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Clinical

Glaucoma

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SpyGlass Pharma completed enrollment in a Phase 1/2 trial evaluating its drug delivery platform for glaucoma and ocular hypertension. Designed for implantation during cataract surgery, the platform delivers bimatoprost to lower intraocular pressure for up to 3 years.

SpyGlass Pharma completes enrollment in Phase I/II study of its long-term drug delivery platform for glaucoma and ocular hypertension

The study, conducted in 2022, highlights significant variations in glaucoma prevalence across different demographic groups, states, and counties.

Study estimates glaucoma and vision-affecting glaucoma prevalence by demographic factors

The switch may produce an additional 25% IOP reduction in mild to moderate forms of disease

Efficacy, safety of switching to latanoprostene bunod 0.024% in patients with OAG and OHT 

Ophthalmologists have discussions about driving with glaucoma patients.

Driving with glaucoma: Steering clear of vision issues

According to investigators, retinal aging caused by stress produces symptoms similar to those resulting from natural aging.

UCI-led study shows repeated stress accelerates aging of the eye

Ophthalmology Times Omar Salamanca Orbis Glaucoma

, Omar Salamanca, MD, staff ophthalmologist, Orbis Flying Eye Hospital, discusses Orbis's tailored glaucoma training programs, which focus on hands-on surgical skills, early detection, telemedicine, and personalized follow-up care, helping underserved regions improve glaucoma management and blindness prevention.

This transcript has been lightly edited for clarity.

. I'm joined by Dr. Omar Salamanca, staff ophthalmologist, Orbis Flying Eye Hospital, to discuss how Orbis treats and trains in glaucoma. Thanks for joining me. First, how does Orbis tailor its glaucoma treatment protocols to meet the specific needs of the regions where you provide care?

: Hi, David. Thank you for this interview, for providing this information to the people. My team, we normally visit the country 6 months or 1 year before. So, we try to understand what is happening in the ophthalmology field in the country. We have to understand what the level of training is, and we can tailor the program according to that. We can scale up or down according to the needs. Because we, as Orbis Flying Eye Hospital, can provide different levels of training, starting from basic, intermediate, or advanced. So, after these interviews, we decide what kind of surgeries we’re going to teach during the Flying Eye Hospital program.

: What role do you see telemedicine and virtual reality playing in the future of glaucoma training through Orbis, particularly with the Flying Eye Hospital?

: Well, technology definitely is something very important now to train all the personnel in eye care—not only in eye care, but in medicine. So, it’s a very important tool. And with Orbis, we have different platforms. We have Cybersight, and with Cybersight, we have a lot of courses, nearly 20 different courses, again at different levels: intermediate, basic, and advanced. We also have this system to telementor for the doctors. So, that means that we can ask the doctor to upload the information of a specific patient, and they will be connected with a glaucoma expert anywhere in the world. Within 24 hours, they will have recommendations, and they can start this conversation about the patient. It’s a very interesting platform that helps. That platform allows you to include images, which are very important in ophthalmology, and you can also upload videos. You can do it from your laptop or even from your cell phone. And another important thing is about the artificial intelligence in Cybersight. We have a system where you can upload the single images of the fundus. So, it works very well for diabetic retinopathy because it can tell you if it’s positive or negative for that disease. But we can also check for the optic disc. The system, within 10 or 20 seconds, will tell you if the optic disc is normal or abnormal. After that, you can make a decision as a doctor. I have to say that glaucoma diagnosis is a little bit more complex, so we need to consider age, intraocular pressure, and visual fields, but it’s a very important tool that we have available in Cybersight.

: What are the key challenges you face when diagnosing and treating glaucoma in underserved regions, and how does Orbis help overcome these barriers?

: Yes. There are many different barriers, according to the countries that we visit, of course. But first is sometimes the doctor doesn’t have the surgical skills to deal with this disease. But sometimes, they don’t even have the clinical skills to properly diagnose the disease. So, this is where Orbis is focused, mainly doing the MTH programs. But again, it’s mentioned in the access to the health services. Sometimes, the patients don’t live close to the centers. So, with this technology that we mentioned before, we try to close that gap. Sometimes, there’s a lack of instruments, lack of special equipment, and Orbis not only provides the training through the FEH programs, but we also work with Orbis offices in the country, so we try to do some long-term programs to address these needs.

