Cross-Linking

Corneal cross-linking (CXL) is a treatment for a spectrum of eye diseases called corneal ectasias, the most common of which is called keratoconus.

Experts in Corneal Cross-Linking.

Why you should choose ELZA

Pioneers of Corneal Cross-Linking

Story began in 2003 Zurich; Hafezi joined team pioneering corneal cross-linking.

Global leaders in Research

ELZA leads global CXL research with top-ranked, highly cited scientific output.

Organizers of the largest CXL congress

ELZA members organize world’s largest CXL congress, uniting experts for global collaboration.

Authors of the most comprehensive textbook

Our team co-authored the leading global CXL textbook, soon in edition three.

Creators of new CXL technology and devices

ELZA developed slit-lamp CXL and C-eye device—innovative, patient-focused treatment solutions.

Dedicated to Global Access

CEO Nikki Hafezi expands CXL access globally through treatment, training, and advocacy.

What is it?

What is Corneal Cross-Linking?

Corneal cross-linking (CXL) is a treatment for a spectrum of eye diseases called corneal ectasias, the most common of which is called keratoconus.

Cross-linking stiffens the cornea and thus prevents further progression of the ectasia.

The term “ectasia” means the stretching or expansion of a tissue. This occurs as a result of the cornea becoming weakened for some reason. As the eye is pressurized, the weakened region begins to bulge outwards into a cone shape, and this causes vision to deteriorate. Ectasias like keratoconus are often progressive, which means treatment is required to strengthen the cornea and stop the disease from progressing further. The treatment is corneal cross-linking.

Cross-Linking

The reason why the technique is called “cross-linking” is because the UV light interacts with the riboflavin to make “reactive oxygen species” in the cornea, which immediately react with the collagen fibers in the cornea, creating chemical bonds between them, so called cross-links. This makes the corneal tissue stronger and more rigid, so that it can better resist the intraocular pressure that was causing the weak parts of the cornea to bulge. The major benefit of this approach is that until the introduction of corneal cross-linking, the only treatment option was corneal transplant surgery. This can now be avoided in all but the most severe cases.
Read more…CXL

In CXL, doctors use vitamin B2 eyedrops - riboflavin - and ultraviolet (UV) light from a cross-linking device to strengthen your cornea.

What Happens During the Procedure?

First, you will receive anaesthetic eyedrops to numb your eyes. If you require an “epi-off” cross-linking, then the doctor will bring you to a slit lamp, then use a cotton swab and a solution to remove the epithelium, the top layer of the cornea. If you are receiving an “epi-on” cross-linking, then this step can be skipped. Then, your surgeon will ask you to lie back in your chair while they apply specially formulated riboflavin eyedrops, which can take between 15 and 30 minutes until it has soaked into your cornea.

Then, you’ll be brought back to the slit lamp, and have your seat adjusted to make you feel comfortable, then you simply look at the light source for what usually takes around 10-15 minutes, in an entirely painless procedure.

Cross-Linking
The options

Corneal Cross-Linking Types

There are two types: epi-off and the epi-on.

epi-on

With epi-on CXL, your ophthalmologist loosens your epithelium with eyedrops before they put the riboflavin eyedrops in.

epi-off

In epi-off CXL, your ophthalmologist removes the epithelium before applying the riboflavin drops to your eye.

Who Should Get CXL?

Anyone with a progressive corneal ectasia – and all children with one. It’s important that corneal cross-linking is performed sooner, rather than later, as CXL does not typically reverse the changes to the cornea made by the disease; it simply keeps the disease from getting worse. The earlier you treat, the greater the amount of vision loss is avoided.

How to Prepare

Please note that you will be on sick leave for one week.

CXL is not normally performed with a general anaesthetic, so it is fine to eat a light meal and drink fluids beforehand. However, please don’t wear any eye make-up, mascara, perfume or aftershave on the day of the surgery.

As the procedure will affect your eyesight, you will need to bring someone with you to help you get home afterward. You won’t be allowed to drive a car yourself.

What Happens Afterwards?

After the procedure, here’s what you need to know to take care of your eyes:

It’s crucial to not rub your eyes and not to let any water come close to your eyes for at least 1 week after the procedure, or as long as the doctor tells you.

You will be given medication and a scheme for how and when to use them. It is important that you follow this exactly, for your comfort but more importantly for the proper and safe healing process.

You will probably experience discomfort, foreign body feeling and light sensitivity for a few days. Your eyes might even itch, burn or also hurt or produce lots of tears.

To make sure that your symptoms are just the normal reaction of your body, your doctor will do regular check-ups after the surgery.

