new ones — I gave you a little bit of the story of Iopidine, which was the name brand for apraclonidine. And Alphagan P. And these are now available generic. The nice thing about apraclonidine — it’s a great short-term drug. So I use it, and it lasts a true 12 hours. This one lasts 8 to 12 hours. Right? So if I get a retina patient with glaucoma, or a glaucoma suspect, they’re getting nerve changes, but their pressures are seemingly good, they have an outflow problem. Right? Glaucoma patients don’t filter flow, out through their outflow well, and then you go there, and you get some Avastin injected into your vitreous. You’re increasing the eye’s volume, and my theory is: They do not clear that extra volume as fast as a normal eye. So when they look like they’re getting optic neuropathy, or their seemingly stable glaucoma is getting worse, I have them get apraclonidine and put that in the morning. Some of them I have to put a tube in them, because they’re already on everything. But if they’re not on everything, they get a prescription for this, and they use it — I say every time you go in to see your retina doctor, put that in, in the morning. If you get your shot, put it in later on in the afternoon. So I try to cover them for that day with something that I know has got good potency, and it’s gonna last them 12 hours, and I try to blunt what I believe are IOP spikes from their injections. And some, if they’re on everything, I give them Diamox. I go: Okay. I want you to take these two pills in the morning. Go to the retina specialist. If you get a shot, take two pills when you get home. And I treat them with the acetazolamide in that situation, if they can take it. So I give them some extra something. All right? The Alphagan P was only 0.1%, or it is currently, and it’s in a very soothing solution. It’s like in an artificial tear. Very hard to get if you’re on government insurance, so we have to write for the generic, which somehow, in the government’s wisdom, they don’t have generic 0.15% available. They want everybody on 0.2%. And the more antigen in your tear film, the more risk for allergy. So you do have a correlation there. But we have to give them 0.2%. But they all have the same effect. Because it just depends a little bit on the solution. So many, many of our patients are on brimonidine, 0.2%. And then I try to fight for the dry eye patients and stuff, to go on the more soothing drop. And then, like I said, we used to have single use vials, which I haven’t seen in a long time, and now we just use it, and it still for some reason has a white cap, and I never really understood why. Sometimes they do show up with a purple cap, the generics. But they can have white caps. And when you get an allergy to this, it really is often a dermatitis. And you can see it coming. They come to clinic, and they’re looking a little red around the lids. Right? And that’s when I start… Well, you know what? There’s also lasers for glaucoma. And I start prepping them like that. Because I can see the allergy coming. Right? They just start… They may not be red in the eye, but their lids, around the lids, are starting to get red. And I go… Uh-oh. And then this poor lady — I was out on vacation or Orbis or somewhere, and she came in, and she said: Oh my God, my eye is all red. And the person on call was the pediatric ophthalmologist. And he said: Oh, you look like you’ve got cellulitis. So he put her on some antibiotic pills and some erythromycin ointment. And so forth. Right? And then I get back and she comes to see me, and it wasn’t getting better. It was getting worse. And I said: Oh, Miss Dorothy. Her name was Dorothy. Probably long gone now. I said: You go home and you stop that… Whatever. I forget if she was on Iopidine or brimonidine, but I said: You go home and stop that drop! And I’m gonna call you in three days, and you tell me how you’re doing. And magically, it’s gone all the way. Right? Because she had this toxic kind of dermatitis. It’s a delayed sensitivity reaction. So you usually don’t get it until you’ve been on the medicine at least four months. But sometimes it happens when you’ve been on it a year. But it doesn’t happen right away. It’s a delayed type of immune response, and it really affects the lids a lot. You can’t take this drug with MAO inhibitors. So those are still used sometimes for depression. So if people are on those, they really shouldn’t be on Alphagan. They shouldn’t be on it if they have Raynaud’s. It’ll make Raynaud’s worse. This class of drugs. You avoid it for them. We often use it Q12, because it’s very hard for people to do Q8 drugs. So I’ll put them on it Q12, and