Cross-Linking der Hornhaut (CXL)

Corneal cross-linking is a treatment designed to strengthen the cornea when it is becoming weaker and more unstable, most commonly in keratoconus and other corneal ectasias. It works by combining riboflavin (vitamin B2) and UV-A light to create new chemical bonds within the cornea, helping it resist further shape changes.

Hintergrund

To strengthen the cornea and help stop progressive ectasia from getting worse.

Conditions

Patients with progressive keratoconus, post-LASIK or post-PRK ectasia, and some other corneal ectasias.

Setting

Usually an outpatient procedure.

Erholung

Вepends on the protocol. Epi-on is faster to recover from, while epi-off involves longer epithelial healing.

Hintergrund

What does corneal cross-linking actually do?

Corneal cross-linking is designed to solve a very specific problem: a cornea that is becoming biomechanically weaker and progressively changing shape. In keratoconus and corneal ectasia, the cornea can thin and bulge forward over time, leading to worsening distortion and reduced visual quality. Cross-linking helps make the cornea stiffer and more resistant to further deformation.

This is important because many patients assume every treatment is meant to “fix vision.” Cross-linking is different. Its main purpose is to preserve the eye’s future by slowing or stopping progression. Vision may improve in some patients, but the primary goal is stabilization.

When

When should cross-linking be done?

Timing matters. Cross-linking is generally most valuable when progression is identified early enough to preserve corneal structure before more advanced distortion develops. Mayo Clinic notes that cross-linking may reduce the risk of progressive vision loss by stabilizing the cornea early in the disease.

In practice, this means the treatment is usually not offered simply because someone has keratoconus. It is offered because the cornea appears to be getting worse. In children and younger patients, this decision may be made earlier because progression can be more aggressive. ELZA’s current page also notes that the most powerful epi-off approaches are still reserved for situations where maximum biomechanical effect is needed, such as particularly aggressive disease in children.

How

How does the treatment work?

Cross-linking combines riboflavin eye drops with UV-A light. Together, they trigger a photochemical reaction inside the corneal stroma, the main structural layer of the cornea. This reaction creates new cross-links between collagen molecules, binding them more tightly together and making the cornea mechanically stronger. ELZA’s current page states that this stiffening effect is immediate and that the cornea becomes substantially stiffer after treatment.

ELZA’s page also explains that cross-linking has effects beyond mechanical stiffening. UV-A activated riboflavin can generate reactive oxygen species with antimicrobial effects, and the cross-linking process can increase resistance to enzymatic digestion and may reduce corneal swelling. These added effects are part of why cross-linking technology is also relevant in fields such as infectious keratitis treatment.

Was kann ich während der Behandlung erwarten?

Mit Augentropfen wird Ihr Auge betäubt, so dass die Behandlung meist angenehm ist.

Je nach der verwendeten Technik sitzen Sie entweder im Liegen oder an einer Spaltlampe.

Das gesamte Verfahren dauert etwa 45 Minuten bis eine Stunde, je nach der verwendeten Technik.

Is it Safe?

Risks and Limitations

CXL’s safety has been demonstrated time and time again in many studies. Currently (as of May 2025), more than 3,000 peer-reviewed scientific articles can be found in the medical database, and our group has contributed over 160 of them.

A major safety principle in traditional CXL is protecting the corneal endothelium by ensuring enough riboflavin-soaked tissue remains between the UV treatment zone and the deepest cell layer.

The main limitation is that cross-linking is primarily a stabilization treatment. It does not guarantee better unaided vision, and it does not eliminate the need for other treatments such as specialty contact lenses or, in more advanced cases, additional corneal procedures. Also, not every protocol is equally effective in every clinical situation.

Der letzte vorteilhafte Nebeneffekt der durch CXL erzielten Hornhautverstärkung besteht darin, dass das Hornhautödem reduziert werden kann, wodurch die Hornhaut ihre Form und Klarheit und letztlich auch die Sehschärfe der Patienten beibehält.

Treatment

Welche Technik bei mir?

Over the years CXL for keratoconus and other corneal ectasias has evolved, and today various protocols exist. The treating ophthalmologist needs to assess which technique is scientifically sound enough to be used on a case-by-case basis.

