Epi-on or epi-off Cross-linking?

We are often asked which CXL treatment methods we prefer, most frequently on so-called “epi-on” or “transepithelial” cross-linking. We only do this in special cases. Our method of choice is still the classic “epi-off” cross-linking. Here’s why.

Epi-off Cross-Linking

The first step of classical cross-linking requires the removal of the outermost layer of the cornea, the corneal epithelium, so that riboflavin (vitamin B2) can penetrate the cornea correctly. The success rate of this “epi(thelium)-off” protocol is extremely high, well over 90%. A relative disadvantage is that the cornea has to heal again. In the first few days there are inconveniences such as a burning and biting sensation in the eyes, and of course you have to make sure that no infection occurs. However, with professional surgery, patient education and meticulous follow-up, these risks are extremely low. We have not seen a single case of post-CXL corneal infection in 10 years.

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Epi-Off Cross-Linking Procedure

Epi-on Cross-Linking: not yet 

The idea of ​​epi-on cross-linking came up because it does have theoretical advantages: less postoperative burning sensation of the eyes and a reduced risk of infection. After an initial euphoria, the “hype” about epi-on cross-linking has subsided. The reason is that the success rate, which is well over 90% for the classic “epi-off” CXL, falls to 60–70% for the epi-on procedure. Why?  In 2013, our research group discovered that in addition to vitamin B2 and UV light, the presence of oxygen is another essential factor for successful cross-linking.





In a detailed study in our basic science labs, we were able to show that CXL can only work if there is enough oxygen.

Oxygen must penetrate into the cornea and this is prevented by the corneal epithelium. Accordingly, several clinical studies, including a Multi-center study under our guidance, showed that the efficacy of epi-on cross-linking is only 60-70%.

International leading cross-linking experts, including Prof. Hafezi from ELZA, commented on this in January 2018.

Our Choice

We find that the most effective method is also the best method for our patients, even if it means that the healing takes a little longer. What use is a “gentle” method, if it does not work?

Therefore, in most cases we do an “epi-off” cross-linking. An exception are cases where we fear that there could be infections after surgery due to poor patient co-operation, for example, severe eye rubbing after surgery. This mostly concerns small children and people with a developmental deficit. Here we apply an “epi-on” cross-linking. This is deliberately less effective because we have to avoid infections after surgery.

What effect does corneal cross-linking have after 10 years? This August, ELZA doctor and researcher, Emilio Torres-Netto MD was interviewed by TouchOphthalmology on a recent congress presentation he gave on 10-year cross-linking follow-up data collated from two treatment centers in Zurich, and was asked about what the research group found.

The ELZA Institute