Kassi Jackson

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Dr Sunir J. Garg discusses the benefits of hypersonic vitrectomy as a novel technologic advancement for retinal surgeons in a presentation at the 2022 Retina World Congress.

Yeah, so hypersonic vitrectomy is one of the really most novel ways we have of removing vitreous, and our traditional guillotine cutters are really amazing. And as they've gotten faster and faster, they take smaller bites of the vitreous gel. And as you take smaller bites of the vitreous gel, you reduce viscosity. When you have less viscosity, you're able to remove the gel a lot more efficiently.

And over the past 10 to 15 years, our cutters went from 2500 cuts a minute to 15,000 cuts a minute to getting closer to 30,000 cuts a minute. But there's certain inherent limitations. Smaller bites are still small bites, but they're not tiny particles.

One of the other limitations of our standard guillotine cutters is they're a needle and needle design. And as you may remember from high school physics, the smaller you make a lumen, the exponentially more resistance you have. Hypersonic vitrectomy not only takes small little particles of the vitreous gel, but it doesn't have a needle and needle design. So the single lumen gives you an effectively larger internal radius, enabling you to remove the vitreous gel a lot more efficiently.

So we looked at a bunch of different cases using this technology. And we found that we could do pretty much a whole host of retinal surgeries with it: retinal detachments, retain lens material, silicone oil cases. And for a lot of cases, it was really great. And surgeons found that was particularly advantageous for removing vitreous gel in mobile retina. So in retinal detachment cases it was terrific. We could use that same port to remove retain lens materials, we didn't have to open up a frag in these cases. And some of my colleagues actually used it to remove silicone oil.

And it was kind of neat to be able to do basically the entire surgery with one instrument. There was a couple of cases in which I don't think anything's going to be better than a guillotine cutter, particularly in really thick, dense diabetic membranes. Using scissors or guillotine cutters are really fabulous. And there's a couple of cases that had a really kind of glassy, thick vitreous gel, that this didn't work that great, but honestly, neither did my guillotine cutter so I think that was just those cases.

One of the other potential advantages of this is you don't need gas, so you don't need big gas tanks and you don't need to be tethered to an operating room. So whether you're in places around the world that don't have easy access to those things, or whether you're looking at doing vitrectomy outside of the traditional or this might be really advantageous.

There are some limitations about it, you know, we're still refining the different port technologies. So one of the great things about this is you can change the port. So you can make it into a teardrop shape; you can make it into a sigmoid shape, and some of our new iterations seem to be a lot more efficient than our old ones.

We're also adjusting some of the parameters of the handpiece. One of the things that we found is by increasing the frequency, we can dramatically increase the force or the ability of the instrument to cut the vitreous gel. And we're currently working on a new sigmoid shape, which seems to be a major improvement over what we had before.

But considering that the technology is really new, and there's only been hundreds or maybe 1,000 cases done, I'm really impressed with how dramatically better the technology continues to get. And as we use it more often, I think we'll continue to refine it.

Videos

Though the speed of traditional guillotine cutters has increased significantly in recent years, there are certain limitations. With the advent of hypersonic vitrectomy, Dr Sunir J. Garg explains how retinal surgeons can remove the vitreous gel with more efficiency.

Hypersonic vitrectomy a novel technology for removing vitreous

In Fort Lauderdale, Florida, United States, Dr Justis P. Ehlers presented a talk entitled, “The impact of compartmental exudative volatility on visual acuity and ellipsoid zone integrity in neovascular AMD.”

So it's my pleasure to share some of the results from our research today. As many of you know, there's been a lot of work done recently examining the impact of central subfield thickness, volatility and the overall impact on visual acuity in clinical trials in wet AMD.

One of the big questions that remains is: What's driving that volatility in retinal thickness changes, and do those changes actually end up with important anatomical sequela that we can understand and strive to minimize as clinicians?

For this study, what we did is we looked at the Phase 3 Hawk clinical trial, we're able to use machine learning augmented, multilayer segmentation, as well as feature extraction to pull out specific fluid compartments including intraretinal fluid and subretinal fluid, as well as subretinal material.

Using this, we're able to look at volatility from week 12, after the loading phase all the way to the end of year one and to evaluate the impact of high volatility in each of those compartments on visual acuity outcomes and on anatomic sequela.

What we found was that each of those compartments intraretinal fluid, subretinal fluid, as well as subretinal material all had a negative impact on visual acuity if it was in the high volatility group, whereas eyes that were in the low volatility group continued to improve vision over time. When we looked at the anatomic sequela, what we found was, in fact, the subretinal fluid compartment had the biggest driver towards negative anatomic outcomes, particularly increase in subretinal fibrosis and subretinal material, as well as poor maintenance of ellipsoid zone integrity.

