Melanie Cole, MS (Host): Welcome to Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole. And we have a round table thought leader conversation for you today with three Northwestern Medicine physicians to share conference highlights from the 2024 annual Meeting of the American Academy of Ophthalmology with insight from glaucoma, cataract, and retina specialists, as they reflect and share their key takeaways from the event, which took place in Chicago.

Joining me is Dr. Angelo Tanna, he's the Vice Chair in the Department of Ophthalmology, the Director of the Glaucoma Program, and a Professor of Ophthalmology; Dr. Surendra Basti, he's the Director of Cataract Service and a Professor of Ophthalmology and Vice Chair for Innovation; and Dr. Manjot Gill, she's a Professor of Ophthalmology and Medical Education and Vice Chair for Quality, Safety and Performance.

Dr. Tanna, on to you.

Angelo Tanna, MD: Thank you. Thanks, Melanie. So, we had a great academy meeting, and I would love to hear my colleagues' thoughts on some of the most important topics that were addressed during the meeting and their subspecialties. Let's start with Dr. Basti. Surendra, in the cataract surgery and cornea world, what did you find to be the most important and exciting new discussions at this year's academy meeting?

Surendra Basti, MD: Thank you, Angelo. An important study that we got results of at the American Academy of Ophthalmology meeting is the study called the ZEDS Study, Z-E-D-S study. And this is a study that evaluated where the patients who get shingles need a prophylactic dose of antivirals given to them over the course of the first year after the episode of shingles. All patients who have shingles get antivirals for the first 10 days. But many of those patients, over the first 12 to 18 months have recurrent episodes of inflammation in the eye. And so, this study was designed to address the question whether giving prophylactic antivirals, specifically valacyclovir, would decrease the episodes of ocular inflammation that patients with shingles tend to get over the first 18 months.

And in this study, there were two groups, one that received the antiviral, the second group, which received the placebo. And so, the results of the study are well-founded in that they showed a 26% decrease in the amount of ocular inflammation episodes that these patients developed in the first 18 months, a 26% decrease in the group of patients that got the antiviral. So, it's a very clear benefit that patients who get prophylactic antivirals in the first 18 months have. So, it's a study that gave us results that we can put to practice immediately. And so, I thought I would bring that up as an important revelation at the AAO meeting.

Angelo Tanna, MD: Yeah, that's a very important finding. I completely agree. So instead of just 10 days of treatment with oral valacyclovir, patients with herpes zoster ophthalmicus, we're going to treat them now for a full year with valacyclovir. What was that dose, Surendra?

Surendra Basti, MD: So, it's one gram of valacyclovir for a year.

Angelo Tanna, MD: One gram daily for one year. Anything else that caught your eye in the corneal world?

Surendra Basti, MD: Well, another important report that was very revealing was a clinical experience with 26 patients that was reported from a group in India for patients with an inherited condition called Peters anomaly. So, children with Peters anomaly are born with a corneal opacity. It's thought to be a developmental disorder where the patient has a corneal opacity at birth in Peters anomaly. And a corneal opacity seriously interferes with vision development in that eye. And doing a cornea transplant, the traditional cornea transplant, has an extremely high failure rate, which is why the results of this study was relevant. And what these authors did was they peeled the Descemet's membrane and endothelium in the central six millimeters of the cornea, and let the peripheral endothelial cells proliferate and cover the cornea. So, this was a study where just the central part of the Descemet's membrane and endothelial cells were peeled off.

And over the course of three months, the cornea began to clear because presumably the endothelial cells from the mid-periphery and periphery began to proliferate and cover the area of endothelial defect. So effectively from the three-month point onward, these patients showed significant clearance of the cornea without really having a traditional cornea transplant. So, this study I think was the other important revelation at this meeting for me.

Angelo Tanna, MD: That's fascinating. That's similar to what others have tried with Fuchs' corneal dystrophy, and with adjunctive use of a Rho kinase inhibitor like ripasudil. Was that also used in these Peters cases?

Surendra Basti, MD: It was. So, that's quite central to promote endothelial proliferation. And so, yes, these patients had both peeling of the Descemet's membrane and topical ripasudil eyedrops.

Angelo Tanna, MD: That's fantastic information. So, how about in the world of cataract surgery? What news did you find to be the most important at Academy this year?

Surendra Basti, MD: The most important takeaway for me in the cataract surgery arena was the emerging role of office-based surgery for routine cataract surgery, that many surgeons had begun to incorporate. So, traditionally, we've done cataract surgery in ambulatory surgery centers or hospital settings. And it's becoming obvious that there may be a place for office-based cataract surgery for patients who are otherwise healthy, whose cataracts are what we consider routine. And I was surprised myself at the experience that was reported at the Academy.

