A newly FDA approved procedure has the power to save children from a painful cornea transplant. Keratoconus presents in about 1:2000, with a high prevalence in the Down Syndrome population. The disease causes the cornea to become thin and bulge. Corneal crosslinking improves the connections among the membranes of the cornea by a factor of four, preventing the need for a cornea transplant.
Erin Stahl, MD is here to explain that Children’s Mercy Kansas City provided one of the first FDA-approved pediatric treatments in February 2017, providing new hope for Keratoconus.
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Crossing Over: How a New Procedure Heals Keratoconus
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Learn more about Erin D. Stahl, MD
Erin Stahl, MD
Erin D. Stahl, MD, is a Pediatric Ophthalmologist at Children’s Mercy Kansas City and an Assistant Professor of Pediatric Ophthalmology at the University of Missouri-Kansas City School of Medicine. She completed her medical degree and residency at the University of Kansas School of Medicine and fellowships in Pediatric Ophthalmology at Children’s Mercy Kansas City and Cornea and Refractive Surgery with Durrie Vision Centers in Overland Park, KS. Dr. Stahl is certified in Ophthalmology and is one of the nation’s few providers trained in both pediatrics and cornea.Learn more about Erin D. Stahl, MD
Transcription:
Crossing Over: How a New Procedure Heals Keratoconus
Dr. Michael Smith (Host): So our topic today is “Crossing Over, How a New Procedure Heals Keratoconus.” A new FDA approval procedure may replace painful coronary transplants. My guest is Dr. Erin Stahl. She’s a pediatric ophthalmologist at Children’s Mercy Kansas City and an assistant professor of pediatric ophthalmology at the University of Missouri-Kansas City School of Medicine. Dr. Stahl, welcome to the show.
Dr. Erin Stahl (Guest): Thanks for having me.
Dr. Smith: So why don’t we do this – let’s start off – could you just explain the condition and how it affects the children who have it, first?
Dr. Stahl: Keratoconus is actually a relatively common condition, which occurs in about 1 in 2000 people. It typically shows up in early adolescence through the mid-30s. What happens when you have keratoconus is your cornea, which is the clear window on the front of your eye, loses its strength and so it starts to vault forward and becomes steeper. It’s supposed to be nice and smooth, and round and so as it steepens up, it affects your vision pretty significantly.
Dr. Smith: Have we – I know that for the most part we don’t really know what causes it, but are there any new theories out there of what the cause of this is?
Dr. Stahl: Probably the most common thing that leads to Keratoconus is eye-rubbing, so kids with a significant history of allergies who spend a lot of time rubbing their eye are probably the most likely group to get Keratoconus. Kids with Downs Syndrome also are more likely to develop Keratoconus, and then there’s a lot of people who don’t have a significant history of rubbing, or Downs Syndrome, or other condition who also can develop Keratoconus.
Dr. Smith: Right, so other than the rubbing, it largely remains unknown the cause. When you look at the history of this, and you look back at patients who have been diagnosed with this, is there some sort of predisposition – like the eye-rubbing is causing some irritation, maybe they’re more prone to inflammation in the eye – is there any link like that?
Dr. Stahl: I think that what the eye-rubbing does is it starts to break down the connections within the cornea. The cornea is made of collagen fibers, which are like pages of a book and so they’re connected together, and I think what the thinking is, is that the rubbing starts to break down the connections between those corneal layers.
Dr. Smith: And so for most children, what’s the common treatment?
Dr. Stahl: The common treatment, up until this year, was that you put the child in glasses – typically they’ll have astigmatism and nearsightedness because of the condition, so you start with glasses, and when you no longer have a good corrective vision with glasses you move to contact lenses. At some point in time if you can no longer see well with contact lenses, or they’ll no longer fit on your eye, then you’ll require a corneal transplant. That was up until last year when the new treatment that we are going to discuss was approved.
Dr. Smith: Yeah, so when you look at the number of children that are diagnosed with this, how many ends up with the transplant surgery?
Dr. Stahl: Most of them end up with some vision changes, which means they may not see 20/20 despite glasses and contacts, but it’s only a small percentage, around 10-20% that end up needing a corneal transplant during their lifetime.
Dr. Smith: So let’s talk about – you had mentioned this before that until the last year – so what happened last year with a new procedure that I think really is helping to treat this better?
Dr. Stahl: Yeah, it’s really been revolutionary -- but it’s actually not last year -- and you’re right about that. About 15 to 20 years ago, in Germany, people started experimenting with different combinations of light and vitamins to strengthen the cornea, and they landed on the combination of Riboflavin, which is a vitamin and a certain type of UV light when combined together actually increase the stiffness of the cornea. There was a number of years of research and early studies, and then for about the last 15 years, it’s been standard of care outside the US to use this procedure called Corneal Cross-Linking. It wasn’t until April of 2016 that it was approved by the FDA and finally available inside the United States.
