GAMBUZZA: Good morning. It's Friday, October 2, and this is The OT Roundup.

Here's what's ahead on this episode: we're circling back to a story we teased last time, new 4-year data on MOGENRY for retinitis pigmentosa. Then, a new report on the state of retina care from Retina Consultants of America. After that, a story that connects straight back to episode 1's myopia coverage, the FDA is reviewing SYD-101 for pediatric myopia. And later, my co-host Dr. Veeral Sheth joins us to break down new Phase 2 data on a one-time gene therapy for geographic atrophy.

Let's get into it.

I'm Lucia Gambuzza, a producer at Ophthalmology Times. As this is only our second episode, here's a background on this show.

Every other Friday morning we take the stories that moved on Ophthalmology Times over the last two weeks and summarize the key findings. The goal is simple: you should be able to listen on the drive in, during your morning coffee, or between cases, and feel caught up.

Every episode also includes Expert Insight from Dr. Veeral Sheth, a retina specialist and a longtime contributor to Ophthalmology Times. He'll join us for an exclusive interview on the new Phase 2 data for OCU410 presented at the Retina Society meeting in LA.

Good note to add, everything I mention is linked in the episode description if you decide you would like more information.

All right, here's the news.

Remember back in episode 1, we told you Nanoscope was set to present 4-year data on MOGENRY, formerly known as MCO-010, at the Retina Society meeting? That data is in, and it's good news.

In case you missed out last episode, here are the details: MOGENRY is a one-time eye injection for people with advanced retinitis pigmentosa. Instead of targeting the photoreceptor cells that RP destroys, it works on a different set of cells in the retina, bipolar cells, and makes them sensitive to light instead. In the original trial, patients who got the treatment gained about 3 lines of vision on an eye chart. Now, at the 4-year mark, doctors are seeing that about 40% of treated patients kept that improvement, while patients who didn't get the treatment stayed the same or got worse.

Dr. Christine Kay, who presented the data, had a message for eye care providers: "It's no longer okay to tell our RP patients that there's nothing that we can do for you or that we don't need to see you again." Kay discussed the full findings in a video interview with Modern Retina. You can watch that interview by visiting the link in the description.

Next up, Retina Consultants of America published its first-ever State of Retina Care report, surveying more than 115 of their retina specialists.

The headline number: nearly 80% said RCA's support, things like research infrastructure and billing help, made a real difference in their practice. On the research side, more than 80% said their ability to run clinical trials improved, and 53% said patient access to trials improved significantly.

RCA is backing that up with investment too, nearly $40 million toward 18 new clinics since last year. That matters because access is a real problem right now. About 1 in 20 Americans live more than an hour from a retina specialist, and the federal government projects the US could be short almost 30% of the ophthalmologists it needs by 2038.

Worth noting, this is RCA's own survey of RCA-affiliated doctors, so take the numbers with that in mind. Read the full breakdown by our producer Kassi Filkins, linked in the description.

Our next story connects back to episode 1. Remember the AMA's move to classify myopia as a formal disease, in part to open the door to insurance coverage? Here's a real example of that gap.

The FDA has scheduled an Advisory Committee meeting for October 30th to review SYD-101, a low-dose atropine formulation for slowing myopia in kids. Right now, there's no FDA-approved version, so doctors prescribe compounded atropine instead.

We sat down with Dr. Nimesh Patel, a pediatric retina specialist at Mass Eye and Ear and Boston Children's Hospital, who told us "the formulation doesn't actually contain more than 80 to 90% of the intended drug," which raises real questions about cost and consistency. Patel also flagged something bigger: retinal detachments, usually thought of as an adult problem, are starting to show up in myopic teenagers, sometimes without any symptoms at all. His advice to eye care providers is simple: when in doubt, dilate and refer.

Patel published his own take on Ophthalmology Times this week. I'll link that in the description, along with the video interview with Dr. Patel, produced by Matt Hoffman, and the FDA's announcement by Jordana Joy.

Our last story is about a different approach to geographic atrophy, or GA, a disease usually treated with injections every month or two.

New Phase 2 data presented at the Retina Society meeting looked at OCU410, a gene therapy given as a single subretinal injection. In the medium-dose group, patients saw their GA lesions grow about 32% slower than untreated patients. The higher dose, interestingly, didn't show that same benefit, and the treatment was well tolerated with no drug-related serious adverse events.

To dig into what this data actually means, let's call up Dr. Veeral Sheth, my co-host and retina specialist at University Retina.

GAMBUZZA: Hi, Dr. Sheth, thanks for joining today. From my side, it looks like there's a lot of movement in the world right now.

SHETH: Yeah, totally agree, Lucia, and thanks for having me back.

GAMBUZZA: Okay, let's talk about OCU410. What is OCU410, and why does a one-time gene therapy for GA matter?

