Lecture: Crosslinking Approaches for Keratoconus

Treatment of early Keratoconus through Crosslinking can be an effective way to help your patients. Join this webinar hosted with SightLife and learn how to define the parameters for proper identification, treatment and management of Crosslinking.

Lecturer: Dr. Balamurali Ambati, Cornea Specialist, Pacific ClearVision Institution, Eugene Eye Care, Oregon, USA


Hello, everyone, and welcome. Thank you so much for joining. My name is Nashrah Mazhar, and I’m thrilled to have you join the seminar this morning about crosslinking approaches for keratoconus. Before introducing our phenomenal faculty, I wanted to share a little bit more information with you about what SightLife does. SightLife’s mission is to eliminate corneal blindness by the year 2040. To begin, I want to thank Orbis for our longstanding partnership. The first program is advocacy and policy program work. This is to ensure that barriers to a successful health system are removed by advocating for governments and working with them to build policies that address access to care and ultimately increase the number of corneas donated, to ensure that the entire health system as a whole is working for the people in their community. The second program is prevention, treatment, and awareness programs. This program specifically helps prevent eye injuries from progressing into corneal blindness, by working with community health workers and eye hospitals in very rural communities around the world. The third program is clinical training. This program provides high quality training on cornea care to ensure that there are qualified health care providers that are available to treat patients who ultimately need sight-saving surgery, as well as treatment. The fourth program is eye bank development. This program supports the eye banking ecosystem to ensure that eye banks are implementing best practices and functioning at high efficiency rates, to provide tissue for transplants. Lastly, we work on bringing innovative solutions to improve access to high quality and affordable care, by empowering local health care providers to treat their communities not only quicker, but more efficiently. Through these five key programs, we ensure that the entire health system is supported and self-sufficient, to meet the needs of the entire country. Many of you joining today are clinical care providers, and have a particular interest in learning about the clinical training program. Since the inception of this program, in 2013, we’ve trained more than 1400 ophthalmologists in low and middle income countries around the world. And the way we accomplish this is that we develop peer reviewed curriculum for short-term corneal fellowships, various surgery techniques including PK, DSAEK, DMEK, and simple limbal, and for other personnel, including nurses, optometrists, and general ophthalmologists. Additionally, we’re so fortunate to have hundreds of surgeons and cornea care providers worldwide. I’m extremely lucky to work with Dr. Ambati, cornea specialist at Pacific ClearVision, to share with you more about approaches to crosslinking in keratoconus. Should you have any questions, feel free to reach out, and thank you so much. Without further ado, Dr. Balamurali.

DR AMBATI: Thank you, Lawrence. I appreciate it. In the background, I want to thank Lawrence for his AV support. It’s really an honor for me to be with you all today. Thank you for your time and attention. I’ve been working with Orbis since 2006, and with SightLife since 2012, as I recall. And today, I’d like to speak with you about crosslinking approaches for keratoconus. There is a Q and A portion in the talk, about halfway through. There will be some audience response questions that Lawrence will do through Zoom, and then show the results of the audience response, and then I’ll go through the answers to those questions. Separately, there’s a chat box, where attendees can post their questions, and I’ll address those at the end. So let me get started. So keratoconus is a condition that affects hundreds of thousands of people in the US, and millions of patients worldwide. It remains the leading cause of cornea transplant in the US, and many other countries. Because it really often affects the full thickness of the cornea. There’s posterior ectasia and bulging of the back of the cornea, and sometimes the Descemet’s can rip, causing a corneal hydrops, and there can be anterior scarring and stromal thinning through the rest of the cornea. This imposes a significant economic burden on patients, because they can’t see well, they have reduced opportunities in education and work, and so this is a substantial burden to patients, that affects them over a very long period of time, because onset is typically in the teenage or early adulthood years. Crosslinking has dramatically reduced the need for corneal transplantation. So the nations that have large corneal registries have demonstratively shown that the introduction of crosslinking has reduced the need for future PK in these patients. By 25% to 50%. And that’s because the effects of crosslinking do tend to persist with significant corneal flattening, up to ten years. So how did crosslinking all start? So it initially started with Theo Seiler and Eberhard Spoerl, in Dresden, Germany. Who showed in 1998 that you could stiffen the cornea. And ten years later is when the clinical trial got underway in the US. After substantial experience in Europe. And 8 years after the clinical trial got underway in the US is when it got approved. So I want to thank Dr. Peter Hersh for the next several slides that will kind of go through the standard of care or epithelial-off crosslinking that’s currently the most commonly used technique. So these next several slides… I