February 14, 2019
3 min read

What characteristics are needed to be a good candidate for cross-linking for keratoconus?

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Some cases can have corneal topography, visual acuity improvement

Corneal collagen cross-linking is a treatment designed primarily to decrease the progression of keratoconus. Indeed, the FDA-approved indication is for progressive keratoconus in patients 14 years of age or older. This was based on a randomized controlled clinical trial that we recently published. Therefore, the best candidate for cross-linking is a patient with documented progression of disease. This documentation is based on clinical discretion. For instance, serial corneal topography may show an increase in the keratoconus cone. Irregular astigmatism may be increasing, and correctable vision may be decreasing. In addition, younger patients with keratoconus are at greater risk for progression than are older patients; thus, earlier intervention should be considered. Keratoconus patients should be followed carefully. Any indication of progression suggests consideration of cross-linking. I recommend yearly corneal topography to assure continued stability. Even in patients previously cross-linked, continued follow-up is important even though most patients remain stable long term after the procedure.

Peter S. Hersh, MD, FACS
Peter S. Hersh

Although not a labeled indication, other patients may be considered for cross-linking as well. In studies that our group has performed, we have found that cross-linking also can have beneficial visual and optical effects in addition to disease stabilization, such as an improvement in corneal steepness, visual acuity, topography regularity, higher-order aberrations and subjective visual function in some patients. In the U.S. multicenter prospective clinical trial, the CXL group showed a decrease in corneal steepness by an average of 1.6 D and an improvement in corrected and uncorrected visual acuity of 5.7 logMAR and 4.4 logMAR, respectively. To identify what made a patient a good candidate for the procedure or contraindicated cross-linking, our group analyzed gender, age, cone steepness, visual acuity and corneal thickness to see which preoperative characteristics would predict a good or unwanted outcome. Specifically, those patients whose cones were 55 D or greater were 5.4 times more likely to flatten by 2 D or more, suggesting that patients in whom keratoconus was worse were more likely to improve. Looking at corrected distance visual acuity, patients with 20/40 or worse preoperatively were about six times more likely to improve by two or more lines, while patients who were 20/30 or better had a slightly greater risk of losing one line. Thus, in addition to the primary indication of disease stabilization, using these guidelines, cross-linking may be indicated for improvement in corneal topography or visual acuity in select cases.


Peter S. Hersh, MD, FACS, is the founder of The Cornea & Laser Eye Institute – Hersh Vision Group. Disclosure: Hersh reports he is a former consultant for Avedro.


Good and best candidates have range of characteristics

Christopher J. Rapuano, MD
Christopher J. Rapuano

Corneal cross-linking has been an integral part of the management of keratoconus for more than a decade in many countries around the world. It was FDA approved for use in the United States in 2016 for the treatment of progressive keratoconus and the treatment of ectasia after refractive surgery for patients 14 to 64 years old.

Who are the best candidates for CXL for keratoconus? In my practice, I recommend CXL to patients:

  • between the age of 14 to about 35 years old;
  • with relatively mild keratoconus (without corneal scarring);
  • with relatively mild corneal thinning (ideally the thinnest cornea should be greater than 450 µm); and
  • who have documented progression of keratoconus over the past 6 to 12 months.

I feel these are the best candidates because they fall within the FDA-approved age range, they are demonstrating active progression, so they have an excellent chance of benefiting from the CXL procedure, and they are likely to have a corneal thickness that is above the 400-µm FDA-required minimum after epithelial removal and riboflavin instillation for the UV light treatment.

While many patients fall in this “best” candidate category, many do not. Who else do I consider to be “good” candidates for CXL?

  • Patients under the age of 14 years who otherwise fulfill the above criteria should be considered good candidates, as long as the patient and the guardian both understand that is an off-label use.
  • Because younger patients are at greater risk for rapid progression, patients up to about 20 to 25 years old with concerns for progression but without objectively documented progression should also be considered good candidates. Note that some insurance plans may only cover the procedure if there is documented progression.
  • Patients with thinnest corneal thicknesses between 400 µm and 450 µm, while not ideal, should be considered good candidates, as the vast majority of the time, use of hypotonic riboflavin solution can thicken the cornea to the required 400-µm level just before the UV light treatment.

Christopher J. Rapuano, MD, is the director of the Cornea Service and co-director of the Refractive Surgery Department at Wills Eye Hospital. Disclosure: Rapuano reports he is a consultant and lecturer for Avedro.