Emily Kaiser

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Penny Asbell, MD, FACS, MBA, discussed data from the ARMOR study with the editors of 

 at AAO 2021. The ARMOR study is a 10-year nationwide study examining in vitro antibiotic resistance among isolates that have been collected from ocular infections. The data sheds light on the effects of antibiotic resistance while treating ophthalmic infections, such as endophthalmitis.

The Antibiotic Resistance Monitoring in Ocular Microorganisms (ARMOR) surveillance study has identified high levels of in vitro antibiotic resistance among ocular staphylococcal and pneumococcal pathogens, resistance that may affect treatment success.

Penny Asbell, MD, FACS, MBA, is the director of the Hamilton Eye Institute at the University of Tennessee Health Science Center.

So, you know, ophthalmologists, we really like to get a lot of data. We take pictures, we take images, we take measurements. But with infection, we really got to start treating right away. And one of the questions is, what antibiotic should we start with?

So actually the ARMOR study, which is the only surveillance study done in the United States of ocular isolates, is a real good source of information when you're getting started.

So, we collect ocular isolates from over 44 sites and 22 states over the last 10 years. And in this particular study, we looked at isolates that were collected from either the aqueous, or the vitreous, presumably a patient who had serious infections such as endophthalmitis.

And what was most interesting is that nearly 50% of them were staph isolates that were methicillin resistant, so a high level of resistance to methicillin. But equally interesting is those methicillin resistant isolates, over 70% of them were resistant to three or more other groups of antibiotics. So you got to realize resistance is out there.

Now, this is laboratory testing. It's a standardized method. It's not actually clinical. In clinical, you might do a lot better than laboratory test suggests, but you got to start somewhere. It's a really good way of getting some information right off the bat, even while you're waiting for those cultures.

So think about resistance, it's not uncommon, whether it's staph aureus—we didn't see as much with strep pneumonia, and pseudomonas did pretty well, and so did the H. flu. But that staph still is a problem for us with the methicillin and the multi-drug resistance. So keep that in mind when you're picking an antibiotic.

So, you know, we've collected in the ARMOR study over 6000 isolates, and we're starting to try to understand what are the mechanisms of pathogenicity? What makes an isolate more serious than another isolate? And is it actually the isolate itself, or the interaction between the isolate, the organism, and its genetics and the person who gets infected?

So there's a lot of information there and a lot of opportunities to really understand infection more specifically, and maybe have new interventions for treating more effectively. So, we're gonna use that data to the best we can to give us the best information to be able to treat our patients the best way. So stay tuned for ARMOR data, we keep coming. Thank you for listening.

Videos

At the 2021 American Academy of Ophthalmology annual meeting, Penny Asbell, MD, FACS, MBA, discussed data from the ARMOR study and its effects on treating ophthalmic infections, such as endophthalmitis.

Dissecting ARMOR study data on antibiotic resistance in ophthalmology

At the 2021 American Academy of Ophthalmology annual meeting, Greg Kunst, CEO of Aurion Biotech, presented their plans to initiate clinical trials for cell therapy for the treatment of corneal endothelial disease.

This technology propogates healthy cells from donor cornea, allowing up to 100 recipient eyes to be treated from a single donor sample. In Japan, the clinical trial has successfully demonstrated safety, efficacy and tolerability of Vyznova, the lead candidate of Aurion Biotech.

 Yeah, so we presented on what could be a potential to be a major game change in the way that we treat corneal endothelial disease here in the United States around the world. So we're doing this with cell therapy. Today that cures blindness, restores vision, to potentially 16 million people in the US, Europe and Japan affected by corneal endothelial disease. And the reason why I think it's a potential game changer is really for four simple reasons.

One, it's an injection of cells, and therefore can be used by a broad spectrum of ophthalmologists around the world, dramatically increasing the number of treaters available for corneal endothelial disease.

Two, this, this is using natural human endothelial cells, because of that safety profile is quite pristine, potentially allowing us to move this treatment earlier in the treatment paradigm.

Third, it's already been proven. We've done this drug now, in over 100 patients with some of those patients with five more years of experience in four different trials with Japan and in El Salvador. We know the drug works.

Fourth and most importantly, it scales. Unlike today, where we need a donor for every person treated for corneal endothelial disease, with every donor with a part in cell therapy, we get 100 treatments today. In the future, you know, one to 1,000, maybe one to 10,000. This all has all the hallmarks to be the really the next great innovation in ophthalmology.