We had many practices where they had gone through accreditation with either JCAHO or AAAMC, I think they call it, both accrediting agencies, which ensured that the surgery is being performed under standard conditions in terms of sterility and so on. But the surgical suite itself was located in the office, so it's in some ways similar to office-based oculoplastic surgery or even LASIK surgery that we perform, except that in these suites, these surgical suites, intraocular procedures are performed. And the impetus for exploring this option really comes from surgeons having difficulty with getting surgical times in ambulatory surgery centers and hospital settings, which I think has been an important prompt for surgeons to explore this kind of option. And it really took me by surprise that the interest in this option, the American Academy of Ophthalmology entrusted me with conducting a symposium on this topic where we looked at the pros and cons of every element of doing office-based procedures, medical, legal, billing, anesthesia, risks, and so on.

So, we had a very productive and informative symposium at the Academy on Sunday where all aspects of office-based surgery were explored. It's interesting to note that this is clearly out there. I have myself visited a setting where this is done at Chicago Cornea Consultants, and it seems like there are practices across the country that are exploring this in earnest. Many that have put this already in place. And, you know, I predict that this is something that we'll increasingly hear in the times ahead. So, this was another important revelation in the field of cataract surgery for me.

Angelo Tanna, MD: That's great information too. And I agree, it's an exciting area. Let's shift gears and go to retina. Dr. Manjot Gill, what were your most important highlights from Academy this year?

Manjot Gill, MD: Thanks, Angelo. You know, there were several, so I'm going to start first with an area that I think is of importance to all of us, no matter what field of Ophthalmology we're in. And that is really looking at representation of underrepresented minorities in research and clinical trials. So certainly, you know, we see patients from underrepresented minorities in our practices every day. And generally, in relation to diabetic retinopathy, they'll often have more aggressive disease with poor outcomes, but unfortunately, they are not well represented in many clinical trials.

So, an attempt to look at this, the ELEVATUM study was an open label study for the treatment of patients with DME or treatment-naïve. And they were followed for a year with an extension study into two years. So, the results of this were reported at subspecialty day, and it really, really was exciting. They were able to meet their recruitment goal. The study did show very quickly and found that there was about 45% African American patients enrolled, 45% Latino, and 10% American Indian Pacific Islander. And the results were really quite amazing. So, what they found was that at baseline, Hispanic patients tended to have worse visual acuity and thicker retinas, compared to say the African American population. But the Hispanic patients tended to, even though they started with worse vision and thicker retinas, they were the ones who gained the most visual acuity and had the best drying effect.

African American patients also gained visual acuity, but had a little bit less in terms of drying compared to the Hispanic population. But these results were generally seen very, very early on. So, what it's telling us is that the understudied populations really have so much potential for improvement. So, it really should encourage us to do a better job in trying to identify these patients very early and then start treating them very aggressively early on. So, I certainly think that this was a very important study and the results of this are very important, which have real tremendous implications for how we manage this sometimes very difficult-to-treat disease in very challenging patient populations.

Another study that I thought was interesting, particularly given that, you know, it's COVID season is sort of upon us, and there's always a question surrounding COVID vaccinations, was looking at the association between COVID-19 infection and vaccination and retinal vascular occlusion, both arterial and venous occlusion. There have been some kind of anecdotal case reports and some question of whether there is an association between COVID-19 and vaccination and these occlusions. And what they did in an attempt to answer this question was look at the iris registry. And they looked at all the retinal vein occlusions that were diagnosed from 2017 to '19 to sort of establish a baseline, and then compare it to actual diagnoses post COVID from June '20 to '22. And they concluded that there was no increase in the number of patients who presented with retinal vein occlusions in the latter time period.

So, I think this will hopefully answer the question that there really is no association or causation with COVID-19 and retinal vascular occlusions in particular. They also looked at vaccination, and a big data source in South Korea found no increase in arterial or venous occlusion after COVID-19 vaccination. Another study looked at over three million patients who were vaccinated for COVID-19 and found an extremely low rate of retinal venous occlusion, less than 0.003% within the first 20 days after the first dose. Although there have been multiple cases of retinal disease that have been reported anecdotally after infection or vaccination, the causality has not been borne out in these large databases. So, that should be reassuring to us and it should be reassuring to be able to tell our patients.

Angelo Tanna, MD: It's a really powerful use of virus registry. You know, big data can be misused sometimes, but this is a really good example of an important finding that we can, I think, hang our hats on to some degree. So, that's great information. Dr. Gill, we had discussed some interesting findings about geographic atrophy. Why don't you share those with the group?

Manjot Gill, MD: Yes, absolutely, Angelo. So, you know, as we all are aware, we now have two FDA-approved complement inhibitor drugs that have been shown to slow disease progression in phase III trials. So, this is an exciting time for geographic atrophy in that we sort of are at the forefront of some therapeutic options. But we know that not all patients experience significant best corrected visual acuity improvements. So, a study was done looking at the AREDS1 and AREDS2 populations to determine which eyes, which kind of baseline characteristics were associated with deteriorating best corrected visual acuity in the hopes of trying to identify patients which may be more likely to benefit from these complement inhibitors.