want to thank Dr. Hersh for sharing them with me. And they focus on the use of the Avedro KXL system, which delivers 365 nanometer UVA light, at a wattage of 3.0 milliwatts per centimeters squared. The indications for crosslinking in the US on the FDA approval side are patients greater than 14, outside of the US, patients much younger are being treated. I’m aware of patients who have been treated down to about age 9. It’s really patient cooperation that dictates whether it can be used or not. It’s also indicated for the treatment of ectasia after LASIK or PRK. So the epi off procedure, which is the most commonly used form, involves removal of the central 9 millimeters of epithelium. This can be done using a spatula, alcohol, a moils brush, blade, anything you can use to remove epithelium. And then soaking the corneal stroma for 30 minutes with one drop every two minutes. Then it’s important to check for riboflavin uptake. On this slit picture, you can see nice riboflavin uptake, shown in green on the corneal stroma. It’s probably even easier to see this with blue light than with white light, but the effect is the same. You want to say riboflavin penetration into the deep corneal stroma before performing the surgery. Because you’ve scraped the cornea and left it open for 30 minutes, it is important to check the corneal thickness. If the corneal thickness remains over 400 microns, you can proceed with the crosslinking procedure. If at this point it’s less than 400 microns, administer hypotonic riboflavin until it swells to more than 400. And the reason this is important is: That riboflavin with UV light induces photooxidation. That’s how it actually crosslinks the amino acids of the corneal collagen. But oxidation, as you probably recall, can be toxic. Indeed, riboflavin UVA crosslinking kills corneal keratocytes. That’s okay, because the keratocytes recover. But if the corneal thickness is too thin, the riboflavin crosslinking procedure can actually kill corneal endothelial cells, which is not okay for this purpose, because although SightLife wants us to use more eye bank tissue, I’m sure they don’t want us to do unnecessary transplants. And so the whole purpose of crosslinking is to avoid the need for transplantation, so it is very important to make sure that prior to applying the UV light, that your corneal thickness is more than 400 microns. Once that’s done, proceed to centering the instrument. Make sure you’re in good focus and centration, and then you apply the UV light. Continue with the riboflavin drops every couple of minutes, both to make sure there’s enough riboflavin and that the cornea stays moist. Afterward, there will be a bandage contact lens for about five days, antibiotic and corticosteroid, and that’s the usual post-op protocol. So the next few slides are from Dr. Hersh’s clinical trial. This was the approval study for the riboflavin sold by Avedro. And the top line result — this is the primary efficacy endpoint set by the FDA — was looking at K max change in treated versus placebo patients at one year. And as you would expect, the placebo patients got worse over a year. And as predicted, the crosslinking patients improved over one year. So this met the FDA benchmark, and that’s what enabled approval for this technology. In addition to the K max effects, the asymmetry indices improved. The higher order aberrations, spherical aberration, coma, and trefoil also improved. And so the quality of vision for these patients improved. And this was reflected in improvements in letters on the ETDRS scale. About six letter improvement on corrected distance visual acuity, and about four and a half letter improvement on uncorrected distance visual acuity. Furthermore, patient visual function — my self-report questionnaire — indicated reduced night driving glare, halo, and starbursts, and all of these were significant. Out of the 512 eyes that were submitted for the clinical trial approval, one patient had a corneal ulcer. About 57% of patients developed haze at some point in the one year observation. So stromal haze is a very common effect of epi off crosslinking. And the time course usually is worse in the first three months. So if you look at these corneal OCT pictures, you’ll see stromal haze in the stroma down to about half depth or so. And that is clinically relevant. These patients do have visual disturbances from corneal haze, for the first several months, but typically it goes away by 6 to 12 months. We do like to look for the demarcation line on corneal OCT. That indicates the depth of the crosslinking effect. And that’s usually visible on subsource OCT at about 250 to 300 microns. So which patients are most likely to benefit from crosslinking? So the worse the K max is, the more likely they are to have flattening of the cornea. So when they looked in the clinical trial at the distribution of K max, at one year after crosslinking, about three and a half patients — 3.5% of patients, actually — did get worse. The vast majority had no change or improvement. And what they found in the subgroup analysis was that if K max was more than 55 diopters, these patients were fivefold more likely to flatten by 2 diopters at one year. Furthermore, the worse they start off, in terms of vision, the more likely it is for them to have visual gain. So again, the vast majority of patients or the plurality of patients have no change in visual acuity, a fair proportion have improvement, and about 3.5% of patients did lose some vision with the crosslinking procedure. So the purpose of treatment is to stabilize the disease. Minimize the loss of visual acuity, and normalize the corneal topography. You do have to advise the patients that they’re not going to get better immediately. Their K max actually got worse in the first