Scott Walter M.D. M.Sc

Bonjour et bienvenue. Hello and welcome to the 44th annual ASRS Annual Meeting in beautiful Montreal, Canada. I’m Scott Walter, and on behalf of the SRS, I’m delighted to be joined by Dr. John Miller from the Mass Eye and Ear Infirmary.

John, thank you so much for joining us. Thanks for having me, Scott.

So John, your talk at the meeting is about methotrexate for proliferative vitreoretinopathy. This was a concept that originally came out of Mass Eye and Ear with Dean Elliott about eight years ago, and there’s been a lot of excitement about methotrexate.

We hear about it meeting after meeting, lots of small single-center case series. But a lot of these data sets that we’ve been looking at don’t have a great control group. And I know that recently the GARD trial was established as an effort to more scientifically approach this question of whether or not methotrexate really works, but there were some problems with that trial that led to some inconsistent statistical conclusions.

So tell us a little bit about why you decided to do yet another large single-center study of methotrexate and how your study was designed. Yeah, so we saw a real need to look at a control group with methotrexate, and we have a very large tertiary care center at Mass Eye and Ear.

As you said, we are one of the early adopters of methotrexate. So I hope to design a study to answer that question, because the GARD trial was just comparing to historical controls. So we looked at all complex retinal detachments repaired at Mass Eye and Ear with a CPT code for complex RD. We excluded eyes that had exudative, uveitis, trauma, and open-globe injuries to try to make a more homogeneous group. We found that there was no statistical difference when we looked at those who received methotrexate than those who received standard techniques.

And that was irrespective of whether they used the full GARD protocol of 13 injections or any of the other mixed protocols we’ve seen published. We also found there was no difference when we looked at those who had oil removed. That’s one potential other consideration.

I do think overall, the methotrexate may still have some benefit in various select cases like pediatrics, trauma, uveitis, or maybe our worst surgical disasters. But I think we need better biomarkers so that we deliver it to the right patients. Absolutely.

So just give us your impression. Are we still using methotrexate? If we thrown it in the wastebasket, where do we go from here? I think we’re still using it, but we’re still using it maybe more judiciously. I have been seeing more widespread use of it outside of even the basic thresholds that were applied for the GARD study.

Great. Well, thank you so much for joining us. On behalf of the ASRS, we appreciate you listening in to this exciting update from the field in Montreal, Canada.

Hello and welcome to the 44th Annual ASRS Annual Meeting in beautiful Montreal, Canada.

I’m Scott Walter, and on behalf of the ASRS, I’m delighted to be joined by Josh Walsh from the Retina Macula Institute in Torrance, California.

Josh, thank you so much for joining us.

Thank you for having me.

So since 2023, we’ve had the FDA approval of two intravitreal complement inhibitors, Syfovre and Izervay, for the treatment of our patients with dry AMD, specifically with geographic atrophy.

And now that we’ve had these in our hands in clinical practice for about 3 years, we’re starting to see some real-world evidence of efficacy and safety.

So tell us a little bit about what motivated you to look into this question that you approached with your study?

Well, I feel like it’s an important point to know the effectiveness of the two products compared side by side.

You know, in clinic, we can compare anti-VEGFs and other treatments. We can see the treatment effect on patients.

But with these drugs, we’re really relying on the data that’s out there to drive our understanding of what’s working and what’s not working.

And I feel like an important point in trying to determine which drug is the right choice for our patients is knowing how they compare side by side.

So that was really what drove me to do a comparative analysis of the two drugs against each other.

Absolutely.

I totally agree that it can be difficult in real-world clinical practice to measure GA lesion growth.

So tell us a little bit about the design of your study, how many patients were enrolled, and exactly what you looked at.

So we had a subset of 20 eyes from 12 patients that underwent treatment with both products.

They all ended up transitioning from Avacincaptad Pegol to Pegcetacoplan. It was due to insurance issues, but this was a good set of patients for us to utilize to actually compare their GA lesion growth rate while on Avacincaptad Pegol and on Pegcetacoplan, to compare whether these same eyes had similar effects with both products.

Very interesting.

So tell us what you found.

Well, I’ll get to the meat of it.

The two products work equally well, essentially.

They both slowed GA lesion growth rate. It was a statistically significant decrease from pretreatment levels.

