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ELZA-PACE: Customized Cross-Linking
ELZA has developed ELZA-PACE customized cross-linking
ELZA-PACE stands for ‘PTK-assisted customized epi-on corneal cross-linking” and is a procedure that improves the shape of the cornea in keratoconus and other corneal ectasias.
ELZA-PACE - our results
A traditional cross-linking procedure stabilizes keratoconus by “locking in” the cornea’s shape at the time of treatment. In contrast, ELZA-PACE customized cross-linking works differently, offering significant vision improvements of 20, 30, and sometimes even up to 60 percent—without the need to remove corneal tissue.
Here’s a comparison of simulated vision (based on corneal wavefront analyses) before and after the ELZA-PACE treatment. After the treatment, issues like double vision and halos improve, and the sharpness and contrast of what you see gets better. If the patient wears glasses, their prescription might change or even become stronger after ELZA-PACE. The primary goal is to improve vision and contrast while wearing glasses and contact lenses.
How is this possible?
Through the combination of these three advanced technologies: the Schwind AMARIS excimer laser, the C-eye cross-linking device, and the MS-39, the combined Placido ring/ anterior segment OCT-based corneal topographer/tomographer
Elements needed for ELZA-PACE
First-generation customized cross-linking was introduced in 2016 and straightforward in concept. Cross-linking was performed as an epi-off procedure and different amounts of UV energy were delivered to different parts of the cornea. The principle was: the more energy, the greater the flattening effect. And this principle worked – albeit to a modest extent (approx. 3 diopters flattening).
ELZA-PACE customized cross-linking achieves more.
There are four biological and photochemical reasons why ELZA-PACE customized cross-linking delivers a much stronger improvement of the cornea than first-generation customized CXL.
1) Epithelial map-driven PTK
First, we treat the tip of the keratoconus with an “epi-off” procedure, where only the epithelial cells on the cornea’s surface are removed. This maximizes the amount of cross-linking possible in that area. By using an epithelial map-driven PTK with an excimer laser (not a standard PTK), we can precisely remove just the epithelium over the cone region without affecting the stroma.
The epithelium over the keratoconus tip absorbs oxygen and UV light, creating a barrier that limits riboflavin penetration into the stroma. By removing this layer, we enable stronger cross-linking, leading to a greater flattening effect.
2) Mixed epi-on/epi-off CXL with riboflavin gradient
The second reason ELZA-PACE customized cross-linking achieves better results than earlier methods is due to its unique mixed epi-on, epi-off approach, which creates a riboflavin gradient. We use a specially developed epi-on riboflavin solution that penetrates through the intact epithelial cells. In the epi-off area, however, riboflavin saturates the stroma more quickly because the epithelium has been removed.
This riboflavin gradient allows for stronger cross-linking ( =more flattening) where there is more riboflavin, and less cross-linking in outer regions where riboflavin concentrations are lower.
3) Oxygen gradient
ELZA-PACE also creates an oxygen gradient, which is essential because oxygen must be present in the stroma for cross-linking procedures to strengthen the cornea. During treatment, oxygen is consumed by the UV light-riboflavin interaction, and its availability limits the extent of cross-linking—less oxygen means less cross-linking. The epithelium not only blocks oxygen but also consumes it, so this gradient enhances the difference in cross-linking effects across regions.
By removing the epithelium over the keratoconus tip, which absorbs oxygen and UV light and blocks riboflavin, we enable stronger cross-linking ( =more flattening) in that area.
4) Energy (fluence) gradient
Finally, we also apply more UV energy to the tip of the cone compared to the rest of the cornea.
It all combines to give a far greater gradient in cross-linking effects, which translates to a far greater flattening effect than first generation procedures.
Why ELZA-PACE customized cross-linking works better than “normal” cross-linking.
The flattening effect in ELZA-PACE customized cross-linking is driven by the difference in cross-linking strength between the keratoconus tip and other corneal regions.
While first-generation cross-linking approaches achieved some flattening using only UV light gradients, ELZA-PACE goes further by incorporating riboflavin, oxygen, and epi-on/epi-off gradients. This combination maximizes the potential of customized cross-linking to regularize the cornea’s shape—all without removing any corneal tissue.
In the end, ELZA-PACE not only achieves significant flattening of the keratoconus but also greatly reduces corneal asymmetry and astigmatism, leading to improved visual quality and acuity—all without removing even a micrometer of corneal tissue.
How immediate is the ELZA-PACE customized cross-linking effect?
Since it’s a photochemical reaction, the effect is immediate.
In these images, you can see a dramatic flattening achieved within just five minutes, compared to the corneal topography before ELZA-PACE—so much so that the keratoconus is no longer visible.
Notice the red area in the right image. This is what we call a “coupling effect.” To understand this, imagine pressing into an inflated balloon; as you push in one area, the top moves forward. In the cornea, this movement balances corneal steepness, which greatly benefits the patient’s vision.
Before ELZA-PACE -> 5 minutes after ELZA-PACE
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What is the difference between ELZA-PACE to protocols like the Athens Protocols, Cretan Protocol, STARE-X, and TREK?
In excimer laser protocols, the main effect comes from the excimer laser that reshapes the corneal tissue. This goes along with tissue removal. Because removing tissue weakens the cornea’s stremgth, the cornea needs to be cross-linked to compensate for the weakening produced by the laser.
In ELZA-PACE customized cross-linking, the whole effect comes from cross-linking without removing any corneal tissue (the epithelial cells removed over the cone grow back within days). The excimer laser is simply being used as a very precise tool to remove the epithelium during the customized cross-linking – and unlike these other procedures, we have the additional benefit of the coupling effect described above.
Frequently asked questions
What can I expect from ELZA-PACE?
You can expect a regularization that in selective cases can be up to 12 diopters. In many cases, best-corrected visual acuity with glasses also improves by 20, 30, sometimes even up to 60%.
Does ELZA-PACE only work with progressive keratoconus?
ELZA-PACE customized cross-linking can not only be used to treat patients with progressive keratoconus but can also be used in patients with stable keratoconus who want better vision with glasses.
Is there any means to further improve the cornea after a ELZA-PACE procedure?
Yes. Six to 12 months after ELZA-PACE customized cross-linking, we can evaluate whether wavefront-guided transPRK with the excimer laser is possible to improve the cornea and “fine-tune” vision even more.
What can I expect from ELZA-PACE?
In standard CXL, we use the same amount of irradiation over the entire cornea. This usually stops the progression of keratoconus – and in some cases, may even lead to a minor beneficial flattening effect in some of the patients 6 months to one year after surgery.
But what little flattening occurs after CXL is unpredictable, and this cannot be relied upon to improve patients’ vision after the procedure.
In ELZA-PACE customized cross-linking, we establish gradients of riboflavin, oxygen, and UV irradiation between the tip of the keratoconus and the and non-cone regions of the cornea. As detailed above, this method induces significant corneal flattening and regularization. ELZA-PACE customized cross-linking has been consistently associated with notable enhancements in visual quality, and this underscores its effectiveness in improving vision.
