Corneal Updates

Host Gary Wörtz, MD, speaks to Ken Beckman, MD, about his contributions to innovations taking place in the cornea space. He touches on different topics surrounding corneal crosslinking and the challenges the treatment presents.

Speaker 1: 00:00 Today on Off The Grid I'm lucky to be joined by Dr. Ken Beckman. Ken is in practice at Comprehensive Eye Care of Central Ohio, and is also a clinical assistant professor at the Ohio State University. Ken, I'm excited to have the chance to talk to you about some of the innovations taking place in the cornea as well as your contributions you've made to this space. With that, welcome.

Dr. Ken Beckman: 00:19 Okay. First I want to thank you for having me and for the kind introduction from a Michigan man. I appreciate it.

Speaker 1: 00:24 Yeah, yeah. You got it, Ken. So, uh, let's, let's just dive right in. Uh. You've been very active with the development of corneal crosslinking, so I was wondering if you could just tell us a little bit about where that treatment stands today.

Dr. Ken Beckman: 00:35 Okay, well, cross linking. Well, first I'll tell you about my involvement. I first became involved in crosslinking in ... about five years ago, I think it was 2013. Uh, I was involved in two of the Avedro, uh, clinical trials. The first one was through ACOS, and that was an accelerated treatment trial. And uh, the second one ... and that was, I'm sorry, the first one was an accelerated treatment trial using three different, uh, energy levels and three different durations of treatment. And there was another one I did around the same time that was just a placebo controlled, um, accelerated treatment trial.

So that was in 2, in 2013. Then the, the procedure became approved, I believe, in 2016. So we've been doing this for, you know, for about five years. Uh, since that time I've actually been involved in three more clinical trials with the Avedro. I had, um, an investigator initiated trial, uh, of Epi-on cross linking, which all the patients had been treated. We're just completing their final visit, so this should be done in the next few months.

I'm on one of their phase four Epi-off ectasia trials. And I'm also just starting, we have a brand new Epi-on trial that Avedro is running and we were one of the first sites to enroll any patients, and we just started treating those.

So I've been involved in cross link for about five years. I'm involved in now five clinical trials. And we've treated, I'm not, I can't even tell you how many hundreds of patients. I couldn't count them.

Speaker 1: 02:09 That's fantastic. Um, I was wondering if you could share with us a little bit about the current conversation surrounding the different coronal cross linking approaches, you know, like Epi-on versus Epi-off. Where do things stand?

Dr. Ken Beckman: 02:20 Well, first explain a little bit, little bit about the treatment in general. Um, corneal crosslinking involves treating the cornea with, with Riboflavin, which is a vitamin that we all have in our diets. It gets absorbed into the cornea. It's put, it's treated as a drop form, and it gets absorbed in the cornea. Then the cornea is treated with ultraviolet light. The combination violet-, ultraviolet light with oxygen causes this reaction in, within the cornea that has riboflavin in it to form bonds or cross links. And the goal is to stiffen the cornea, ah, to sort of lock it in place. It's the same, a similar process to vulcanizing rubber like you hear about with a tire. So it makes it firm. So, um, that's goal number one, to stop it from progressing.

Goal number two is that it may actually flatten and become more regular and give patients a better quality of vision, so it's not like ... You, you really have to explain to patients: this is not LASIK surgery or the next day they're going to wake up and, aha, their vision's great. What we're trying to do is:

1. Not let them get worse.

2. Hopefully it'll start to flatten.

So, with Epi-on and Epi-off: Epi-off, or the removal of the epithelium, is what's been approved--Avedro got this approved two years ago--and what that involves is removing the corneal epithelium, then giving the riboflavin drops, and then the ultraviolet light. The, what we know about it is it works really well. In their trials there was obviously a significant improvement in these patients, relative CBO or control arm, and it works.

The negatives are that you're creating an epithelial defect. What does that mean? It means that there's going to be discomfort or even pain for the first several days or up to a week. The patient needs a bandage contact lens. They're at risk for infection, so they're on antibiotics. They're also at risk for scarring and haziness to the cornea, and it's a slower rehabilitation, even when the epithelium heals. As you know, when you have a corneal abrasion, it may not heal so regularly right away, so these are obviously things that are concerned, are concerning.

The advantage, the theoretic advantage if you could get to Epi-on would be not removing epithelium, obviously, so you don't have nearly the risk of the pain and irritation. You have much less risk of infection because the epithelium is intact. A much quicker recovery because they don't have to wait for the epithelium to heal, and theoretically, hopefully less scarring and haze, which will be hopefully proven as the, as the trials go along.

