This video was part of a roundtable discussioninvolving surgeons Christina Y. Weng, MD, MBA; Mrinali Gupta, MD, FASRS; Nimesh A. “Nemo” Patel, MD; and Frank Brodie, MD, MBA. An edited transcript of the case presentation and discussion follows below:

Frank Brodie, MD, MBA: I wanted to show a technology from a group I've been working with and it's less familiar to US ophthalmologists and retina surgeons. A lot of the work has actually been done in Europe. It's the PRIMA subretinal implant for vision restoration in geographic atrophy (GA). The pivotal trial was PRIMAvera. It was just completed and they published the results this past year. It really did show remarkable improvement in vision in these patients.

What it is—and I'm going to show a little animation, but I'll set it up—is a subretinal photovoltaic implant. So photovoltaics, think of the same solar cells that you have on the roof of your house, that turn light into electricity. If we think about what our photoreceptors do, it's basically the same thing: light to electricity, pings our bipolar cells, up to our ganglion cells, and down our optic nerve.

So this is an implant for patients in GA who really have just lost their RPE and photoreceptors. You create a subretinal bleb and slide it underneath the area of GA. The patient then wears these infrared goggles, which shine light on the implant, and it has a camera that's front facing, takes the image in front of the patient. It sends that information to the implant, and then it uses the full processing power of the retina—as opposed to an epiretinal implant going right to the ganglion cells, the subretinal implant goes through the bipolar cells, goes up to the ganglion cells and down to the brain. We saw that 80% of patients who were 20/400 or worse were reading and could read letters and numbers. It was really pretty incredible. So it’s something I’m very excited about, and something we're trying hard to bring to the United States. But the surgical technique is obviously very new, very different, and is something I wanted to share.

I figured I'd start with the animation. Here you see those photoreceptors being lost in GA.

Here's the animated version of vitrectomy. I'm sure all of ours look just like that. There's the subretinal bleb.

Here’s the injector. You'll see that it's a small 2 mm by 2 mm implant. It’s actually an array of 378 individual photo cells.

You slide it under the subretinal bleb, put down some perfluorocarbon (PFC) to hold everything in place, and then you can move it transretinally with a Flex Loop (Alcon) or soft-tip cannula or something like that. That’s where it sits. And this is what the patient’s seeing. In the upper left-hand corner, there’s that dense scotoma. They put on their infrared glasses and they can see. And so this is that infrared light being shined onto the implant.

I'll show you real surgery, I promise. I just wanted to do that for orientation. This is Mahi Muqit, MD, PhD, FRCOphth, out of Moorfields Hospital in London, doing this. He's a beautiful surgeon. Here’s the subretinal bleb, and here he's going to do some diathermy to mark his retinotomy. Some folks will do the whole marking out of the incision; some folks will just do the vessels.

Here we're using some vertical scissors to create the incision. Now the chip is 2 mm. You'll see the injector’s a little bit bigger, so you aim for about a 3 mm retinotomy here. You want this to be just adjacent to the area of GA.

As you know, GA is pretty stuck down. You have that inflammation from all those dying photoreceptors. So you actually have to go in and bluntly dissect out. The bleb doesn't propagate into the area of GA. This is a Thomas pick used to gently go in and bluntly dissect this out. We were fortunate that in the trial, there were 38 patients and no instances of buttonholing or anything like that.

There is the implant you'll see on the tip of the injector. He's got the PFC at the ready using a chandelier. He's going to come right in, get it in there and insert, gets it lodged in there. And this implant is just a few grams of weight. It’s thin—it's 30 µm thick. So you really want to get that PFC on pretty quickly to stabilize everything. Otherwise, you do run the risk of it whipping around the eye with infusion. You do have your big sclerotomy and you want to close that as quickly as you can. Here he goes with the Flex Loop. It's just going to gently move it into that area of GA. Now you can move it transretinally with the Flex Loop. Like I said, you can also move it with a soft-tip cannula. And there we go, it's under the fovea.