Now, that wasn’t all 20 eyes, but we had 18 eyes that had pretreatment data, and both products slowed lesion growth significantly.

When comparing the two products side by side, there was no statistically significant difference.

The Avacincaptad Pegol group was 0.18 millimeters per year, and the Pegcetacoplan group was 0.21 millimeters per year, which is a very small difference between the two products.

Well, it’s certainly very reassuring to see.

Of course, we have the clinical trial data, which shows a similar efficacy profile for the different drugs, but to see an individual patient’s experience on both products showing comparable treatment effects is really reassuring.

So give us your take-home message for how this is influencing your treatment decision-making in the real world.

Well, I think it’s an important point that both products seem to be equally effective.

As clinicians, we can, in some ways, remove that from our treatment algorithm as far as which product to use and instead use other factors, such as safety and treatment burden, to decide which product we want to give to our patients.

Great.

Well, very interesting study.

Thank you so much for joining us this year in Montreal to share the results of this comparative analysis.

On behalf of the ASRS, thank you so much for joining us for this segment of Updates from the Field.

Hello and welcome to the 44th Annual ASRS Annual Meeting in beautiful Montreal, Canada. I’m Scott Walter, and on behalf of the ASRS, I’m delighted to be joined today by Dr. Odette Houghton from the Mayo Clinic in Arizona. Odette, thank you so much for joining us at this year’s meeting.

Thank you for having me. So we talk a lot about the safety of anti-VEGF agents, you know, safety is paramount to everything that we do in retina. And of course, we know a lot about the ocular safety profile of these medications, but something we don’t talk as much about is the systemic safety profile.

So I’m curious what inspired you to ask questions about the systemic safety of these agents. Well, it started from a simple clinical problem. Our retina service was frequently asked to stop the antivitrile anti-VEGF injections around the time of incisional surgery that was non-ophthalmic.

So our colleagues were concerned because it stemmed from the oncology literature, where systemic Bevishepimab increased the risk of wound healing impairments. There’s been very little human clinical data that has evaluated whether individual anti-VEGF increased the perioperative risk. We felt uncomfortable basing our decision on theoretical risk, and so we wanted to get real data, because the consequences of stopping the medication was potentially harming vision.

Absolutely, yeah. We don’t want to stop anti-VEGF therapy if we don’t have to, but on the other hand, we don’t want to compromise the results of the surgery or the safety of the surgery. So tell us how you went about answering this question.

What was the design of your study? Well, we went out to set out to perform a retrospective match multi-site cohort study using real-world data. We evaluated adults receiving interventional afliversep, Bevishepimab, and ran a vision map with dose one month before and three weeks after incisional surgery. Most of the surgeries were plastics, orthopedics, or vascular.

And then we matched these anti-VEGF patients, one to two, to controls based on surgical risk using the American College of Surgeon Risk score. We then looked at the medical records, and we looked for interoperative and post-operative complications, and we matched to a non-inferiority of 10%. Great.

All right. So it sounds like a very sophisticated approach. Yeah.

Tell me what were the results of the study. Well, we found that complication across the board were pretty low. It was less than 1% interoperative complications, and the post-operative complications was 14.3%. 5% in the controls versus 11.6% in the anti-VEGF group.

Interestingly, the anti-VEGF group had higher comorbidity rates, more anemia, diabetes, and kidney disease. So that was very interesting. And despite that, it still met the non-inferiority test.

Great. That sounds pretty reassuring, so let’s just kind of take it home into a soundbite. How do we answer the question if we’re asked by our non-ophthalmic physician colleagues who are looking to do some sort of incisional surgery, and they want us to stop the anti-VEGF, how do you respond to them now? Well, the message is really reassuring.

Individual anti-VEGF injections around the time of incisional surgery does not increase post-operative risk or wound healing risk. I know you have to treat every case individually, but the evidence from our data does not support routinely stopping anti-VEGF injections for these surgeries, nor does it support stopping or holding the surgery for our anti-VEGF injections. Great.

Well, thank you once again for this important contribution to our understanding of the safety of anti-VEGF therapy, obviously our workhorse drugs in retina, and we appreciate your contributions this year at the annual meeting in Montreal, Canada. On behalf of the SRS, thank you so much for joining us today.

Bonjour et bienvenue.

