Melanie Cole, MS (Host): Welcome to Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole. And today, we have two expert guests from Northwestern Medicine joining us for a panel roundtable to share conference highlights from the 2023 Annual Meeting of the American Academy of Ophthalmology. Joining us is Dr. Robert Feder, he's the Director of Cornea Service and a Professor of Ophthalmology at the Feinberg School of Medicine, Northwestern University; and Dr. Manjot Gill, she's a Professor of Ophthalmology and Medical Education, and she's the Director of Vitreoretinal Fellowship at the Feinberg School of Medicine, Northwestern University.

Doctors, thank you so much for joining us today. Dr. Gill, I'd like to start with you. I'd love you to tell us about the retina highlights from the 2023 AAO Annual Meeting. Which presentations stood out to you? And what were some of the most exciting research breakthroughs that you saw?

Manjot Gill, MD: Hi, Melanie. Thank you for having me here today. I think I'll begin by discussing the realm of macular degeneration and specific non-exudative macular degeneration or dry AMD in the area of geographic atrophy. Currently, we don't have, or at least we didn't have, really any treatment options available for treating patients with geographic atrophy. And most recently, we do have an FDA-approved drug. So, what was presented were some of the further analysis on some of the agents that are currently used for non-exudative macular degeneration.

So, the first was the two-year results of the GATHER2 trial that looked avacincaptad pegol for geographic atrophy. This basically looked at examining the two years outcome of patients who were treated every other month compared to every month. And they saw that in year two, there was a statistically significant decrease in the geographic atrophy lesion growth compared with sham, while patients who were continued to be dosed every other month saw comparable results. So in other words, the year-two study, whether patients were treated every other month or monthly saw fairly comparable reduction in geographic atrophy lesion growth.

So, this is pretty exciting. It does validate what was found already at year one with this agent. And it is encouraging to see that, even in year two, we're still continuing to see comparable results, whether or not patients are dosed with monthly versus every other monthly intravitreal injections. So, that was really looking at absolute reduction in geographic atrophy growth.

Similarly, the GALE one-year data were presented. And so, the GALE study is evaluating a second agent, which is pegacetocoplan. This looked at treatment of geographic atrophy. This was an extension study on the drug Syfovre. Basically, it's giving us results on the long-term efficacy and safety of Syfovre following the two-year phase III studies. And it also did find that patients that they continue to show reduction in geographic atrophy, lesion size that continued into year three of treatment. And so, that treatment effects continues to increase as patients continue on with these drugs. So again, a very encouraging finding in this realm of treating patients with geographic atrophy.

Melanie Cole, MS: Thank you for that. Dr. Feder, why don't you tell us about the cornea highlights that stood out for you?

Robert Feder, MD: Okay, Melanie. It's great to be here with you and with Dr. Gill. Before I tell you about the scientific highlights, I want to tell you about a highlight that was very special to me at the Academy. one of my good colleagues, Dave Verdier, has been a cornea specialist for decades and very respected. He was invited to give the Payton Lecture. And the Payton Lecture is a very prestigious talk, given to roughly 500 corneal specialists, who are both domestic and international. I was off teaching another course on cataract surgery, so I wasn't able to hear Dr. Verdier's talk. But all of a sudden, I start getting all these texts from colleagues of mine. And apparently, Dr. Verdier singled me out during his speech as one of his mentors. And I bring this up because obviously this meant a great deal to me to be singled out in this way in front of such an audience of cornea specialists. But both Dr. Gill and I, we are in a position of mentoring every day. Every day we come to work, we're mentoring young physicians, fellows, and residents. And it's just incredible when you're recognized for your mentorship.

So back to the question that you asked me, Melanie, about the highlights of scientific cornea, I've watched the development of cornea transplant surgery from penetrating keratoplasty full-thickness transplant to partial-thickness endothelial keratoplasty, both DMEK and DSAEK. And what I witnessed was what I think will be the future of cornea transplant surgery. And this is the injection of cultured endothelial cells into the front of the eye. And then, these cells know where to go after three hours of the face-down positioning. And those endothelial cells will repopulate the back of the cornea and pump out the excess water in patients with bullous keratopathy.