I’ll have them come see me, last appointment of the day. So they did it 6:00 or 7:00 in the morning, it’s quarter to 5:00 now, and you see: Is the pressure going up more than you want it to? Because they will have a trough effect, where it drifts up a little. And you want to see if you’re comfortable with that. So you have to remember that. Because if they come in the morning, when it’s peaking, they’re gonna have a great pressure. But you want to know how it’s doing at trough also. And that’s kind of the thing on it. One thing to know too is the dry mouth and sleepiness. So if they have Sjogren’s syndrome, you might make their dry mouth worse. And that’s where punctal occlusion comes in. Sleepiness — like I said, I can hardly get people on 0.1%. You put a little tiny 100 pound old lady on this, she’s probably gonna be sleepy. And you have to talk to your patients. Because I had a gentleman — he was kind of slight build. He said: Oh, I never take my afternoon brimonidine. He had horrible glaucoma. Because I can’t get in the car and drive. I’m too tired. I had a poor lady come in. She was on timolol and brimonidine, with this big long note, all about this cancer workup she was going through. Because she was just so fatigued, and her internist was sure she had a cancer. And she was getting a lot of cancer evals. And I said… Let’s try something. Let’s stop all your eye drops, your timolol and your brimonidine, and then come back in a few weeks and see how you’re doing. She perked right up. She was just so somnolent, and actually, I could give her back the beta blocker. It was the brimonidine just wiping that lady out. And she would take her dose and she would be so sleepy, and then she would take it again in the afternoon and be so tired. And so all day long, she was tired. And they thought something was wrong with her, serious, but it was really her eye drop. So you have to think about that in the little people. They don’t have a good body volume. You can’t give it to toddlers. You give this to a kid, it’s like they’re in a coma. They’re somnolent. You want a little kid to be lethargic? Give them some brimonidine. It just wipes them out. It goes right to the brain. So that’s the difference with brimonidine, compared to Iopidine. You might have a little more allergy with apraclonidine, because the percentage — or because the drug is not lipophilic. It’s the opposite. Lipophobic. So when you put Iopidine on, there’s more prodrug left in the tear film. With Alphagan, the reason — it may be part of why it’s not tachyphylaxis going on — it is lipophobic. So that’s why it crosses the blood-brain barrier, and it’s the central nervous system effects that make us tired and give us dry mouth. So it’s because it’s a lipophobic drug. It can get across those barriers. Okay. And here’s, like I just said, it’s less lipophilic, so you don’t tend to get the fatigue with the apraclonidine. You get, like I said, the tachyphylaxis. You can see maybe he’s getting a little redder in the right lid than the left. Right? He’s using it in one eye. And you can see how you get a little lid retraction. And now I’m seeing patients who have a little bit of droopy eyelid, and the neuro-ophthalmologists are putting them on apraclonidine, so they can have a wider fissure. And I saw a patient recently on it from her plastics doctor. I guess they’re seeing if it would be worth doing a bleph or something. They put them on this, and they use it for checking, I think, for… Maybe it’s Horner’s syndrome or something. Anyway, I notice that it’s getting popular with neuro, and with plastics, because of the lid effect. And they’re doing it to test for various things. So it’s kind of interesting. Okay. The topical CAIs. Dorzolamide is the one that has the worst taste, compared to the brinzolamide. So that one — you might want to tell them: You might taste your drop. Try to do punctal occlusion. Again, it’s hard to use them Q8. You know, practically speaking, Q12, and check them at trough, and make sure they don’t have a drift up. They don’t really do anything in the body. If you have a kidney stone, no big deal. You’re not gonna get a kidney stone. You never had aplastic anemia from this. In a normal cornea, there’s no edema. They did patching tests, where they patch people overnight. And induced corneal edema with and without dorzolamide — no big deal. You know, when you have the sick cornea, you may not want to use it up front. You might want to save it, because the cornea doctors worry about that, when there really is edema. But in a normal cornea, it does nothing, for sure. Azopt, because it’s a suspension, when they first