: How does Orbis ensure that training participants acquire hands-on experience in glaucoma surgery and postoperative care, especially in complex cases?

: It’s a very dedicated process, because we plan in advance, like 1 year. One of my jobs at Orbis is to visit the country 1 year before to understand how the situation in ophthalmology is, and especially glaucoma, because that’s my specialty. So, I have a lot of interviews with the doctors who have an interest in glaucoma, trying to understand what the level of training is, because there are different surgeries that we need to perform to treat glaucoma. And those are very basic, like trabeculectomies, and sometimes include tube insertions or the MIGS. So, regarding that assessment, we decide what kind of surgery we will teach during the program, and we identify the expert in that surgery. Before we start the program, we do a simulation training week in the Flying Eye Hospital. So, that’s part of my role. I teach them with the plastic eyes, with models, and in the very safe environment without patients. I try to teach very, very specifically—how to hold the instruments, how to grab the eye. This is very important. And the following week, we have the surgeries with patients. The expert should have a lot of experience teaching residents and doctors in their home countries, so they teach them and also follow up on the outcome of the surgery. And when we finish the program, in 6 weeks or 8 weeks, it depends, one of the staff visits the country to see the outcomes and to provide feedback. It’s a very, very connected program. We try to connect.

: What kind of follow-up care is typically provided for glaucoma patients after Orbis has completed a project, and how are they monitored for disease progression?

: Yes, through our platform, Cybersight, we are able to upload the information before surgery, during surgery, and after surgery. We encourage local doctors to communicate with the volunteer faculty, our expert, but also the Orbis staff is visiting the country to be sure that the outcome is according to the clinical standards. If we identify something that is not going well, we have to provide the advice regarding how to treat the patient, and we also provide, not only advice, but sometimes some medications to treat the patient after surgery. As mentioned before, sometimes we support them with technology. So, it’s very important, not only to do the surgery, because most of the time it goes well, but with time, especially with glaucoma, you can identify some specific conditions that you need to treat to prevent the progression of the disease.

: How do the Orbis glaucoma training programs address the differences between open-angle and angle-closure glaucoma, particularly in those diverse populations with varying genetic predispositions?

: That’s a very, very interesting question. Glaucoma, in the end, is a problem in the optic nerve, which is in the back part of the eye. What you mentioned is something in the anterior segment. So, we try to focus the training, because the diagnosis may be different and treatment also may be a little bit different, but that’s part of the program that we decide. If we are going to Asia, for instance, we will find more narrow-angle glaucoma. But if we go to Africa, there’s going to be more prevalent open-angle glaucoma. So, we try to understand that context for the countries. We also identify and provide the structure or the content of the training lectures—how to make a distinction between narrow-angle and open-angle. We have to focus on gonioscopy, which is something very specific to identify if the angle is narrow or not. When you’re a glaucoma specialist, you see glaucoma as a whole, but you have to check for the details. And we’re very good at trying to identify those details because it’s very important regarding the prognosis and also the treatment.

: How do you balance teaching new glaucoma surgical techniques with the importance of improving early detection and preventive care while you’re on a training mission?

: That’s definitely a must. We cannot focus only on training in the latest surgical techniques. We have to go to prevention, and that’s not including only ophthalmologists. We also have to include local doctors—I mean, general practitioners, nurses, optometrists—because what we know about glaucoma is if we detect it earlier, we will have more chances to provide proper treatment. So, during the program, specifically, we have lectures in our classroom, and we broadcast the surgeries. But between surgeries, we are speaking about how to understand the risk factors for glaucoma, which is very important, how to properly assess the optic nerve, intraocular pressure. So, we have to do a balance. The other thing is that we raise awareness about blindness prevention. We invite people from the government, sometimes prime ministers or the Ministry of Health, and other important people, so we can bring attention to blindness prevention, and this is where glaucoma screening in the early stage has a very, very important role.

: What kind of feedback do you get from the trainees afterwards?

: Well, we have the professional feedback, which is regarding the cases. But it’s also a very good thing because we establish a good relationship with them. So, they start speaking not only about the cases that we did there in the program, but we also start having new conversations about new cases, new opportunities for them to be trained. Sometimes, we interact with them in medical conferences or at the Congress. So, it’s a very interesting part, not only in the professional field but also in the personal field. We start growing this community that’s been trained with the Orbis program. We try to establish this fair communication. And sometimes we become friends with them.

