September 2017


Update on Crosslinking
Patient selection for crosslinking

by Ellen Stodola EyeWorld Senior Staff Writer

Patient undergoing epithelium-off corneal collagen crosslinking
Source: Sumit “Sam” Garg, MD

Experts discuss ideal patients and factors to consider with crosslinking

With crosslinking approved in the U.S. for more than a year now, more physicians are using the procedure for their patients. Sumit “Sam” Garg, MD, Gavin Herbert Eye Institute, Irvine, California, John Berdahl, MD, Vance Thompson Vision, Sioux Falls, South Dakota, and Michael Raizman, MD, Ophthalmic Consultants of Boston, discussed patient selection, ideal patients, contraindications, and other crosslinking considerations.

Lessons learned from early phases of FDA approval

The FDA has approved the crosslinking procedure for patients age 14 and older, Dr. Raizman said. In the clinical trials, he treated patients as young as 12 who did extremely well with the procedure. “I would recommend treating patients with progressive keratoconus even under age 14,” he said, adding that there probably weren’t enough patients under age 14 for the FDA to feel comfortable approving it for younger patients, but the worldwide experience on younger patients is excellent. “They tolerate the procedure quite well,” he said.
“Because the patients with progressive keratoconus at a very young age are most likely to advance to the point of needing keratoplasty, I would recommend finding a way to accomplish crosslinking as soon as possible once progression has been documented,” he said.
Dr. Raizman said he reserves crosslinking for progressive keratoconus, but he added that there are some situations where keratoconus is severe and you wouldn’t want to wait to document progression. He added that crosslinking can be combined with PRK for certain corneas with relatively small refractive errors and Intacs (Addition Technology, Lombard, Illinois). “I have not achieved much benefit in crosslinking older patients whose keratoconus has been stable for many years,” he said. The protocol that was approved in the U.S. has been studied for years, and there’s a large database that physicians can access and use to make reasonable assumptions based on European data, Dr. Raizman said.
Dr. Berdahl said that the crosslinking labeling is for progressive keratoconus, but he thinks that most young patients who have keratoconus are progressive by nature. “As I’ve gotten more experience with crosslinking, I’m more inclined to do it right away on patients who have keratoconus,” he said. These young patients likely didn’t have an abnormal cornea when they were born, and now they have an abnormal cornea, so by definition they’re progressing. Dr. Berdahl compared keratoconus treatment to treating glaucoma. “When you do an evaluation for glaucoma, you don’t [wait until they] get worse before initiating treatment because you can’t get that vision back,” and he feels the same way about keratoconus. “You don’t want the cornea to become more misshapen.”
“As physicians, our calling is to do what’s right for the patient,” Dr. Berdahl said. “The question I ask myself is what I would want for myself or my child.” He will have a straightforward discussion with patients about risks and benefits and come to a mutual decision.
“I think this is best for a young patient who has mild keratoconus,” he said, because you’re able to freeze the cornea in position and shape before it becomes more misshapen, and you can avoid decades of challenges, as well as a cornea transplant.
Dr. Berdahl has some experience in combining crosslinking with other procedures. “We have found a resurgence of using Intacs in our practice to try to normalize the shape before we freeze it in place,” he said. It can be done at the same time, but he tends to do Intacs first followed by crosslinking later. Dr. Berdahl added that he is looking forward to the option for custom topo-guided ablation to normalize the shape of a cornea that’s been stiffened after crosslinking to help get a patient back to good vision corrected by glasses or contacts lenses instead of needing a specialty lens.
Dr. Garg said that he is currently sticking with on-label indications. Ideal patients, he said, are young, with progressive keratoconus, no scarring, and good vision in contact lenses or glasses. Dr. Garg added that it’s important that patients be able to follow instructions and stay still during the procedure.
He agreed that patient selection could expand as more surgeons in the U.S. gain experience with crosslinking. “I think there are many exciting applications for this technology,” he said. “I hope that it will gain an indication for keratitis.”

Contraindicated conditions and patient types

“At this point we have not been able to do any patients who require IV sedation/general anesthesia,” Dr. Garg said. “Certainly this is a group that will greatly benefit from the procedure. I’m hoping that as the procedure becomes shorter/more efficient, we will be able to treat these patients in the operating room with adequate anesthesia support.”
There have been a few reported cases of endothelial decompensation with irreversible corneal edema when treating patients whose corneas are too thin, Dr. Raizman said, noting that he has treated patients with corneas as thin as 350 microns. In those cases, he was able to swell the cornea prior to UV light treatment, but patients with thin corneas should be warned in advance that their corneas may not swell enough for treatment, he said.
Dr. Berdahl said that crosslinking is a safe procedure, and risks are low. The risk of infection after removing the epithelium is the main concern, he said, noting that he doesn’t see any strong contraindications. If the patient has a history of herpetic eye disease, it’s a little riskier. Additionally, a patient with a very thin cornea could pose a challenge. Dr. Berdahl said if a patient is older, the benefits may not outweigh the risks of the procedure because these patients may not be progressing any longer. He stressed that while some of these concerns may make him less likely to perform crosslinking on a patient, none are an absolute contraindication.

Impact of crosslinking on corneal transplantation

Dr. Garg hopes there will no longer be a need for transplants for keratoconus in the next 10–20 years.
Dr. Raizman said he sees less need for transplants. “I think we’re going to be doing far fewer corneal transplants for keratoconus because we’re going to be preventing the progression to that stage,” he said. Additionally, he added that when penetrating keratoplasty (PK) is done for keratoconus, it’s not unusual for the host cornea to continue to steepen over time, altering the refractive error of the eye.
Dr. Berdahl thinks that crosslinking will decrease the need for deep anterior lamellar keratoplasty (DALK) and full thickness corneal transplants in the future. “If we can eliminate full thickness corneal transplants, that would be ideal,” he said, noting that it’s unlikely that the need for these transplants will be completely eliminated because they may still be required for corneal scars and traumatic damage. “The only concern I have is I think full thickness corneal transplantation is at risk of becoming a lost art,” Dr. Berdahl said, adding that these cases are some of the most complicated. He is doing less than half the full thickness corneal transplants he was 5 years ago, which means that there are fewer cases for fellows to learn from.

Editors’ note: Dr. Raizman and Dr. Berdahl have financial interests with Avedro (Waltham, Massachusetts). Dr. Garg has no financial interests related to his comments.

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