put it in, they’re a little blurry. Right? So they get a more comfortable drop, but they get some blur. And then dorzolamide in about 30% of people stings. And if you go back to medical school, and we learned about all those nerve tracts and proprioception and this and that, the same nerves carry temperature and pain. So if you put your dorzolamide in the refrigerator and you apply it, the body tends to feel the coolness more than the sting, because the two sensations are trying to use the same nerve bundles. So you can tell them: If you can remember to do your drop, it’ll feel better if you keep it in the fridge. So I tell patients that. You think it stings too much? Put it in the fridge. And the reason it stings is because of the pH. So to force the CAI into a solution, the pH is different than our natural pH, and so sometimes pretreating with tears — I’ll say put some tears in. Start doing your day. And then ten minutes or so later, you can put in your dorzolamide. And it will tend to sting a little less, if they precoated their eye, or they can put it in the fridge. But we can’t do anything about that pH. And again, I don’t give it to people who had a serious sulfa allergy. I’m a little scared. So if they had anaphylaxis, they had a big rash, I’m like… Okay, that’s not the drug for you. If they told me their Bactrim made them nauseous, eh, who cares. They’re gonna be okay. You can just do the punctal occlusion, and they usually don’t get any nausea from this. Okay. So now we come to the fixed combinations. And this isn’t exactly a new thing, because back in the day of epinephrine and pilo, when I first went into residency, we had these things called, like, E1P4, and that was the combination drugs. And then they went away for a long time, until a more recent time, where people started to combine the beta blockers with other things, because beta blockers were the most potent, and then they’d say… Oh, let’s put the beta blocker with something else, and then some smart chemist figured it out, and so now you’ll have things like Cosopt, which — generic is dorzolamide-timolol. And so you get two drugs in one, and there actually was a paper by Martin Wand that said you get better compliance and probably better pressure because of that. Because they’re meant to go in the eye together. You don’t get any washout. They put one in, and they don’t have to wait for the other. They’ve got both of them in there together. They don’t have to say — oh, I forgot to do the second drop. The phone rang. Or whatever. So actually there was better pressures, because we’ve got better compliance. We’ve got two in one. So personally, I love this kind of thing. I change people all the time to this. There’s been a lot of shortages in the last year or so. It’s harder to get, for some reason. We do have a preservative-free Cosopt available in the United States that I can revert to. It’s like $45 a month. It’s not as cheap, but patients can go on that if they have dry eyes or they have problems getting their dorzolamide-timolol. And then you don’t have any gel effect. It’s not like you’ve got the once a day beta blocker. You’ve got to do it twice a day, or you won’t get the CAI effect. So you’ve got to do it every 12 hours. So you do get a little more beta blocker, potentially, than if you’re, say, doing timolol in the morning, or using a timolol gel. And you could get a side effect from either one. So it could taste bad, because of the Trusopt, they could feel a little lethargic or wheezy, because of the beta blocker. So you just have to screen your patients for side effects from both. And then we have Combigan. So Combigan is the timolol with the 0.2% brimonidine. So if you switch them from Alphagan P, for example, you’re gonna get more brimonidine in this. So a little more potential for the brimonidine allergy. Again, it’s Q 12 hours. It may be more potent than Cosopt. There was a Canadian study. I don’t know if it was financed by the company, but there was a little bit of difference. But they’re pretty close. So I don’t worry too much, if I have to switch back and forth between them for allergy or something. It’s usually about the same pressure. And this is my go-to when you want the pressure down right away. A CAI topically does not bring your pressure down acutely. It takes a little time to suppress that enzyme. And if you look at the package insert, the last time I looked at it, it said it takes eight weeks for steady state. So I don’t expect a quick response when I put them on a topical CAI. If you just had your cataract, and you have a pressure — you’re having problems with your pressure, postop, Combigan. Because