Dr Quan Dong Nguyen discusses the Monte Carlo simulation model that demonstrates the scalability of intravitreal anti-VEGF therapy for severe non-proliferative diabetic retinopathy (NPDR) before the disease progresses to proliferative diabetic retinopathy (PDR).

Dr Nguyen is a professor of ophthalmology at the Byers Eye Institute at Stanford University School of Medicine.

Yes, we have looked at the question of how intravitreal anti-VEGF therapy can help to decrease the significant complication that non-proliferative diabetic retinopathy [NPDR] progress to proliferative diabetic retinopathy [PDR], given the fact that PDR has many complications that can be avoidable, preventable by early treatment.

So, in our study, we cleverly start out with a group of real-world patients, of about 78,000 patients, that have different stages of diabetic retinopathy from non-proliferative—mild, moderate, severe—to proliferative. And then from there, we use a model called Monte Carlo model, simulation model, where we make into a model of about 2 million people from that aspect. So we can now see the big effect. And remarkably, we see some very similarity.

Throughout the last decade or so there have been numerous studies that demonstrate the potential benefit of intravitreal anti-VEGF therapy in decreasing the complications that occur with proliferative diabetic retinopathy when NPDR progress to PDR. We have the RISE and RIDE study, which I chaired several years ago, we also have the PANORAMA study.

The RISE and RIDE investigate ranibizumab; PANORAMA investigates aflibercept. And then we also have Protocol W from the DRCR. And in each of these studies, in each of this protocol, it demonstrates to us that early treatment in a patient with severe NPDR can lead to remarkable reduction in complication that lead to PDR.

So for example, in the RISE and RIDE is about 51.7% or so reduction in the risk of progression to complication. In the PANORAMA with aflibercept is similar 51.5%. And then when we look at the overall simulation model, remarkably, it's come out just around that area to about 50% or so. It clearly demonstrates that if you were to treat patients with severe NPD early, you can decrease the risk of PDR events just like vitreous haemorrhage, neovascularization, and so on in that aspect. So that's very helpful.

The other aspect we also looked at was the incidence of severe visual loss—so blindness. In the United States, we define blindness at vision is 20/200 or worse, and so many patients with PDR also had severe loss of vision. And we also looked at this aspect, and we indicated that yes, in fact, when we treat patients with NPDR and not let them progress to PDR, we'd reduce down by at least 57-58% reduction in number of patient that will develop severe blindness.

So clearly from different aspects—from just the regular complication of PDR to severe vision loss due to blindness level—early treatment does help. And we like to treat it when they get to, let's say severe stage of NPDR.

Certainly, we don't advocate treating of any patient with NPDR because that would not be appropriate nor practical. But if the patient has reached to the stage of severe NPDR, then we definitely believe that there's strong evidence, a lot of them come from very well-designed study. And now with this Monte Carlo model that we have done, they've shown that.

And by the way, I’d like to recognize also our colleague with this: Dr Andrew Moshfeghi, from University of Southern California and Dr Jennifer Lim from the University of Illinois, near in Chicago, along with Steve Sherman, and our colleagues over at Regeneron who have worked closely with us to develop this model and to answer this very important questions.

 This transcript has been lightly edited for clarity.

Videos

Dr Quan Dong Nguyen reviews a Monte Carlo simulation that showed evidence that treating severe NPDR with anti-VEGF therapy garners positive results.

Anti-VEGF therapy slows progression of severe NPDR in Monte Carlo simulation model

Dr Raymond Douglas sat down to discuss his study analyzing the real-world adherence to teprotumumab (TEPEZZA; Horizon Therapeutics) as a treatment for thyroid eye disease (TED). While 90% of patients completed the therapy successfully, about 10% discontinued due to adverse effects. Investigators are digging into which of these effects are disrupting the treatment.

Dr Douglas is an board-certified aesthetic and reconstructive oculoplastic surgeon at Cedars-Sinai Medical Center. Dr Douglas contributed to the body of research that led to using teprotumumab as a treatment for TED. He continues to research the topic to improve adherence.