month, and then slowly, over the next year, it improved. And based on the European data, this improvement continues somewhat, up to about two years. So what are the challenges? So as I mentioned to you, crosslinking involves scraping the cornea. You’re causing a complete corneal abrasion. So all these patients have pain for several days. Maybe a week or two. Because you have an open corneal stroma, there is some infection risk. These patients need antibiotics until the epithelium is closed. The majority of patients do develop corneal haze. A small proportion develop scarring, but generally, with adequate treatment of the haze with steroids, you can prevent scarring and clear the cornea within a few months. The vision changes. Visual fluctuation is common, up to a year. In the US system, insurance coverage remains a challenge. And because the cornea has a lot of inflammation at the time of the surgery, with the corneal debridement, you can’t do Intacs at the same time. You generally have to do that at a different date. And Intacs is a very nice procedure to have in your keratoconus toolkit, because that will have a substantial reduction of corneal astigmatism. So if you feel that the patient needs both epi off crosslinking and Intacs in both eyes, that’s four procedures. And four post-op sets of visits. So that requires a lot of patient commitment. And so that needs a good discussion before embarking on therapy. So as an overall framework for keratoconus therapy, I think the most important thing you can advise your patients is to stop eye rubbing! I actually tell the loved one of the patient that they can charge the patient a dollar every time they rub their eyes, and that’s a very good way of getting the patient to stop their eye rubbing habits. If they have allergies, give eye drops for the allergies. Talk to them about cold compresses. If they do need to rub, use the finger pad, rather than the knuckle. A lot of these patients, if you ask them to show you how they rub their eyes, they use their knuckles and really press on their cornea. And that knuckle is bone. The cornea is not. And so you want them — to stop them from using their knuckles to rub their eyes. I find Intacs to be incredibly helpful in normalizing the contour and reducing astigmatism and myopia. And crosslinking stops progression. So the purpose of crosslinking is to stop it from getting worse. The purpose of Intacs is to hopefully improve the corneal symmetry. It is very valuable to work with an optometrist who is experienced in keratoconus therapy. Someone who can do piggyback lenses or hybrid lenses or scleral lenses or soft torics. Because these can make a huge difference to patients. For advanced disease, that may still need a transplant, either a PK or a DALK — and before embarking on therapy, understand that this is not your typical LASIK or cataract patient. Where you do the procedure, they’re happy within a day or two, and life is grand. This is a patient that you’re going to get to know very well, over the next several years. So you need to advise them that their expectations cannot be a goal of 2020 uncorrected. Many times, keratoconus patients have been struggling with their contacts, struggling with their glasses, struggling with their vision and life. They come in looking for LASIK. You tell them they can’t have LASIK. But they should get crosslinking. That’s medically right. But in their mind, they’re thinking: Your crosslinking is going to fix their vision. Especially if they’re paying thousands of dollars for that. And so they have expectations that you need to reset. They cannot be allowed to proceed to surgery with LASIK expectations. Because this is not LASIK. And so you really need to emphasize to them: The purpose of therapy now is to keep them from needing a cornea transplant in the future. And hopefully will improve their vision somewhat. Hopefully we can improve their contact lens tolerance somewhat. But this is not about getting them out of glasses or contacts to a 2020 uncorrected endpoint. So that reset of expectations has to be set at the very start, in the informed consent process. So that’s the standard of care, approved crosslinking. What I would like to share with you today, for the next part of the talk, is our issue approved clinical trial. It’s a phase 1, 2a study. That uses epi-on crosslinking, with pulsation and an accelerated protocol. This is using the Peschke PXL 330 device. I’m a consultant for Peschke. I should disclose that. The research, however, has not been sponsored by Peschke. The objectives of this clinical trial in our practice are: To look at the treatment of keratoconus and post-Excimer ectasia. This is a bit of a different protocol. We do the same loading of riboflavin before the surgery. But there’s no scraping. There’s no epithelial debridement. And this is enabled because the riboflavin solution comes in a transepithelial formulation. So there’s additives in the riboflavin formulation that enable it to cross the epithelium without removing the epithelium. I adjust the aperture size of the crosslinking light to the cone. So based on topography, I might change the cone — the aperture of the crosslinking — from 9 millimeters down to 8 or 7 or 6 millimeters. So I’ll shrink the crosslinking light to where the treatment needs to be applied. So very often, I decenter the treatment, somewhat inferotemporally, to apply the UV light to the ectatic cornea. And the nice feature with this trial is that we can apply 30 milliwatts for 10 minutes in pulsed fashion. 