Corneal Collagen Cross-Linking: A New Standard of Care

Leading up to the recent FDA approval, Gary Wörtz, MD, invites Bill Trattler, MD, to talk about his experience with corneal collagen cross-linking and how it is becoming the new standard of care. Dr. Trattler explains the significance of having this treatment option for patients with ectasia and keratoconus and sheds light on the importance of early intervention.

Speaker 1: This episode of Ophthalmology off the Grid is brought to you by Bausch + Lomb, offering a range of eye health solutions including contact lenses and lens care products, pharmaceuticals, intraocular lenses, and surgical devices and instruments, dedicated to helping patients see better to live better. For more information, visit

Gary Wörtz: Open. Outspoken. It's Ophthalmology off the Grid. An honest look at controversial topics in the field. I'm Gary Wörtz. The corneal crosslinking landscape can be tough to navigate. In this episode of Ophthalmology off the Grid, Dr. Bill Trattler sheds some light on some key aspects of corneal crosslinking, sharing insights into the progress of this promising treatment and which patients we can expect to benefit the most. Listen in, it's going to be a great episode.

This is Dr. Gary Wörtz with Ophthalmology off the Grid, and today I have with me Dr. Bill Trattler. Bill, I just want to say thank you so much for taking a little bit of your time here at the AECOS meeting and spending some time talking about some current topics in ophthalmology. Just to start, Bill, give us a little bit of rundown of where you're from for those who don't know, and then we'll talk about some of the details of what we're going to get into today.

Bill Trattler: Gary, thank you so much for having me here. This is always a great venue, a great conference, and I just love being part of it. Myself, I'm an ophthalmologist. I'm in practice in Miami, Florida. I'm part of a very large multispecialty ophthalmology group. We have 15 ophthalmologists and a few optometrists. We have a great team. We've been in practice all together for about 20 years.

Gary Wörtz: That's just incredible to hear about that. I know that you practice with your father, and Dr. Buznego is with you also. You just have a really vibrant group. We actually met ... it's sort of funny, we met through an online ophthalmology chat room through the ASCRS a few years ago, just talking about some interesting cases and PRK and LASIK and interesting cataract cases. Really, we got to meet at a meeting a few years ago. Really, from the time we met, we really hit it off. You introduced me to a lot of other people in the industry. For me, that's really been a nice window of opportunity to get more involved with consulting and doing things like this, talking about current topics in ophthalmology.

I was just wondering, just because of your unique position and being in a lot of meetings and knowing a lot of people both in the industry and ophthalmology, I'm sure there's a lot of other young guys out there and maybe people even in mid-career who are looking for opportunities to either consult or get more connected with what's going on in ophthalmology with meetings and speaking. I was just wondering if you could give a brief rundown of what you feel like are important aspects of networking inside of ophthalmology.

Bill Trattler: Right. I think to really start you have to think of what do you value as an ophthalmologist or in someone working in the eye care field. Obviously, we have great training, and we take care of our patients. People try to stay current, but if you don't go to conferences, and not just the big conferences like American Academy of Ophthalmology or the ASCRS meeting, you may miss and not really understand all the new things that are happening in our field and realize that there are so many opportunities to take better care of our patients.

I really feel that is why I go to so many meetings. At every meeting, I'm learning new things, and I get to take better care of my patients. If you start to develop the philosophy that it's okay to miss a few days of work here and there, but in exchange, you're going to be a better doctor for your patients, I think that's where the value is. I've been a huge fan of going to conferences.

Then when I get a chance to meet you and many other younger ophthalmologists, I realize that if they get the bug, if they get excited to come to the conferences, that just opens the door for them to be better doctors and take better care of their patients. From that, they realize too that industry, companies that are developing new medications, new devices, new technologies, also add to taking better care of our patients.

Gary Wörtz: That's just so key. Sometimes in medical school and in residency, we're sort of taught to stay away from industry and that the reps are going to just give you a biased view of things. When you peel back the onion a little bit and you get to meet some people and you're at a meeting perhaps and you're out to dinner or other venues, you get to realize that these people are there to give you, sure, some promotional material, but when they become your friends and you really gain their trust, they're going to give you the honest opinion about different products.

When you find a product that you really believe in and you feel passionately about and it dovetails nicely with the messaging that the company is wanting to promote, I find those to be really the organic opportunities where I'm able to speak very passionately about a product, and that's what companies want. Don't you find the same thing?

Bill Trattler: Absolutely. No, you're absolutely correct. It's really, you get a chance to work with different companies, different technologies, and you realize that, at the end of the day, if you figure out how to make a product work well for your patients, then at the end of the day, it's very successful. But there are some technologies that just don't quite work for you. They may work for other physicians but not for you in your practice. It's kind of also getting a good sense of what you're working on in your practice to be successful and again, at the end of the day, take the best care of your patients.

