Beyond MacTel: Could encapsulated cell technology become a platform for other retinal diseases?

One year after revakinagene taroretcel-lwey (Encelto; Neurotech Pharmaceuticals) became the first and only FDA-approved treatment for macular telangiectasia type 2 (MacTel), retina specialists are gaining real-world clarity on patient selection, surgical technique, and how to counsel patients on a therapy that halts progression without producing visible anatomic change. For a historically underserved and often underrecognized population, the encapsulated cell technology platform represents a rare treatment option in a disease with no prior therapy, but it also introduces new challenges in explaining efficacy to physicians accustomed to anti-VEGF therapies’ before-and-after results.

To mark the 1-year milestone, Modern Retina spoke with Charles Wykoff, MD, PhD, director of research at Retina Consultants of Texas in Houston, who served as a clinical investigator on revakinagene taroretcel’s pivotal phase 3 trials and performed the first commercial revakinagene taroretcel procedure outside a clinical trial last August. Wykoff discussed patient selection criteria, stepwise surgical technique, early real-world safety findings from roughly 20 commercial implantations, and where encapsulated cell technology could go next as a delivery platform beyond MacTel.

Note: Transcript edited lightly for length and clarity.

Since MacTel is underdiagnosed, has the availability of an approved treatment changed how referring physicians and general ophthalmologists are screening and sending patients your way?

Charles Wykoff, MD, PhD: This is a big step forward for patients. I’ve been following MacTel patients as part of the MacTel Project for probably greater than a decade at this point. [Patients with MacTel] were previously an underserved population—they had these progressive visual symptoms in many cases without any available therapy. So, it’s a big deal to have something to offer these patients and discuss with them and see if they’d be a good candidate.

And I have been talking broadly with referring physicians and eye care professionals at large, as have many of my colleagues, because it’s a big deal to have something now available for these patients who, before, did not have anything. So I do think there’s growing awareness of this.

MacTel is not a common disease in eye care, but I do agree with you that it’s probably underrecognized in many areas. And so broad education about the findings in MacTel, the patient symptoms related to MacTel, and the progressive nature of this disease in many patients is very important.

How are you identifying and selecting candidates for revakinagene taroretcel now? Are there patient profiles, disease stages, or imaging findings on optical coherence tomography (OCT) that you’ve found are most predictive of who benefits most?

Wykoff: I think the phase 2 and phase 3 clinical trial enrollment criteria are a good place to start. First of all, you want to make sure the diagnosis is correct. And then on imaging, I do think it’s important that there be the presence of ellipsoid zone (EZ) loss—that was a key enrollment criterion in the clinical trials. Some of the other findings on imaging and exam: I’m looking for the absence of active neovascularization.

So one of the potential adverse events of this disease itself, with or without [revakinagene taroretcel] treatment, is the development of a neovascular complex and bleeding in the macula. And so I don’t want to have active neovascularization. I actually try to make sure patients are off of anti-VEGF agents and don’t need additional anti-VEGF agents before I consider them a potential candidate. And then, patient conversation is also important for eligibility criteria and who I think could be a good candidate.

In particular, I’m looking for patients who notice they have a visual problem in the eye we’re talking about, and they also notice that it’s getting worse. I kind of require both of those things to think that a patient is eligible, because what we don’t want to treat are patients who are A) asymptomatic and B) patients who are not getting worse. The reason is that data show us that [revakinagene taroretcel] slows or stabilizes disease; it does not reverse disease. I am very clear with patients about that.

We’re not trying to improve their visual function. I certainly wish we could, and hopefully in the future we’ll have therapies for MacTel that can improve their visual function, but that’s not what my expectation of what [revakinagene taroretcel] does for patients, based on the clinical trial data. And so if patients aren’t noticing worsening and they’re stable, then I hesitate to move forward with surgical implantation initially.

Many times in patients like that, I’ll educate them about how to track their visual function—using an Amsler grid—and sometimes I’ll perform detailed visual field analyses like microperimetry to follow them over time to confirm stability if they think they’re not progressing. But many patients do feel like they’re progressing, including noticing their metamorphopsia or progressive difficulty reading. So that’s what I’m looking for: patients who notice they have a problem and that it is progressing over the last 6 to 12 months.

So once you’ve identified the right patient, can you walk us through what the actual implantation procedure looks like?

