sub400: cross-linking extremely thin corneas

The original Dresden protocol allows CXL to be performed safely when the thickness of the cornea is 400 μm or higher. However, in advanced cases of keratoconus, pellucid marginal degeneration and post-LASIK ectasia, the cornea may be thinner.

One way to treat such a cornea nonetheless is the use of hypo-osmolar riboflavin. This special vitamin B causes the cornea to absorb water and swell. This technique was developed in 2007 and published in 2009 with Prof. Hafezi as first author (1). Since then, this application has become a global standard.

2008: The "Birth" of CXL in ultrathin corneas

Zurich, Switzerland: A 26-year-old patient is being treated with epi-off CXL. After removal of the epithelium and application of “normal” iso-osmolar riboflavin, the corneal thickness is 325 microns; too little to do a safe CXL. In a second step, we used hypo-osmolar riboflavin. After 10 more minutes, the cornea had “swollen” to 407 microns, and the CXL could be performed safely.

The treatment of extremely thin corneas requires a lot of experience as many factors have to be considered – from how often the vitamin B2 is applied, to how long the speculum is left open. Our experience is one of the longest in the world and allows us to safely perform a CXL on thin corneas (and thicker corneas too!).

The future is now - the sub400 protocol

Several strategies have been developed to treat very thin corneas over the years. ELZA’s Medical Director, Farhad Hafezi, has helped to clinically and experimentally verify the effectiveness if these techniques (see below), including swelling the thin cornea to a safe thickness for cross-linking (as described above) (1) contact lens-assisted CXL (CACXL) (2) and the Epithelial Island technique (3) where an island of epithelial cells are left above the thinnest point of the cornea.

Which technique is chosen must be carefully considered on a case-by-case basis. Swelling the cornea can be unpredictable, as each patient’s cornea swells to a different extent. CACXL reduces the strengthening effect by 30%, and epithelial islands result in unpredictable stiffening effects.

ELZA’s clinicians and researchers, led by Professor Hafezi, have developed a new technique for cross-linking thin corneas, that is tailored to each patient’s individual corneal thickness (4). Instead of modifying the cornea, we customise the dose of light delivered to deliver safe and effective cross-linking, even in ultra-thin corneas. 

Our researchers discovered the essential role oxygen plays in cross-linking (5) and modelled how riboflavin, UV light, and oxygen interact in the cornea to cross-link it over time. This resulted in an algorithm, which is fully clinically validated (6), that predicts the depth of cross-linking, and means that surgeons can customise the duration of UV irradiation to achieve a safe depth of cross-linking, even in corneas as thin as 220 µm.

This protocol, named sub400, enables the ELZA Institute to treat ultra-thin corneas, without resorting to methods like artificially thickening the cornea through swelling, leaving epithelial islands or needing a contact lens, helpfully avoiding the drawbacks that have been associated with these methods (i.e. unpredictable effects and sub-optimal corneal strengthening).

In 2021, the sub400 protocol was published in the American Journal of Ophthalmology (4) and has a success rate of nearly 90%.

References

  1. Hafezi F, Mrochen M, Iseli HP, Seiler T. Collagen crosslinking with ultraviolet-A and hypoosmolar riboflavin solution in thin corneas. J Cataract Refract Surg. 2009;35(4):621-624.
  2. Jacob S, Kumar DA, Agarwal A, Basu S, Sinha P, Agarwal A. Contact lens-assisted collagen cross-linking (CACXL): A new technique for cross-linking thin corneas. J Refract Surg. 2014;30(6):366-372.
  3. Mazzotta C, Ramovecchi V. Customized epithelial debridement for thin ectatic corneas undergoing corneal cross-linking: epithelial island cross-linking technique. Clin Ophthalmol. 2014;8:1337-1343.
  4. Hafezi F, Kling S, Gilardoni F et al. Individualized corneal cross-linking with riboflavin and UV-A in ultra-thin corneas: the sub400 protocol. Am J Ophthalmol. 2021; 224:133–142.
  5. Kling S, Richoz O, Hammer A, et al. Increased biomechanical efficacy of corneal cross-linking in thin corneas due to higher oxygen availability. J Refract Surg. 2015;31(12):840-846.
  6. Kling S, Hafezi F. An algorithm to predict the biomechanical stiffening effect in corneal cross-linking. J Refract Surg. 2017;33(2):128-136.
The ELZA team of surgeons and researchers were all in attendance, and today saw Prof. Hafezi give the attending delegates a lecture on “How to treat thin corneas”, where he examined the history of performing corneal cross-linking (CXL) for the treatment of corneal ectasias like keratoconus. He then brought delegates up-to-date on the research that has been performed over the years to improve how thin corneas are cross-linked. Finally, Prof. Hafezi demonstrated the results of the latest thin cornea cross-linking protocol, sub400, developed by ELAZA, which simplifies the process, and can let surgeons, for the first time, cross-link corneas that are as thin as 200 µm.
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Augeninstitut ELZA
4.8
Based on 110 reviews
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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
Squitieri Elias
Squitieri Elias
12:43 08 Sep 21
Die Behandlungen waren bei mir erfolgreich, alle waren sehr nett und haben mein Leben vereinfacht.Danke
Eliane Bossart
Eliane Bossart
13:01 05 Sep 21
Vor einem Jahr war ich einer ganz verzweifelten Situation und total im Stich gelassen. Meine Augen wurden aufgrund... eines ausgeprägten Kerakotonus immer schlechter, ich hatte Angst und war alleine mit meinen Problemen. Zudem vertrug ich die Kontaktlinsen nur noch ganz schlecht und hatte jeden Tag Schmerzen.Professor Hafezi hat mir mit zwei Operationen wieder das auf Grund der Situation mögliche an Lebensqualität zurückgebracht. Es war ein starpaziöses Jahr mit vielen Entbehrungen aber es hat sich gelohnt! Herzlichen Dank fuer die Unterstützung.read more
Gabriela Meyer
Gabriela Meyer
18:32 22 Aug 21
Ich wurde von meiner Optikerin auf Prof. Dr. Dr. Hafezi aufmerksam gemacht. Es war mir vorher nicht bewusst, dass meine... Augenkrankheit (Keratokonus) operativ mittels Cross Linking behandelt und so gestoppt werden kann. Die Beratung und Behandlung war sehr kompetent und ich fühlte mich jederzeit wohl. Die Operation verlief gut und das Ergebnis ist einwandfrei.read more
Naomi
Naomi
11:38 11 Aug 21
Ich bin sehr glücklich, dass ich das Elza Institute gefunden habe. Ich wurde von anderen Augenärzten abgewiesen, da... meine Augen zu kompliziert/schwierig zu behandeln waren. Prof. Dr. Dr. Hafezi konnte mir jedoch helfen und ich bin sehr glücklich und zufrieden mit dem Resultat. Vielen Dank!read more
Till B
Till B
08:30 19 Jul 21
Ich habe eine überaus kompetente Beratung und Behandlung erlebt. Die gesamte Betreuung war sehr freundlich und... professionell. Herzlichen Dank!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
Ashley Faulkes
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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