Interestingly, this flies a little bit in the face of what we know in terms of subretinal fluid. We've seen in the past that this can be linked with overall better visual acuity at specific time points, but what this shows is that potentially overall activity and the volatility of that compartment is an important discriminator between eyes that may do well with tolerating subretinal fluid, that static, versus really minimizing that subretinal fluid that may be volatile and dynamic. So overall, more work needs to be done in this area. It's really an exciting opportunity given the new and advanced image analysis techniques that we have, and we're excited to share it here at Retina World Congress.

This transcript has been lightly edited for clarity.

Dr Justis P. Ehlers dissects the revelations from the data in the Phase 3 Hawk clinical trial regarding the impact of central subfield thickness, volatility and the overall impact on visual acuity.

Clinical trials in wet AMD: Impact of central subfield thickness, volatility on visual acuity

In Fort Lauderdale, Florida, Dr Dilsher Dhoot gave a presentation: “Effects of Time Since Diagnosis to Intravitreal Aflibercept Injection and Baseline BCVA on Outcomes in CRVO: Post Hoc Analysis of the COPERNICUS and GALILEO Trials.” The study found that treatment soon after diagnosis resulted in better visual acuity gains.

So we did a post hoc analysis of the Copernicus and Galileo trials. These are the Phase 3 registration trials for macular oedema in central retinal vein occlusion.

In this trial, patients are randomized to receive either aflibercept or sham injection. Aflibercept patients were treated every four weeks for 24 weeks, at which point primary end point, which was loss of three lines or more, was read out.

In this post hoc analysis, we were very interested to see if a delay in treatment resulted in differences in anatomy or visual acuity gains. And so patients were divided into one of three groups: patients who were enrolled in the trial within one month of diagnosis, one to three months of diagnosis, or greater than three months from diagnosis.

So the interesting part of this trial was that there was visual acuity differences. Patients who had the best visual acuity gains were those patients who were treated within one month of their diagnosis, compared to those patients who were treated after three months of diagnosis were the worst visual acuity cases. Interestingly, their anatomy was the same. So the anatomy improved in all groups, and there was no difference.

The second part of this analysis was looking at baseline visual acuity. And the baseline vision acuity had any bearing on final visual acuity. And in fact, those patients with the best baseline visual acuity have the greatest vision at the end of the trial. The greatest gain was in those patients with the worst baseline visual acuity. And this may have to do with ceiling effect. But it turns out that their final visual acuity were not as good as your counterparts who started off with good vision.

And so I think this trial provides information for our patients and physicians and helps manage expectations; namely, that if a patient is seen with macular oedema secondary to central retinal vein occlusion, it really is important to get started on treatment right away.

Dr Dilsher Dhoot discusses the post hoc analysis of the Copernicus and Galileo trials, which investigated if a delay in treatment would affect visual acuity gains or change in anatomy.

Post hoc analysis of Copernicus, Galileo trials find time since diagnosis affects BCVA outcomes in CRVO

At Retina World Congress in Fort Lauderdale, Florida, United States, Dr Carl Regillo presented a talk entitled, “Results of the KSI-301 Dazzle Neovascular AMD Pivotal Clinical Trial.” While the study failed to meet its primary endpoint, KSI-301 demonstrated good initial visual gains and anatomic effects as well as positive durability.

Dr Regillo is the director of retina service at Wills Eye Hospital.

I had the opportunity to present the top line results of the Phase 2/3 pivotal study on the use of KSI-301 to treat neovascular AMD.

This is all very new information, so a lot of people are probably not aware of the results. Unfortunately, the study did not reach its primary endpoint in terms of KSI being noninferior in mean change BCVA from baseline to the primary endpoint compared to aflibercept.

So, we saw some initial visual gains that look good, in addition to some good anatomic effects early on during the induction phase, the monthly injections of the therapeutic, but some loss of vision over time. And so the amount of vision gain at the primary endpoint was not as much as aflibercept.

What we saw was very good durability, actually. And there's the positive aspect to the way KSI performed. Sixty percent of patients were able to be extended out or be treated as infrequently as every 5 months. So that is impressive, with 60% of patients going 5 months and doing very well, visually, anatomically, on par with aflibercept. It was the 30% of patients that were getting KSI-301, every 12 weeks or three months that didn't perform as well.

It is pretty clear from case studies in further analysis that those patients probably need to be dosed more frequently than every 3 months, because we saw a good initial drain 1 or 2 months after a given KSI dose. But then disease activity recurred significantly and that accounted for vision loss. It was that 30% of KSI patients getting treatment every 3 months that sort of brought the whole population visual acuity down over time to the primary endpoint.

While the DAZZLE trial failed to meet its primary endpoint, KSI-301 demonstrated good initial visual gains and anatomic effects as well as positive durability.

Author | Kassi Jackson

Articles

Clinical trials in wet AMD: Impact of central subfield thickness, volatility on visual acuity

Post hoc analysis of Copernicus, Galileo trials find time since diagnosis affects BCVA outcomes in CRVO

Clinical trial offers insight into development of KSI-301

Hypersonic vitrectomy a novel technology for removing vitreous