The Next Cycle of Retinal Surgery Innovation, with Stanley Chang, MD

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If you want to predict the future of eye surgery, ask someone who has pioneered the techniques used today.
OIS Podcast host Firas Rahhal, MD, speaks with Stanley Chang, MD, recipient of the OIS Lifetime Innovator Award at the OIS Retina@ASRS, about how the surgical innovations he pioneered in the 1980s and 1990s have come full circle.

Dr. Chang was the first to use perfluoropropane gas in the management of retinal detachments caused by scar tissue proliferation on the retina, a condition known as proliferative vitreoretinopathy (PVR). In the 1980s, he used sulfur hexafluoride (SF6) and perfluoropropane (C3F8) gasses in vitreoretinal surgery, but he wanted to find a longer-lasting gas, just as drug developers today want longer-lasting therapies for retinal disease.

Dr. Chang predicts the next cycle of innovation may bring a new gene therapy, drug delivery device, or compound that provides even longer-lasting benefits. To brings those innovations to market, however, Dr. Chang emphasizes that physician-researchers need strong scientific and corporate teams.

Listen to the podcast to hear Dr. Chang discuss:

• What drove the process for the use of perfluoropropane gasses and perfluorocarbon liquids in retinal surgery.
• What he views as the future of eye treatment, and why he hopes patient benefit will prevail over dollar volume.
• The next step for tamponades used in retinal detachment surgery.

Click “play” to listen.

TRANSCRIPT:

Firas Rahhal: Stanley in the beginning, and I saw some of this and we just heard numerous high-level experts talk about it. Those early advances in complex vitreoretinal surgery that we’ve all just talked about for a few minutes, how you brought it along, how you brought along the tools, the gases. What was that? Like? What was driving the process other than your own will? How did you come up with these tools?

Stanley Chang: Well, when I finished fellowship during fellowship, I was exposed to SF six gas who Ed Norton and Bob Machemer had developed at Miami and when I was a resident mass I near they never used expanding gases. So when I went to Cornell, I was quite interested in the subject. And Harvey Linkov who was there had found the family of gases called perfluoro propane, perfluorocarbon gases and these gases. One of them C3f8, lasted almost two months in the eye. And he didn’t Harvey was not a vitrectomy Vitria surgeon and so he asked Jack Coleman and I to use it and I as junior faculty, you always got the worst cases, you got the failed cases, the cases nobody else wanted to do. And those would be the PVR, so the complex traction detachments from diabetics, and so I started getting interested in them. And one of the problems was that we when PVR, we had about a 25% success rate, where we put SF six in at the end of our surgery, fix the retina. But about two or three weeks later, when the gas bubble went away, the retina would re detach. So I had a couple of those patients and I decided I would inject Harvey’s gas c3f8. So I wouldn’t have to keep inject, where I get a retinal detachment again, and we often laze with them after we injected the gas and reattach the retina. So this gas lasted good six weeks in the eye. And I was thinking about this as I was, as Firas is going to ask me, because this is the same cycle we appeared now because in the 80s, we started doing gas injections, we injected gas in the office, we put needles in the eye. And this is what route retinal surgeons routinely did to try to reattach the retina with gas. And now 30 years later, we’re injecting drugs in the eye. And at the time, 30 years ago, I was looking for a longer lasting gas a longer lasting agent, now we’re looking for a longer lasting anti-VEGF or other drug that has greatest sustained sustainability. So these cycles just return. And we’re in the same cycle again, looking for a longer agent, longer action molecule might be through gene therapy, it might be through a long, longer model, a drug delivery device, or it might be a compound that releases more slowly. So we’re looking, we’re all doing injections. But if it hadn’t been for retinal surgeons injecting the gas, the intro vitriol probably would have never developed on its own because we’re all familiar with intravitreal injections, but now he’s, and those days, we would do one or two a month. Now we’re doing 10 a day.

Firas Rahhal: It’s a fascinating comparison. And until you brought it up to me, I hadn’t thought about that evolution. And that idea. And I’m glad you brought it up. How do you view the development process? You’re still involved? How do you view the development process of devices or even drugs then, versus now you kind of commandeered these programs in the 80s and 90s? What do you see as the differences or advantages to now if any?

Stanley Chang: Well, I think now, it’s much harder because you could try things. With less regulatory oversight, the regulatory oversight really makes things difficult. And also you need a good partner because all the bureaucracy of getting something FDA approves so much greater.

Firas Rahhal: Did you face that? Let’s move to the other things that you know the list again is long I wanted to hear about both the heavy liquids and the wide angle that everyone just mentioned, but did you face those kinds of challenges with the heavy liquids and the wide angle?