Videos

Orbis Flying Eye Hospital's glaucoma training programs are tailored to meet the specific needs of underserved regions, focusing on hands-on surgical skills, early detection, telemedicine, and personalized follow-up care. The programs utilize technology platforms like Cybersight for remote mentoring and AI-assisted diagnostics. Challenges in these regions include limited surgical and clinical skills, access to healthcare, and equipment shortages. Orbis addresses these through comprehensive training, simulation exercises, and long-term support. The programs emphasize balancing new surgical techniques with early detection and preventive care, fostering a collaborative community among trainees.

Omar Salamanca, MD, staff ophthalmologist, Orbis Flying Eye Hospital, discusses Orbis's tailored glaucoma training programs, which focus on hands-on surgical skills, early detection, telemedicine, and personalized follow-up care, helping underserved regions improve glaucoma management and blindness prevention.

Adapting glaucoma training and treatment: Insights from the Orbis Flying Eye Hospital

During a presentation at the Glaucoma 360 New Horizons Forum, L. Jay Katz, MD, presented “Understanding What is Behind the Trabecular Meshwork.” We caught up with him to discuss the topic.

A complete understanding can help ophthalmologists get better results for their       patients.

 Understanding what is behind the trabecular meshwork

Donald L. Budenz, MD, MPH, shares the key takeaways from his Shaffer-Hetherington-Hoskins Lecture, focusing on glaucoma epidemiology, presented during the 2021 Glaucoma 360's 25th Annual Glaucoma Symposium CME. 

Studying glaucoma epidemiology at the center of the Earth 

 Ocular surface disease (OSD) is a very common, if not the most common side effect or complaint from patients using glaucoma medications, especially the effect of benzalkonium chloride (BAK). How do you address this in your patients?

 That’s a tough question to answer because there are patients that complain about OSD and then there’s the OSD that just bothers me when I actually have to look at the eye. I’m always worried that these patients are going to need surgery down the road. And when that surface looks beat up, when that surface looks rough, I’m concerned about how my glaucoma surgery is going to do.

It’s actually quite hard sometimes to correlate what the patient feels with what we see on examination. I have plenty of patients who look like they have a good amount of OSD and who are quite happy. And on the flip side, I have people who are miserable despite what I think is okay-looking OSD. But I think in general glaucoma specialists are more aware of ocular surface health, and we’re doing more and more to try to improve the satisfaction of our patients. We’ll treat blepharitis more aggressively, we’ll treat dry eye more aggressively.

One of the biggest reasons our patients have difficulty is the medications, the toxic medications that they’re pouring on their eye. We know that certain classes of medicines tend to aggravate the ocular surface more than others. I personally am a big fan of preservative-free medications, whether it’s preservative-free timolol or preservative-free dorzolamide-timolol; or even preservative-free tafluprost. I think that these medicines are a little bit nicer on the ocular surface.

In terms of their efficacy, I think they’re comparable to a lot of our standard medications. The issue is the availability of these medications. As we talked about before, cost and availability of medicines is definitely a big deterrent as to why we don’t actually write scripts for a good number of these medications.

 What are your thoughts about the limitations or the benefits of using preservative-free medications?

 Preservatives, unfortunately, are a necessary evil. While we would like to have all of our medications in a preservative-free form, it’s just not going to happen. I think a lot of the medications that we have out there are good medications. They work for our patients. And I will honestly say, some of my patients who have a new vial every day actually are not always the happiest. Some of the patients who have that one bottle are actually happier than some other patients. So while I think preservatives are an issue, and it would be nice to find a better preservative for some of our different classes of medications, I think this is what we have.

 What effect do you think do you think the topical medications have on the ocular surface disease?

 Each of the individual medicines can have an effect on the ocular surface, as well as the preservative itself. In terms of which medication classes give me the greatest cause for concern with regard to ocular surface health, it’s the alpha-2 agonist (ie., brimonidine). That is often one of the medicines that I find causes a lot more ocular toxicity compared to some of the other medications that I tend to prescribe daily.

