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PACE: Customized Cross-Linking

ELZA has developed PACE customized cross-linking

PACE stands for ‘PTK-assisted customized epi-on corneal cross-linking” and is a procedure that improves the shape of the cornea in keratoconus or other corneal ectasias.

PACE – our results

A classic cross-linking procedure stabilizes keratoconus by “freezing” the shape of the cornea at the time of the procedure.

PACE customized cross-linking acts differently and can greatly improve vision by 20, 30, and sometimes 40 percent, all without removing corneal tissue.

Before PACE -> 7 days after PACE
Increase of daytime vision with glasses from 50% to 80%
Before CXL -> After CXL
Increase of daytime vision with glasses from 40% to 80%
Increase of daytime vision with glasses from 50% to 80%
Increase of daytime vision with glasses from 40% to 80%
Increase of daytime vision with glasses from 30% to 50%
Increase of daytime vision with glasses from 60% to 90%

How is this possible?

Through the combination of these three advanced technologies: the excimer laser, the C-eye cross-linking device, and the MS-39, the combined Placido ring/ anterior segment OCT-based corneal topographer/tomographer

SCHWIND AMARIS Excimer Laser
EMAGine C-eye Corneal Cross-Linking Device
CSO Italia MS-39 OCT/Placido corneal topographer/tomographer

Elements need for PACE

First-generation customized cross-linking was was introduced in 2016 and simple 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).

PACE customized cross-linking achieves more. 

There are four biological and photochemical reasons why 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 cone with an epi-off procedure, in which we remove only the epithelial cells at the top of the cornea to maximize the amount of cross-linking that can be achieved in that region. We can precisely remove just the epithelium (and not the stroma) over the cone region by performing an epithelial map-driven PTK with the excimer laser (not a normal PTK).

The epithelium over the tip of the keratoconus absorbs oxygen and UV light and forms a barrier for riboflavin to enter the stroma. By removing the epithelium, we will perform stronger cross-linking.

 

2) Mixed epi-on/epi-off CXL with riboflavin gradient

The second reason why PACE customized cross-linking achieves better results than first-generation approaches, is that this mixed epi-on, epi-off approach creates a riboflavin gradient. We use an epi-on riboflavin solution developed by ourselves, which penetrates through the intact epithelial cells. Still,  in the epi-off region, the riboflavin saturates the stroma even faster because the epithelium was removed.

The riboflavin gradient means more cross-linking where more riboflavin is present, and less cross-linking in outlying regions, where riboflavin is present in lower concentrations.

 

3) Oxygen gradient

This approach also creates an oxygen gradient. Oxygen needs to be present in the stroma for the strengthening effect of all cross-linking procedures to occur. It gets consumed by the UV light-riboflavin interaction, and its availability is rate-limiting: less oxygen equals less cross-linking. As the epithelium acts not only as a barrier to oxygen – but also consumes it – this oxygen gradient further enhances the difference in cross-linking effect between regions.

 

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 PACE customized cross-linking works better than “normal” cross-linking.

What drives the flattening effect of PACE customized cross-linking is the difference in cross-linking (and therefore flattening effect) between the tip of the keratoconus and the other corneal regions.

The first-generation customized cross-linking approaches achieved flattening to a certain extent by using only UV light gradients. PACE also exploits this, but additionally brings a riboflavin gradient, an oxygen gradient, and an epi-on/epi-off gradient to the procedure, unlocking the true potential of customized cross-linking to regularize the shape of the cornea, all without having to remove any corneal tissue.

Ultimately PACE results in not just a major amount of flattening of the keratoconus, but also a major reduction in corneal asymmetry and astigmatism – all without removing even a micrometer of corneal tissue.

This is an example that shows PACE customized cross-linking has produced a dramatic improvement in astigmatism in the pupil area (dotted line) – something that greatly improves visual quality during daytime. Furthermore, the corneal irregularity seen before has been improved by up to 10 diopters.

Before PACE -> 7 days after PACE
Before PACE -> 7 days after PACE

How immediate is the PACE customized cross-linking effect?

Because it is a photochemical reaction, the effect is immediate.

These images show that a massive flattening is achieved within 5 minutes, compared with the pre-PACE corneal topography – to such an extent that the previous keratoconus is no longer visible.

You will notice the red area in the image. This is what we call a “coupling effect”.

To explain how this works, imagine you were pushing into an inflated balloon. This results in the upper part of the balloon moving forward. In the case of the cornea, this movement harmonizes corneal steepness, which is highly beneficial to the vision of the patient.

Before PACE -> 5 minutes after PACE

What is the difference between 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.

PACE and other CXL laser protocols

In 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.

What can I expect from 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.

 

Does PACE only work with progressive keratoconus?