 Hi, I'm Raymond Douglas and I am from Cedars-Sinai Medical Centre, and we're based in Los Angeles. And today I was speaking about the real-world adherence for teprotumumab treatment.

And you know, it's really a fun study to do because we did the Phase 2 and Phase 3 clinical trials, which demonstrated the teprotumumab, reversed the proptosis, and improved patients and thyroid eye disease. But one of the things we really wanted to know is whether the adverse events and whether patients in the real world were following through on this therapy, the same way that they did in the Phase 2 and Phase 3 clinical trials. And so that was our poster today.

And the poster demonstrated that the adverse events were very similar to what we saw in the clinical trials in Phase 2 and Phase 3, which sometimes you don't see that in the real world versus clinical trials. And that over 90% of patients finished the whole course of therapy during this study period in time.

And there were dropouts, and there were adverse events reported and that led to these dropouts. But what was reassuring is that those were the same adverse events that we saw during the trial, which namely were muscle spasms, fatigue, nausea, some diarrhea, and those were the—accounted for the vast majority of adverse events that led to discontinuation.

So overall, you know, we were pleased to see that the real world is tending to coalesce with clinical trials—and how often does that happen?—but that 90% of our patients were actually able to finish these therapies, and there was very similar to what we saw in early clinical trials.

So the next step is to really look at and dive deeper into these adverse events. Because we want to know, you know, in those 10% of patients, we didn't know exactly which adverse event led to their discontinuation. We know that there was a group of them, but we want to know why and how we can help to overcome that [and] how we can help with any of the pain points that these patients are experiencing during their treatment.

This transcript has been lightly edited for clarity.

Dr Raymond Douglas discusses real-world adherence to teprotumumab as a treatment for thyroid eye disease.

Studying teprotumumab adherence in patients with thyroid eye disease

Dr Katherine Talcott sat down to discuss how baseline factors affect diabetic macular oedema (DMO) resolution. This study was conducted using VIVID/VISTA data sets to assess baseline vision, CST thickness, and haemoglobin A1C.

Dr Talcott is retina specialist at the Cole Eye Institute at the Cleveland Clinic.

One of the things that we're interested in as retina specialists looking into is diabetic macular oedema and trying to see sort of what baseline risk factors are associated with how quickly the oedema gets better if you treat it.

So one of the ways in which we sort of looked at this is by utilizing the VIVID and VISTA data sets where patients were either treated without anything, with laser, or anti-VEGF treatment. And we try to sort of see if there were any baseline characteristics that were associated with faster rate of clearance of the diabetic macular oedema.

One of the things in particular that we were interested in is if the degree of diabetic retinopathy severity was associated with how fast patients clear their oedema. But we also looked at sort of other baseline characteristics, including baseline vision, how thick or how large, the CST was on the OCT and what the haemoglobin A1C was.

We utilized the VIVID and VISTA data set to be able to sort of examine these risk factors, and I think the results that we found were somewhat interesting. Patients who had thicker CSTs at baseline took longer to sort of clear their oedema, which sort of makes sense, because if there's more fluid there, it takes a little longer to clear.

We also looked at baseline vision. Patients who had better vision actually took longer to clear their oedema, which is interesting. I think we can sort of speculate why that might be the case, maybe their oedema sort of existed for longer than patients who had worse vision and thus took a little longer to clear, but I think that was sort of a curious finding that we found.

One of the things that we were really interested in is to see if baseline diabetic retinopathy severity would affect sort of how quickly swelling cleared, and it didn't at all. It wasn't associated with that.

We normally sort of think about diabetic retinopathy severity and diabetic macular oedema as sort of being sort of separate entities that aren’t related; the results that we found sort of go along with that, that they are—that they are separate.

We're also interested in sort of how well a patient's diabetes is controlled so looking at their A1C, if it affects how quickly their oedema is cleared. And there was no association either.