So theoretically if Epi-on is as effective as Epi-off there would really be no reason to ever remove the epithelium. The concerns though of why you would want to remove, remove the epithelium is the epithelium does several things:

1. It may be a barrier to the riboflavin penetrating, so therefore you may not get enough concentration of riboflavin in the cornea.

2. The epithelium, which will have soaked up riboflavin, may absorb some of the ultraviolet light as the shined on the cornea so it may not get in, the light may not penetrate as well into the Stroma to get the, to get the response.

3. Oxygen may not be available to the, to the tissues because of the barrier of the, of the epithelium.

So these are the hurdles that are, that are, that we have to face. There are a number of trials that have been going on. Um, there's other companies that have started looking into on. They have a unique formulation of their riboflavin, and they may or may not have, ah, techniques as far as, ah, allowing the riboflavin to penetrate, and they've shown good results.

The Avedro trial, which I'm on, what they're doing is a couple of things:

1. They've changed the concentration and the formulation of the riboflavin so it penetrates the epithelium better.

2. We're providing supplemental oxygen blown onto the cornea during, during the procedure. So theoretically you have more oxygen exposure to the eye.

3. It's also a pulsed treatment. The light is pulsed rather than continuous, so it sort of gives the cornea break in between pulses to let the oxygen, um, recollect so to speak.

So theoretically, if this works, there would be no reason that I can think of that you would prefer to do Epi-off.

Speaker 1: 06:43 So, Ken, it seems that Epi-on versus Epi-, Epi-off is sort of like the difference between LASIK and PRK. You know, they both work great but with PRK there's more discomfort, more wound healing. Whereas with LASIK we're achieving great results with much less downtime.

Dr. Ken Beckman: 06:57 It is, except even more so because LASIK itself had its own inherent risks and complications because you're creating a flap. In this case, so you could, you could argue that there's operative risks that make the LASIK technically more difficult than PRK. So in the moment it's, it's even higher risk. Uh, in this case, surgically or procedural wise, it's not any, any more difficult. But the other part is definitely true from a, from a recovery and comfort standpoint.

Speaker 1: 07:24 So if the efficacy of the two approaches is similar, then Epi-on may be more preferable given the increased patient comfort, faster recovery.

Dr. Ken Beckman: 07:33 Well, so far it seems like it does very well. The Epi-off definitely works. I've done it several ways. Like I said, when I did it in the clinical trials a few years ago, it was the accelerated form, so it was more energy over a shorter period of time. That's not the format that was improved. The approved format is the Dresden protocol that we're all more familiar with, and it's 30 minutes of light in 30 minutes ... I mean, 30 minutes of drops followed by another 30 minutes of the light. And um, that seems to work very, very well.

In my experience with the ones that I've done with Epi-on in the, in my investigator initiated trial, they've also done very, very well. I've had some patients with dramatic improvement. One thing that I do notice though is significantly faster recovery. I usually, I give them a contact lens and I take it off the next day, and usually the epithelium is totally normal. There may be a little bit of SPK, but for the most part visually they're the same as they were pre op the next day. And usually by that, the evening of the procedure, by that evening, they feel pretty much normal. Whereas, when I do an Epi-off, they're quite uncomfortable for the first day or two and it may take, I usually end up leaving the contact lens in for about a week before, um, before the epithelium is healed.

From a standpoint of scarring, haze, and infection; I haven't seen any of that with the Epi-on patients, but I did have a number of who had either an infection or scarring in the cornea, um, and haziness with the Epi-off. They all did fine. I didn't, I didn't see any that limited their, um, acuity afterwards. But you do see that.

So, so yeah, if the results ended up being the same, it's just, it's a much better procedure.

Speaker 1: 09:13 And now how does Topo-guided PRK fit into the equation?

Dr. Ken Beckman: 09:16 Well, I, I have not done any. I do think it's definitely an area of opportunity from what I've seen, um. I don't have any personal experience. I think it's really exciting the prospect of being able to stabilize the cornea and at the same time reshape it to get rid of some of the, you know, obviously the refractive error and the aberrations, and I do think there's a future there. I just don't have any experience with doing it.