Dr. Smith: So let’s talk about the cross-linking, what actually is going on when you combine the Riboflavin with the UV light?
Dr. Stahl: So as I talked about those pages of the book, like the corneal fibers not being well held together because of rubbing, so what it does is it increases the cross-links, or the linkage between those fibers, so it strengthens the cornea and doesn’t allow the disease to progress.
Dr. Smith: You mentioned – so this is – in Europe and some other areas this was going on and been using this treatment for 15 plus years – why did it take so long to come to the United States?
Dr. Stahl: It’s a really long discussion. But the basis is we needed – the way our FDA works is you need a company to bring the product to the FDA, and it’s very difficult to take a vitamin and a light and bring them to the FDA and say we want approval to use these together. It took just a lot of work between people with Keratoconus, and the FDA and a couple different companies actually to bring it all to fruition.
Dr. Smith: So looking back to the use of this in the past in Europe, what kind of results do we see with this? Is it curative? What is your expectation?
Dr. Stahl: Well, it wasn’t great to have to lag so far behind, but the great point at this time is we have 15 to 20 years’ worth of data in children and adults and all sorts of different conditions, and it’s really shown that most people are stable permanently after being cross-linked. There’s been a number of different protocols used and a number of different concentrations of the drug and timing for the light and so some people who had some of the alternate treatments needed to be re-treated, but with the protocol that was approved in the US, the data looks really solid long-term.
Dr. Smith: Yeah, and so when you think about the pathology here, and you get the bulging of the cornea, with this cross-linking procedure, do you visibly see that that is decreasing? Obviously, the results are pretty good in Europe, but what is it actually doing to the shape of the cornea?
Dr. Stahl: The thought of the procedure initially was that we were just going to freeze things in place, that we weren’t going to fix any damage that has already been done, which is why early diagnosis is so important. But actually, as data has come in over the years, there’s actually a little bit of flattening of that cone, so the disease does get a little bit better, but the most significant thing is freezing it in place and not letting it progress.
Dr. Smith: What do you think is – so with the cross-linking that’s going on her – is it the Riboflavin? Obviously, it’s a combination of the two, but what exactly do you think the Riboflavin is doing in here? We know it’s a good antioxidant, is that part of it? What're your thoughts?
Dr. Stahl: Well, I think what’s interesting about this is that this is a natural process and you’re just accelerating it. There’s Riboflavin in our tears, and then the UV light is around us at all times, and so people with Keratoconus only develop until their 40s or 50s, and then they never have any further progression because they’ve been naturally cross-linked. This is a process that’s going on naturally, and it’s just increasing those bonds within the collagen fibers within the cornea.
Dr. Smith: Yeah, that’s very interesting, so this must be exciting for you. Let me ask you, though, what kind of follow-up happens. When a child undergoes this therapy, what’s the follow-up for them?
Dr. Stahl: So the surgical procedure takes an hour. There’s a 30 minute application time for the Riboflavin, and then there’s a 30 minute application time for the light. Then we put a contact lens on the eye because it’s a little bit sore for about two days afterward. I see them about 4 days afterward and take that contact lens off. After that, we see them monthly for the first couple of months to make sure everything looks good and that everything is stable. Eventually, they’ll be seen every three to six months just to make sure they’re doing okay.
Dr. Smith: Let’s talk about how it’s actually applied then. So what exactly – how are you administering the Riboflavin, for instance?
Dr. Stahl: Really, the main surgical step of the procedure is to remove the epithelium, which is that first layer on the front of their eye and I always tell people if you ever had a scratch on your eye before, that’s because the epithelium was removed in that area, so essentially I’m going to create a large scratch on the eye, and that lets the Riboflavin penetrate the cornea. To make the scratch, we just use topical numbing medicine for older kids. Younger kids will be asleep for the procedure, but topical medicines take off the epithelium. And then, every two minutes for 30 minutes, you apply a drop of the FDA-approved Riboflavin Solution.
Dr. Smith: The Riboflavin actually goes first, right?
Dr. Stahl: Yes, and saturates the cornea.
Dr. Smith: And then that’s the 30-minute procedure and then follow that with the UV light, and then that combination is what’s increasing the cross-linking, which is what we do naturally when we’re just being outside and getting Riboflavin actually from food and so forth. It’s a very, very interesting procedure. How many kids at Children’s Mercy have you treated so far?