I’m gonna give it to you now, and in 20 minutes, your pressure’s gonna be going down. It works immediately. It’s got two short-acting, quick-acting drugs in it. So you’ll get a quick effect. So this is, besides Diamox, which works right away, this works right away. And then my residents will say: Oh, I put some Trusopt in. I’m like… What for? Where was the Combigan? That’s gonna bring it down right away. They’re in acute angle closure, they’re in whatever, this is a great drug for a quicker response. And Combigan is the go-to for that, or the two components, when you’re thinking about pharmacology and what’s gonna bring the pressure down quick. These are drops — the day you use them, they work. And then you tell the patient: These are short acting. If you don’t put your drop in, you’re not getting an effect. You’ve got to do it every day, just like brushing your teeth. This is gonna be part of your life, is doing your drops. You’re maintaining your eyesight. Because these are not forgiving if you start skipping them. Okay. Oops. How did I do that? Somehow I got my things — this is like a little quiz. I should have said: What’s wrong with this slide? Like a little quiz. Okay. So the prostaglandins, the first one was Xalatan. And that was a blockbuster drug. First time we ever get a drug that’s more potent than timolol, and it’s truly a once a day drug. That was just amazing, and more and more places I go are getting Latanoprost now, kind of across the world. It’s generic. It’s been here a long time. And this works on the uveoscleral outflow. And so you don’t have much side effects. It’s like dorzolamide. If you’re gonna have a side effect, it’s on the eye. So you’re gonna get a local side effect. You’re gonna get occasionally — and not even one in a hundred, I don’t think — and some of that’s because we know to screen — you’re gonna get occasionally somebody with eye inflammation. You’re going to get — even CME has been described, and I’ve seen it a few times, where they have no history of it, and they’ve got CME. I had a great patient I saw one time. I was on call. The patient was supposed to be seeing retina. They came in. They had bilateral CME. They had had cataract surgery. It was months away. Both eyes had CME. And I said… Well, I’m sorry. The retina doctor’s not here. You’ve just got me. I’m gonna do my best. I take a look at them, and I go… You know what? Let’s just stop this Lumigan. Guess what? Cured the CME. Right? I say… Oh, you got to skip a retina consult. We figured it out. It was the Lumigan. Because just the whole thing was a little fishy. They were far away. It was both eyes. And so you see it sometimes. So you keep that in the back of your head, because then you’re like… Oh! You helped the patient, even though you were the wrong doctor of the day. Okay. And then sometimes people complain about weird things. They swear to God they got a headache when they take it. They swear to God their knees swell. I don’t know. I mean, I have little old ladies who tell me that the Trusopt makes their ankles swell. I tell them that is scientifically impossible. Right? But they still insist — oh, no, it’s my drops. I’ve got swollen ankles. I had another one where Pred Forte makes her get up and pee at night. I’m like… I really don’t think so. But they’re in their head sometimes. This is the cause. They just don’t want to be doing drops, and they come up with something. So I’m not sure I believe them. But you’ve got to take it with a grain of salt. So this one’s nice. I let patients do it in the morning. Once you’ve been on it about a month, your metalloproteinases have been inhibited, you’ve got different collagen synthesis in your uveoscleral outflow, and then they’re just on maintenance. They’re putting that drop in to keep that pathway open. It does not matter. If they fall asleep at night with the news or whatever, I just tell them: Do it in the morning. Right? It’s okay. When you’re putting all your other little pills and stuff in, do your eye drop. Or do this, and ten minutes later, do your timolol, and you’re all set. And you get 24-hour coverage. And I try to make it easy for their lifestyle. Because not everybody is a night person. A lot of people like to take it at night, but you’re gonna have some really morning people, and they’re better off just doing it in the morning. Okay. And this is one I was telling you. This is a slide from an article back when these things would come out, and you can see how Latanoprost was better than timolol. That was just an amazing find and a great thing. And this is weeks. And you see how both of them lower the pressure and