5 seconds on, 5 seconds off. So this is a much faster treatment. Rather than a 30-minute per eye treatment. It’s only a 10-minute treatment. And using the pulsing allows the cornea to reoxygenate. And so we do deliver oxygen by blow-by. And that extra oxygen facilitates the crosslinking photooxidation. Afterward, we do a combination Pred-Gati, prednisolone/gatifloxacin eye drop. I do prednisolone for a few days in some patients, but not all. Generally I’ll reserve this for patients who have had ocular surface disease, or are at risk for ocular surface inflammation. But most of the time this is not necessary. It is important for them to wear sunglasses. And if the patient has pain, they can get percocet for a couple of days. But generally most patients don’t need anything more than Tylenol or ibuprofen. I do put a soft contact at the time, with an estimate as to what their myopic correction needs to be. I’m not gonna go through all the inclusion and exclusion criteria. But with this protocol, we can treat down to age 12. And we don’t really have to worry about corneal thickness so much. Because we’re not removing the cornea. So as long as the total corneal — removing the corneal epithelium. So as long as the total corneal pachymetry is more than 400 microns, then we can proceed with this epi-on protocol. Patients who have prior herpes or acanthamoeba or scarring are not eligible for the crosslinking. Because the UV light can sometimes reactivate those pathogens. And obviously, if they have some other chronic disease that affects healing, such as poorly controlled diabetes, or non-compliance, we may not enroll them in this study. So far, we’ve treated 28 eyes, 16 with crosslinking alone, 12 with Intacs and crosslinking. There have been no adverse events, and there’s been no loss of best corrected visual acuity. 11 eyes have completed one year of follow-up. One patient in one eye did require retreatment. Due to progression. And let me go through what we have at the one-year — six month and one year follow-up data. So the patients who underwent crosslinking and Intacs — there was a substantial improvement in uncorrected visual acuity. And that’s to be expected. Intacs dramatically decreases corneal astigmatism. So that helps their uncorrected visual acuity. In addition, there was about 10 letter improvement on the ETDRS best corrected visual acuity. On the crosslinking-only group, there was still a visual acuity improvement. Both on uncorrected, as well as three letters of improvement on the ETDRS scale. Visual concerns by patients did decline. In terms of those self-reported night starbursts and halos and so on. After the initial procedure, there was a slight increase in the K max, with the Intacs patients, and the reason that’s occurring is: Intacs is displacing that cone from the inferotemporal cornea, and it’s displacing that towards the center. So we expect that. But then it stabilizes. The crosslinking-only group also had stabilization of the K max. So I’m gonna go share with you some comparison reports. So this is a very useful technology that’s available on both the Galilei and the Pentacam. So you can compare topography before surgery, after surgery, and then do a comparison report. So this patient was initially evaluated in August of 2017, and this is two years later. Their topography. And what you’ll see is: This is not a curative procedure for keratoconus. But their K max substantially reduced, from 61.3 to 52. And so there’s a dramatic normalization of the corneal contour, all across the cornea, such that it’s much less asymmetric. So this is the effect that can be seen, a couple of years after the procedure. And this next patient — very similar effect. This is the other eye of that same patient. August 17th to December 19th. So both eyes were treated, and this initial crab claw pattern again… Less corneal steepening. Two and a half years after the procedure. Compared to start. And the K max is substantially reduced. This next patient — this is about a year after treatment. June of 2017 to July of 2018. Let’s see the effect of what the Intacs and crosslinking did. Was to substantially reduce the size of the cone. As well as the steepness of the cone. So again, this patient was not able to tolerate a soft contact lens. But was seeing a lot better, and able to tolerate a soft contact lens after treatment. These effects do take time to build. So this patient — we only have 8 months of follow-up so far. And at 8 months, there is reduction of the cone size, and flattening of the cone. But it’s only been 8 months. So we’re not seeing as much effect as on the prior two cases, where we had two and a half years of follow-up, or a year of follow-up, and this matches the long-term literature, shown in Europe, where after crosslinking, you do have this disease modifying effect, where you take the patient off of the corneal steepening pathway, and put them on a corneal flattening pathway, that tends to progress and get better over time. All right. So here we’ll do a little pause. I’ll do a little Q and A session. So this is where I’ll ask a question. And then Lawrence will put an audience response question on the screen, and we’d love to hear everyone’s responses, and then I’ll go through the answer. So question one. Which of the following is not a Rabinowitz criterion — Rabinowitz developed the first set of criteria for keratoconus — so the choices are: Mean keratometry more than 47.2, inferior-superior asymmetry more than 1.5 diopters, mean intereye difference of keratometry more than a diopter, or skewing of radial axis, less than 20 degrees. Which of these is not a criterion for keratoconus? So if everyone can take a little bit of time, and choose their answer, and then hit submit, then Lawrence will be able to collate the data, and show us the audience poll, and then I’ll go to the answer and explanation. Okay. So the plurality said skewing of radial axis, less than 20 degrees. That is correct. We’re gonna go to the next slide here. And the classic criteria