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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.

Videos

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

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

Researchers at the University of Virginia School of Medicine have made a discovery linking lupus, a potentially debilitating autoimmune disorder, and macular degeneration, a leading cause of blindness.

The two diseases share a common contributor to harmful inflammation, the scientists found. The insights could let researchers develop new treatments for those diseases and other conditions driven by the newly discovered inflammation source.

“We were quite surprised at the common link between lupus and macular degeneration,” said Dr Jayakrishna Ambati of UVA’s Department of Ophthalmology and the founding director of UVA’s Center for Advanced Vision Science. “It appears that the new inflammatory pathway we identified could be therapeutically targeted for many chronic diseases.”

Dr Ambati and his collaborators have discovered an unknown role for an inflammasome – an agent of the immune system – called NLRC4-NLRP3. Inflammasomes play an important role in marshaling the body’s defenses to protect it from invaders such as viruses and bacteria.

In lupus and atrophic macular degeneration, however, it appears that NLRC4-NLRP3 contributes to harmful inflammation, the UVA researchers found. In lupus, it helps drive the hyperactive immune response that leads to symptoms such as joint pain, rash, fever and more. In macular degeneration, meanwhile, NRC4-NLRP3 appears to contribute to inflammation that destroys the vital light-sensing cells in the eye’s retina.

Dr Ambati’s new work helps explain why. The inflammasome, he found, is sent into action by a special class of genetic material called “short interspersed nuclear element RNAs,” or SINE RNAs. This type of RNA makes up more than 10% of our genomes, and it activates in response to cell stresses such as infection, genetic damage and aging. The resulting inflammation caused by SINE RNAs can be harmful in many chronic diseases.

SINE RNAs are elevated in both macular degeneration and lupus, Dr Ambati found. In addition to discovering the role of SINE RNA in the two diseases, Dr Ambati and his colleagues identified an unknown receptor for the SINE RNAs called DDX17. Scientists have been looking for this receptor for decades, and the new discovery helps them better understand the process that leads to the harmful inflammation.

“These findings indicate that blocking a single inflammasome might not be enough, and that targeting both the NLRC4 and NLRP3 inflammasomes would be a superior strategy,” Dr Ambati said.

Using this new information, scientists may be able to target the source of harmful inflammation in lupus, macular degeneration and other diseases driven by SINE RNAs. That could lead to new treatments to benefit patients, the UVA researchers say.

“We’re excited to have developed drugs called Kamuvudines that block this dual inflammasome, which we anticipate will be in clinical trials next year,” Dr Ambati said.

The researchers have published their findings in the scientific journal Science Immunology. The work is featured on the journal’s cover. The research team consisted of Shao-bin Wang, Siddharth Narendran, Shuichiro Hirahara, Akhil Varshney, Felipe Pereira, Ivana Apicella, Meenakshi Ambati, Vidya L. Ambati, Praveen Yerramothu, Kameshwari Ambati, Yosuke Nagasaka, Dionne Argyle, Peirong Huang, Kirstie L. Baker, Kenneth M. Marion, Kartik Gupta, Bo Liu, David R. Hinton, Scott W. Canna, Tamer Sallam, Srinivas R. Sadda, Nagaraj Kerur, Bradley D. Gelfand and Jayakrishna Ambati.

Jayakrishna Ambati is a co-founder of iVeena Holdings, iVeena Delivery Systems and Inflammasome Therapeutics and has done consulting work unrelated to the research. A full list of the authors’ disclosures is included in the paper.

The study was supported by the National Institutes of Health, grants DP1GM114862, R01EY028027, R01EY29799, R01EY031039, R01AI148741, R00EY024336, R21EY030651, R01EY028027, R01EY031039 and R01EY032512. It was also supported by the John Templeton Foundation, grant 60763; the UVA Strategic Investment Fund; the DuPont Guerry III professorship; a gift from Mr. and Mrs. Eli W. Tullis; the BrightFocus Foundation; and the Owens Family Foundation.

Author | OTE Staff Reports

Articles

Delving into ancillary testing frequency based on the IRIS registry

Investigating best practices for MicroPulse transscleral therapy for glaucoma

Inflammation link discovered between lupus and macular degeneration

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