Dr. Stahl: Well, we just got it, so it was finally all set up and ready to go in February and I treated my first two kids that week, and we have a number of kids now that are on the schedule and waiting to be treated.
Dr. Smith: Wow, that’s fascinating. Well, Dr. Stahl, I want to thank you for the work that you’re doing at Children’s Mercy and for bringing this procedure over, and I want to thank you for coming on this show today. You’re listening to Transformational Pediatrics with Children’s Mercy Kansas City. For more information, you go to ChildrensMercy.org, that’s ChildrensMercy.org. I’m Dr. Mike Smith, thanks for listening.
Crossing Over: How a New Procedure Heals Keratoconus
Dr. Michael Smith (Host): So our topic today is “Crossing Over, How a New Procedure Heals Keratoconus.” A new FDA approval procedure may replace painful coronary transplants. My guest is Dr. Erin Stahl. She’s a pediatric ophthalmologist at Children’s Mercy Kansas City and an assistant professor of pediatric ophthalmology at the University of Missouri-Kansas City School of Medicine. Dr. Stahl, welcome to the show.
Dr. Erin Stahl (Guest): Thanks for having me.
Dr. Smith: So why don’t we do this – let’s start off – could you just explain the condition and how it affects the children who have it, first?
Dr. Stahl: Keratoconus is actually a relatively common condition, which occurs in about 1 in 2000 people. It typically shows up in early adolescence through the mid-30s. What happens when you have keratoconus is your cornea, which is the clear window on the front of your eye, loses its strength and so it starts to vault forward and becomes steeper. It’s supposed to be nice and smooth, and round and so as it steepens up, it affects your vision pretty significantly.
Dr. Smith: Have we – I know that for the most part we don’t really know what causes it, but are there any new theories out there of what the cause of this is?
Dr. Stahl: Probably the most common thing that leads to Keratoconus is eye-rubbing, so kids with a significant history of allergies who spend a lot of time rubbing their eye are probably the most likely group to get Keratoconus. Kids with Downs Syndrome also are more likely to develop Keratoconus, and then there’s a lot of people who don’t have a significant history of rubbing, or Downs Syndrome, or other condition who also can develop Keratoconus.
Dr. Smith: Right, so other than the rubbing, it largely remains unknown the cause. When you look at the history of this, and you look back at patients who have been diagnosed with this, is there some sort of predisposition – like the eye-rubbing is causing some irritation, maybe they’re more prone to inflammation in the eye – is there any link like that?
Dr. Stahl: I think that what the eye-rubbing does is it starts to break down the connections within the cornea. The cornea is made of collagen fibers, which are like pages of a book and so they’re connected together, and I think what the thinking is, is that the rubbing starts to break down the connections between those corneal layers.
Dr. Smith: And so for most children, what’s the common treatment?
Dr. Stahl: The common treatment, up until this year, was that you put the child in glasses – typically they’ll have astigmatism and nearsightedness because of the condition, so you start with glasses, and when you no longer have a good corrective vision with glasses you move to contact lenses. At some point in time if you can no longer see well with contact lenses, or they’ll no longer fit on your eye, then you’ll require a corneal transplant. That was up until last year when the new treatment that we are going to discuss was approved.
Dr. Smith: Yeah, so when you look at the number of children that are diagnosed with this, how many ends up with the transplant surgery?
Dr. Stahl: Most of them end up with some vision changes, which means they may not see 20/20 despite glasses and contacts, but it’s only a small percentage, around 10-20% that end up needing a corneal transplant during their lifetime.
Dr. Smith: So let’s talk about – you had mentioned this before that until the last year – so what happened last year with a new procedure that I think really is helping to treat this better?
Dr. Stahl: Yeah, it’s really been revolutionary -- but it’s actually not last year -- and you’re right about that. About 15 to 20 years ago, in Germany, people started experimenting with different combinations of light and vitamins to strengthen the cornea, and they landed on the combination of Riboflavin, which is a vitamin and a certain type of UV light when combined together actually increase the stiffness of the cornea. There was a number of years of research and early studies, and then for about the last 15 years, it’s been standard of care outside the US to use this procedure called Corneal Cross-Linking. It wasn’t until April of 2016 that it was approved by the FDA and finally available inside the United States.
Dr. Smith: So let’s talk about the cross-linking, what actually is going on when you combine the Riboflavin with the UV light?
Dr. Stahl: So as I talked about those pages of the book, like the corneal fibers not being well held together because of rubbing, so what it does is it increases the cross-links, or the linkage between those fibers, so it strengthens the cornea and doesn’t allow the disease to progress.