Well, so number one is we know there are about 13 million people around the world that are corneally blind. And usually one of the primary reasons that we see corneal blindness is the lack of available corneal tissue around the world. Even the United States, we reserve corneal surgical transplant really for the worst patients. And because of this, we believe that we can reach many more patients with corneal endothelial disease, including Fuchs dystrophy or post keratopathy.

And so I think, certainly, it's an area where lots of people are untreated. And now in the future, with the approval, we'll have a way to treat patients most early disease process.

So our next stages is to enter trials for the United States. Obviously the clinical trial process takes time. This is a rare technology because of the prior clinical data, generated in Japan and El Salvador, we know it works. Now it's the test of time of clinical trials, and at the end of these trials, we are hopeful, optimistic, that we'll be able to get approval from the FDA and many other regulators around the world.

New cell therapy drug makes treatment of corneal endothelial disease more accessible.

Cell therapy emerges as treatment option for corneal endothelial disease

At AAO, Jay Duker, MD, sat down with the editors of Modern Retina to discuss EyePoint Pharmaceuticals’ pipeline product EYP-1901. As a sustained-release anti-VEGF, EYP-1901 has the potential to be a durable treatment option for wet AMD, possibly extending time between injections to six months.

EYP-1901 has completed phase 1 clinical trials for treatment of wet AMD. The biannual injection is vorolanib, a tyrosine kinase inhibitor, which is distributed by EyePoint Pharmaceuticals’ proprietary Durasert implant. The implant is bio-erodible and has a history of safety: four products have been FDA-approved for use with Durasert.

 I'm going to talk about our new exciting pipeline product, EYP-1901. EYP-1901 is a sustained-release anti-VEGF, which has the potential to be an every six month injection for wet macular degeneration. EYP-1901 is vorolanib, which is a tyrosine kinase inhibitor which has activity against all the VEGF receptors. It is in our proprietary Durasert implant. The Durasert implant and the EYP-1901 is bio-erodible. We've had four FDA-approved products using Durasert, so there's a long history of safety for the product.

Vorolanib was tested previously in both a phase 1 and phase 2 trial in humans for wet macular degeneration as an oral preparation. And while it showed good efficacy signals in those investigations, unfortunately, it was toxic systemically. So by using it locally, we expect to get around the toxicity. And in fact, the phase 1 results which were recently presented at the AAO meeting by David Boyer showed that we had a very impressive safety profile.

In the 17 patients in the phase 1 trial, we had no ocular serious adverse events. We had no drug-related systemic adverse events. The adverse events that were reported were grade two or less in all cases, except one, which was not drug-related. So we feel that the safety profile looked very strong.

We also showed evidence of efficacy. All of these patients who were previously treated and previously treated wet AMD patients get most of their visual acuity improvement in the first three months. Since they all were enrolled four months or longer, we didn't expect any visual acuity improvements, but we hoped for stability. And in fact, that's what we found. With the 17 patients at the end of six months, the only change in visual acuity across the whole cohort was approximately minus two letters.

With respect to OCT, which is a measurement of VEGF activity, again, we expected stability in this previously treated group. And that's we found. At the end of six months, there was a small decrease in the retinal thickness on OCT of a very minimal amount, about two microns.

We also had what we feel is a very impressive rescue free rate, up to the four-month visit. 76% of the eyes did not require a rescue standard of care injection, and up to six months, 53% of eyes did not require a standard of care rescue injection. We also measured what we refer to as treatment burden. How many injections on average per month did the patients get prior to enrollment? And then for the six months, after how many injections standard of care did they require? We had what we feel as a very clinically significant decrease of a burden of the injections by 79% across the entire cohort.

So we're very excited by David Boyer’s presentation and we look forward to taking this product into multiple phase 2 trials in 2022.

Jay Duker, MD, discusses EYP-1901, EyePoint Pharmaceuticals’ sustained-release anti-VEGF drug for the treatment of wet AMD.

New sustained-release anti-VEGF formulation EYP-1901 proves safe, effective in phase 1 trials

At the 2021 American Academy of Ophthalmology annual meeting, Ted Leng, MD, presented his talk entitled “Variations in Vitreoretinal Physician Utilization of Ancillary Testing: An IRIS Registry Analysis” during Retina Specialty Day. The IRIS Registry Analysis considered how many ancillary tests were ordered on a per patient basis, accounting for a variety of factors to identify patterns.