continue. Some people believe this tachyphylaxis with timolol — I’m not always sure of that either, because glaucoma changes, and earlier in the week I showed you some patients who took their timolol for a decade, and their pressure used to be 30, and you stop the timolol, and it goes back up, you put them on it, and they’re 20 or they’re 18, and they’re great. So timolol can last a long time also. I think it’s more the glaucoma that changes. You know, we lose more of our outflow as the years go by, and we need more drugs and more treatment, and not everybody is able to be treated and stay down. Because you can see they both kind of do that, and I have seen patients on both drugs, where they get many years of this similar lowering, and it’s just working, and I think their outflow is stable in their TM. This is the prostaglandin thing, which you won’t have much issues with in the Caribbean. Although I take that back. Because I’ve been to Curacao, for example, where there was a lot of Dutch, mixed with the native, mixed with the Africans, and so I did see eyes of a lot of colors. A lot of different complexes. So if a person has a mixed iris, they don’t have a totally brown eye, they’ve got some hazel in there, in between, usually they’re brown around the pupil and hazel beyond that — as they use their prostaglandin, you’re gonna have more melanosomes. The eyes get darker. Right? So they didn’t even notice that initially. Somebody, his name was Murray Johnstone, went back. This was the original paper. And they were monitoring everybody, and they didn’t even notice the lashes ’til they went back and looked at the pictures years later. They were monitoring all these irises, but, see, the lashes get thicker too. So if you use — and that’s where Latisse came from. So if you’re a ritzy lady, you go to your dermatologist, and you pay $100 a month for a little Latanoprost, so you can put it on your eyelashes. Or Lumigan. I guess it’s dilute Lumigan. And you can make yourself have luscious lashes, like all the glaucoma patients. So I had an ocular hypertensive like that. She came back, and her pressures, instead of being 26, 28, they were in the teens. I said… That’s strange. Then I’m talking to her, and she was on Latisse. I said oh! Well, I’ll just put you on Latanoprost for $15 a month, you’ll save $85 for something else, and you’ll still have your luscious lashes. And you’re treating your glaucoma at this point, so we’ll just treat your glaucoma. Or your pressure. She didn’t have glaucoma. Everything was normal. She just ran high pressures. So I said okay. There you go. So I switched her. So we don’t write for Latisse much. Because we don’t see those patients. We see… But they do get luscious lashes. It does bother the men. They come in, and they want me to trim them sometimes. Because it rubs on their glasses. But the women never complain. They all like it. So often I’ve got to treat both eyes, even if I only need it in one eye, because their eyes are hazel. And if they say… Oh, I don’t care… I had an old pediatrician with it in one eye, and he definitely turned it from a hazel to a brown eye, and he couldn’t tell. I’m like… You notice your eyes are a little different now? No, no. No, no. Does your wife tell you you’ve got two different eyes? No, no. I’m like… Okay. You know? One lady told me, when she went for her driver’s license, instead of writing hazel, they wrote brown. You know? Because she turned brown. So you’ll see it once in a while. But in people with homogenous brown or homogenous blue, no difference. Green? My mother had green eyes. She was on prostaglandins for… I don’t know. 20 years. Never changed her eye color. So it didn’t do anything to a green eye. But hazel are the ones. You’ve got to tell them: You know, it might change your eye color a little. And then, like I was saying, the lashes. Here’s the lady. Look how her lashes are longer. This is the Lumigan eye. That’s the non-Lumigan. And then some of these people with the bony faces — you know? I call them the New England specials. When I worked up there, everybody had these really deep set eyes. And they’ll get periorbital fat wasting. More from the Lumigan, because it’s got more antigenic — you know, deposited on the surface. Because it’s not from intraocular. It’s from treating on the surface. So I tell them: Put your drop in and pat it dry. So then we get a little less periorbital puffiness. And darker skinned people, they’ll come in and they’ll get extra melanosomes in their skin. So they get a little bit of a raccoon eye. You know, who wants that, right? So then you get this attractive lady coming in, and now she’s