So, Dr. Kinoshita, who's done a lot of the landmark research, he's treated 65 patients in Japan, and he found no increase in intraocular pressure with injection of these cells, no malignant transformation, and little immune response to these cells. And what was presented at the Academy this year was five-year data. He presented the corneas, showing the corneas clearing, that the thickness decreased and the cell count increased. Visual acuity was stable. And now, this procedure of injecting cultured endothelial cells has been approved in Japan. In doing this culturing, you can take one cornea and you can treat a thousand patients because you're going to culture these cells and grow these endothelial cells. It's an absolutely revolutionary way to approach endothelial dysfunction.

Another exciting research project that I learned about was the development of synthetic biopolymers, which can be used to, in a sense, spackle thin areas of the cornea. So if you've got an area where the cornea has melted, you could just put some of this substance in that thin area. And one of my colleagues here at Northwestern, Ramez Haddadin, is currently doing research just on this with a different biopolymer than the one that was presented at the Academy. Really exciting stuff, artificial cornea. So instead of injecting cells or injecting tissue, there is a new flexible 50-micron thin artificial endothelial layer. Now, this is not tissue. This is an artificial endothelium that matches the posterior curvature of the cornea. This is manufactured by a company Ion Medical in Israel. And basically, you take a patient with corneal swelling. And you stick this artificial endothelial layer in, push that up against the back of the cornea, and the corneal edema will decrease. Now, these are not devices designed to make somebody 20/20 or even 20/40. But in third world countries where they don't have access to tissue to be able to place an artificial cornea into the front of the eye, and then have that clear the cornea, reducing pain from bullous keratopathy and improving vision somewhat, can be an incredible, incredible device.

So, there are many more topics that I could speak about and maybe we'll come back to later, but these three I found particularly interesting.

Melanie Cole, MS: What an exciting meeting. Thank you both for sharing that. Now, Dr. Gill, will you be leveraging any of these learnings into your practice? Were there any standout findings that you think could directly influence how you're approaching patient care?

Manjot Gill, MD: Yes. You know, we discussed kind of the new area of geographic atrophy, which really there hasn't been a lot by way of treatment. I reviewed some of the long-term data on those studies, but we recently had another FDA-approved drug, faricimab, which is a combination of a VEGF inhibitor and an Ang-2 inhibitor. And they did report on the effect on eyes that have pigment epithelial detachments. Now, these can be very difficult-to-treat eyes, and can often be refractory to treatment. So, a post hoc analysis was performed and reported on pooled data from the TENAYA and LUCERNE trials, and they found that eyes that were treated with faricimab found greater reductions in pigment epithelial detachments than aflibercept in head-to-head dosing within the study.

So specifically, they found that the time to absence of intraretinal fluid and subretinal fluid was achieved at week eight with a median of two injections in those that received faricimab compared to week 12 and three injections with aflibercept. And they also found that eyes that had a serous pigment epithelial detachment at baseline showed a lower proportion of those who received faricimab, and that continued to show the presence of a serous PED at week 12 compared to eyes that were treated with aflibercept. And essentially, what this points towards is in eyes that have pigment epithelial detachments and fibrovascular pigment epithelial detachments. One may want to consider treatment with faricimab given these favorable results.

Another area that is worth mentioning is the high dose aflibercept. This is looking at eight milligram of aflibercept. And the results of that was presented in the context of diabetic macular edema and the results in exudative macular degeneration had already been presented at an earlier meeting this summer at the ASRS meeting. So at Academy, they reported on an ongoing 96-week non-inferiority trial that reported on eight milligrams of aflibricept in patients with diabetic macular edema. And what they found was that the mean change in baseline visual acuity with eight milligrams versus two milligrams had achieved its primary endpoint of non-inferiority. So, this, you know, certainly is very promising when we think about treating patients going forward. It just certainly gives us many more treatment options in terms of approaches to patients.

Melanie Cole, MS: Dr. Feder, take us from bench to bedside. Will you be leveraging any of these learnings into your practice? Tell us what stood out for you.