Im Folgenden werden die heute verfügbaren CXL-Behandlungsansätze für die Ektasie vorgestellt:

1. Epi-Off (Dresdner Standardprotokoll):

The epithelium is removed to allow riboflavin to penetrate fully before UV-A irradiation. This is suitable for patients with progressive keratoconus or ectasia and sufficient corneal thickness (≥400 µm). It is considered the gold standard with the most extensive long-term data supporting its efficacy, however, this procedure may cause some discomfort and requires a longer healing period as the epithelial cells regrow and recover the cornea. It’s also slow. To deliver the dose (or “fluence” of UV energy required, 5.4 J/cm², it requires 30 minutes of UV light being delivered at an intensity of 3 mW/cm². Today, this procedure has been reserved for patients requiring the absolute maximum cross-linking effect, such as children with particularly aggressive forms of the disease.

2. Accelerated CXL:

Uses higher intensity UV-A over a shorter time to reduce procedure duration, although the more the procedure is accelerated, the less effective it becomes. However, the trade-off in efficacy is relatively minor, when, for example, the Dresden protocol’s 5.4 J/cm² UV energy is delivered at 9 mW/cm² for 10 minutes in an epi-off manner. This has led to this accelerated CXL protocol becoming the default treatment option for many ophthalmologists performing CXL today, unless there is a good reason not to.

3. Epi-On (Transepithelial) CXL:

The epithelium layer of the cornea consists of epithelial cells that are tightly bound together with “tight junctions,” and this forms a very effective barrier from the outside world from entering the eye any further. This also includes riboflavin. Epithelium-on (epi-on) CXL, therefore, requires an extra step to have the riboflavin pass through and into the stroma. One approach is to use penetration enhancers, which temporarily degrade the tight junctions binding the epithelial cells together, enabling riboflavin to pass through the gaps. The alternative approach is to use ionotophoresis, which involves using a special apparatus that applies an electrical charge to the riboflavin to electrostatically pass through the epithelium and into the stroma. This requires a riboflavin-filled chamber to be placed above the cornea, with one electrode, and another electrode attached to your head elsewhere to complete the circuit. Both methods are less invasive than epi-off CXL and have faster recovery times This method is less invasive and better suited for patients with thinner corneas or ocular surface disease. It typically has faster recovery but may provide less biomechanical stiffening than epi-off – but ELZA has been working on eliminating this effectiveness gap… [link to epi-on vs epi-off page]

More about Epi-on CXL

4. Customized CXL (ELZA-PACE):

ELZA-PACE ist ein individuelles CXL-Protokoll der zweiten Generation, das auf eine starke Abflachung der Hornhaut abzielt, um das Sehvermögen von Menschen mit Keratokonus und anderen damit verbundenen Hornhautektasien zu rehabilitieren. Bei ELZA-PACE werden mit dem SCHWIND AMARIS Excimer-Laser selektiv Epithelzellen über dem Konus auf der Basis von Epithelzellkarten des CSO MS-39 abgetragen. Der AMARIS führt dies mit einer solchen Präzision durch, dass absolut kein Stromagewebe entfernt wird, so dass die Hornhaut ihre gesamte strukturelle Integrität beibehält. Auf diese Weise entsteht ein partielles Epi-on und Epi-off-Vernetzungsverfahren, und der Unterschied in der Vernetzungswirkung zwischen den beiden Regionen ist die Grundlage für diesen beeindruckenden Hornhautabflachungseffekt.

5. Dünne Hornhaut CXL: ELZA-sub400 Protokoll:

Das ELZA-sub400-Protokoll ist die modernste Methode zur Durchführung von CXL bei dünnen Hornhäuten. Ältere Protokolle für dünne Hornhäute (wie z. B. das Anschwellen der Hornhaut mit hypoosmolarem Riboflavin oder die Verwendung einer mit Riboflavin getränkten Kontaktlinse, um die Hornhaut aufzuschwemmen) brachten Nachteile mit sich, wie z. B. unvorhersehbare Schwellungsreaktionen oder eine deutlich schlechtere Vernetzungseffizienz. Das ELZA-sub400-Protokoll ist das Ergebnis jahrelanger Arbeit an der Modellierung der CXL-Reaktion zwischen Hornhautgewebe, Riboflavin, UV-Licht und Sauerstoff und ermöglicht dem Chirurgen die sichere Durchführung von CXL bei Hornhäuten mit einer Dicke von nur ~200 µm, wobei der unvernetzte Sicherheitsabstand von ~70 µm an der Basis des Stromas zum Schutz des Endothels erhalten bleibt. Das Prinzip ist einfach: Jede Hornhaut wird kurz vor der UV-Bestrahlung an ihrer dünnsten Stelle gemessen, und die maßgeschneiderte UV-Fluenz wird berechnet, um die gewünschte Vernetzungstiefe zu erreichen. In der Praxis ist dies einfach: Es muss lediglich die Dauer der Bestrahlung angepasst werden.