Generally, you want the fovea to be at least 50 µm thick. We did have a couple instances of macular holes in the study. So you do want to make sure you have enough thickness and do a lot of preoperative planning.

But that is the case. Pretty neat, right?

Christina Y. Weng, MD, MBA: That's so awesome, Frank. It's like sci-fi but real. Absolutely phenomenal. Thank you for showing us that. That is so cool to see.

One question: You said it's being used for patients or tested in patients with geographic atrophy; do you think this could be used in a broader way for patients with other retinal atrophies from different diseases?

Dr. Brodie: Yeah, definitely. If you think about the technology, it's really disease agnostic. It just requires certain anatomy. You want to have an intact inner retina and it replaces those photoreceptors. So there's actually a clinical trial that just started in Sydney, Australia, with Matt Simunovic, MB BChir, PhD, looking at Stargardt disease, which is kind of a perfect IRD candidate for this. And then we're also going to explore things like retinitis pigmentosa (RP). RP is a little bit more of a heterogeneous disease, but there might be some more intraretinal challenges in some of those patients. I think Stargardt is a nice next target for us. 

Mrinali Gupta, MD, FASRS: Super cool. The rationale for infrared—is it just because the rest of the retina is pretty good and you don't want to stimulate it? 

Dr. Brodie: Exactly. So this technology was originally developed by Dan Palanker, PhD, down at Stanford, and he figured that out. He actually has a really nice study—and I'm blocking what journal it's in—where he shows these patients actually can integrate the image. They’ll see something peripherally, they’ll see it prosthetically, and the brain puts it all together. Now it does drop down to black and white centrally, but then he showed them these kind of complex pictures and the patient could just see it as one image, which was really cool.¹

Nimesh A. “Nimo” Patel, MD: This is really cool because when I'm with patients, a lot of questions we get are, what’s available to help me see better? And currently our treatments in GA are slowing things down from getting worse. And I think these type of things give us also a lot of hope for what’s coming in the future down the line for other parts of the eye that are lost or nerves that are damaged that we can no longer use. So there may be alternative ways to get the patient to see that doesn’t have to do with rebuilding the nerves themselves. So I think this is a really cool idea.

One question I had for you was, can you dissect that off with something maybe thicker, like a viscoelastic? So could you use a viscoelastic to get underneath there, almost like we do with a viscodissect for traction retinal detachments (TRDs)?

Dr. Brodie: Yeah, I think that's a really cool idea and I've heard it from a couple folks. They haven't tried it clinically yet. We are kind of playing around with it in some animal models to see. The problem is that its actually very hard to simulate GA in an animal model. I don't have a good sense of whether the RPE will suck down visco sufficiently or you'll be left with a lot of residual. We know it'll suck down BSS, so if there is a small fluid layer, it's going to go away. I don't have a good intuition whether the hyaluronidase has good penetration in a subretinal space. So I think that's something we'd have to figure out before recommending it. But I think you're absolutely right. I think that when I watch the video to me, always I think the most challenging part is that blunt dissection into the area of GA and it seems naturally if you could do that with a heavy liquid, I think that’s a really natural, easy way to do it that feels a little bit safer too.

Dr. Gupta: Frank, I've employed subretinal viscoelastic for some complex or recurrent macular holes sometimes. And in that setting, it dissects nicely, but only about a millimeter distance. It doesn't go super far, so you might have to thread something under that bleb. And once or twice, when we were first learning how to do that technique, we didn't get all that viscoelastic out. I wonder if PFO would push a lot of it out, but in our case, we didn't use PFO. We didn't get it out. It failed to close the hole, but it did get pumped out.

Dr. Brodie: Oh, okay. That's great to hear. Thanks for telling me that. We'll try it. Keep you guys updated.

Dr. Weng: Frank, do you have to laser that retinotomy that you open before you slip in the chip?

Dr. Brodie: No. So none of the patients were lasered in the trial and then none of them had RDs from that. There was one patient that later developed a PVR tractional detachment, but nothing from that retinotomy.

Dr. Weng: No tamponade either? 