In general we know that all of our medications are going to have side effects. Prostaglandins have issues with hyperemia, we have issues with periorbital fat atrophy. With our beta-blockers we have some systemic side effects that can be troubling. Alpha-2 agonists can often lead to a follicular conjunctivitis. Topical carbonic anhydrase inhibitors can lead to some burning and some bitter tastes. Whatever medicine it is, there are often going to be some side effects, and it’s all about trying to find the balance of that efficacy that we get from the medication with its safety and adverse effect profile.

Even speaking to our newer medicines - with netarsudil, we do see some hyperemia with that medication, and as well with latanoprostene bunod. So I think we have to try medications. We have to try to see what kind of efficacy we get, and we have to see, is it a problem more for us or is it a problem for our patient?

I have plenty of patients who have a significant amount of hyperemia when I examine them. But when I ask them how do their eyes look, they say, “My eyes look fine, doc, my pressure is great, I’m going to keep using this medicine.” So I think there are things that bother us and there are things that bother the patient. But in the end, our goal is to make sure that that pressure is within the range that we want it to be, and the range that’s going to keep the patient from losing vision. And if that means that they have to tolerate some side effects, then so be it. I think it’s exciting to have newer ways to deliver drugs that might minimize some of these side effects and it will remain to be seen how well these medications work.

How can some of the limitations be overcome by the newer pharmacologic agents in the pipeline or submitted for approval?

 These newer agents that are coming out really aim to do dropless therapy, which basically saves the ocular surface from all of those medications and preservatives. And I think certainly it addresses it. That’s the goal with these medications, not only to have a medication that is local, that works well, that is in low dose, but one that is not affecting the conjunctiva, and the eyelids, and the cornea in the same way that we currently are using our drugs. There is a great avenue for improving our IOP reductions, and certainly patient compliance won’t be an issue because devices or implants are already be placed in the eye, so the patients don’t have to actually do them every day.

 Do you see patients still taking topical medications when they are receiving some of these newer medications that are going to be delivered via either intracameral injection, or via ocular inserts? Do you think that we will still need topical therapy?

 I think glaucoma is a tricky disease to treat, and it would be too idealistic to say, “Oh, these things we’ll put it in the eye and nobody needs another drop again.” The truth of it is it may help reduce IOP in some patients where patients don’t need to use any drops. But it may not, and we may need other medication, and we may need surgery, may need laser, may need any and all of these things. But I think this is an avenue in the right direction for progress and frankly speaking, I’m very excited about it.

 I think that’s the biggest question for me: with a lot of these new drug delivery modalities is the fact that it is still a single drug. And whether or not we can get the desired efficacy we want when we have a patient who’s on multiple classes of medication. That does remain to be seen at this point.

But I think one of the nice things we saw from the Phase III, bimatoprost SR data is that there were a good number of patients who were on multiple classes of medication who were actually able to maintain a reduction in their pressure at the same level when they were solely being treated with bimatoprost SR.

Thank you Dr. Bedrood for your participation in this insightful discussion. And thank you to our viewing audience for joining us during this Ophthalmology Times presentation on open-angle glaucoma. We hope you found this presentation to be useful to your clinical practice.

Effect of Open-Angle Glaucoma Medications on Ocular Surface

 If a patient is knowingly non-adherent, what do you do? Do you switch medication classes? Do you suggest laser? Do you move to surgery earlier?

 If a patient is knowingly nonadherent, I will ask them why they’re not using the drop. If they say, “I forget,” I don’t think adding another drop is going to help them remember, quite frankly. So I will give them the options of SLT laser or I will give them a very open and frank discussion on the possibilities of surgery, either minimally invasive surgery (MIGS) or if they’re a little bit more advanced, we can do traditional trabeculectomy or tubes. And I give them all of these options.

I talk about surgery with patients because it perks their ears up and they say, “Oh, wait, I don’t want surgery.” And sometimes it reminds them that maybe it’s better for them to use the drops. Sometimes I will offer them surgery a little bit sooner because frankly, I want their pressure lower. And whether or not they remember or they don’t, I want their pressure lower and so I will offer them surgery a little bit sooner than someone who would be using the drops on a daily basis.