 This is a really exciting study that we conducted using the American Academy of Ophthalmology’s IRIS registry, given just a large amount of data that's in there. And as a retinal physician, we are super reliant on ancillary testing in our everyday practices to see, you know, which patients have retinal disease and how we're managing them.

So what we wanted to do in this study was to look at the utilization of ancillary tests by retinal physicians in the United States on retinal patients.

To go into some more detail, this was a three-year study, where we looked at retinal physicians from January 2018 to December 2020. And look at the amount of OCTs, fundus photographs and fluorescein angiograms they were performing. And then we normalized that data and looked at how physicians in different regions throughout the United States were using these tests, whether certain payers like Medicare or non-Medicare were utilizing these tests, and then also different practice settings, such as academic medical centers versus nonacademic medical centers.

What we found was actually quite interesting. Once we did normalize the data, we did see that physicians in the Midwest region—and we use the four regions of the US Census Bureau—so the Midwestern states actually were performing more OCTs on a per patient basis than physicians in other regions. Medicare patients were getting more OCTS on a per patient basis per year than non-Medicare patients. And lastly, patients cared for in a nonacademic medical center, were getting more OCTs on a per patient basis than that not.

So I think, while those results in and of themselves are interesting, we then delve deeper into trying to ask why we saw these differences in practice patterns amongst retinal physicians. And one of the things that we looked into was the volume of wet macular degeneration patients as a kind of benchmark to see if that affected the use of OCT-A, for example.

So what we did was we asked, does a physician who sees more wet AMD patients per year use more OCT or less OCT than someone who doesn't do as many wet macular degeneration patients.

And what we did find was that retinal doctors who saw more wet AMD patients also ordered more OCTs in general.

And what we did with that information, is we went back and did a reanalysis of the data, our findings, and saw that yes, indeed, Midwestern physicians also see more wet AMD patients than non-Midwestern physicians. And that could help to explain why more OCTs are being performed in the Midwest on a per patient basis.

And similarly, in the Medicare population, there are more new wet AMD patients. And in the nonacademic medical center setting, there are more wet AMD patients that are new. So that's why it could help to explain why we are performing as a specialty more OCTs and other ancillary tests in those regions. And in those pair types in this practice settings.

What are the implications for the larger community? I just think it's really good to know, you know, how we're practicing medicine, what the patterns of utilization of our ancillary testing is, so that we can then better inform how to make our practices more efficient, how to better deliver care to the patients, and maybe even identify underserved populations.

You know, one thing we did see was that in the Medicaid population, there was less OCT-A utilization. And so we do need to delve deeper into maybe an explanation as to why that is, but they could be an indication that that populations being under cared for and underserved. And maybe, you know, we need to be ordering more tests to, to better manage those patients. So I think that's one of the potential takeaways from this presentation.

The American Academy of Ophthalmology (AAO) annual meeting was held November 12 to 15 at the Ernest N. Morial Convention Center in New Orleans, Louisiana. The event included Subspecialty Days and a virtual component for remote participation.

Ted Leng, MD, discusses his IRIS Registry analysis presentation regarding variations in vitreoretinal physician utilization of ancillary testing.

Exploring ancillary testing orders by retinal specialists according to the IRIS registry

At the 2021 American Academy of Ophthalmology annual meeting, Robert J. Noecker, MD, MBA; Director of glaucoma, Ophthalmic Consultants of Connecticut, assistant clinical professor, Yale School of Medicine and clinical professor, Quinnipiac University School of Medicine; spoke with the 

team about the IRIDEX consensus paper. This paper tackles the best practices and treatment settings for the IRIDEX MicroPulse transscleral therapy for glaucoma.

 All right. So I was honored to be a member of this consensus panel looking at MicroPulse treatment for glaucoma. And it was a consensus panel where we did a delphi method of coming to kind of best practices around treatment settings for the IRIDEX MicroPulse transscleral therapy for glaucoma. And some of the takeaway points were, in terms of the treatment parameters, is slowing down sweep speed.

So this concept of fluence which is most influenced in this treatment by sweep speed. So how quickly we move the laser probe during therapy really was one of the biggest drivers when we determine what the best way to treat or what's the best way to influence the amount of energy delivered for the therapy.

So also, we discussed optimal power settings on the laser as well as total treatment time.

So as initial settings what the consensus panel came to the best settings use or 2.5 watts, for at a sweep speed of 20 seconds per sweep. And then 80 seconds per hemisphere for a total treatment time 160 seconds. So we sweep back and forth in one hemisphere 20 seconds, go back, do that four times and then go around the top. 