Stanley Chang: Sure the heavy liquids grew out of perfluorocarbon technology because as the perfluorocarbon chain got larger, they became liquids, and we knew that they were heavy liquids heavier than water. And some other people had worked on it before, but we knew that perfluorocarbon itself would be very stable, and it would be inert. So when I started working on them, I knew that they were heavy enough to flatten the retina, but I had to assemble a team. And I got a fluorine chemist, a cell biologist, Janet Sparrow, and also a pathologist, Dr. Yamamoto, who helped me do the pathology to study these eyes. And then I did worked in found someone in industry to help me make a pure perfluorocarbon. This and his unfortunately, his mother had had a retinal detachment. So we became very interested in the project. And we developed a very pure perfluorocarbon that eventually could be used clinically. And we were ready for it. And once we had done all the preliminary work with the histology, and how electron microscopy, I couldn’t get any companies interested, it went the Alcon went to the major companies stores and at that time pharmacy, it was a company that had produced healant. And I wanted to, we want to healant to pharmacies that felt that they took it for a year and put it on the shelf. And after a year, they told me they weren’t interested. So finally, there was a small company started in St. Louis, based in St. Louis called Infinitech. And they decided they would run the clinical trial. And fortunately, they did a good job with the clinical trial. And I think we got the drug approval in 18 months, which was pretty amazing. Because there were a lot of people in the community already using it and knew that was quite effective. So I was lucky there, but it took a long time to find the partner. And then this chemist that had worked with started his own company to manufacture the perfluoro octane. And he also gave it to Morefield so they could have it for their patients. And then finally, to have a partner like Alcon come and they were a great partner, when they took over at these two small companies for somebody had to teach how to use perfluoro how to keep it safe, and also to monitor the safety throughout the rest of the world as people were adopting this technology. So Alcon was a wonderful partner in educating our surgeons, and then making sure that the regulatory aspects were followed. And I think that during that period of time, I was fairly, very fortunate to have a great corporate partner who could help us. They didn’t always listen to all my suggestions, but somehow it is a lasting contribution that I was lucky to have made. We weren’t so lucky with the wide angle viewing Avi as a one-man company. And how did we start that? Well, the Volk had developed a quadrats ferric lens, which is a wide field lens. And we’re all quite impressed with that early on. I said why can’t we use this lens in the operating room so that we could see real panoramic view of the retina, we could see the entire retina when we’re in the operating room instead of seeing the little 30-degree field of view. And so Avi had come to me and say he’s interested in this idea, and he had already developed an inverter because the image is inverted and reversed. And then we work together to miniaturize the lenses that we could use in surgery, and it changed the way we did. Again, it’s another field that it’s difficult to get someone to make those lenses because the market size was limited. And it was a great problem with the volt company where we made the prototypes revolt, but Volk claimed the intellectual property. It was always a struggle to deal with them as a company. But ultimately, it’s the surgeons that changed the end you had friends like you saw on the screen here. Harry Flynn, Mark Blumenkranz, Hillel Lewis, they all took this technology so rapidly that it became incorporating that into our routine care. So I’m grateful to them not only for their comments, but also their help and getting this technology developed and used in day-to-day practice.

Firas Rahhal: Amazing there’s so much there when Stanley was recounting the first year or two of taking the perfluorocarbon liquids out to corporate event. Ericka and being denied sounds like Michael Jordan’s 10th grade basketball coach not letting him make the team. I wonder what those folks would think now. I’m sure if you bring products now, they probably pay attention. Thank you, Stanley, what about? I don’t want to keep you too long. But what about moving forward in those two areas Tamponades. Viewing systems, as you know, have evolved a lot, I still use the context system that you just described, a lot of younger surgeons are using non context systems, which I feel might be a little inferior in quality. But what’s your thought on that, and the tamponades?

Stanley Chang: Well, I think Maria is right, and we don’t want a tamponade with a patient has to keep their head down for weeks. If we could develop a tamponade where they can fly, they don’t want to keep their head down, and the retina would heal. Hydrogels seem to be the future. And I think there are many, quite a few people working on hydrogels now. I’m a little worried about this technology, because then the volume and the dollar volume is not going to be a high one. So we have to do things not only for money, but also really for the benefit of our patients and hope that some company will develop it and we’ll be able to make some profit, but also really, it’ll be a big help to patients and change the way we do things. In terms of my advice to people, I would say make sure that when you try to introduce something new, make sure that it’s going to have a lasting effect and it’s not going to have problems in the future. And secondly, for our doctors find a good partner because that’s so important in getting your technology developed and working and taught around the world.

Firas Rahhal: Young companies take note about the hydrogel comment I think that perfluoro thing worked out pretty well for Alcon so you might want to take heed. Stanley, I can’t thank you enough for taking time to come. And it’s been a pleasure.

Stanley Chang: Thank you so much.