January 2019


Crosslinking playbook
CXL playbook for intraop and postop management

by Vanessa Caceres EyeWorld Contributing Writer

An in-treatment image of a patient undergoing corneal crosslinking using the FDA-approved Avedro protocol
Source: J. Bradley Randleman, MD


Surgeons share pearls for better CXL outcomes

As U.S. surgeons increase their use of corneal crosslinking (CXL) to treat keratoconus, better intraoperative and postoperative approaches can help improve outcomes. EyeWorld asked some seasoned CXL users for their intraop and postop insights.

Is epi-on an option?

For now, only the epithelium-off system from Avedro (Waltham, Massachusetts) is approved in the U.S. However, Avedro is doing an epi-on CXL clinical trial, and surgeons are eager to see the results, said Parag Majmudar, MD, president and chief medical officer, Chicago Cornea Consultants, Chicago. In addition, the CXL USA study group (Bethesda, Maryland) has done epi-on treatments since 2010. “That group is currently evaluating a proprietary epithelium-on system, and the clinical results have been outstanding,” Dr. Majmudar said. He has performed epi-on treatments with CXL USA since 2010.
Because epi-on treatments appear so promising, Dr. Majmudar is concerned about surgeons who want to perform epi-on CXL, especially in the pediatric population, and may use the current epi-off technology in an epi-on fashion. “Or even more concerning, some surgeons may obtain non-Food and Drug Administration-approved devices from overseas and try to perform epithelium-on crosslinking with those devices, which have not been evaluated for epithelium-on crosslinking,” he said. “It is not possible to use technology that has not specifically been designed for epi-on CXL and expect the same level of efficacy as we are getting with currently approved epi-off or proprietary epi-on devices.”

Riboflavin and light sources

The doctors interviewed by EyeWorld get their riboflavin from their trial sponsors, be it Avedro, as Audrey Talley Rostov, MD, Northwest Eyes, Seattle, does, or CXL USA. “I use it according to their standard protocol, 30-minute soak with 3-minute light time,” Dr. Talley Rostov said.
Dr. Majmudar shared his experience. “Currently in the CXL USA trial, we are varying the fluence and duration of UV exposure between 20 and 30 minutes,” he said. This is not considered accelerated CXL, which is typically described as a UV exposure of only 3 to 5 minutes, he added.

Determining corneal thickness intraop

Corneal thickness measurements during the procedure can help decide whether surgeons should use hypotonic riboflavin or if they should thicken up the cornea.
“I measure before applying UV light with a PachPen handheld pachymeter [Accutome, Malvern, Pennsylvania],” Dr. Talley Rostov said. “I usually use standard riboflavin, but with a thin cornea or if I’m leaving the speculum in during riboflavin drops, I will alternate with standard and hypotonic riboflavin,” she explained.
Although the original CXL trials in Europe used 400 microns as the “magic” number to initiate UV light treatment, Dr. Majmudar said, corneal thickness is less vital with epi-on technology. “Our current clinical protocol requires us to have the thinnest portion of the cornea above 375 microns. In the vast majority of cases that we treat, this is easily attained, especially if we start to treat patients at earlier stages of keratoconus,” he said.

Decentering the CXL light source

William Trattler, MD, Center for Excellence in Eyecare, Miami, said research from Michael Mrochen, PhD, Zurich, Switzerland, presented in recent years showed the importance of rotating the eye so that UV light is centered on the thinnest or weakest area of the cornea. “For pellucid marginal degeneration, where the cornea is thin inferiorly, the patient is asked to look above the light, and the center of the light is decentered inferiorly,” Dr. Trattler said. More recently, Theo Seiler, MD, published results demonstrating that customized crosslinking provides greater flattening and reshaping compared to standard CXL.1
Dr. Majmudar does not decenter the light source over the cone as his current protocol uses a 12 mm beam that encompasses the entire cornea.