So I think overall, the results that we found are interesting. I think, in particular, the vision findings, and the diabetic retinopathy severity findings are sort of interesting, but I think also help us as clinicians be able to know what to expect, as we begin treating the patients.

Patients who often have diabetes tend to be younger than some of our other retina patients, and often they have a lot of health appointments going on at the same time. So lots of sort of burden on them. But they're often patients who are still working. They're not like our retired patients who have like AMD. And so they want to know if their vision is impaired by macular oedema, sort of how fast they're going to be able to see again. If they're not able to drive because of this, how quickly are they able to get back to that?

So I think this gives us some factors that we can look at to sort of prognosticate once we initiate treatment sort of how they're going to do. So I think for us, those are sort of the findings that we found that were interesting and can help us guide patient treatment and patient expectation.

One of the things that's interesting to us is we looked at anti-VEGF treatment and how this is correlated with baseline factors. One of the correlates that might be interesting to look at is looking at patients who were treated with steroids for diabetic macular oedema and seeing if we found sort of any different findings. That might be able to tell us—because anti-VEGF treatment is sort of impacting a more VEGF-dependent disease, but do we see the same findings with steroids or not? I think that's one of the next steps that would be sort of interesting for this project.

Dr Katherine Talcott discusses baseline factors—CST thickness, hemoglobin A1C, and baseline vision—and their effects on DMO resolution.

VIVID/VISTA: How baseline factors affect DMO resolution

Dr Preeya Gupta, ophthalmologist at Triangle Eye Consultants, shares her four pearls for corneal collagen cross-linking.

Dr Gupta recommends that ophthalmologists manage patient expectations, monitor epithelial cells and warn about infectious keratitis. Because every patient is different, it is crucial that patients understand that their healing process may not look like another patient’s. Ophthalmologists may find clinical and interpersonal success when they see patients frequently postoperatively, according to Dr Gupta, because they can monitor how the epithelium is healing and counsel patients at the same time.

Well today I talked about corneal collagen cross-linking, which is a very important procedure in managing our patients with keratoconus. It has really been a sight-saving procedure to help halt the progression of keratoconus, which can be an extremely blinding condition.

The do's and don'ts: So we're talking about the FDA-approved protocol, which is the epithelial-off protocol.

I think my four pearls here are related to first and foremost setting expectations for our patients. Sometimes they think of cross-linking as a refractive procedure, which it can have refractive changes as part of it, but I like my patients to really think of cross-linking as a medical procedure that's really aimed at halting the progression of their disease.

I also think it's really important that patients understand that their vision can change for up to a year after this procedure. We certainly see patients that have reduction in their prescription, flattening of their cornea, and while I hope that for everyone, everyone comes out a little bit different.

Epithelial management is very important with cross-linking. Some of the potential complications of cross-linking include haze formation and infectious keratitis. So I think it's very important for clinicians to see their patients frequently postoperatively. And in those cases where perhaps the epithelium is not healing as quickly as we want, we know that these are abnormal corneas, often very steep corneas, which can make epithelial healing a difficult process for some patients. So we want to see them more often; we want to be aggressive about treating their epithelium.

I have a low threshold to actually remove the soft contact lens and place a cryopreserved amniotic membrane to accelerate the healing. I try to remove preservatives from the ocular surface, and then sometimes even lower the steroid dose initially to aid with epithelial healing.

Last but not least, infectious keratitis is something to consider. This is of course a dreaded complication of really any surgery. And so I have my patients stay on an antibiotic drop until re-epithelialization occurs, and I have a very low threshold to culture and you know, see my patient more frequently so that we can identify any infectious keratitis quickly and treat it.

Dr Preeya Gupta walks through her four pearls for successful corneal collagen cross-linking, including handling patient expectations, managing the epithelial cells and preventing infectious keratitis.

Corneal cross-linking and epithelial management: four pearls for success

Dr Lisa Nijm reports that use of a dexamethasone intracanalicular insert (Dextenza, Ocular Therapeutix) after cataract surgery saves a practice up to 40 hours when compared to a standard postoperative drop routine.