Dr. Smith: You mentioned – so this is – in Europe and some other areas this was going on and been using this treatment for 15 plus years – why did it take so long to come to the United States?
Dr. Stahl: It’s a really long discussion. But the basis is we needed – the way our FDA works is you need a company to bring the product to the FDA, and it’s very difficult to take a vitamin and a light and bring them to the FDA and say we want approval to use these together. It took just a lot of work between people with Keratoconus, and the FDA and a couple different companies actually to bring it all to fruition.
Dr. Smith: So looking back to the use of this in the past in Europe, what kind of results do we see with this? Is it curative? What is your expectation?
Dr. Stahl: Well, it wasn’t great to have to lag so far behind, but the great point at this time is we have 15 to 20 years’ worth of data in children and adults and all sorts of different conditions, and it’s really shown that most people are stable permanently after being cross-linked. There’s been a number of different protocols used and a number of different concentrations of the drug and timing for the light and so some people who had some of the alternate treatments needed to be re-treated, but with the protocol that was approved in the US, the data looks really solid long-term.
Dr. Smith: Yeah, and so when you think about the pathology here, and you get the bulging of the cornea, with this cross-linking procedure, do you visibly see that that is decreasing? Obviously, the results are pretty good in Europe, but what is it actually doing to the shape of the cornea?
Dr. Stahl: The thought of the procedure initially was that we were just going to freeze things in place, that we weren’t going to fix any damage that has already been done, which is why early diagnosis is so important. But actually, as data has come in over the years, there’s actually a little bit of flattening of that cone, so the disease does get a little bit better, but the most significant thing is freezing it in place and not letting it progress.
Dr. Smith: What do you think is – so with the cross-linking that’s going on her – is it the Riboflavin? Obviously, it’s a combination of the two, but what exactly do you think the Riboflavin is doing in here? We know it’s a good antioxidant, is that part of it? What're your thoughts?
Dr. Stahl: Well, I think what’s interesting about this is that this is a natural process and you’re just accelerating it. There’s Riboflavin in our tears, and then the UV light is around us at all times, and so people with Keratoconus only develop until their 40s or 50s, and then they never have any further progression because they’ve been naturally cross-linked. This is a process that’s going on naturally, and it’s just increasing those bonds within the collagen fibers within the cornea.
Dr. Smith: Yeah, that’s very interesting, so this must be exciting for you. Let me ask you, though, what kind of follow-up happens. When a child undergoes this therapy, what’s the follow-up for them?
Dr. Stahl: So the surgical procedure takes an hour. There’s a 30 minute application time for the Riboflavin, and then there’s a 30 minute application time for the light. Then we put a contact lens on the eye because it’s a little bit sore for about two days afterward. I see them about 4 days afterward and take that contact lens off. After that, we see them monthly for the first couple of months to make sure everything looks good and that everything is stable. Eventually, they’ll be seen every three to six months just to make sure they’re doing okay.
Dr. Smith: Let’s talk about how it’s actually applied then. So what exactly – how are you administering the Riboflavin, for instance?
Dr. Stahl: Really, the main surgical step of the procedure is to remove the epithelium, which is that first layer on the front of their eye and I always tell people if you ever had a scratch on your eye before, that’s because the epithelium was removed in that area, so essentially I’m going to create a large scratch on the eye, and that lets the Riboflavin penetrate the cornea. To make the scratch, we just use topical numbing medicine for older kids. Younger kids will be asleep for the procedure, but topical medicines take off the epithelium. And then, every two minutes for 30 minutes, you apply a drop of the FDA-approved Riboflavin Solution.
Dr. Smith: The Riboflavin actually goes first, right?
Dr. Stahl: Yes, and saturates the cornea.
Dr. Smith: And then that’s the 30-minute procedure and then follow that with the UV light, and then that combination is what’s increasing the cross-linking, which is what we do naturally when we’re just being outside and getting Riboflavin actually from food and so forth. It’s a very, very interesting procedure. How many kids at Children’s Mercy have you treated so far?
Dr. Stahl: Well, we just got it, so it was finally all set up and ready to go in February and I treated my first two kids that week, and we have a number of kids now that are on the schedule and waiting to be treated.
Dr. Smith: Wow, that’s fascinating. Well, Dr. Stahl, I want to thank you for the work that you’re doing at Children’s Mercy and for bringing this procedure over, and I want to thank you for coming on this show today. You’re listening to Transformational Pediatrics with Children’s Mercy Kansas City. For more information, you go to ChildrensMercy.org, that’s ChildrensMercy.org. I’m Dr. Mike Smith, thanks for listening.