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 PACE procedure? 

Yes. Six to 12 months after 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 is the difference between PACE and standard CXL?

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 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. PACE customized cross-linking has been consistently associated with notable enhancements in visual quality, and this underscores its effectiveness in improving vision.

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Augeninstitut ELZA
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mike
mike
09:02 04 Jan 23
Overall as a 50 year old, who wanted to continue to avoid wearing glasses and/or contact lenses, my goal was 100%... achieved with ELZA and Dr. Hafezi. I greatly appreciated the overall approach by Dr. Hafezi and his friendly and competent team in reviewing my vision at the start and following a comprehensive eye exam- the explanations of my options. For me I chose PRK in one eye for a monovision solution to correct short sightedness which was becoming more prevalent in night driving and sports such as skiing and cycling. PRK heals slowly but the outcome is worth the wait- and the cost- you use your eyes every waking moment- and for me I cannot see any reason not to pursue better vision with the ELZA team! A great quality of life enhancement!read more
Zuzana Fecko
Zuzana Fecko
21:48 31 Oct 22
Thank you so much, Dr. Torres and prof. Hafezi. 26 years I was only “dreaming” about the eye surgery due to possible... complications. I was worried ..Thank you for encouraging me to make a decision and thank you for your professionalism, explanations and great work!I wish you all the best, lots of success and only happy patients!read more
Serena Fazio
Serena Fazio
11:15 06 Mar 22
I have been to the ELZA clinic to have surgery for my miopy, as my eyes were rejecting the contacts and I was tired of... wearing glasses. From the first preliminary visit, to the actual surgery and post-surgery care Dr. Hafezi and all his collaborators have been extremely professional, considerate and helpful. All the steps of the (very short!) surgery were thoroughly explained to me in order to be as calm as possible, together with the medication plan and precautions to be aware of so that my eyes could heal in the best way possible. By following their exact instructions, the healing process has been very successful and smooth, and after about one week I was able to see perfectly. I absolutely recommend this team and their expertise!read more
Robin A
Robin A
11:43 16 Feb 22
Top experts and professional team. Highly recommended
Thunder Shiviah
Thunder Shiviah
14:05 23 Nov 21
After some research on local options I decided to go with ELZA since it stood out as the best. The operation and the... post-operation recovery went extremely smooth (something I was worried about with PRK). Now my vision is much better than I had hoped and I have no side effects such as dry eye or night vision problems. Thank you!read more
Thomas S.
Thomas S.
09:37 07 Jul 21
My left eye had to be operated on because of a cataract. As I had an Artiflex lens implanted a few years ago, it had to... be removed first before a modern lens could be implanted to correct the cataract. Prof. Hafezi treated me in an very competent and friendly manner. I am very happy with the result.read more
Selma A. Rahim
Selma A. Rahim
19:45 02 Jul 21
Dr. Hafezi.. the KING OF CXL🤴
Gianluca Ricci
Gianluca Ricci
12:46 10 Apr 21
Great team and service!
rehaneyecare
rehaneyecare
05:36 08 Apr 21
Excellent surgeon
Steven H.A
Steven H.A
16:13 11 Jan 21
Prof. F. Hafezi s expertise is enormous and he has a very pleasant and calm nature which gives the patient... security.Thank youread more
Online Commande
Online Commande
09:19 05 Dec 20
Totally creepy, very arrogant Prof.He just want your money.It may explain, why this Prof. is not in the center of the... city of Zürich and why he has been thrown away from University of Geneva.read more
Elena Churilova
Elena Churilova
10:06 17 Nov 20
At the moment, 3 months have passed since the moment I made laser vision correction in this clinic. and I can say that... I am happy that I chose this particular clinic and Prof. F. Hafezi. The entire staff of the clinic is very friendly, treats patients with sympathy and patience if they are nervous before surgery (my big gratitude to Aida Alili for all support and patience). The doctor Hafezi and other doctors of the clinic are very professional and ready to explain to you as many times as you need. I can only recommend!read more
Michele Aggiato
Michele Aggiato
18:17 10 Jan 20
The day I had Prof Hafezi checking my keratoconus I knew I was finally in the right place after years of searching for... a good ophthalmologist. Prof Hafezi recommended a surgery due to a drastic degeneration of my cornea. The surgery was performed by himself with the assistance of Dr Rodriguez, one more collaborator of Prof Hafezi’s team who got my full trust.read more
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Ashley Faulkes
15:30 21 Mar 16
Professor Hafezi and the team at the ELZA Institute have done an amazing job of creating a first class eye clinic, with... cutting edge technology and support. I went there for a dry eye issue and other issues with my prescription, and they were easily able to help me and put me on the road to better vision! High recommend them to anyone in the Zurich/Aargau area.read more
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