 I’m curious what your thoughts are on what you now consider the maximum medical therapy? Traditionally for me when I finished Fellowship, maximally tolerated medical therapy often involve multiple classes of medicines, three or four classes and possibly even an oral agent. But I think in my hands nowadays, if I have a patient come see me, if they’re on two bottles and they’re not doing as well as they should, I’m starting to think about doing either laser treatment or possibly even surgical intervention, given the really nice safety benefits of a lot of these newer procedures that we have.

For me, right now maximally tolerated medical therapy often is two bottles. And, again, often that is the combination agent coupled with probably a prostaglandin analog. So three classes of medications in two bottles is usually where I’m starting to draw the limit. Because as you add more bottles, I think we decrease compliance. For a variety of reasons, we increase cost, we really make it more difficult for our patients to do what we’re asking them to do. Given that we have so many procedures that are available that do help lower pressure, while we’re not putting our patients at too much risk, I think I am moving more towards discussing surgery earlier in my treatment algorithm.

 I completely agree with you. I don’t think that we need to wait three or four drops in order to do surgery. Sometimes I will. If the patient is really high risk for surgery, if they’re monocular, if they’re really hesitant, of course, I’ll put them on all the drops that they can tolerate. But, if they’re not any of those things and they’re open to doing something a little bit more, a tiny bit more invasive, then we will move forward with surgery. And I think in this day and age we do it a little bit sooner than we did 10 or 15 years ago.

 That’s definitely becoming sort of a shift in the practice patterns in many glaucoma specialists across the country.

How are emerging pharmacotherapies addressing these issues?

 It’s an exciting time. We have all kinds of new things coming on the horizon. The sustained release, the implants, the ocular inserts, all of these things that promise a way to deliver medications without having the patients do it. And having it in a very sustained, steady way is a really exciting part of our future in glaucoma. And I think that it will really help our patients in the long-term.

MIGS Surgery to Manage Non-Adherence in Open-Angle Glaucoma

 What advice, if any, is there to offset open-angle glaucoma beyond lifestyle changes?

 This is a question I get every single day from my patients. There is no hard evidence that shows a lifestyle change is going to change your rate of glaucoma progression. We do, however, I, propose an active healthy lifestyle.

There’s a study by Ramulu et al that showed patients with advanced open-angle glaucoma who exercised before visual field, they actually did better on their visual field than someone who didn’t exercise. And so in general when patients ask me this question I do say, “You know, there’s no real hard evidence, but I always promote exercise and healthy eating.”

 Patient adherence and/or compliance is a recognized issue with topical medications, especially as patients require more than one medication. How do you address the importance of adherence?

 I have open, frank conversations with my patients. I ask them how they’re doing on the medication, if they’re using it. I tell them the importance of being able to tell me if they’re not using it because if they’re not, then they might be headed towards surgery. Usually when I say the word surgery, they tell me the truth. Compliance is a real issue. Not just the, “Are you using it,” but, “Are you able to open the cap? Are you putting into the eye properly?” So oftentimes we’ll ask the patient to demonstrate for me how they do that. They open it up and they’ll put it into their eye. And it oftentimes takes a very long time for them, or they’re not doing it properly. So those are things that I kind of go through in my clinic visit with them.

 I find that engaging with the family members is really beneficial. Oftentimes it’s a caregiver giving a drop, or a nurse in a nursing home. They may or may not be there. But if a family member is present, I usually like to ask them, “Who’s giving the drop, and how often?” And it places kind of an onus of responsibility on whoever is in the room to help with this whole regimen.

 I feel like that’s been my secret. I either engage the patient’s wife or the patient’s child and I really make it their responsibility. And I ask them every time they come in. I turn to them first. I say, “How is so and so doing with their medication?” It’s helpful when you actually try to bring some of the other family members in so they can better understand why this is so important, and I think they help reinforce it when we’re not there.

What are your thoughts on the fact that patients will often take medicines for their diabetes, for their hypertension, but they really don’t use their glaucoma medicines quite as often?

 I think there are a number of issues that patients face. When they’re glaucoma patients, they physically have to open up the bottles and place it in their eyes every single day. That act is very different than taking a pill, and it’s oftentimes more difficult for patients. So simply the logistics of doing it can change. Cost is always a deterrent for patients. Eye drops can be far more costly than some of the generic medications for other things. And then lastly, I think because of the nature of glaucoma being so asymptomatic, patients are less aware of their disease and less likely to start the medications or use them because they think, “Oh, I’m fine, I’m not feeling anything, I’m not seeing any differently and I’ll skip my dose today.” Whereas, when someone has a symptomatic issue like congestive heart failure or diabetes, they are more apt to using their medications - hopefully - because they’re a little more symptomatic and they remember that something is wrong with them.