Right after the surgery your doctor will put a contact lens in your eye to protect it and to help it heal. If it falls out, let your doctor know. Do not try to put it back in.

Your Vision After CXL

After a CXL procedure, your eyesight will be blurry at first. You may notice changes in your vision from time to time to time during the healing process. You may be more sensitive to light and have a poorer vision for about 1-3 months after the surgery.

The goal of corneal cross-linking is to slow your disease and prevent future vision problems, but in some cases, your eyesight may get better over time.

Once you’ve had corneal cross-linking, you might need new glasses or contacts.

Risks

Corneal cross-linking is a safe and effective procedure, but as with all surgical procedures, some small risks are associated with the procedure, and the recovery period afterward.

These include pain, inflammation, infection, and blurred or hazy vision in the period after surgery. However, these risks are all managed with eyedrops taken after surgery, to control pain, haze, and any infection risk.

It’s worth noting that corneal cross-linking sterilizes the cornea (the reactive oxygen species generated by the UV light interacting with the riboflavin kills pathogens), so the risk of infection is mostly concentrated in the first week after surgery, where taking the antimicrobial eyedrops is so important.

Video Interview: 25 Years of CXL

Frequently asked questions

General

What is corneal cross-linking (CXL)?

Cross-linking is a method of mechanically stabilizing and remodelling the cornea using Vitamin B₂ (riboflavin) and ultraviolet A (UV-A) light.

CXL increases the number of cross-links between the collagen fibres of connective tissue of the cornea, thereby strengthening it.

By way of an analogy, think about the Eiffel Tower. The structure would be far less stable without the iron elements criss-crossing the long vertical metal structures that binds the entire tower together.

We have one of the longest clinical experiences worldwide. Members of the ELZA Institute have been instrumental in introducing CXL technology into clinical practice since 2002. ELZA member Prof. Farhad Hafezi and his research group have published more than 120 scientific papers on CXL so far, and Prof. Hafezi is considered a pioneer of this technique. In 2014, he was honoured with the ARVO’s (Association for Research on Vision and Ophthalmology) prestigious Carl Camras Award for Translational Research, for his research in this field.

Prof. Hafezi co-founded the International Cross-Linking Congress and co-organized it since its inception in 2006. He is the publisher of the most comprehensive CXL textbook: “Corneal Cross-Linking”, published by Slack, Inc, New York. A literature analysis study, published in 2022, showed that Farhad Hafezi is the world’s top-ranked author in terms of CXL publications.

Members of the ELZA Institute were the first to use CXL in the postoperative treatment of ectasia after LASIK / PRK, in very thin corneas, and for infectious keratitis.

In addition to scientific expertise, patients from all continents are treated at the ELZA Institute using the latest scientifically proven CXL technique.

No. Cross-linking has been used clinically in other areas of medicine since the 1980s (orthopaedic surgery, ear, nose, and throat surgery, cardiac surgery). In ophthalmology, CXL has been performed since 2001.

The CXL treatment for keratoconus is used in over 160 countries, including the EU and the US. The world’s longest experience exists in Dresden and Zurich. CXL is now considered the gold standard for stopping keratoconus progression.

Yes. Cross-linking of the cornea is achieved through a combination of UV-A irradiation and riboflavin eye drops (Vitamin B₂). The intensity of the radiation was already determined 20 years ago in numerous experiments so that no deeper eye structures can be damaged. The method has been used clinically since 2002, and Farhad Hafezi from the ELZA Institute is one of the world’s most experienced CXL experts.

Scientific publications show that CXL has a high safety profile in children, comparable to that of adults.

The greatest risk is a corneal infection in the first few days after cross-linking. But this is minimized by antibiotics after surgery. This risk is less than 0.1% in our patients.

If you are an adult patient and cross-linking surgery has been recommended, this is because your disease is progressing. CXL surgery is not typically recommended if a person’s ectasia is stable. If your disease is progressive, then your cornea will continue to thin, your vision will continue to worsen, and it is likely that you will eventually require a corneal transplant.

If you are a child or adolescent, then it is recommended that you receive CXL as soon as possible, as in children, corneal ectasias (in this case almost exclusively keratoconus) tend to be aggressive and progress rapidly. The consequences of non-treatment are the same as in adults.

For these conditions, it is recommended that you receive CXL as soon as possible.

The costs of standard epi-off cross-linking for progressive keratoconus in Switzerland are, in principle, covered by health insurance, although as this announcement is so recent, we do not know the extent of the coverage.

Patients from abroad

How long do I have to wait?