got dark circles, because she’s on a prostaglandin. So I tell them: Go ahead and pat it off. Close your eyes. Let the drug absorb. And take a Kleenex and pat the extra off. So I don’t get the periorbital fat wasting in the people with those deep set bony faces. I don’t get my darker complected ladies telling me they’ve got circles. I don’t have the men telling me I need to trim their lashes. So you try to control the local environment a little bit, just with something simple, patting it dry. Okay. Let me go back a minute. I didn’t tell you what’s special about Travatan. There’s a lot of studies in the French literature. Travatan has a different preservative. So most drugs are preserved with BAK. Right? Alphagan P has got, I think, its own preservative. It’s kind of in an artificial tear. It tends to be soothing. Travatan Z has Sofzia in it. So that’s a different preservative than BAK, and it tends to sting more. So I tell the Travatan patients: This drop is gonna sting a little bit. Because it changes something about it. Maybe it’s the pH also. So it has a little sting when they take Travatan, but it’s supposed to be healthier for your goblet cells and the surface of your eye. So Travatan has that special to it. And sometimes the pharmacist, they’ll fail Xalatan treatment, and they won’t want me to put them on Lumigan, and they don’t understand Travatan is an esterase, just like Latanoprost. They work the same. I really don’t see differences between those two drugs. They get in the eye. They’re the same prostaglandin analog. But they use esterases, whereas the Lumigan is a little different, and it’s got a different prodrug, and it can lower the pressure in some people, like a point or something, a little more. So sometimes if they’re failing this, or they’re a frank non-responder, I put you on Latanoprost, you come back, your pressure is still 24, and then I’ll switch you to Lumigan. So there’s no point in switching you to Travatan. It’s too much the same. Lumigan sometimes makes the difference, and they maybe have a different corneal enzyme profile. So Lumigan is its special own drug, and these two kind of get in the eye the same way, and seem to have the same efficacy. Okay. Now we have a new one that I’ve had for a little while now. Actually released first in the United States, which is rare. Almost all the drugs are in Europe or Canada or someplace else first, and we get them eventually. So Vyzulta is a Latanoprost drug, but it has a nitric oxide moiety. And this is based on research that says that glaucoma eyes, when you analyze the aqueous, they don’t have as much nitric oxide. And nitric oxide relaxes cells. It relaxes endothelial cells. It’s like a vasodilator. But they think in this case it’s working on some smooth — like some of the more smooth muscle-type cells that are in the TM. So it relaxes the TM, and you get better outflow. And so for some reason, the FDA had them compare it to timolol and not Latanoprost, to get approval. So for so long, timolol was the gold standard, when really now a once a day prostaglandin should be, in my mind. But they had to compare that it wasn’t inferior to timolol, and actually, it lowered pressure more. And actually, a little more than your typical prostaglandin. And I usually will get — when people respond to it, I get some non-responders. So they’re on Latanoprost, their pressure isn’t low enough. I put them on Vyzulta, sometimes they’re the same, other times they come back, and instead of being 17, they’re 14. So it’ll go down 3 to 5 points, it seems to me, in my hands, compared to the prostaglandin alone. Which, if you think about it, IOP — some people don’t get 9 points out of their prostaglandin, right? They can just get 6 points. I mean, I get probably 5 to 10 point reduction when I put somebody on a prostaglandin. And you watch them and you see what their new range is. But when you add this or you change them to this — and what’s really wonderful, when you change them, no redness, no nothing. They’re already used to the prostaglandin, and the new moiety doesn’t seem to do anything to the surface. So you put them on it, and it’s the same for the patient. And so they don’t come back and you have to worry that they’re red, they’re inflamed, they’re whatever. Itchy or something. It’s a very easy switch from a prostaglandin. So I like it for that. It’s still expensive. I have to kind of fight for them to get on it. It’ll probably take a bit to trickle into the Caribbean and other parts of the world. But it is a nice drug. It’s by Bausch and Lomb, the ones who brought it to market. And what’s kind of interesting is: Many years