Wykoff: Many patients are bilaterally symptomatic, so we frequently have a detailed discussion about which eye [to treat] first. My typical process there is that if a patient is interested in doing both eyes, I will often start with their worst eye, and patients often know which is their better and worst eye. If they don’t, we walk through that process together to help decide. I pick the worst eye first because, as I say to patients, “This is a new implant for you—no one’s ever put it in you before. We understand the risks, benefits, and alternatives for patients from the clinical trials, but you’re unique. And let’s say there is a problem—let’s say there’s a reaction to the implant or something—I think that’s rare, but let’s start with the worst eye first.” That’s usually what I do in patients who want bilateral implantation.

To your question, the surgical procedure fits nicely within the wheelhouse of what retina specialists are used to doing. In most cases, you actually don’t need a vitrectomy machine. In the operating room, we sterilize and prep the eye in standard fashion, then make a small conjunctival peritomy—usually 7 × 7 mm. I usually place it inferotemporally to keep the implant out of the visual axis. Then you make a 3-mm-wide sclerotomy, about 3.75 mm posterior to the surgical limbus. You implant the device after placing a double-armed 9-0 polypropylene suture through the titanium fixation loop. And then you use that polypropylene suture to fixate the titanium fixation loop just inside of the scleral wound—so the polypropylene suture is not a wound closure suture; it’s to attach the implant just inside of the wound. Then the wound itself is closed with two 9-0 nylon sutures with knots that are buried. Then you make sure that the polypropylene suture lies flat, and then you close the overlying conjunctiva and Tenon’s capsule.

Importantly, you need to confirm the intraocular location of the implant before you finish the procedure, so put on the indirect and look before concluding the case. All of these steps are within the wheelhouse of a retina surgeon. I think the biggest challenge is manipulation of the double-armed 9-0 polypropylene suture—it’s a fine suture that likes to kink, so you have to be very careful, intentional, and cautious with it.

You performed the very first commercial revakinagene taroretcel procedure outside of a clinical trial August 2025. Now that you and your team have had a full year of real-world experience, how has the procedure evolved in practice compared with what you observed in the clinical trial setting? Has anything surprised you?

Wykoff: It was a comprehensive development program. We have good phase 2 and phase 3 trials to guide what to expect in clinical practice. So far, everything I’ve seen has been consistent with that. I’ve implanted approximately 20 of these commercially, and so far have not had any reoperations. I’ve had a few patients with very mild inflammation in the routine postoperative period that goes away with a topical steroid taper. So nothing unexpected from my perspective.

I think the biggest challenge we have with these implants is actually how to answer the question that patients have: Is it working? We’re so used to, as retina specialists, giving an anti-VEGF agent in an eye with macular edema for whatever cause, and the edema goes away. And so we can point to imaging and say, “Great, the drug is working.”

The challenge with [revakinagene taroretcel] is that the anatomy doesn’t immediately change. So there’s no before-and-after difference on OCT or on fluorescein angiography or the color fundus photography—I don’t have anything definitive to look at and tell a patient, “Yes, it looks like it’s working.” And so, really, what we’re going to have is natural history compared to the progression of EZ loss in these eyes over time. And those analyses are just beginning now because we’re only a year past FDA approval.

I think it’s really important to do those real-world analyses where we look at the images and we look at the EZ loss before implantation and then after implantation and compare that to what we would expect from the clinical trial data. That will, I think, give us a better indication of the real-world efficacy of this, because the goal is to slow photoreceptor loss.

The last point to consider is that patients want good anatomy, but what they really want is function—patients want to see, and they want to see better over time than they would have without treatment. And so some of us are doing more sophisticated visual function analyses—things like microperimetry—over time, to follow these patients before and after implantation to see if we can document the visual benefit. Because I think the phase 3 program was helpful there—it did show a meaningful reduction in the loss of microperimetry sensitivity and also meaningful preservation of reading speed compared to the natural history in the control arm. And I think it’s important that we try to validate that in the real world.

Where do you see revakinagene taroretcel encapsulated cell technology going next? Could this platform be used for other eye diseases beyond MacTel?

Wykoff: Yeah, it certainly could be a platform technology. It’s fascinating technology—a little cylinder with these little filament-type placements inside of the cylinder, where little cells are living that have been engineered to produce a therapeutic protein that diffuses into the eye. Really neat technology—it combines cell therapy with gene therapy. It’s fascinating and remarkably well tolerated in this population of patients.

The couple of adverse events I do talk about are miosis and delayed dark adaptation—we know those from the phase 3 clinical trials. I do always discuss the possibility of extrusion of the device and possible damage to other intraocular tissues. I think all of those are infrequent. You know, it would be great, for example, to have an anti-VEGF agent that you could put in this and then place it in the eye and remove it if needed. And it could certainly be used for the delivery of other therapeutics.