I know Avedro has been working on one procedure called LASIK Xtra, and what that involves is at the time of LASIK creating a flap, doing the LASIK procedure, then putting Riboflavin on and closing the flap and doing cross linking in the moment, but those are, as far as, I believe those are not done on cones. Those are done on patients who may be at higher risk or maybe not. I don't have the specifics on that. But to, to allow them to have stability.

I think that's an interesting one. They are also looking into a procedure now that's called Pixel, which is kinda like PRK, I guess. It's modifying the shape of the cornea by cross linking to correct small refractive errors, and it can be done for near or far depending on what part of the cornea you would treat. You could have a corn-, the center part of the cornea shielded and have like a ring of exposed area to make the cornea steeper to theoretically help with near, or you can treat the center to get flattening to correct, ah, mild myopia.

And again, I'm not, I have not been involved with those clinical trials as well, but I think there's a lot of opportunities with that and it would be nice to find tune small refractive errors with cross linking.

Speaker 1: 10:49 So it sounds like Pixel may provide some pretty interesting opportunities in the future.

Dr. Ken Beckman: 10:53 Oh, absolutely. And just taking patients who underwent crosslinking, cones that were treated and they've stabilized over the years. It makes me wonder, you know, how well they will do with PRK after the crosslinking, not as necessarily as, ah, simultaneous treatment like we talked about earlier. So there's so many options for how these are going to be worked together over the years. Um, I guess the research will show us.

Speaker 1: 11:17 So switching gears a bit, I wanted to talk with you about the role of optometrists and ophthalmologists in referring patients for crosslinking. So when do you consider it inappropriate time to send a keratoconic patient to a corneal specialist to be considered for crosslinking?

Dr. Ken Beckman: 11:32 Okay. Yes. When, when the procedure first, a lot of the gatekeepers, the optometrists in general ophthalmologists who are seeing these cones, were used to the old pattern. They'd see a kid at 16 years old and he's 20/20 and they'd watch him. And then he's 18 years old and he's 20/20 minus or 20/25 and maybe they fit them in a contact, and before you know it he's 25 and now he's 20/30 in glasses or 20/40 and that's as good as you can get him, but he's still corrects to 20/20 in contacts. And they waited until all of a sudden he's 29 and he's 20/80 in glasses and he's 20/40 and contacts or contact lens intolerant and they send him for a graft.

So the first hurdle we had was getting the gatekeepers to realize this works best when the vision is still good to prevent progression. So as we've educated the gatekeepers, the optometrists are actually sending a lot of cones early on now. I'm seeing the 17-year-olds who are still 20/20 but have a clear cone and you know they're progressing and you know they're going to need a, a graft in 10 years. They're actually sending those in.

What I used to say to them was, "It's kinda like 50 years ago they came out with a polio vaccine. Everyone got it, no one felt any different afterwards. But now 50 years later, no one gets polio." So from the keratoconus standpoint, we hope that we can catch these 17 year olds at the first sign of, of keratoconus, get them treated, and then you don't have to worry about 30 years later them needing graphs. That's what we're hopeful for. And that's starting.

The tougher issue is the more advanced cases. And this I think is in the hands of the corneal specialist and less of the optic-, ah, optometrist. I found in my experience I've had many advanced cones, vision's 20/70, 20/100, you know, at a level where ordinarily you would have been thinking about keratoplasty, but in my experience, as long as they're optically clear and they don't have a central scar, I think they deserve an opportunity for cross linking. And I've done many of these. In a high number of them all of a sudden change from 20/100 or 20/30, or maybe they were not contact lens tolerant before and now they can wear a scleral contact and they get to 20/20.

I've had a ton of them. In my experience with talking with a lot of the corneal specialists around, a lot of them feel like once they get to that point, they'll go ahead and graft and the logic may be in my hands they could still end up 20/25. That's a great result. From my perspective, if you're a 23-year-old, even if you did a graft and you ended up 20/20, you're 23. You have a lifetime of wear and tear. You have the risk of trauma, there's a high likelihood you're going to need a second graft in your life and maybe a third. Based on that I feel like they deserve the opportunity. Then they also deserve the opportunity of a scleral contact fit. Most patients now with a really good fit or you can get a contact on, and again, if the, if the cornea's optically clear, you should be able to get good vision.

So to me in almost every cone, unless there's a true contraindication, such as scarring, even a thin cone, I think if they're at graph level they deserve the opportunity to at, at least explore the crosslinking, because at the end of the day if it fails, they get the graft anyway.