And that way when we do this transscleral treatment for lowering eye pressure, we found that the side effect profile was very minimal. Many of the treating experts often don't see the patients for the first post-op week, it is a very safe therapy. Patients can really resume their lifestyles very quickly.

Also, the efficacy was maintained. So we found that the best efficacy—because historically with, with MicroPulse therapy, many early users were probably under treating a bit and that would sacrifice efficacy as well. So we found that the power settings of 2.5 watts with the slower sweep speed, both increasing total energy as well as the fluid supplied to the eye really resulted in optimal and results with this therapy.

So what this means ultimately for patients going forward is I think it really expands the range of therapy that we can use MicroPulse transscleral treatment. It gives us confidence to get good efficacy in patients with more advanced disease, where the most important thing, high pressures—we really need to lower the pressures down into the normal range again and try to reduce some of their medication load—but also in the earlier patients where they may be on a few medications but not having problems with tolerability or acquisition, but not like crazy high pressures. We can lower intraocular pressures down but also more importantly in that group, get them off of eyedrops.

So it's really expanded the utility of MicroPulse transscleral therapy for the treatment of glaucoma.

Robert J. Noecker, MD, MBA, discusses the IRIDEX consensus paper regarding MicroPulse transscleral therapy for glaucoma at AAO 2021.

IRIDEX consensus paper investigates best practices for MicroPulse transscleral therapy for glaucoma

Jill Hopkins, MD, Senior Vice President and Global Development Unit Head, Ophthalmology, Novartis Pharmaceuticals, sits down with David Hutton of 

 to discuss the recent results of the Phase 3a results of the Merlin trial.

Brolucizumab (Beovu, Novartis Pharmaceuticals) is being investigated for the treatment of both wet age-related macular degeneration (AMD) in the MERLIN trial and diabetic macular edema (DME) in the KESTREL and KITE trials.

. We are joined today by Jill Hopkins, Senior Vice President and Global Development Unit Head, Ophthalmology, Novartis Pharmaceuticals, who will provide an update on data the company presented at the American Academy of Ophthalmology is 2021 annual meeting. Thanks for joining us today.

Thanks, David. It's a pleasure to be here. Happy to share with you some of the noteworthy data that we presented at the AAO meeting this past week. We presented on Beovu in both wet AMD and DME, and I'll speak about both of those.

In wet AMD, we presented the results of our Phase 3a Merlin trial, Dr. Khanani presented that. And this was a trial where we looked at the use of Beovu on a monthly basis to treat wet AMD in patients who had persistent disease activity, despite having been treated with prior anti-VEGF. And we were very interested in exploring the capacity, capability, of Beovu to dry the retina and maintain vision in patients in that situation.

And so we looked at monthly Beovu compared to monthly aflibercept. And we found some very interesting results. What we saw, similar to what we'd seen in our pivotal trials with AMD, that we did have noninferiority vision and strong evidence of drying. So we actually were able to show superior drying effects in both the reduction in the central subfield thickness on the OCT measurement, and in the proportion of patients who were fluid free at the end of year one.

We did unfortunately, however, see higher rates of inflammation in the Beovu treated eyes—about 9% in Beovu compared to about 4.5% in aflibercept. And for that reason, we are maintaining our currently labeled dosing recommendation, which is the three loading doses followed then by extension to Q8 or Q12 week dosing and not recommending the monthly in Beovu.

So the other piece of work that we have been presenting and have submitted for approval is our use of Beovu in diabetic macular edema.

So again, we've conducted two pivotal trials, and these were reported at AAO as well, KITE and KESTREL, where we looked at the use of Beovu with a loading phase and then extended intervals. And we're pleased to see in diabetic macular edema as well, this sustained drying, fewer injections and maintenance of visual acuity.

So we're excited by this particularly in a condition like diabetes, where we know that patients are often still working, they're trying to manage multiple health issues related to their diabetes. So anything that we might be able to offer retinal physicians and patients that reduces the burden of injection frequency, while still maintaining very good anatomic control and maintaining vision is exciting to us. And we have submitted those for regulatory approval in the US, in Europe and in Japan. So we're hoping for a positive readout of those submissions in the middle of 2022.

Jill Hopkins, MD, discusses results from phase 3a of the Merlin trial for brolucizumab as a treatment for wet AMD and provides updates on KESTREL and KITE trials for the treatment of diabetic macular edema.