Epi-on or epi-off Cross-Linking?

We are often asked which CXL treatment methods we prefer, most frequently the question is whether we perform “epi-on” or “epi-off” (Dresden protocol) cross-linking. As technology has advanced, our answer has evolved from “epi-off” in most cases, to “epi-on” in most cases. Here’s why.
ELZA's Role

Leading the Way in Cross-Linking Innovation

At ELZA, our surgeons and researchers have been at the forefront of developing corneal cross-linking (CXL) technology since its earliest days. Under the leadership of Prof. Farhad Hafezi, MD, PhD, FARVO, we have continually pushed the boundaries of what’s possible with CXL, making it safer and more effective for patients. Our work in both epi-on and epi-off CXL has helped redefine the way we treat keratoconus and other corneal ectasias.

Why Epi-On?

Epi-On Cross-Linking:
The Obvious Advantages and the Challenges

The appeal of epi-on CXL is simple:

  • It preserves the epithelium, so there’s less risk for infection.
  • The healing process is faster, with less discomfort and quicker recovery.
  • Visual recovery is generally faster compared to epi-off procedures.

Given these advantages, it’s clear why the field has been so eager to develop a reliable epi-on technique. However, the journey to a functioning epi-on CXL has taken over 15 years. So, why did it take so long?

What Went Wrong in the Early Days of Epi-On Cross-Linking?

When epi-on CXL was first introduced in 2009, the results were disappointing. The procedure didn’t achieve the same success rates as the original epi-off CXL protocol, the “Dresden protocol”. Even though these epi-on protocols were able to sufficeintly saturate the stroma – the main structural component of the cornea, where the cross-linking reaction occurs – with riboflavin, ectasia progression rates with early epi-on protocols were significantly higher than those with epi-off protocols.

What was it about the continued presence of the epithelium that could cause this?

How We Solved the Problem

ELZA’s surgeons and researchers quickly realized that oxygen was a crucial, previously overlooked element in the CXL process.

We set out to solve this issue of how to close this “efficacy gap” between epi-on and epi-off CXL. Using advanced imaging tools like the multi-photon microscope, we discovered how to effectively deliver oxygen and riboflavin to the cornea while keeping the epithelium intact.

Introducing the ELZA Epi-On Protocol: A New Era

After years of research and testing, we developed the ELZA epi-on CXL protocol. This method overcomes the challenges of early epi-on attempts by ensuring that both riboflavin and oxygen are delivered to the cornea effectively, even with the epithelium intact.

What Makes the ELZA Epi-On Protocol Unique?

No Iontophoresis: Our protocol doesn’t require iontophoresis, a technique that used special equipment to electrostatically force riboflavin penetration through the epithelium.

Optimized UV Light Settings: We carefully calibrated the UV light dose, and utilized pulsing of UV energy to allow oxygen to diffuse into the cornea during times when no UV light is being delivered.

No Additional Oxygen: Unlike earlier methods, we don’t rely on additional oxygen delivery systems. Our protocol is so optimized, it can work effectively without needing an oxygen tank connected to googles that need to be worn during the cross-linking process.

See the ELZA Epi-On CXL in Action

Watch a video of an epi-on CXL procedure being performed at the slit lamp, showing how our advanced technique works in a clinical setting.

Want to Learn More About the History of Epi-On CXL?

If you’re interested in the full history of epi-on CXL, including the breakthroughs that led to the ELZA epi-on protocol, we’ve recorded a presentation by Prof. Hafezi from two years ago. It dives into the challenges, the discoveries, and how we ultimately perfected this method.

Epi-Off Cross-Linking: Why Do We Still Use It?

While epi-on CXL has made great strides, epi-off CXL remains the go-to option for certain cases.

Why Epi-Off CXL Still Matters

The Dresden Protocol, the original epi-off method, is still the most powerful tool for treating advanced and aggressive forms of keratoconus. When the greatest mechanical strength is needed, epi-off provides the most robust support.

Our High-Fluence Epi-Off Protocol

ELZA has developed a high-fluence epi-off protocol that significantly shortens treatment time without sacrificing efficacy. Using up to 7.5 J/cm² of UV light, our high-fluence method delivers the same mechanical strength as the standard 30-minute Dresden protocol – but in just a third of the time.

  • Faster and More Efficient: The high-fluence approach is designed for advanced cases where stability is crucial, but we want to reduce treatment duration.
  • Targeted Use: This protocol is reserved for patients who need the highest level of biomechanical support.

Conclusion:
Epi-On vs. Epi-Off CXL – A Comprehensive Approach

While epi-on CXL offers many advantages, especially in terms of faster recovery and fewer risks, epi-off CXL remains the treatment of choice in certain severe cases where maximum mechanical strength is necessary.

At ELZA, we are constantly refining our techniques to provide the most effective and personalized treatments. Whether using epi-on or epi-off, our goal is to ensure that each patient receives the best care possible, tailored to their specific needs.

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