In addition to saving practices time and energy, use of Dextenza increased patient compliance and reduce treatment burden as fewer postoperative counselling sessions were required.

My research that I presented today focuses on utilising a dexamethasone intracanalicular insert to assess whether there's time saved on patient callbacks and surgery planning.

For this study, we collected user experience and feedback on utilising Dextenza for cataract surgery patients compared to using standard postoperative drops.

There were 19 practices in total; they performed an average of 160 cataract surgeries per week when we looked across the practices. And for the study, they had to perform at least 10 cataract surgeries utilising Dextenza.

In analysing the data from the study, were able to see that by utilising Dextenza, staff saved 45% time counselling postoperative patients when utilising Dextenza compared to standard drops. This translated to about 15.5 minutes per patient. And when you looked overall, we're over 40 hours, staff hours, per week, so it is equivalent of one full-time staff per week that was saved by utilising Dextenza.

In addition, the satisfaction rate among the staff was very high for utilising Dextenza, with 95% of staff reporting positive feedback in utilising Dextenza versus conventional drops.

So in conclusion, I think that the results of this study show the benefits to practice of utilising a postoperative steroid regime like Dextenza for a practice to be able to time save and really translate into practical benefits for the practice, where they are not spending as much time counselling patients postoperatively using drops, as well as decreasing the overall burden or expense on the practice and ensuring compliance with patients. Thank you very much.

This transcript has been lighlty edited for clarity.

Dr Lisa Nijm discusses how utilising a dexamethasone intracanalicular insert after cataract surgery saves time for practices.

Dexamethasone insert reduces time spent planning cataract surgery, counselling patients

Dr Firas Rahhal discusses the results of Outlook Therapeutics’ pivotal NORSE TWO trial for ONS-5010. The Phase 3 results show efficacy for the ophthalmic solution of bevacizumab for the treatment of wet macular degeneration.

So what we presented today was a new ophthalmic preparation for bevacizumab. And the background is that bevacizumab is a drug we use a lot; currently, for wet macular degeneration and other diseases, but we use it in a compounded form. Something that compounding pharmacies prepare off the intravenous version, and that makes it off-label. And so there's certain problems associated with that type of preparation.

And so what we're doing now is developing this ophthalmic solution made specifically for the eye of the same drug, essentially the same drug, for wet macular degeneration. And we presented the so-called Phase 3 data today of our trial showing efficacy.

So this would be the pivotal study, so there wouldn't have to be a lot of further data collection. What we showed today, just to review, is that 41.7%, or almost 42% of patients receiving this product gained 15 letters, which means three lines of vision gain, which is very good, and historically comparable to our standards with other name-brand drugs.

It also achieved a really high number of lesser gainers—which is also important and often not talked about as much—five and 10 letters or one- and two-line vision gainers was a very high number approaching 70%. That also compares very favourably with our expectation for this treatment class.

But as far as collecting more data, little to none would be needed now for wet AMD. Actually, the next frontier will be at some point for the company to—maybe next year, I think first quarter—apply for FDA approval, but then to consider testing it in other disease processes like diabetic retinopathy, that we use the off-label Avastin for now.

 Interview occurred in November 2021, referencing the first quarter of next year for BLA filing as first quarter 2022.

Dr Firas Rahhal discusses Outlook Therapeutics’ Phase 3 pivotal NORSE TWO trial for ONS-5010.

Phase 3 NORSE TWO proves ophthalmic bevacizumab effectively treats wet macular degeneration

At the 2021 American Academy of Ophthalmology annual meeting, Dr Ted Leng 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 centres versus non-academic medical centres.

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 non-academic medical centre, 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 non-academic medical centre 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.

Dr Ted Leng discusses his presentation, “Variations in Vitreoretinal Physician Utilization of Ancillary Testing: An IRIS Registry Analysis” during Retina Specialty Day at AAO 2021.