 I think that’s very true. I have many patients who skip a lot of their appointments and oftentimes I ask them and they say, “Well, I figured if I come once every 6 months it’s probably okay.” Some of the patients who were going for their intravitreal injections are more likely to actually go to those appointment because they know that they need those injections to see better. So we talk about glaucoma being a silent thief. That is a big problem for our patients is they don’t physically see the need often to come to these appointments, or they don’t see the need to take their drops quite like some other conditions that are possibly affecting them.

How do you address adherence/compliance issues if and when patients complain about medication costs?

 I always have tried to have really frank conversations with my patients. I ask them, of course, how’s it going. I actually ask them is this covered by your insurance, how’s the cost, is it working for you? A lot of times patients will have a hard time with the cost of the non-generic and sometimes even with the generic medications, patients can’t afford them. We really try to address that. I have a whole team of people that try to fill out the prior authorizations. I get patients coupons and programs, into special pharmacies that can get patients better rates for their glaucoma medications. These things are all pretty time consuming throughout my day, to be quite frank with you, as they are for all of the ophthalmologists in the nation. And so something really needs to kind of change on that landscape at some point. But we discuss it and we try our best to basically get these patients back on track, whether it’s from a cost standpoint or a logistical standpoint of how they’re getting the drugs.

 Do you think this might, in the future, make you more likely to move toward using a medicine like bimatoprost SR?

 Absolutely. Something like a sustained release drug that allows the patient to not have to pay for their drugs every month or take them on a daily basis is really beneficial for the patient. And, quite frankly, it also reduces the burden on the surface of the eye because these drugs can be toxic. They can be allergic to the preservatives or the chemical of the drug, and being able to be off the topical drops in general is really kind of remarkable. So I think in all senses, it’s going to be win-win-win for the patient. They will reduce their cost, reduce the burden of having to put a drop in, and reduce the burden on their ocular surface as well.

 I think it will be an interesting question for doctors whose offices are bogged down with a lot of these phone calls trying to get prior authorizations, trying to get good medicines into our patients’ hands. And , if we have an alternative to that, I think we would be happy to use it if it is as safe and efficacious as some of the studies have shown it to be.

Importance of Adherence in Treatment of Open-Angle Glaucoma

  What role does IOP monitoring have in future pharmacotherapies?

 I think as we’ve talked about already, one of the concerns we have is compliance. And for our patients who are not as compliant as we would like, they probably do have more IOP fluctuations. So once again, if we can take compliance out of their hands, if we can inject the eye with the medicine that we want to use for treatment, we could actually probably improve compliance, and I think we will see less IOP fluctuations and hopefully better control of the disease.

 Please explain the role of matrix metalloproteinases in the extracellular matrix and the ciliary body.

 I think this is a good question. It’s important to understand truly at the cellular level what is going on in glaucoma because some of our patients are into this and they actually want to know what is going on. When we’re talking about the trabecular meshwork, the reason that outflow is impeded is there’s a build up of extracellular matrix. What is responsible for clearing away the extracellular matrix are, in fact, these matrix metalloproteinases. So, for patients with glaucoma, we really see that they have a decrease in the matrix metalloproteinases, and that’s because they have an increase in something called TIMMPs, what are called tissue inhibitors of MMPs. It’s really all about this balance of TIMMPs and MMPs. And for our patients with glaucoma, they don’t have the proper regulation, therefore they have a build-up of extracellular matrix. And what I tell patients is this proteinaceous debris, it’s this junk that gets clogged up in their trabecular meshwork, and that’s what is causing their rise in their pressure.

 Other modalities that are on the horizon like ocular inserts, sustained release, nanoparticle technology, implants – how are those going to be used in the future of open-angle glaucoma??

 It’s hard to say at this point which of these is going to have the brightest future. But certainly all can have a role. We’re starting to see some good results from these ocular inserts in the canaliculus. We’ve seen other sustained release therapies that have come out from Ocular Therapeutix. There’s a number of different medicines and a number of different ways we could deliver these medicines. It’s hard to say what’s going to have the greatest value down the road; it’s still a little bit too early to say. But there’s potential to deliver medicines in so many different ways.