Robert Feder, MD: Yeah, there's no doubt. One area was use of different medications for different conditions. For example, there's a terrible disease called acanthamoeba, amoebiasis of the cornea. There are certain medications that we typically use. What you're wanting to do is kill the cysts of the amoeba. One report showed that PHMB, which we typically use in a lower concentration can be used safely in a higher concentration of 0.08%, tolerated well and more effective as a cysticidal agent. There's another agent also called miltofosine. But that is very effective in killing the acanthamoeba, but creates a lot of inflammation in the eye, and you need to be careful of managing that inflammation. Another medication used in the cornea in a novel way was insulin, topical insulin, one unit per mL, given two to four times daily for neurotrophic keratitis. So, I never thought to use insulin in this way, but it's certainly something I'm going to be thinking about. There was a conversation about the use of tacrolimus as a steroid-sparing agent, the 0.03% tacrolimus. It's not approved for use in the eye, but can be a way of reducing topical steroid.

With regard to EK, endothelial keratoplasty, following glaucoma surgery, what was found was that DMEK, there's a real trend towards doing DMEK, which is just a Descemet's endothelium transplant rather than stromal tissue with Descemet's endothelium. But they found that there was an increased cell loss with DMEK compared with DSEK and increased re-bubble rate with DMEK. So in cases where patients have had glaucoma surgery, it could be that DSEK would be the preferable way of performing the endothelial keratoplasty.

And finally, you know, we think of corneal dystrophies as sort of static. We know these dystrophies exist. We know the names of the dystrophies and what they look like. But every once in a while, someone presents something that's completely novel, something that we've not seen before. And that's what Tony Aldave did when he presented a variant of macular dystrophy that he found in families in Vietnam and Thailand. And these, in contrast to the macular dystrophy that we're used to, had posterior opacities in the periphery of the cornea with corneal edema, but no haze or central opacities that you would typically find in macular dystrophy. So, really exciting different ways of using medications and diseases that we should be looking for in this particular population.

Melanie Cole, MS: Dr. Gill, summarize for us some of the takeaways and highlights from presentations from your colleagues at Northwestern Medicine.

Manjot Gill, MD: So, another trial that I would draw attention to is, once again, we have more and more experience with some of the real-world data on faricimab. And the far retina macular degeneration real world outcomes was presented and researchers evaluated information from the iris registry to assess the efficacy and safety of faricimab in eyes with neovascular AMD. And what they found is that most eyes had been previously treated, whereas the smaller percentage were treatment-naïve. Majority of patients were switched from previous treatment with aflibercept. About half of the patients had visual acuity of 20/40 or better at the time the faricimab was initiated, and this held steady, those patients that were switched from one drug to another, while those that were treatment-naïve did experience a gain of 3 letters. The fluid had decreased in all eyes that were treated with faricimab with respect to the central subfoveal thickness. And the interval was able to be extended for more than 50% of eyes after one or two injections. The real-world data does help support a lot of the findings that we would have anticipated based on the phase III clinical trials and that, you know, the majority of patients who are switched over are able to retain vision and at least half of eyes can be extended. So, this really is a significant step forward in our management of patients with macular degeneration.

Melanie Cole, MS: Dr. Feder, what about your colleagues at Northwestern Medicine? Was there anything exciting? You've already mentioned one at the beginning today, but tell us any others that stood out.

Robert Feder, MD: Well, I have something very exciting to share. But before I do, I just want to point out a few takeaways that were very meaningful to me. I listened to a lecture by Carol Shields, who is always just a phenomenal speaker. And she was talking about complexion-associated melanosis of the surface of the eye, pigmentation on the surface of the eye. And she pointed out that microfolds. When you see microfolds at the limbus, that that is a benign appearance and more likely to be CAM, complexion-associated melanosis, in contrast to PAM, primary acquired melanosis. And the point she made, and I've heard her make this point before, so important, always flip the lid, because the pigment that you're seeing on the surface might be looking benign, but underneath the lid is where you might find the conjunctival melanoma.

Lodolaner is a new drop that is available for Demodex eradication. And Demodex is a common parasite that can cause acne rosacea as well as lots of inflammation on the lid margin. So, that's a new treatment for that.