If we receive enough information from you before the examination, the examination can take place on the morning of the operation and the operation in the afternoon. Often, patients from abroad arrive on Sunday. We then do the examination on Monday mornings, the surgery on Monday afternoon, and see you every day until Friday. You can leave on Saturday.

We can safely perform a bilateral CXL procedure if needed. In this case, you are required to stay for 7 days (from Monday to Monday morning of the following week).

No, this is not necessary. You can stay in a hotel nearby. We work with several hotels and are happy to help arrange accommodation for you.

We will send you a quote to give you an accurate picture of the costs. Please contact us directly.

You may pay in cash, by bank transfer, or by credit card. Please understand that we will ask that the sum be paid before the operation.

Preliminary Exam

What do I have to consider before the appointment?

As contact lenses can change the shape of your cornea, it is essential that you do not wear your contact lenses for two weeks before the appointment. Only then can we accurately measure the extent of keratoconus and determine whether your keratoconus is progressive or not. This is also the only way we can confirm after cross-linking whether the keratoconus has actually come to a standstill. We are aware that this is a long time for people who are mostly young and working, but two weeks is absolutely the bare minimum.

All older documents are valuable and should be collected as far as possible and brought to the examination: old prescription glasses, old corneal topographies, and even old lenses.

See above. Two weeks is the absolute minimum. In principle, contact lenses should be discontinued for a full twelve weeks before the examination to obtain an absolutely unadulterated image of the cornea. The reason is that contacts change the shape of your cornea and makes our measurements inaccurate, thereby interfering with your precision treatment. Two weeks is the bare minimum we need to make an accurate statement on the state of your cornea.
 

The Cross-Linking Operation

What is the purpose of the operation?

The goal of the classic CXL surgery is to stabilize the keratoconus. We cannot heal the disease, but we can “freeze” the current condition and prevent it from progressing even further. When using a customized approach, we even manage to reverse the ectasia to a certain degree. However, this can’t be guaranteed in advance.

In a second step, a few months after the surgery, measures to improve the sight can be taken. Whether this might be special contact lenses and/or additional laser treatment depends on the state of each patient’s cornea.

No, that is not necessary.

All cross-linking surgeries are performed by Prof. Hafezi or Dr. Torres.

The eyes are held open by a lid speculum. This is perhaps unusual for patients to experience, but causes no pain.

No. You will not feel pain during the operation.

A total of 45 to 70 minutes, depending on the technique used.

Yes, CXL can be repeated. This is especially necessary if a first CXL has not led to stabilization. This occurs in 3 to 10 percent of the surgeries. In rare cases, a second CXL after pregnancy or additional thyroid disease may be necessary.

The shortest period we can wait between performing each operation is one week.

It is an advantage if you are accompanied during the day of the procedure, as your vision will be limited afterward, and the use of public transport may prove risky. Please note that you are not allowed to drive a car for at least one week after the surgery or until your vision has improved to a point where a professional can declare you as being “safe to drive”.

“Dresden protocol” CXL is the original protocol that takes 30 minutes of irradiation. Before irradiation, the epithelium (outer layer of the cornea) is removed.

These are CXL irradiation protocols that deliver the same total energy as the “Dresden protocol”, but in less time, using higher intensities. Before irradiation, the epithelium (outer layer of the cornea) is removed.

These are CXL irradiation protocols that deliver higher total energy than the classic “Dresden protocol”. Typically, before irradiation, the epithelium (outer layer of the cornea) is removed.

In epi-on cross-linking, the outer layer of the cornea, the epithelium, is not removed. The advantages are obvious: less pain and a faster recovery. The early attempts to perform epi-on CXL (2011 to 2020) were not very successful and it was again our research team that found out why: oxygen is a central element of the CXL process and an intact epithelium blocks oxygen transport. Our research team has performed more than a decade of research to optimize epi-on CXL and our current epi-on CXL protocol is the first in the world requiring neither additional oxygen nor iontophoresis to perform effective epi-on CXL.

Cross-linking is not a “single method” anymore. Which technique is chosen depends on a multitude of factors: the stage of your keratoconus, your visual acuity, your refraction, your age, and so on.

In general, there are two scenarios:

  • if your keratoconus is progressive, we can
    • either aim to stabilize the cornea using Dresden protocol epi-off accelerated CXL, high-fluence or epi-on CXL, or
    • we aim to not only stabilize the cornea, but to improve visual acuity and quality using either second generation customized cross-linking (PACE method, developed by ELZA), or a combination of wavefront-guided PRK and conventional cross-linking, or a combination of PACE first, followed by wavefront-guided PRK a few months later.
  • if your keratoconus is stable, then we do not need to perform CXL to stabilize, but we can still use these techniques to improve upon your visual acuity and visual quality: second generation customized cross-linking (PACE method, developed by ELZA), or a combination of wavefront-guided PRK and conventional cross-linking, or a combination of PACE first, followed by wavefront-guided PRK a few months later.