ago, Pfizer did studies in France on nitric oxide, and then they gave it up. They weren’t happy with how much pressure lowering, so then Bausch and Lomb or somebody else kept going with the research, and brought it to market. So it’s kind of interesting in that. So this has been a nice addition for patients. It’s once a day, just like their prostaglandins. Then we have another new one, called Rhopressa, that’s called Netarsudil, and that’s brought out by this little company called Aerie. And this one doesn’t do lashes and iris color like a prostaglandin, but they get redness. And unfortunately, it works right away, you can have the patient go sit in the waiting room, and within 24 hours or whatever, their pressure goes down 3 points or something like that. So it seems to be kind of quick acting. It works in the trabecular meshwork. It seems to work on your episcleral outflow. And it seems to also have you make less aqueous. Which does a lot in our eye. It’s doing a lot of stuff. And of course, they compared it to timolol, still the gold standard. Okay? And when you use it alone, as monotherapy, its efficacy is between timolol and a prostaglandin. So it’s a little more potent than timolol, but not as potent as a prostaglandin. And to be honest, probably 50% of the patients call up, and they say: I am not taking this drop. My eye is so red. You know, you’ve got to tell them. I try to coach them. Your eye is gonna be red, and it may go away. Because not everybody stays red. And then other people take it. No big deal. So it’s kind of interesting. But some people just — oh my God. I’m not going anywhere with this red eye. I’ve got to stop this. And it can be red like with subconj hemorrhages, injection — it really seems to affect our conjunctival vessels. You know, here’s a study. Some basic science on it that shows you the difference in the trabecular meshwork. And it’s pretty impress to see how it’s pulling open the TM. Maybe like a pilo used to do. But just once a day. So that’s pretty cool. And if you were on this as a young person or whatever, is this gonna preserve your TM function longer? And things like that. Theoretically, it sounds like a good thing for our eye to be on this, if you can be taking it. And now, as of this week, I just got a note on my email from the Rhopressa rep that now we’re going to have Roclatan. So they’re doing just like Bausch and Lomb did, where they added the nitric oxide-donating moiety to the Latanoprost. This one is adding Rhopressa to Latanoprost. So I don’t know if we’ll get even more redness or not. And of course, it’s working on four things in your eye. You’re getting a little more episcleral outflow, you’re getting more trabecular outflow, you’re making a little less aqueous, and you’re gonna have more uveoscleral outflow. And so this is supposed to give a few more points, which I would say it goes up to 3, because when I add Rhopressa to an eye, I usually seem to get 3 points. So it gives you another few points, but again, it’s gonna be once a day, two meds. And to have daily medicines like this, where you get two medicines, is kind of nice. And in Canada and Europe and some places, we have that with Latanoprost or Travatan with — like, we have Xalcom. That’s Latanoprost with timolol. That they take every morning. But we don’t have that in the United States. The FDA didn’t think it lowered pressure enough. But these, when you add them to a prostaglandin, they do drop the pressure 2, 3 points, and they decide that’s clinically significant. So we’ll have these prostaglandin plus. Like, I tell the patient: This is like your green cap, and it’s another green cap, but it’s Latanoprost plus. So you’ll get a little extra out of this, putting your drop in every day. So these are gonna help us with compliance. And there’s even gonna be — I don’t know if I have more stuff. I’ll tell you a little more in a minute. This is the Roclatan study, right? So look at conjunctival hyperemia. If you put Latanoprost, it’s 14%. And I would say most of my Latanoprost patients have mild hyperemia. You look at the eye, and it’s a little red. If they’re real red, they stop it. But not too many stop it. They tolerate these prostaglandins pretty good. But it’s 40% and 50%. And I would say I agree with that, because I think half the patients do call and say: Oh my eye is so red! And it even includes conjunctival hemorrhages. And if your conjunctiva bleeds and it looks like someone put ketchup in your eye, you don’t like that. You don’t want that Halloween-looking, scary-looking eye. And now, another weird thing is verticillata. Patients get corneal verticillata with this, like