Delving into ancillary testing frequency based on the IRIS registry

At the 2021 American Academy of Ophthalmology annual meeting, Dr Robert J. Noecker; 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 honoured 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.

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

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

Investigating best practices for MicroPulse transscleral therapy for glaucoma

At the 2021 American Academy of Ophthalmology (AAO) meeting, Dr Felipe Medeiros of the Duke Eye Centre presented data on Durysta. Dr Michael R. Robinson, Vice President and Global Therapeutic Area Head of AbbVie, sits down to discuss these results.

. I'm joined today by Dr Michael Robinson, who will discuss data on Durysta, presented at the recently concluded American Academy of Ophthalmology 2021 annual meeting. Thank you for joining us today, Dr Robinson.

 Well, thank you, David. And thank you for the invitation. So I could present some of the Durysta data, talk about this at the 2021 AAO annual meeting. In glaucoma, we did present data on Durysta, which is an intracameral, biodegradable, sustained-release implant that slowly releases bimatoprost.

The first author on this abstract was Felipe Medeiros at the Duke Eye Centre. The implant was FDA approved in March of 2020 for single administration, for lowering the intraocular pressure in patients with open angle glaucoma or ocular hypertension.

The preclinical studies show drug release is complete, and intraocular tissue drug levels are undetectable by about four months after implant administration. However, in clinical trials with Durysta, the duration of IOP lowering had extended beyond the implant drug release. We presented data from an ongoing 24-month extension study of the Phase 3 ARTEMIS studies, assessing the efficacy and duration of the bimatoprost implant.

Patients in the Phase 3 trials received three implants total: one at baseline, one at four months, and then the last one at eight months, then they were followed out to 20 months total follow-up.

What we saw was that there were so many patients that had not been rescued at that 20-month time point that we needed to do an extension study to see how long the implant would actually last. They had received a 10-microgram dose, which is the marketed Durysta, or a 15-microgram dose. And we presented the pooled data in this abstract.

After the 20-month ARTEMIS study, patients then could voluntarily enrol in the extension study to look at the duration of IOP lowering beyond the length of that original study that ended at 20 months. Rescue with topical IOP lowering drops was allowed if in the opinion of the investigator of the study eye did not meet or maintain IOP expectations.

The outcome measures included the number of patients who had received no additional rescue IOP lowering treatment in the study eye for greater than two years and three years after the third implant administration in the ARTEMIS trials.

We also looked at the IOP and visual field mean deviation in the study eye of these patients. Results show that approximately 200 patients had volunteered to be enrolled in the extension study after completing an ARTEMIS trial. 69 had not been rescued yet at screening, 54 patients remained untreated for greater than two years after the third implant administration in the ARTEMIS trial, and 18 patients remained untreated for greater than three years after the third implant administration in the ARTEMIS trial.

The main baseline IOP is of these patients in these super responders were in the 23 to 24 range at the start of the ARTEMIS trials, and at the last mean IOP documented in the extension studies, the IOP was in the 16 to 17 range—off drops. The mean deviation of visual field testing of the super responder patients were stable over the past two to three years following their last implant.

So in conclusion, after their last bimatoprost implant treatment in the Phase 3 trials, patients can have a sustained IOP lowering for greater than two years, some greater than three years, without any additional treatment, and they maintained stable visual fields. The prolonged effect on IOP lowering could result from the bimatoprost stimulated upregulation of matrix metalloproteinases, leading to sustained tissue remodelling of outflow pathways. Clinical studies are in progress to further understand the duration of IOP lowering of Durysta and factors that may predict this long-term response.

At AAO, AbbVie presented results from the ARTEMIS study, showcasing IOP lowering that extends beyond the original 20-month timeframe.

Bimatoprost implant successfully lowers IOP in Phase 3 of the ARTEMIS study

Dr Jill Hopkins, 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 oedema (DMO) 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 DMO, 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 labelled 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 oedema.

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 oedema 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.

Dr Jill Hopkins 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 oedema.

AAO