SHETH: Yeah, so OCU410 just released some data at Retina Society, presented some updated data from them. I think before we talk about OCU410, we just got to really briefly talk about the GA treatment landscape, right? Right now, treating GA means you've got to treat your patients with an injection every 1 to 2 months indefinitely. Right, and that's, you know, it's kind of a difficult proposition for patients. And so what OCU410 is, is a single administration therapy. So you're doing a vitrectomy with a subretinal injection of OCU410. And that data was presented, this was a Phase 2 trial, and what we saw in that trial was the medium dose of OCU410 showed a 32% reduction in lesion growth. Right, so that was at 12 months, which was fascinating to see.

GAMBUZZA: Let's talk about that, medium dose outperforming the high dose. What does that tell you about how this therapy is working, and do you think it will change how Phase 3 might be designed?

SHETH: Yeah, you know, it's interesting, right? That was a little bit of the buzz after the presentation as well, which is, you know, we as clinical trials love to see dose dependency in terms of what our treatment efficacy is, because it's very easy to explain. Right, so when we don't see that, the question is, well, why did that happen, right? And so, look, I think in this situation there's a couple of potential explanations for that, right? First, you know, when you have gene therapy using a viral vector, right, the vector itself can potentially cost you something. In other words, you know, when you look at the higher dose, which was three times the dose of the medium dose, you have three times the dose of AAV capsid, right. And so when you put that subretinally, the question is, well, do you cause a little bit of local inflammation and immune response, and does that potentially stress the tissue and then impact potentially efficacy on that side? So we don't know the answer to that, but that's potentially one explanation. The other is that you have to understand the biology of what they're looking at here. Right, which is RORA, which is, it's not an enzyme, right? So you're not replacing an enzyme, so again, there's no dose dependency in that regard. It's a transcriptional regulator that turns a whole bunch of genes up and down. And so when you start to tweak regulators, there's often like this bell-shaped curve, or bell-shaped dose response, to those. And if you push expression too high, you might not get the feedback or the saturation that you're looking for. And so, potentially, with this medium dose, maybe they're hitting the sweet spot, right? And then the last explanation, especially in smaller studies like this, is that it's noise, right? You've got 16 patients in the medium dose arm. We know really well in GA that there's just a lot of patient-to-patient variability. And so when you have a smaller effect, you know, you get a fast growth or a slow growth in one arm or the other, and that can start to skew data. And so, you know, that potentially is another explanation for it, I think.

GAMBUZZA: Thank you for that. You really brought me back to math class with the bell-shaped curve imagery in my mind. That's right. You run one of the larger retinal trial programs in the country. From your opinion, how strong is this Phase 2 evidence, and what should we watch for in the next phase?

SHETH: Yeah, so let's dig into that for a second. So the medium dose, what did we see? We saw that it slowed lesion growth by about 32%. And that was clinically significant. And we saw also, you know, slowing down in EZ attenuation, which is great. We saw good safety, right? The other point of these Phase 2s is to really look for safety signals, and there was no drug-related SAEs, no choroidal neovascularization, which is again something we're kind of growing used to with these GA trials. And so, that's, you know, that's what we saw. You know, there was one interesting thing: in the control group, four patients dropped out. It's interesting, right? Because these trials, you know, this is not a masked study in the sense that the patients know if they're getting treated or not. And it's not a knock against this trial, because the surgical trials often are constructed that way. Right, either the patient knows they're having the surgical procedure, or they know they're not having it. And then what happens in those cases is it's hard to retain those control patients, right? So these four patients that weren't evaluated, you know, the question is how do they skew the data. And so, hopefully, in a larger study we can kind of get rid of that noise as well.

GAMBUZZA: If this pans out, how would a subretinal surgical therapy fit into GA care alongside the injections we use today?

SHETH: Yeah, so, you know, again going back to what's the current, you know, care for GA patients is frequent interventional injections, monthly to every other month, and that's, you know, indefinite, right? And so if the value proposition to the patient is a one-time treatment, you know, certainly I can understand from a patient standpoint why that would be really something that they might gravitate towards. You know, there's also, so that's the patient view of it. The surgeon's view of it is really, you know, do we want to take on a surgical procedure for our patients? Do we feel like it's safe enough? Do we feel like it's worth the trade-off of multiple injections? And so that's the other side of it, from a surgeon standpoint. So we obviously are going to be very, you know, keyed in on safety and those types of things, and then workflow, right? You're taking something that we treat in the office every day and turning it into a surgical procedure. You know, do we have the capacity in the operating room? So these are all the questions we have to answer over time.

GAMBUZZA: Thank you very much, Dr. Sheth. Appreciate it.

SHETH: Thank you.

GAMBUZZA: Thanks so much to Dr. Sheth for breaking that down for us. Read the full study coverage by our producer Lynda Charters, linked in the description.

Every story from today is linked in the episode description, and you'll find all of it at OphthalmologyTimes.com. If this is useful, follow and subscribe wherever you're listening, and send it to the colleague who says they don't have time to read anything.

I'm Lucia Gambuzza. This has been this week's OT Roundup, we'll be back in 2 weeks.