Speaker 1: 14:32 Yeah, I mean I think they at least deserve the chance to explore the option.

Dr. Ken Beckman: 14:36 Right. If they're already graph level, exactly. If your alternative is saying tomorrow, I think they deserve an opportunity and I think the data will show this, and I have a number of patients already, you know, that I've collected that had graph level, ah, vision that we treated and ended up doing very, very well, that are driving now and, and, um, seeing just fine.

Speaker 1: 14:57 So what about patients with keratoconus and cataracts? So how do you address those, um, those people, what, what are the challenges that you face there?

Dr. Ken Beckman: 15:06 Well, that's one of the big discussions we have and, in fact, just to give a little plug, this coming, ah, April of 2019 our Cedars Aspens organization, along with the Cornea Society and APEX, are holding a conference, a freestanding cornea conference called Cornea 360, and it'll take place in, um, Tucson, Arizona, and it's the weekend of April 5th. Uh, it's the Thursday to Sunday, and it's going to be basically cornea. And uh, among the topics are the one that we talked about previously: does every patient with, um, keratoconus deserve an opportunity at a graft and a scleral lens before going to Keratoplasty? And the other one is: how do you deal with a kera- keratoconus and cataract?

So in my opinion there are several different variables. Let's obviously assume we're talking about a cornea that's optically clear, because if there a scar, it's a moot point. You gotta take the cornea off to, to do the cataract if can't see through it. And those are patients that are getting triples. Um. If the cornea's optically clear so that you can do the graft and the cornea's stable, so it's a 70-year-old and you're pretty sure that it's stable, I think it's very reasonable to get the cataract out first, especially if it's a significant cataract. The cornea may change for months to years, and if you're going to do cross linking for the purposes of getting a better cornea, when do you jump in? If you jump in at three months, six months, ah, you're making the patient wait and you may not get to the final target anyhow. So in my experience, on those patients, I usually aim for, ah, leaving them a little bit. [inaudible 00:16:41]

Couple reasons:

1. I feel like the IOL calculations tend to be off and they tend to get a hyperoptic result to begin with.

2. If they do get cross linking later, they will also get a hyperopic shift, so I do tend to target a little more myopia.

But in those patients in general, I'd probably try the crosslinking first. Oftentimes you're amazed at how much vision, visual improvement they get from the cata- I meant the ker-, the cataract first, and oftentimes you're amazed at how much improvement they get with the cataract and you may not need to do anything with the cross linking, and if they do start to progress, you can do it.

On the other hand, if the cornea is really distorted it's not unreasonable to do that. If it was a pediatric cataract where they go very, very rapidly and they have keratoconus, in those patients I would probably want to do to crosslinking first, because then a 15-year-old, ah, six months can make a huge difference. So, I would want to get the co-, I would want to get the cornea treated, but for the most part, most of these I've been comfortable with doing the cataract alone.

As far as the use of a Toric, you have to understand a couple of things. If the cornea is reasonably regular I'm very comfortable with using a Toric, with the understanding to the patient that this may be merely debulking their, their astigmatism without completely correcting it. And I've had a number of patients that have five diopters of astigmatism and you put it in a high level Toric Lens, and they, they're left with one diopter, but they're thrilled because now there are uncorrected vision is 20/40 where before it was 20/400 so they can go out at night without it and they can wear glasses. They're not dependent on contacts.

The big caveat is it's very difficult to get them into a hard contact, which is what they're used to wearing, because of the lens correction on the inside of the eye. So if they were to wear a hard one, it has to be a back Toric and it's very complex, but they may be able to get away with a soft one. So I think, I think all those options are on the table.

Speaker 1: 18:25 Yeah. I think that the, uh, definition of success is a little bit different in keratoconus patients. I think reducing their astigmatism, as you mentioned, is huge and uh, you know, that that can have a huge impact on patients. But I do agree, have to be careful, you know, if they're, um, if they're used to a hard contact lens, there's still some nuance there, so, you know, proceed with caution. But I think there's a, a ton of opportunity to help these patients.

Dr. Ken Beckman: 18:48 Oh, it's been amazing. It really has been amazing. The, the changes in people's lives, especially these young kids. It's incredible.

Speaker 1: 18:54 Ken, That's awesome. I really appreciate all you're doing. Thank you so much for what you're doing to positively affect our patients. And thank you again for sharing your thoughts with us today.

Dr. Ken Beckman: 19:02 Thank you very much. I appreciate it.