for keratoconus based on topography are: A steep cornea, mean K more than 47.2, inferior-superior asymmetry, more than 1.5 diopters. So that’s just saying the inferior cornea is steeper than the superior cornea. And then a difference in the Ks between the two eyes. If that is more than a diopter, that is one of the criteria for keratoconus. Skewing refers to a symmetric bow tie or asymmetric bow tie. If the axes are more than 20 degrees off, that points you towards keratoconus. If the axes of the cornea are symmetric or less than 20 degrees skewed from each other, then that’s within the range of normal. So that’s the first question. So again, this is the classic Rabinowitz criteria. And this presentation is being recorded, and everyone can have the slides after the talk. Question two. In the Randleman ectasia risk scoring system, which of the following adds no risk of corneal ectasia in patients who are being considered for LASIK? So the Randleman ectasia risk scoring system refers to LASIK candidates. And so the potential choices are: Pachymetry of 520 microns, age of 18, residual stromal bed of 270, and correction of -9.5 diopters. Which of the following adds no risk of ectasia? So if you can take a few seconds and submit your answer, we’ll get the audience poll. Perfect. So the plurality said pachymetry of 520 microns, and that is the correct answer. So let’s go through those Randleman criteria. Brad Randleman, who was at Emory previously, published this risk scoring protocol for patients coming in for examination for LASIK. So he assigns points to different features. And if you have 4 or more points, don’t perform LASIK. If you have 3 points, that would push you towards proceeding with caution. Maybe do PRK. And then think about the whole picture. 0 to 2 points is low risk, and you can proceed with refractive surgery. So the interesting thing about this points system is the following: On the age criteria, the only way to have zero points for age is if you’re more than 30, so this is an important point. Keratoconus occurs — or presents itself — in the teenage years or 20s. So if you do LASIK on a 20-year-old, they could get keratoconus when they’re 27. That doesn’t mean you caused the keratoconus by doing the LASIK. Because they could have developed keratoconus anyway. So until you get to age 30, you don’t actually know the natural history of a person’s cornea. That’s the point of this age criterion. So that yes, you can do LASIK in the 20s. But you just don’t know the natural history, because the cornea is a dynamic living tissue. And only until you get to 30, only after you get to 30, is when you’re confident that they’re not gonna get keratoconus, just because they have whatever gene for it. Residual stromal bed. For a long time, we used to say 250 microns was our strong deck. You should leave 250 microns. But that’s not true. It’s more of a spectrum effect. Over time, we’ve come to a hard deck of 300 microns. The more you go underneath 300 microns, the more points you get for risk of ectasia development. Corneal thickness — more than 510. There’s no additional risk, and the thinner you get, the more points on ectasia risk you get. And then in terms of manifest refraction, in terms of how much ablation you do, more than 8 diopters, 8 to 10 diopters, you’ve got 1 point. More than 10 diopters, you get 2 points. I don’t really know anyone doing more than 10 diopters of correction, so the rest of this is fairly moot. And as far as topography, this is really a subjective judgment on the part of the cornea specialist looking at the topographer. There are indices given by the Pentacam, with the Belin/Ambrósio display, or the BAD index, or other indices, which are helpful for giving quantitative methods for keratoconus risk. But at the end of the day, it’s the job of the surgeon to decide: Is this bow tie asymmetric? Is there skewing of the axis? Is there radial steepening? So those are the things to look for on corneal topography. And that’s just a function of experience. Looking at lots of normal topos and looking at abnormal topos. All right. Question three. Which of the following poses a significant risk of ectasia? This is in the context of doing LASIK. An 80 micron ablation after a 100 micron flap in a 550 thick cornea? A 140 micron ablation after 110 micron flap in a 500 micron thick cornea? 60 micron ablation after 120 micron flap in a 600 micron thick cornea? Or a 140 micron ablation after 120 micron flap in a 600 micron thick cornea? Which poses a significant risk of ectasia? I’ll give you a second to submit your answer, and then Lawrence will do the audience poll. All right. You chose answer B. That is the correct answer. So this goes to the percent tissue altered formula. So I mentioned to you classically it used to be 250 micron hard deck. Now it’s a 300 micron hard deck. But a more stringent formula to know and be aware of is the PTA formula. Which basically says: The flap thickness plus the ablation depth should be no more than 40% of the central corneal thickness. That is to say: After the flap and ablation depth, you should have 60% of the cornea remaining. And depending on the patient, this interacts with the Munnerlyn formula. So the larger the optical zone, the more ablation per diopter. So depending on the patient, if you can go to a smaller optical zone, and save significant amounts of cornea, to stay above the 60% corneal thickness residual that you want to keep. So when you’re planning your refractive surgery plans for LASIK patients, pay attention to the PTA formula. The flap and the ablation should be less than 40% of the central corneal thickness. And pay attention to the Munnerlyn formula, which affects the ablation microns per diopter based on optical zone. If you’re doing PRK rather than