they do with amiodarone. And so they don’t know what that’s gonna mean in the future. So you’re getting this — kind of that weird pigmentation in the cornea that we know is not visually significant, but it’s a little strange that it does that. And then the usual. Oh, it stings when I put it in. I get itchy. And that kind of stuff. You see that with all the drops. But this specifically does affect the surface of the eye quite a bit, in different ways than we’re used to. And then here, showing you some of the Roclatan studies. So you’ve got the green. That’s our Rhopressa. You’ve got the red. That’s the Latanoprost. And then if you put in the Roclatan, it’s even better. And this makes you think… Yeah. You can see — because Rhopressa doesn’t lower the pressure as much as Latanoprost. It’s a little better than timolol for a once a day drug. And then you can see it’s not as good as Latanoprost, and then when you add them, they’re quite additive. And so for the patients who can take it, it’s a good medicine. And before we go on to this, I’ll just touch a little bit on some new stuff. So the Allergan company, I think it is, one of them — they’re in trials now where they inject a little pellet of bimatoprostin to the anterior chamber. So it’s a sustained release bimatoprost. So it’s in there for several months. You’re getting your therapy. The patient doesn’t have to do the once a day drop. So you can imagine for patients who need, say, laser and prostaglandin, that takes putting the drop in every day out of the picture. They’re also working on a ring. Kind of like years ago, we had this little pilocarpine insert. Right? So it kind of sat up under the lid, and it gave them sustained release pilocarpine, so they didn’t have to put it in three, four times a day. So the Lumigan, they’re looking at the same kind of thing, where they would come into the office, they would get their little reservoir put in, it would last whatever amount of months, and then they would come back and they can have it replaced. So that will be great for nursing home patients, for people who can’t do drops, because of whatever reason. Rheumatoid arthritis. Things like that. So those things are in development, some novel things. I’ve seen where people are trying to put prostaglandin punctal plugs. I went to a meeting where there was a Singapore doctor who was injecting Latanoprost in nanoparticles or something. Subconj. And the patient was getting three months, at least, of pressure control. So there is some research out there, where we can have a little bit more depot therapy, at some point, and then we give the patient what they need, and we don’t have to worry so much about them putting it in every day, and we know there’s certainly lots of patients who would need that help. So that’s kind of hopeful for the future. So let’s go back to our quizzes and see how we’re doing with the posttest. All right? So you can all take your clickers, and this one should be super easy. Let’s see. And look at you! See how good you pay attention? That is awesome. We did not have 100% to start. So which of the following uses an amidase to cross the cornea? Which drug is distinctive for that? Let me tell you, Latanoprost is an esterase. Okay? It goes through the eye and gets cleaved by a corneal ester. So that makes it very much the same as Travoprost. That uses a corneal ester. Like propine. Propine was the first prodrug like that. Latanoprostene bunod probably uses an ester, because it’s got Latanoprost in it. Right? So you make it into the F2 alpha prostaglandin analog by cutting off the ester component. So Bimatoprost, which luckily is the majority answer, but not as many as I want, Bimatoprost is the amidase. So if you have someone that doesn’t respond to the others, sometimes they’ll respond to the one that uses the amide in the cornea. So that’s — you have amidases in your cornea and esterases, and Bimatoprost is the first drug that uses our amidases instead of esterases. Okay. So now we’re thinking of the older drugs, the drugs before ’95. Okay? Which drug is still used often today? Back from the day? Okay? No more propine. It’s very weak, and nobody wants to make it! You can’t make any money selling propine. It doesn’t work well. It makes your eye red. Gives you conjunctivitis. We’ve got newer things. No more propine. Timolol is the one. Back from the ’70s, and we still use it. They still use it to compare new drugs to. Propine is off the radar. And apraclonidine would be considered a newer drug. That came out in the ’90s, and we don’t use it as much. It didn’t get much market share, because of the tachyphylaxis.
April 06, 2019