So, what the researchers concluded was that patients who had better best corrected visual acuity at baseline, geographic lesions that were closer to the fovea, and that those that demonstrated a higher rate of geographic atrophy growth, that these were the cases that were more likely to get the most from geographic atrophy growth-slowing treatments. So in other words, cases that have atrophy near the fovea with a better starting visual acuity were more likely to be the ones that could derive the most benefit from treatment.

Sort of as a secondary area of geographic atrophy and treatment options for our patients was looking at the value of AREDS2 supplementation. It's well known that AREDS2 supplementation can decrease the risk of progression to late macular degeneration, but we've really kind of assumeD that it doesn't do a lot for geographic atrophy growth. And, again, looking at the ARED1 and ARED2 study populations, a post hoc analysis was performed and what they actually did find was that patients on AREDS show a slower progression of growth of the geographic atrophy to the macular center point, and it slowed the growth by about 55%. So, this really does support that this low-cost oral supplementation can be a benefit to patients who are later in the course of their disease. So, this is really exciting, and something that we can certainly feel very comfortable advocating for our patients, even with more advanced geographic atrophy.

Angelo Tanna, MD: That's great information that we can put to use right away. Thank you, Manjot. So, shifting gears, I'll cover some glaucoma topics that I think are of interest. About two years ago at Academy, the results of the LIGHT trial were reported, and the LIGHT study compared newly diagnosed ocular hypertension and primary open angle glaucoma patients treatment outcomes after either initial medical therapy, or initial SLT. And the six-year report demonstrated that patients who underwent SLT first were less likely to require glaucoma surgery, and they were also less likely to exhibit progression. So, that has really led to more widespread use of SLT as initial therapy.

So, there's an NIH-sponsored clinical trial right now called COAST clarifying the optimal application of SLT, and we're participants at Northwestern in the COAST clinical trial. What we're looking at is two separate questions. The first question was Is low-dose or low-energy SLT similar in efficacy to standard energy SLT? So, standard energy is when you see cavitation bubbles with laser application. Low-energy SLT in the COAST clinical trial used 0.4 millijoules per spot.

So, what was found and reported at Academy was that the low-energy group, after one year, had a higher failure rate. And so, we now know the answer to that important question, which is that low energy is not as effective in terms of duration of IOP control, as standard energy. So, there was also a study that was performed in Europe that addressed a similar question and came to a similar conclusion that low energy was not as effective as standard energy.

So, the COAST clinical trial continues. The second phase of COAST is set to answer the question of whether annual low-energy SLT for patients who had successful pressure control after standard energy SLT do better or as well as patients who receive as-needed standard energy SLT. So, it will take another few years, I'm sure, to arrive at an answer to that question, but it's an important question and will continue to be studied in that multi-centric clinical trial.

Another interesting finding recently reported from Europe was the results of the Treatment of Advanced Glaucoma Study. It's called TAGS, Treatment of People with Advanced Glaucoma. And this study identified newly diagnosed patients with primary open angle glaucoma that was advanced in nature. So, they had a mean deviation of negative 12 decibels or worse, a threat to fixation in both hemispheres, so people with very severe visual field damage. The people who are enrolled in the study, the mean deviation was about -15 decibels, so severe disease. Patients that were 450 enrolled, approximately, were randomly assigned to undergo trabeculectomy first or medical therapy. And what was observed after five years of observation was that the patients who had trabeculectomy first had lower intraocular pressures, about two and a half millimeters of mercury lower than those in the medical treatment group. And they also had less visual field progression. So, the difference in the worsening of the mean deviation was about 2.5 decibels in favor of trabeculectomy first.

So, this is an understudied population historically. It's the first study to really carefully look at patients in a prospective fashion, patients with advanced stage glaucoma. And I think it's very important information that we know now that progression was slower in the group that underwent trabeculectomy first.

Another aspect of the study, in fact, the primary outcome measure was quality of life. And I think it's important to say that there was no difference at the five-year mark between those two groups with respect to quality of life. So, that's something to consider as well. I'm sure that the study will continue to report very important findings that will guide our therapy of these patients with advanced disease. And I very much look forward to continuing to see those results.

So, we had a really great Academy this year with lots of interesting findings. And I hope that our discussion with these experts today was helpful to everyone who's listening.

Melanie Cole, MS: Thank you all. I want to thank you all so much for joining us today and sharing those highlights from the annual meeting of the American Academy of Ophthalmology. To refer your patient or for more information, please visit our website at breakthroughsforphysicians.nm.org/ophthalmology to get connected with one of our providers.

That wraps up this episode of Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole. Thanks so much for joining us today.