LASIK, there’s no flap, but you are removing the epithelium, so in that context, rather than FT in this formula, I put in 55 microns — that’s a general average for corneal epithelial thickness. If you do happen to have an Optovue or an ArcScan or CSO MS-39, those are instruments that can measure corneal epithelial thickness centrally, and you can get an epithelial thickness map, you can plug that in, but those instruments aren’t that common yet. All right. Last audience response question. Crosslinking would not be indicated in which of the following situations? A 25-year-old with keratoconus who has had 1 diopter of steepening over the last 6 months. A 15-year-old with keratoconus who has experienced half a diopter of steepening over the last 4 months, a 30-year-old with keratoconus and scarring from hydrops, or a 25-year-old with a superficial bacterial ulcer, not responding to antibiotics. In which of those situations is crosslinking not indicated? So you can take a second and submit your answer. Lawrence will do the poll. And that is the correct answer. The patient with the hydrops. Excellent. And the reason for that is: If you have a hydrops and corneal scarring, this person is going to need a transplant. Crosslinking isn’t gonna help them. All of the other patients, they have progression. They should be crosslinked. And the person with the superficial ulcer not responding to antibiotics — if you can kill the bacteria with crosslinking, go for it. So I would like to share a couple of cases here. What do you think happened? As well as how would you manage? Normally I do this in the context of a small group. This really doesn’t — with hundreds of participants, we can’t do that. So I’ll just present the topography, kind of share my thoughts, and then we’ll go from there. And whatever questions you have, we can put in the chat box and we can review. So this person is about 70 years old. They came in for their cataract evaluation. But they had PRK. About 24 years ago. And they had PRK that was a -24 ablation. A long time ago. And you can see a very thin cornea here. Down to about 121 microns centrally. The thinnest point is 98 microns. We did cornea OCT. Initially, we didn’t believe this. We did cornea OCT. And the thinnest point in the cornea on the OCT centrally was about 130 microns. So we actually do believe that this cornea is super thin, based on the slit lamp exam, the cornea OCT, and this photography. So what should we do? I talked to this person extensively about doing a PK and cataract, a triple procedure. He was doing reasonably well with contact lenses, with a hard contact lens, until his cataract got bad, so he asked if we could just do the cataract, and we did. My fellow, Dr. Hubble, and I did the procedure. We used a MiLoop to chop up the cataract. Into small pieces. To minimize how much time the phaco probe was inside the eye. Obviously we wanted to spend as little time inside the eye, because we did not want this paper thin part of the cornea to burst. So the person is a couple weeks out from surgery. So far doing well. And we lucked out by not having to do a PK. This next patient is someone with keratoconus. You can see this inferotemporal cone. They have a +5.50/-9.50 prescription. So we decided to do Intacs and center it on the cone. So the cone is over here. The posterior part of the cone. We want to displace that, and what you’ll often notice is that the axis of the cone actually matches the flat axis of the astigmatism. And that’s where you want to put your Intacs. You want to put the Intacs, displace the cone centrally, and change the flat axis of the cornea so that the cornea is more symmetric. You’re taking a cornea that’s a cone, and putting an underwire to make it more round. This next person was also severe keratoconus. But rather than a hyperopic sphere, they had a very significant myopic sphere. But they had a lot of astigmatism. 8 diopters. So similar strategy. We put a single segment Intacs here. To debulk the astigmatism. And then put a -14 soft contact lens. And they were very happy with it. So again, what you’ll notice is the cone — displacement on the posterior side matches the flat axis of the cylinder. And so you’re trying to normalize the cornea, by putting an Intacs, symmetrizing the cornea to reduce the astigmatism, and this person, who could not tolerate a soft contact lens or a hard contact lens, afterward is now functioning very nicely with a -14 soft lens. So both of the last procedures were Intacs and crosslinking. This is the CLMIX map that I showed to you. The Belin/Ambrósio display on the Pentacam is similar. It shows you all of these indices. And the keratoconus is 100%. So I encourage you to play with these Scheimpflug options to get used to this presentation. We look for the CLMI index, 9.33, and that’s what we change over time. So this last case that I want to show is a person with a -7/-2.50. So here there’s some astigmatism, but the main problem is myopia. So we did a double Intacs with crosslinking. Asymmetric Intacs. 