Hello and welcome to the 44th Annual ASRS Annual Meeting in beautiful Montreal, Canada.

My name is Scott Walter, and on behalf of the ASRS, I’m delighted to be here providing coverage of the meeting.

Joining me today is my guest, Christina Wang from the Baylor College of Medicine, who really needs no introduction.

Christina, thank you so much for joining us.

Thanks for having me, Scott.

And it’s never less weird to be on this side of the mic, so hopefully this will go well.

So you’re talking about proliferative vitreoretinopathy. Obviously, one of the greatest challenges we face as vitreoretinal surgeons is when we encounter these recurrent retinal detachments following an otherwise uncomplicated primary rhegmatogenous retinal detachment repair.

And it’s so frustrating when we see these patients.

There’s been a lot of enthusiasm in recent years about methotrexate as a potential pharmacologic strategy, but we still don’t have an FDA-approved therapy that’s really scientifically proven to modulate the PVR response.

So your study looks at statins as a prevention strategy for PVR. I’m curious, what led you to ask this question in the first place? What is it about statins that made you curious to delve into this?

Well, thanks again for having me, Scott.

And you’re absolutely right. The nemesis of every retina surgeon is PVR. Yet, as devastating as its consequences can be, it is really not that uncommon. It occurs in about 10% of our primary RD repairs.

It amazes me that with all the advancements we’ve had in 2026, we still don’t have an FDA-approved therapeutic for the prevention or treatment of PVR.

In this study, we’re looking at statins. You’ve mentioned methotrexate. There’s great data from the GUARD study and other studies. That said, there are some real challenges because it’s not FDA-approved, it’s still used off-label, and it’s going to be hard to access unless you’re close to a compounding pharmacy.

It also requires a really heavy treatment burden, and that’s probably the biggest drawback right now of using methotrexate.

So you’ve got to think back to biochemistry days with statins, which are HMG-CoA reductase inhibitors. But I think people forget, because they’re the most commonly prescribed drug for high cholesterol, that they are also pleiotropic drugs.

They have anti-inflammatory and anti-fibrotic effects, and they’ve been shown to inhibit IL-6, IL-8, and MCP-1 in RPE cells, which obviously has implications for PVR.

Our study really sought to look at the potential effect of statins on the incidence of PVR and complex RD reoperation following a primary RD repair.

Very interesting. So you have some sound scientific basis for looking into this question.

Tell us how you went about actually collecting the data and analyzing it for this study.

We utilized the TriNetX Federated Database, and we used that large database to identify patients who had undergone a primary retinal detachment repair and also had a history of dyslipidemia.

Then we divided them into two groups: one group who were on statins at the time of repair, and the other who had no history of statin use or antilipemic use.

Of course, you’ve got to adjust for potential confounders, so we propensity score-matched these patients based on nine different factors—the things that you would think might be linked to PVR, like giant retinal tears, vitreous hemorrhage, history of trauma, age, race, and all of those nine factors.

That left us with two cohorts of about 4,000 patients each that were relatively well balanced.

The outcomes we were looking at were the incidence of PVR and the incidence of complex RD reoperation within a one-year time period following the index RD repair.

That’s the way we structured the study.

I do want to give kudos as well to my co-authors, especially Jawad Muayed, Darius Bourdbar, and Asad Loya, who did a lot of this work.

Yeah, clearly working with these large databases takes a lot of statistical expertise. I commend you for assembling a team that’s able to do this in a rigorous way.

So tell us what you found in terms of how statin use might modulate the PVR risk after primary rhegmatogenous retinal detachment repair.

It was really interesting.

We found that in this database study, statin users had a 47% lower risk of developing new-onset PVR and had a 48% lower risk of needing complex RD reoperation compared to non-statin users, which is really exciting.

We also took it one step further and were one of the first studies to look at dose response.

There appeared to be dose-response evidence such that the highest intensity levels of statin use provided the most consistent protection, although we demonstrated statistically significant benefits across all statin intensities.

So, really exciting findings.

Absolutely.

Well, this is really wonderful news for our patients, and hopefully we’ll have prospective data in the future that can guide us on the potential use of statins in this context.

Once again, my name is Scott Walter.

I’m delighted to be here with Christina Wang on behalf of the American Society of Retina Specialists.

Thank you for joining us in Montreal.