When is crosslinking appropriate?

Though the main benefit of collagen corneal crosslinking is to stop progression of keratoconus, it is not the sole benefit, said Theo Seiler, MD, PhD (Greece) here during Cornea Day at ASCRS 2016.

New Orleans-Though the main benefit of collagen corneal crosslinking is to stop progression of keratoconus, it is not the sole benefit, said Theo Seiler, MD, PhD (Greece) here during Cornea Day at ASCRS 2016.

Before surgeons can qualify what is a success, they must also define the failure.

“Long-term studies of the Dresden protocol revealed a failure rate as low as 3%,” he said.

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In that protocol, complication rates hovered around 4%, and corneal flattening of more than 2 D occurred in more than 13% of the cases. But other studies reported varying rates, adding to the debate about how efficacious and safe the procedure is-and which techniques may bring the best results.

Defining failure

Some studies defined failure as an increase of more than 1D of Kmax as a failure, but other studies report a failure rate at year 2 of only 2%. One study reported the 4-year failure rate at 0%, “but there were only 40 eyes enrolled,” Dr. Seiler said.

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Safety of the procedure is equally important, he said. Using the FDA definition of a loss of 2 or more Snellen lines to indicate a complication, rates vary from 13.7% in India and Iran to a low of 0% in England. The social environment in the two regions may contribute to the complication rates, he said, as England has stricter follow-up regimens.

In the past 10 years, there have been several changes proposed to the Dresden protocol, but only a select few have been useful. For instance, transepithelial crosslinking resulted in a shallower effect leading to a re-treatment rate of up to 50%, “which is obviously not acceptable,” Dr. Seiler said.

Thinking that there may not be consequences to the procedure or that it is just a cornea procedure would be ill advised, he said.

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He then described a case of documented progression in a patient who underwent crosslinking. At the 1-year follow-up, the patient was happy, there was “a nice regression” of the keratoconus, and “I was the patient’s hero. He could drive without glasses,” Dr. Seiler said.

But unfortunately, crosslinking is not always a “one-and-done” procedure-in this case, after 9 years the patient is now hyperopic but without astigmatism.

The ultraviolet (UV) lamps on the market offer irradiance from 3mW/cm2 to 45 mW/cm2.

Other considerations


Other considerations

During the past few years, other aspects of the procedure have evolved, too, including the amount of solution used and the duration. The isosmotic solution of riboflavin in 16% dextran has been replaced to reduce the imbibition time from 30 minutes to 10 minutes. Dr. Seiler now uses an HPMC solution and has similar effects as his previous techniques.

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“Our current approach is 0.1% riboflavin in 1.1% HPMC, 10mW/cm2 for 9 minutes in an epi-off technique,” Dr. Seiler said. “It’s indicated in all cases of keratoconus with documented progression and in special cases without documentation, including in children, in cases of iatrogenic keratectasia, and in cases of infectious keratitis.”

Increasing the irradiance reduces the irradiation time but also reduces the stiffening effect, he said.

When to perform the procedure is also a question. The main benefit of crosslinking is to stop the progression if there is keratoconus.

“You cannot document progression by any means of refraction,” Dr. Seiler said.

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Medication may be indicated, but only if progression is documented, he said, and this is best achieved with optical coherence tomography and Pentacam images.

Take care with children

Dr. Seiler did add there are a few exceptions-if there are children who are prone to eye rubbing, and keratectasia induced by LASIK. With children, it is important to perform the procedure as quickly as possible but without too much disruption in their school schedules (when possible), he said. He noted waiting could lead to a hydrops cornea.

The clinical community is still debating the benefits of transepithelial-on or –off, he said.

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In children, studies have shown re-treatment is necessary when the initial procedure was epi-off, Dr. Seiler said.

“Shorter operation times may be achieved by means of UV fluence between 10 and 15 mW/cm2 and using a riboflavin solution in HPMC,” he said. “Epi-off is still the standard we should be following.”

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Finally, Dr. Seiler talked about the alternative crosslinking mechanisms being investigated, including rose bengal and green light, but added clinical data is still lacking to fairly evaluate these techniques.


Dr. Seiler reports no financial disclosures.

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