Eye rubbing

The message is clear: Tell patients to avoid eye rubbing.
“We recommend that all patients stop eye rubbing, as this appears to be an important risk factor for keratoconus,” Dr. Trattler said. “Not all patients with progressive keratoconus rub their eyes, but for those who do, we discuss the importance of avoiding eye rubbing.”
“I think that some cases of post-CXL progression may be due to continued eye rubbing,” Dr. Majmudar said. “We try to impress upon patients the importance of not rubbing the eyes.” Dr. Majmudar does not usually counsel patients to avoid sleeping on their face or side, but he said this advice could be useful in severe cases, as it may cause undue pressure on the cornea.

Postop pain control

When helping patients control pain after CXL, Dr. Talley Rostov prescribes four tablets of hydrocodone acetaminophen and one tablet of lorazepam. Patients are also prescribed topical Prolensa (bromfenac ophthalmic solution, Bausch + Lomb, Bridgewater, New Jersey) four times daily for 3 days, topical Lotemax (loteprednol etabonate gel, Bausch + Lomb) or Pred Forte (prednisolone acetate, Allergan, Dublin, Ireland) four times daily for a week and a tapering dose. Polytrim (polymyxin B/trimethoprim ophthalmic solution, Allergan) antibiotic drops are used until the epithelium is healed. Preservative-free artificial tears are also part of the mix. Patients can begin using their contact lenses 2 weeks after the procedure, Dr. Talley Rostov said.
Another consideration is the patient’s updated refraction. “Most patients are advised to wait for 1 month prior to getting a new prescription for eyeglasses or contact lenses in the event that there is some remodeling of the cornea that can be taken into consideration in the first 4–6 weeks,” Dr. Majmudar said.

Monitoring progression

“Typically, once patients are determined to be stable at 6 months or 1 year, annual exams are adequate to monitor for progression,” Dr. Trattler said. “Of course, if patients note changes in vision in either eye, they should return earlier for repeat testing.”
Although CXL strengthens the cornea, some patients have such weak corneas that they require two CXL procedures, Dr. Trattler said. Progression may not be evident for 1 to 3 years because the changes can occur very slowly over time, he explained. When monitoring for progression, surgeons should measure uncorrected visual acuity, spherical equivalent refractive error, best corrected visual acuity, topography, and tomography. If using a Pentacam (Oculus, Wetzlar, Germany), two screens Dr. Trattler recommends are the Belin ABCD screen, which evaluates changes over time, as well as difference maps. “Evaluating changes over time with the Sagittal view difference map is quite helpful. Progression is noted when there is steepening in the steep area and flattening in the flat area,” he said.
Dr. Talley Rostov said she will retreat if there is more than 1 D of consistent change. However, her retreatment rate is only 3% to 5%.
In patients who are 15 to 25 years old, Dr. Majmudar lets them know that there is a higher incidence of progression and that they should be more closely monitored in the first 3 to 5 years after the procedure. “Progression after keratoconus is a controversial topic, and there is no good metric that is widely adopted as the sine qua non of keratoconus progression. At this time, we are using a combination of change (steepening) in keratometric indices coupled with loss of best corrected visual acuity as an indicator of progression,” he said.


1. Seiler TG, et al. Customized corneal cross-linking: one-year results. Am J Ophthalmol. 2016;166:14–21.

Editors’ note: Dr. Majmudar has financial interests with Alcon (Fort Worth, Texas), Bausch + Lomb, and CXL Ophthalmics (Encinitas, California). Dr. Talley Rostov has financial interests with Allergan and Bausch + Lomb. Dr. Trattler has financial interests with Allergan, Bausch + Lomb, CXL USA, Avedro, and Oculus.

Contact information

: pamajmudar@yahoo.com
Talley Rostov: atalleyrostov@nweyes.com
Trattler: wtrattler@gmail.com

CXL playbook for intraop and postop management CXL playbook for intraop and postop management
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