And finally, a takeaway is if you use the iDesign platform for refractive surgery and you're doing retreatment. You don't want to use the iDesign for the retreat. You'd want to use conventional and treatment instead. But on to the person that I wanted to mention, David Chang always does a four-hour cataract surgery symposium. And I would encourage anybody interested in cataract surgery to attend this symposium with panelists. He brings in a new panel to discuss each different topic in complex cataract surgery. And this year, our very own Surendra Basti, who we know to be a guru of cataract surgery here at Northwestern. He was the co-moderator of the symposium and did a phenomenal job. Things we learned about from the panelists were management of rock hard cataracts and the use of chopping and the miLOOP device and vertical chopping for the rock hard lens and creating a capsulorrhexis that would allow optic capture if that was necessary. Obviously, we're interested in the light-adjusted lens. The light-adjusted lens is a lens that can be modified with ultraviolet light after the surgery to try to tweak it. And one of the things that was very interesting is there was a study that showed that when light-adjusted lenses are used post refractive surgery, that only 30% had 20/20 at the end of the day. So, the light-adjusted lens may not be that great for the post-refractive patient.

And finally, Sam Masket, who is a great speaker and has done a lot of research on dysphotopsias, which are either unusual lights that patients will see after cataract surgery or negative dysphotopsias, which are shadows that people will see after surgery, which can be quite troubling. Now, Sam Masket pointed out that positive dysphotopsias, meiotics can be helpful. But the negative dysphotopsias, these are the ones that are dark shadows, the meiotics actually worsen the symptoms. And so for negative dysphotopsia, you may need to do surgery with reverse optic capture where the haptics are in the bag and the optic is in front of the capsular bag.

And then, the final thing I'll mention is the Kelman lecture, which was given by one of Dr. Basti's mentors. And he was looking at the errors in different formulas for calculating the power of implants. And what he found was that it was really the final position of the lens, either more anterior or more posterior that determines the refractive error postop. So, that's something we should be thinking about. So, kudos to Surendra Basti, my good friend and colleague, and Dr. Gill's good friend and colleague, who co-moderated this incredible four-hour symposium on cataract surgery.

Melanie Cole, MS: Well, thank you for sharing that about Dr. Basti. He's always a great guest on Better Edge. So, listeners can look up and hear him on these podcasts as well. I'd love to give you each a final thought here. So Dr. Gill, is there anything else, any other important information or learnings that you would like your colleagues who may not have been able to attend to know about in Retina Sessions?

Manjot Gill, MD: Well, I will just share, there was one interesting study that was presented and, you know, mind you, we have to be careful how much we can actually draw and we are learning more and more through AI that the retinal microvascular can really be a clue to systemic disease. And what they found was that patients who had a history of retinal vascular disease, particularly central retinal vein occlusion, were much more likely to develop dementia. So, what they did was find that patients who had presented with retinal vein occlusion had an odds ratio of 1.74 compared to the control group of a greater risk of developing dementia. And that risk was particularly higher in individuals who were of African-American origin compared to the white population. So, certainly, there is a correlation and certainly warrants further investigation. But I always find the association of retinal vascular disease with systemic disease to be very fascinating. And I think this is an area that we are going to be learning more and more on as time goes on.

And kind of on the same note as AI, another study was presented that looked at using multi modal AI risk scoring to predict development of referable diabetic retinopathy. What they found is that through AI models, they were able to evaluate retinas and identify which eyes with patients who currently have mild or no diabetic retinopathy are going to likely need treatment or within three or five years using a deep learning model. So, this is, I think, an area that we are going to just see an explosion of information and will validate already what we know, is that the utility of AI is just going to really just transform how we manage and care for our patients.

Melanie Cole, MS: Thank you, Dr. Gill. And Dr. Feder, last word to you. Is there anything else, anything important that you'd like to share with colleagues that may not have been able to attend or know about for Cornea Sessions?

Robert Feder, MD: Let me just start by saying, I really appreciated being on this podcast with Manjot Gill. I don't spend a lot of time learning about retina studies and I feel like I've had like a mini course on what's new in retina from Dr. Gill. So, I really appreciate that.

The final thought that I have is, for several years during the height of COVID, we would not attend live Academy meetings. So, we did it virtually, which was the next best thing. But to attend the Academy live and be with your colleagues and have dinner with your colleagues and chat about the symposium that you attended or the research project that you heard about, it's absolutely wonderful. And next year, it'll be wonderful being in Chicago, our hometown. And we welcome everyone listening to this podcast to come to the Academy live in Chicago next year.

Melanie Cole, MS: I want to thank you so much, both of you, for joining us today and sharing those highlights from the annual meeting of the American Academy of Ophthalmology. Thank you again. This was fascinating and so interesting to listen to. And 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. And that concludes this episode of Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole. Thanks so much for joining us today.