What should be the goal for a standard of care in cross-linking?

Cross-linking will become the standard of care in the US

R. Doyle Stulting

Internationally, the “traditional” method of cross-linking involves epithelial removal and a 400 µm minimum thickness. Thinner corneas are treated by swelling them to less than 400 µm using the traditional method. More recently, transepithelial cross-linking has been introduced, either by pre-treating with topical anesthetic to enhance penetration or by using Ricrolin TE (Sooft Italia), which is a commercially available product that contains enhancers to facilitate penetration through an intact epithelium.

International data indicates that cross-linking stops the progression of keratoconus, with slight regression over 3 years, then stabilization indefinitely. Some patients obtain an increase in uncorrected visual acuity and best corrected visual acuity. Some can be fitted better with rigid gas-permeable lenses.

In my opinion, cross-linking will become the standard of care for the treatment of ectatic corneal diseases (including keratoconus, ectasia and pellucid marginal degeneration) at the time of diagnosis in younger patients who are likely to progress and in older patients with evidence of progression. It has the potential of preventing almost 50% of the corneal transplants performed in the United States, assuming it is used optimally for all indications.

We have less information to support its efficacy for the treatment of corneal edema, infectious keratitis, noninfectious corneal melts, and prophylactic use for the prevention of ectasia. These are areas that are ripe for further research.

R. Doyle Stulting, MD, PhD, is an OSN Cornea/External Disease Board Member. Disclosure: Dr. Stulting is a consultant to Peschke GmbH.

Epithelium-on procedures reduce haze, inconvenience for patients

Roy S. Rubinfeld

I can tell you that based on our experience across many of our centers, we do almost exclusively transepithelial treatment now. We have found that if you do epithelium-off cross-linking, then you have all the risks associated with a 9- or 10-mm epithelial defect, such as infection or delayed epithelial healing. And we have found that haze is more common with epithelium-off treatment and rare with epithelium-on treatment.

Epithelium-off treatments are not just riskier in terms of infection or haze, but also extremely inconvenient for the patient. When the epithelium grows back, the cornea is actually steeper for 3 to 6 months than it was preoperatively, so you have effectively made corneal curvature worse for several months postop while it is healing. With transepithelial procedures, we are finding the patients do not have an increase in their corneal curvature, their vision is generally at baseline by the next day, and they are able to return to their normal activities quickly.

By December 2006, all European Union nations had approved cross-linking. Delays in getting approval in the United States are not a safety issue; it is a regulatory issue. Getting devices approved is a challenging process.

I have watched the Europeans do these treatments since the 1990s, and it has become clear to me that cross-linking works. Up until now, all that we have had for the treatment of keratoconus was to tell people not to rub their eyes. Watching people lose their vision from keratoconus was frustrating for those of us who are corneal specialists and eye doctors.

One of the questions that I get asked often is: When should you have cross-linking? Should you wait until it is really bad? It is a common question, but the answer is obvious. Prevention of a severe disease beats treatment of a severe disease any day. If we can treat people early and prevent them from losing vision, that is preferable to stabilizing someone with severe disabling astigmatism or leaving them with poor vision. Especially with epithelium-on, because the risks are so low, this should be a first-line treatment, not a last-ditch effort. Comparing epithelium-on cross-linking to corneal transplantation, the risks are not even of the same order of magnitude, and I am a corneal transplant surgeon. If I never had to do another corneal transplant for keratoconus, I would be delighted.

Roy S. Rubinfeld, MD, is in practice at Washington Eye Physicians & Surgeons. Disclosure: Dr. Rubinfeld is an owner or shareholder of CXLUSA LLC.