Dr. Brodie: So there’s tamponade in all these patients. Sorry, I should have mentioned that in the video. They can either get oil or gas per surgeon preference, and oil was taken out. By protocol, it was supposed to be 4 weeks. It ended up being obviously somewhere between 4 and 8 weeks, but a lot of patients did great with SF₆ too. You would do 1 hour of positioning supine and then prone per the investigator's protocol. 

Dr. Weng: Have you ever seen the subretinal implant displaced? 

Dr. Brodie: So in one of the early feasibility studies, there was one that displaced. And then one patient in PRIMAvera got up and got coffee—he was an Italian guy, and said, “I can't live without my espresso.” He got up immediately postoperatively as soon as he was awake enough. His implant displaced to the edge of the area of GA. He was taken back to the OR the following day, it was nudged back in place, and he did great. And we have had cases where the patients had macular holes and later had to move the implant out of the area of the macular hole and it was able to do it without any issue. It didn’t affect the natural or prosthetic vision. So they are still kind of movable. 

Dr. Weng: I love how you use the Flex Loop to kind of nudge the chip. That's probably the hundredth application of the Flex Loop. We use that for all sorts of uses.

Dr. Brodie: I know. It’s the Swiss Army knife of retina.

Dr. Weng: It really is. And then Frank, you said that you're working hard to bring this to the United States. Can you just tell us about next steps? What's the process and where are we in that? 

Dr. Brodie: So the company is working with the US Food and Drug Administration (FDA) and looking at the European data. And again, this is intended for patients with pretty severe, very end-stage GA. The label in Europe is going to be worse than 20/320 in the surgical eye, worse than 20/200 in the fellow eye. So this is a really small group of very end-stage GA patients. The FDA recognized that this year and awarded the company a humanitarian use designation. And so now we’re working with the agency on figuring out the approval using that pathway. It's similar to what the Argus implant (Second Sight) got. They were also brought to market through a humanitarian use designation.

Dr. Weng: Frank, how do the patients describe the vision? What's it like to them? 

Dr. Brodie: So it has a whitish-yellowish color. And what's cool is—and we presented this at ARVO—they’re able to represent the letters and numbers. It's not like they’re interpreting phosphenes and saying, “Oh, that phosphene is the such and such.” They’ll draw the letters and numbers they see, and they are really the letters and numbers that are being presented. We had one patient read a 300-page book. One woman is doing crossword puzzles and Sudoku. It’s really incredible.

Now the results are a little bit heterogeneous. Some patients really flew and did great with this. Some patients struggled, and some patients had very specific use cases. Some patients use it a lot. So, we're still sorting through all the data. It wasn't a huge study, 38 patients. The hope is that it will come to Europe commercially this summer, and as [we gather data from] all those patients in the postmarket study, I think we'll learn a lot more about who uses it, how it’s used, and who can really benefit the most from it. So, I’m excited to see what those results show.

Dr. Gupta: Frank, that’s way better vision than prior implants. Is that because you're getting the bipolar cells? Or are there better pixels in your implant?

Dr. Brodie: Both. Exactly right. So, these are 100-µm pixels, which just gives much higher resolution than in prior implants. But on top of that, I think it's that processing power. First, your retinotopic representation is all preserved vs if you're on the ganglion cells on top, you're going to get these big phosphenes from all the cells, all the photoreceptors all across. It's really the first time patients have had “formed vision,” which is letters and numbers and actually seeing what's out there as opposed to just interpretation of phosphenes. So its super exciting.

Dr. Weng: Very exciting. Frank, thanks for sharing that case with us. We really appreciate it.

Dr. Brodie: Thank you so much. Hopefully we'll all get to do it here soon in the United States.

Dr. Weng: Hopefully. All right, that is a wrap. Thank you so much for everyone joining tonight and taking part of your busy evenings to do this. RP

Reference

1. Palanker D, Le Mer Y, Mohand-Said S, Sahel JA. Simultaneous perception of prosthetic and natural vision in AMD patients. Nat Commun. 2022;13(1):513. doi:10.1038/s41467-022-28125-x