One of the more important advances might be in better ways to deliver eye drops. We all know that when we put an eye drop into the eye, we’re delivering way more medicine than we actually need. There’s definitely some work being done on trying to better deliver the medication to the tear film, to the surface of the cornea which is where we need the medicine to be placed. Some of that technology might be more beneficial to our patients down the road.

Targeting MMP to Treat Open-Angle Glaucoma

 Discuss the potential for bimatoprost sustained release for open-angle glaucoma.

Joseph F. Panarelli, MD: This is definitely one of the more exciting advances in our field. The fact that we actually have an injectable form of glaucoma therapy. So bimatoprost SR is going to be probably the first of several medicines that are going to be hitting the market over the next several years. I think this really does have the potential to be a game-changer. We talk a lot about compliance and really when we have an injectable form of medicine, we really take compliance out of our patients’ hands. And so all we ask of them to do is to come once every several months to get their treatment. The big question we have with injectable forms of medicine is going to be, is the safety there? Are there any issues at all with these medications being delivered once every 6 months into the eye? We have questions regarding issues with the cornea, and we have concerns about infection. If we can show that there is very good safety profiles for these medicines, I think we’re going to see a lot of physicians using this treatment early in their treatment algorithm.

One of the questions that remains to be answered is if you have a patient who’s on several classes of medications, can you put them on one medicine that you inject once every several months and get that same level of efficacy? So, if you have a patient who’s taking two or three bottles and is compliant, say, 50 to 60% of the time, if you give them an injection of one medicine, can you achieve some of the same effects? Can you stop their disease progression? I think that’s a big question that remains to be answered.

 What do we know about the safety and efficacy of this product?

 We’ve seen several abstracts at the Academy of Ophthalmology and there will be several more abstracts at the American Glaucoma Society that provides us more insight into the results of the phase III trials with bimatoprost SR. But from what I’ve seen, the safety and efficacy data is actually quite good.

One of the things that has impressed me most is the fact that a lot of patients (up to 80%) that receive three doses over the first year did not need to be rescued over the next year that they were followed.

This can have a meaningful impact for our patients. It’s one thing to talk to a patient and tell them that they’re going to have an injection once every 4 to 6 months for the rest of their lives, but if we can give a patient a loading dose of a medicine and not need to reinject them from anywhere from 1 to (maybe) 3 years, that will resonate well with our patients. This is something where the patients will look at the risk-benefit, and many of them would actually be more excited about getting an injection versus starting topical therapy for the rest of their lives.

As the clinician, we really need to be the ones also that feel comfortable. We do have some safety questions. We want to be sure that are no detrimental effects to the cornea. We want to make sure that the infection risk is low. But I think we’ve seen from our retina colleagues that serial injections, if performed properly, can have very low rates of infection and can be done safely in the office.

For a lot of us as glaucoma doctors, we’re very excited to have an injectable form of medicine because we do think that this will increase our compliance and may actually even cause some changes to the outflow pathway that may modify the actual disease.

 How do you foresee this product being used in clinical practice?

 Like with some of our topical therapy, many physicians will not go and start using this as a first-line therapy. I think many physicians will use it as a second-line treatment modality when a patient is progressing despite treatment with, say, a prostaglandin or the physician had not gotten the pressure reduction that they expected from SLT. They may move onto bimatoprost SR. I think as we get more comfortable with the injection, as we’re more certain about the safety of this procedure, you may start seeing doctors use it earlier in the treatment algorithm. For me, if I have a patient who has more advanced disease who needs better pressure reduction, I may actually move on to this and start with an injection rather than starting with topical therapy.

One of the other nice things about bimatoprost SR is the fact that the side effect profile is rather nice compared to topical therapy. We all know with prostaglandin analogues, we have issues with hyperemia, iris pigmentation changes, skin pigmentation changes, and even periorbital fat atrophy. We’re not going to see these problems with the injectable form of the medicine. So I think for a lot of our patients who are apprehensive about starting a prostaglandin analogue for those reasons, this might be a suitable alternative.