Personalisierte Behandlungsplanung

At ELZA, every patient receives a detailed assessment including corneal imaging with advanced corneal biometers, such as the Pentacam and the MS-39, as well as a comprehensive biomechanical evaluation with the CorVis ST. This information guides our experts in recommending the safest and most effective CXL protocol tailored to the patient’s unique condition and needs. Our goal is to maximize treatment benefit and minimize risks, and this detailed imaging and corneal assessments enables us to achieve that.

Warum wir?

Why ELZA for corneal cross-linking?

At ELZA, cross-linking is not just one treatment among many. It is one of our defining areas of expertise. Our current CXL page states that Prof. Farhad Hafezi was part of the Zurich team that developed the first UV irradiation lamp used for clinical cross-linking, and the page emphasizes ELZA’s long-standing role in the scientific development of the field.

We also do not treat cross-linking as a one-size-fits-all procedure. ELZA’s own pages explain that the treating ophthalmologist must understand the full range of scientifically sound protocols and decide which approach is appropriate on a case-by-case basis. That includes epi-off, accelerated approaches, and evolving epi-on methods, as well as customized treatment pathways such as ELZA-PACE. Our institute also highlights dedicated support for international patients and online consultations, making specialist access easier for patients traveling from abroad.

Corneal focus

CXL treatment benefits from strong experience with the corneal surface, not only basic excision.

Academic & clinical credibility

ELZA highlights published expertise and international reputation in cornea and ophthalmology.

International access

ELZA offers dedicated pathways for international patients and online video consultations.

FAQs

Häufig gestellte Fragen - FAQ

Will cross-linking improve my vision?

Its main job is to stop progression. Some patients may notice some improvement, but that is not the main guarantee.

Does cross-linking hurt?

Discomfort depends on the protocol. Epi-off is usually more uncomfortable during healing than epi-on.

Wie lange dauert der Eingriff?

That depends on the protocol. The traditional Dresden protocol uses 30 minutes of UV-A at 3 mW/cm², while accelerated versions shorten the treatment time using higher intensity.

Do I still need glasses or contact lenses after cross-linking?

Often yes. Cross-linking stabilizes the cornea but does not necessarily eliminate the need for visual correction.

What is the difference between epi-on and epi-off?

In epi-off, the surface epithelium is removed before treatment. In epi-on, it is left in place and special strategies are used to help riboflavin penetrate. Epi-on is generally more comfortable, while epi-off still remains important for cases needing the strongest biomechanical effect.

Geschichte des Corneal Cross-Linking

CXL wurde in den 1990er Jahren als bahnbrechende Behandlung entwickelt, um die Hornhaut zu stärken und die fortschreitende Ausdünnung der Hornhaut, z. B. bei Keratokonus, aufzuhalten.

Die erste Forschungsarbeit wurde von Professor Theo Seiler in Dresden, Deutschland, geleitet. Er und sein Team untersuchten Methoden zur Stärkung geschwächter Hornhäute, indem sie mit ultraviolettem (UV-)Licht in Kombination mit dem Vitamin Riboflavin zusätzliche molekulare Bindungen - so genannte Querverbindungen - zwischen den Kollagenfasern erzeugten.

Im Jahr 1999 zog Professor Seiler nach Zürich, Schweiz, wo er von Dr. Farhad Hafezi (damals) unterstützt wurde. Gemeinsam führten sie einige der ersten klinischen Studien zu CXL am ELZA-Institut und den angeschlossenen Zentren durch und entwickelten die Protokolle, die die Grundlage der modernen CXL-Behandlung bildeten. Zürich wurde zu einem internationalen Zentrum für klinische Innovationen im Bereich des Corneal Crosslinking.

In diesen Anfangsjahren war die Behandlung unter verschiedenen Bezeichnungen bekannt, darunter Corneal Collagen Cross-Linking (CCL) und X-Linking. Im Jahr 2006 einigten sich die Experten auf einem internationalen Kongress in Zürich auf den Begriff "Corneal Cross-Linking" (CXL), der seitdem zum weltweiten Standard geworden ist.

Dank ihrer frühen Arbeit und der fortlaufenden Innovationen des Teams des ELZA-Instituts hat sich CXL heute weltweit als Goldstandard-Behandlung etabliert, um das Fortschreiten des Keratokonus aufzuhalten und die Ergebnisse der Patienten zu verbessern.

Conditions We Treat

Treatments We Offer

Centers of Excellence

Planning your visit

Downloadbereich

Research at ELZA Institute

Scientific Publications

ELZA Dietikon

ELZA HB Zürich