Gary Wörtz: Right. Well, I'd like to get into a little bit of what actually brought me to this meeting the first time, which is corneal crosslinking. Two years ago, you invited me to come out to Deer Valley to talk at the corneal crosslinking congress. It was really invigorating for me to learn more about crosslinking from the experts. I'm not sure about other ophthalmologists, but before I came to that meeting, it was just really confusing about what does the landscape look like with crosslinking. Should we be doing epi-on? Should we doing epi-off? Where does the FDA kind of come down, and what does the progress for crosslinking look like in the future? What should we be expecting in terms of results, and which patients will benefit?

Really, there's a lot of confusion for me about crosslinking. Coming to the meeting, I really felt like I got something that I couldn't get from a journal, I couldn't get from any other venue, but I got to hear passionate dialogue between people who are in both camps of the different techniques involved with crosslinking. While we're on the topic, I'd love for you to give us a little bit of an update over the past couple of years. Where do you feel like crosslinking is now, both in terms of the regulatory side and also the procedure? How do you see the procedure fitting in and evolving to where we can really be helping more and more patients?

Bill Trattler: Absolutely. Those are awesome and great questions and topics, but let's just focus on the first and most important thing, which is that even though the technology may not be FDA-approved, for certain patients, it's critical that they get the treatment. For patients with keratoconus or patients who have had LASIK surgery or PRK surgery and are developing weakening of their cornea, ectasia, the sooner they can get crosslinking treatment, whether it's here in the US, and there's so many clinical trials and there's lots of availability, or outside the US, it just will stop their condition from getting worse and typically will make things better.

I do see that a lot of physicians tell their patients, "You know, nothing's really available yet. Nothing's FDA-approved." That's true: There's no FDA-approved treatment for keratoconus for crosslinking yet, but there's so much availability, and the sooner people get involved and patients get treated, the better.

Gary Wörtz: Well, to be honest, this really is becoming standard of care. I think this is the first time that a non-FDA-approved technique/surgery/procedure has become standard of care prior to becoming approved. I even know of a case that is potentially going to litigation where a surgeon did not offer, an optometrist did not offer crosslinking for a patient who went on to get a lot worse. There's a question of violation of standard of care because cross-linking wasn't discussed and offered. That's really an awkward position to be in as a physician, where you feel like you almost are required to talk about a procedure and offer the treatment even though it's not FDA-approved yet.

I know, from our conversations, how much you believe in this technology. Who would you say is an ideal patient? If you're looking at a group of people, there's obviously going to be some who respond quite nicely, some who don't respond at all, and maybe those in the middle. If you were someone who was just starting in crosslinking or you see a patient out there, who would be those really that low-hanging fruit that's going to get the most bang for their buck from crosslinking?

Bill Trattler: Absolutely. First of all, I do want to point out that talking about things that are not FDA-approved that are standard of care, the most common thing that we do every day is when patients have to go to eye surgery, like cataract surgery, there's no FDA-approved antibiotic to prevent infection, yet pretty much every cataract surgeon uses a non-FDA-approved antibiotic. It's approved for other things, but it's still used, so it is standard of care to use an antibiotic.

In regards to patients and who's the right patient, believe it or not, you want to catch patients early. When I have a patient that comes in and they want to have crosslinking and they want to have just one eye have treatment and you have a patient that has some mild keratoconus in one eye and more advanced keratoconus in their second eye, the patient comes in thinking they want to treat their worst eye first, but in reality you always want to treat their better eye to prevent it from getting worse because patients with keratoconus who are asymmetric, where one eye sees well and one eye doesn't, their whole life depends on their vision in their one good eye. It's a progressive disease. If they come back 3 months later, they could be worse, so you want to catch that eye as fast as possible. So, the real answer is as soon as it's diagnosed. The quicker you can treat the patient, the better.

Gary Wörtz: Okay. I think that's key. In your experience, what kind of results do you see? Obviously, one part of crosslinking is just to make sure they don't get worse and really to halt the natural progression of this disease. To me, that's what gets me so excited about crosslinking is it's the first treatment we have that really just changes the natural course of the disease. When you do crosslink someone, on average, what kind of results are you getting in terms of maybe change in the Ks or regularization of the cornea?

Bill Trattler: Right. That's a great question. The crosslinking treatment is very effective at stopping progression. It's about 99% successful, whether you're doing epi-on or epi-off. All the studies show that, in general, if you do the right technique, and we can go through more details on the techniques, but it's about a 99% success rate with one treatment.