4.50 over here. And 2.10 over there. By having a double Intacs, you can reduce the myopia substantially. But by having asymmetry, you can reduce and treat the astigmatism and get the person into a soft contact lens. So this was the plan. We did a 450 there, 210 there, we’re trying to center the cone, and treat both myopia and astigmatism. So with that, let me stop. There’s about 10 minutes left. And I’m going to stop the screen share. And then I’ll open up the Q and A. And I’ll address some of the questions. All right. Let’s see how many questions I can get through. I want to thank everyone for their attention. So let’s go through the questions. Dr. Qamar asked: At what age can I do crosslinking, lower limit? I would say down to about age 10. In our protocol, we do age 12. I do know physicians who have done it down to age 9. It really is dependent on patient cooperation. There are even reports of Down syndrome children who have been put to general anesthesia and then underwent crosslinking. In the less than 10 age group. So if you have the setup to do general, and you want to go younger, you can. But that is up to you. You have to really look and see how well the parents can manage that child afterward. Next question. Once you do crosslinking, how much time do you wait to see a reduction in the cylinder, or when can we fit contact lenses? Great question. So I put on a bandage contact lens that’s a soft lens with what I predict to be the myopic power needed. About two weeks later, I’ll fine tune it. And then about a month after that, I’ll get them to the contact lens specialist, to try to do a soft toric if necessary. So you can fit the contact lens on the day of the surgery. I would fine tune it a little bit with contact lens overrefraction, a couple of weeks later. And then get them back to the optometrist, to do further fits over the next several months. Because it is gonna change. It’s gonna change over a couple of years. So I try to do a couple of fine tunes in the first couple of months, and then let the optometrist adjust things every six months for the next two years. What are the criteria for selection of patients for C3R? So takeaway messages: If you have a person with keratoconus progression, they should be crosslinked. Any age. If they have progression, you’re seeing the topos get worse, the astigmatism is getting worse, do the crosslinking. You want to stop progression. Now, if it’s a young patient and you don’t have prior topographies, let’s say they’re less than 25, certainly less than 20, they have a 99% chance of progression. And so I don’t think you need to wait, in a young patient, to do crosslinking, because you know they’re gonna progress. After crosslinking, is there an effect on transparency of the cornea? This is from Dr. Singh. If you have epi off crosslinking, yes. The majority of patients are going to get haze that resolves over about 6 to 12 months. Epi on crosslinking, generally there’s no haze. Next question. Dr. Agarwal. What is the minimum age? We talked about this already. I would go down to probably age 10, personally. Some have gone down to age 9. Next question. Which is better, riboflavin with or without dextran? The purpose of not having dextran is to have hypotonic solution. So the hypotonic solutions don’t have dextran. That swells the cornea. The dextran is there normally just to keep it in isotonic solution. So it depends on the corneal thickness, whether you want dextran or not. So look at the Photrexa formula or the Peschke formulas, and see whether you need a hypotonic solution or not. Next question. How does it affect post-op corneal thickness? What we’ve seen is a slight reduction. The corneal collagen crosslink — it becomes more compact. So at about one year, there’s probably about a 5 micron reduction in central corneal thickness. Next question. Repeat crosslinking and how early can we repeat? If you see worsening at six months or nine months, I would repeat it. And indications for repeat therapy are progression. So you want to follow these patients with regular corneal topographies, and see: Is their astigmatism getting worse? Is their K max getting worse? As far as how often to advise topography, I would probably do it at least every six months. In our clinical trial, we’re doing it at every study visit. But if you’re not in a clinical trial, I would do the topography at least every six months. Next question: What is the minimal thickness? If you’re doing epi on crosslinking, in our protocol, it’s 400 microns. If you’re doing epi off crosslinking, if the cornea is between 300 to 400 microns, you want to swell it with hypotonic solution, and then get it above 400, to do the crosslinking. And yes, the protocol is the same in the postrefractive ectasia. Okay. Next questioner. Dr. Morteza Fard. Do you recommend crosslinking for the second eye of the keratoconus patient while the UCVA is 20/20? So if you have a patient who is having progression on topography, their cornea is getting worse, their asymmetry, their cone, talk to them. This is not just about 20/20. Very often they’ll tell you they’re having difficulty with their sight. Night driving or glare or whatever task they do. Just because uncorrected visual acuity is 20/20, we all know keratoconus patients have a very good visual brain. Keratoconus patients can sit there at the Snellen eye chart. If you give them enough time, they can get an extra line or two. They’re not reading fast, but they can make things out. Because their visual brain is better than the average patient. And so it is not just about 20/20. It’s about: Does the patient notice progression? Are you seeing progression on the topography? If the answer is yes, I would encourage them to have crosslinking, even if their uncorrected vision is 20/20, with informed consent about the risk of surgery. Next question. No rub, no cone? Well, rubbing is probably the biggest risk factor for keratoconus. But there are patients who don’t rub and still get keratoconus. Next question from Dr. Ullah. If one eye is 20/20 and no cylinder, and they have visual acuity one month, 8 diopter cylinder, fundus is normal, any need to do crosslinking? This is hard to realize without checking topos over time. Is there progression or not? If there’s no progression, you don’t need crosslinking. If there is progression, then do the crosslinking. This particular patient, it looks like 8 diopters of cylinder is the main issue. So Intacs are probably going to give you a much better effect than crosslinking. Sheri Morgan. Coming