After the operation

Will I receive drops/ointment/medication?

We will give you an exact medication schedule and all the medication you need. To minimize glare, you should wear sunglasses outside, which you will also get from us.

During the day, no actual bandages are required. You will only have a soft “bandage” contact lens to protect the surface of the eye in the days after surgery.

At night, however, you will have to wear an eye shield to stop you from rubbing your eyes when you are asleep.

You will feel a certain degree of discomfort after the procedure. The degree of discomfort depends on the CXL method performed and this level is different from one individual to another. Please note that the youngest patients we treat under local (eye drops) anaesthesia with our clinical protocol are 9 to 10 years old, and they tolerate the procedure quite well.

Yes. Even if you do not feel any pain, the pills are prescribed to reduce not just pain, but also inflammation. Inflammation can slow and impair the recovery process, and you must take the prescribed medications as directed by your physician to ensure the best possible recovery.

Yes, for up to 6-8 weeks. We will prescribe artificial tears, which you can use as often as necessary.

Above all, the bandage contact lens is for your comfort and is not strictly medically necessary. Should you lose them, continue with the drops and, before going to bed, put some of the ointment that you received from us in the eye. We will carry out the check the following day as usual.

After surgery, you must not rub your eyes at all. Rubbing can irritate the eyes, cause inflammation, and it increases the risk of infection during the period that the eye is healing. Furthermore, you may injure the top layer of the cornea, which causes pain and prolongates the healing process.

In general, it is recommended not to rub one’s eyes at any time, as eye rubbing has been linked to ectasia progression.

Usually one week for 100%. If necessary, we will extend it to 10 or 14 days.

In the first week you can do almost all activities, e.g. light fitness, jogging, being in the sun, etc., with one exception: no water should reach the eye (shower water, swimming pool, lake). From a medical point of view, you can safely spend the first few days after surgery in front of a screen, but you will probably get a headache.

At 5 Days after the CXL, when the risk of infection is usually over. However, we might advise you to wait longer if your cornea is still at risk of infection through tap water.

Sport (except swimming) is possible after one week without any restrictions. Please refrain from swimming for two weeks. For the first five days please do not let shower water get near your eye, so do not wash your hair and face. Showering up to the neck is possible at any time. Make-up is possible after one week. Please dab at make-up removal, do not rub firmly.

This is not possible for the first week after the operation. After one week it depends on how your visual acuity develops.

The controls take place daily for the first 4 days, then after one week, 4 weeks, 3, 6, and 12 months, then annually. Depending on your age, the exact diagnosis, and the stability of your cornea, the interval might be prolonged to 18 or 24 months after a few years. Lifelong monitoring is important to enable us to act quickly, should the disease start to progress again.

Immediately after the operation, your vision is blurry. However, you should be able to orient yourself in a room at any time.

In the first 4-5 days, the view is still blurry, then it gets better with each passing day. After about 14 days your eyes achieve about 70-80% of what they did before the operation. Then a fine mist might appear in the view, but this should not frighten you. It manifests because of long-term healing effects and will be noticeable for a few weeks, without significantly affecting your vision. As a rule of thumb, the mist will be gone and vision will be restored after no longer than 6 months after surgery.

In classic CXL (Dresden protocol, and also certain accelerated protocols), the aim is to stop the progression of the disease. However, as a side-effect of the corneal strengthening that occurs during cross-linking, some corneas may become flatter. If this does occur, it tends to result in more symmetry and may improve patients’ quality of vision. The extent of flattening of the cornea or any potential improvement after cross-linking is not predictable beforehand and the dioptres in your glasses might change.

When the customized CXL PACE method is performed, the aim is not to stabilize keratoconus, but rather to improve your vision by selectively flattening the cornea. For this reason, we also perform PACE in corneas that show stable keratoconus.

Yes, absolutely, for the 6-month inspection. Only then can we tell you if the cross-linking operation was successful, that is, if the keratoconus has come to a standstill.

You can fly again from the fifth day after the operation. The eye should be well moistened because of the dry cabin air.

As a rule, contact lens wear is possible 3-4 weeks after the treatment.

The cornea reacts very slowly. Only after 6 months can it be clearly judged whether CXL was successful.
 

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