Here at AECOS, at our meeting, we actually talked about retreatments as well in a patient. It's a simple procedure. In 3 to 6 months, a year later, if you need to do a second treatment, it's just additive. In general, patients can do well. What it does is, besides stopping progression, you typically will see improvement in both vision, in best corrected visual acuity, as well as the shape of the cornea.

Gary Wörtz: Do you have patients, for example, who maybe wore hard contact lenses who have been able to get out of hard contact lenses and maybe be managed with glasses or soft contact lenses? Is that a reasonable outcome to hope for?

Bill Trattler: It is. Every patient is different because it really depends on where they're starting from. If your patient has a -2.00 D, so a low refractive error, and they have keratoconus, if you stop their progression and improve their shape, they may be able to walk around without glasses, but if you have some patients that are -10.00 or 12.00 D ...

Gary: Sure.

Bill: Every patient is very unique, but definitely, we have patients ... I'll just share the story of my own daughter. When she was 12, I diagnosed her with keratoconus. At the time, she was wearing contact lenses, and her best corrected visual acuity was in the 20/20 range. By doing the crosslinking treatment, it not only stopped her disease from getting worse, but now she does not wear contacts anymore, and she barely wears glasses. I saw a nice improvement in her for her life.

Gary Wörtz: Well, I think that's … the most powerful testimony about this technology is this is something that you've actually used on your own daughter, and you have the benefit of watching her grow up and continue to have good vision. Those are the impact stories that make us feel proud at the end of a career. When you're able to impact your own daughter's life, I think that's just incredibly powerful.

Bill Trattler: Right, absolutely. Just to mention, she was part of a clinical trial. Since it's not FDA-approved, we do have an ongoing clinical trial that she enrolled in. I just want to mention that.

Gary Wörtz: You did mention there are clinical trials going on around the country. If someone is diagnosed with keratoconus or you have a patient in your practice diagnosed with keratoconus, what's the best way to find a resource if, as a physician, you're not participating in a trial? What would you tell other ophthalmologists to do to get their patient in the right hands?

Bill Trattler: Absolutely. The National Keratoconus Foundation does have a current list of all the ongoing clinical trials. You can go through that direction or through the Clinical Trials' website that's online. There's all the ongoing clinical trials that are currently available to doctors. Pretty much there's a trial going on in almost every state in the US.

Gary Wörtz: All right, Bill. There's been a lot of talk about epi-on versus epi-off crosslinking. I've heard your opinion because we've had a chance to talk about this at length many times, but for those who are listening, give us your opinion on epi-on versus epi-off and maybe the pros and cons of each as you see it.

Bill Trattler: Okay. Well, I think the key thing to understand is that, just like anything else, when we use the word epi-on, what epi-on means is that the procedure is very simple. We put riboflavin drops in the eye. Without removing the epithelium, we let the riboflavin soak in. We confirm at the slit lamp that there's plenty of riboflavin, and then the UV light source is used.

There are many techniques to do epi-on, and so we can look at results from 10 different doctors in 10 different sites, and the results can be very different depending on the technique. Some doctors may be successful. Some may not. If you adjust your technique, you can become successful. That's the first thing to understand.

Epi-off is a very simple technique, as well, where you just slide the epithelial cells off, apply the riboflavin drops, and then when there's plenty of riboflavin in the cornea, again you add the UV light. The first thing to understand is that both techniques can be very effective. As long as you follow the protocols and do the appropriate treatments, both techniques are very effective.

The advantage of epi-on is, by not taking off the epithelium, there's faster recovery and less risk of developing an infection, corneal haze, or delays in epithelial healing, but both techniques are very effective. In the US, we expect that the FDA approval will be for epi-off crosslinking, so that would be the first available treatment.

Gary Wörtz: When I'm doing any new procedure, my main thing is, first, do no harm. If I'm looking at two techniques, my general bias would always be to go to the one that is going to be potentially less harmful, and so epi-on seems to have a lot of benefits as I look at both techniques. But as you mentioned, crosslinking is such an important new technique for altering the natural history of keratoconus that getting patients crosslinked on either technique, I think, is really of utmost importance. I do agree with you.

It just seems like the epi-on, as long as you can load the cornea and you can confirm that at the slit lamp and you're following the right protocols that have really worked time and time again, I think there's really a lot of advantages with epi-on. Thanks for listening to this episode of Ophthalmology off the Grid. To hear more, download other episodes on Until next time.

Speaker 1: This episode of Ophthalmology off the Grid is brought to you by Bausch + Lomb, offering a range of eye health solutions including contact lenses and lens care products, pharmaceuticals, intraocular lenses, and surgical devices and instruments, dedicated to helping patients see better to live better. For more information, visit