Emerging Therapy for Open-Angle Glaucoma

 For the first time in decades, two new class of drugs have been introduced for the treatment of open-angle glaucoma (latanoprostene bunod and netarsudil). How do their mechanisms of action differ from prostaglandins, beta blockers, and carbonic anhydrase inhibitors?

 For the first time in a long time we have new classes of medicines to hit the market, and I think it’s very exciting as a glaucoma specialist. We all talk at meetings about how this is really a renaissance in a time of glaucoma. And so to have new medicines to be able to offer our patients is very, very exciting.

Starting first with netarsudil, this is a Rho-kinase inhibitor, and this is one of the newer medicines that actually targets the outflow pathway. And this is really a medicine that’s unique in that none of the other medicines out there on the market actually work at the level of the trabecular meshwork. By inhibiting Rho-kinase, we’re really able to relax some of the actin and myosin contractions. And by relaxing those contractions, we’re able to enhance outflow through the physiologic outflow pathway.

So netarsudil is unique in having this mechanism of action. What’s also particularly appealing about this medicine is that it has other mechanisms of action. We have seen from various studies that it has the potential to lower the episcleral venous pressure (EVP), again something that we often do not see with other medication classes.

Latanoprostene bunod is actually a second new medicine to hit the market, and I think it is sort of a latanoprost on steroids. It’s a new version of a prostaglandin that also has a nitric oxide donating moiety. And what that does is it allows for some smooth muscle relaxation. We do think we get some potential enhanced outflow through the trabecular meshwork. And there may even be some effects on blood flow to the optic nerve. So, once again, it’s nice to have some new medicines that are out there on the market because I think they all fit into our armamentarium somewhere. And I think as clinicians we’re still figuring out exactly how to use these medicines and how to mix them in with our other available agents.

 Briefly comment on the safety and efficacy of latanoprostene bunod and netarsudil.

 So the new medicines that have hit the market, we have seen some of the phase III trials. We have seen the results of the APOLLO and the LUNAR trials, as well as the ROCKETS-1, 2, and 4 trials. And I think what we can safely say is that these medicines work. They have proven noninferiority to our standard topical therapy.

What is unique about the netarsudil/latanoprost combination is this is really one of the first times we actually had a medicine go up against latanoprost alone. And latanoprost we know is one of our bigger guns out there, so it is encouraging to see that we have these new medicines, and it’s nice to see data that does support good efficacy with these different agents.

 How are you personally using these agents in your clinical practice?

 With the two new classes of medicines, many of us are still unsure where to use them in our treatment algorithm. For me, I will often use them if a patient is not doing as well as I’d like on a prostaglandin analogue, and I will use it as sort of switch therapy. I will switch them from either latanoprost to latanoprostene bunod or from latanoprost to a combination of latanoprost and netarsudil.

One special place where I do like these medicines are for my patients with low tension glaucoma. These patients are traditionally some of the hardest to actually lower the IOP to a very low number. And I think what the medicine such as netarsudil where we can lower the EVP, I have found that some of my patients can get down to that single-digit range which is sort of a number I often cannot get with traditional carbonic anhydrase inhibitors, or alpha-2 agonists, or even beta blockers.

For those patients that is a sweet spot for me when it comes to netarsudil. Latanoprostene bunod, while it may not get me quite as low of a pressure, because I don’t really feel it can lower the floor like netarsudil can, I think I may get some improved blood flow. It’s this theoretical benefit that is one of the reasons for some of my patients who are progressing with low tension glaucoma that I might switch them over to that medication.

I actually will occasionally use netarsudil as first-line treatment. Some of my patients who just will not start a prostaglandin analogue. I have several patients who I have discussed the fact that their eye color may change and that they may develop periorbital fat atrophy. And for some of them that’s a big deterrent to starting that medicine.

Similarly, some patients are not too excited about starting a topical beta blocker or they may perhaps be on an oral beta blocker already. So, for these patients, it’s quite nice to start with a medicine such as netarsudil that has once daily dosing. And I think that is a big thing for me. Again, when I’m starting to topical therapy, I like to go with the simplest possible regimen.

I’ve had several patients where I’ve talked about having surgery. We started netarsudil and it’s actually been great in that they’ve gotten to their target IOP without me having to perform a trabeculectomy which is huge for my patients.

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