from a public health background, are there current estimates of global burden? Can you see crosslinking scale up on a global scale? There are many crosslinking manufacturers out there. New World and Peschke and several others have very affordable units. Riboflavin outside the US should be very affordable. So yes, I do see crosslinking scaled up. It does require follow-up and compliance, of course. As does any surgical procedure. Next slide, Dr. Temelkovska. I hope I pronounced that correctly. When patients have keratoconus in one eye and have done crosslinking and the other eye has borderline values for keratoconus, should we perform crosslinking immediately? I would check and see if it progresses. If it does not progress, observe. If it does, do the crosslinking. In that situation, I would probably do a repeat topography in 3 or 4 months in a younger patient. If they’re over 30 or 40, maybe every 6 months. What is the importance of warming alcohol? I don’t. Next question. What is our approach for post-DALK ectasia? So keratoconus can recur. Either with a PK or DALK. If you’re seeing recurrence after PK or DALK, generally that’s because of incomplete removal of the peripheral inferotemporal tissue. So when I do transplant on these patients, I’m doing a large transplant, and very often, I’m decentering the removal, the trephination, so that I’m getting that peripheral inferotemporal diseased tissue. And when they recur, what you’ll notice is that that wasn’t done. So they actually had some remaining keratoconus tissue left. These patients tend to come back years later, and they have this recurrence. If they’re no longer contact lens tolerant, you can actually do thermokeratoplasty, with handheld cautery. A little zapping on the apex of that peripheral rim, and a little bit of heat scars that peripheral rim, and then you can get them into a contact lens. How much time between crosslinking and Intacs? This is from Dr. Vizcarra. I try to do them at the same time. Because I can, with epi on crosslinking. If you do epi off crosslinking, I wait two or three months to do the Intacs. Order doesn’t matter. You can do either one first. Next slide. Next question. Dr. Pandya. When we’re doing LASIK with crosslinking, should we do it simultaneously? If you’re doing LASIK extra — I have not done this — but if you’re doing LASIK extra, I would do the flap, do the ablation, do the crosslinking on the stromal bed, then put the flap back on, or put the flap back on and then do the crosslinking. A lot of it depends on corneal thickness. But I would do it simultaneously. What’s the highest K max deemed acceptable for crosslinking? I would really rephrase the question. What’s the minimum corneal thickness? When you get into corneas above 70 diopters, most of those patients probably have a lot of corneal thinning, and probably need a transplant. So I have gone up to 68 or 69 diopters. Next question from Dr. Uwakwe. How soon can one who just had crosslinking start using an RGP lens? If it’s epi off crosslinking, I would wait until the epithelium heals and stabilizes, so at least a couple of weeks. Next question, Dr. Olvera. If the keratoconus is stable, does the patient need crosslinking? Probably not. The purpose is to stop progression. What is the thinnest pachy? Minimum, at least 400. If you have sub-400 micron crosslinking, you’ll want to swell the cornea to get it above 400. Next question: Dr. Ali. Least time for follow-up to detect progression? You can often detect progression within 3 or 4 months. Just a few more questions. Home stretch here. Dr. Aritonag. If the patient is age 35, when can they get scleral lens after crosslinking? Probably in a couple of months. I would probably wait at least a couple of months for the cornea to get to a relative area of stability. Do you recommend lubricating eye drops, from Dr. Bhandary? Yes. What’s the maximum age of patients for crosslinking? There is no maximum age. If you have an older patient, 55 or 60, who is having progression, do the crosslinking. It’s rare, but I would do it. Even though they have progression. How long should we wait postpartum? That’s an interesting question. Well, I would wait probably at least a couple of months. Dr. Ullah, my patient is 6 years old. Can they do crosslinking? They can, I suppose. I would look at doing general anesthesia. And doing it in an operating room in that context. But I think that would be a discussion with the parents. Criteria for PK in post-crosslinking. That’s the same criteria as for any PK. How bad is the vision, and can a PK help? And then do you recommend contact lens assisted crosslinking for a thin cornea? I have not done that. Dr. Grawe in Mexico would be a good resource for that. Last question, 420 CCT with keratoconus — if there’s progression, then yes. And Dr. Kumari. Patient got diabetic retinopathy after injection. They should be treated for their diabetic retinopathy. It doesn’t sound like this person has keratoconus. So I would get them to the retina specialist. So with that, I think we’ve done the blitz of answering questions. The speed question session. So thank you all very much. Oh, there’s one more. Is it a disease of myopia or hyperopia? You can have it with either. I’ve had hyperopes with a lot of keratoconus. Astigmatism. And they’re hyperopic. So that depends on not just the cornea, but also the axial length. Thank you all very much. You all have a wonderful day. It was a pleasure. And you can all email me. If you have any questions. My email is [email protected]. Thank you. I appreciate Nashrah and Lawrence and Orbis and Cybersight. Thank you all very much.

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September 23, 2020

Last Updated: October 31, 2022

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