Crosslinking, also known as cross-linking of bonds, cross-collagenization of the cornea or CXL (ICLX) is a procedure developed in the late ’90s and designed to cross-link corneal collagen with riboflavin and UV-A light to restore sufficient mechanical stability.

When the collagen molecules of the connective tissue supporting the cornea are disrupted between the collagen molecules in the cornea due to disease or trauma, the biomechanical stability of the cornea is reduced due to insufficient cross-linking of the collagen.

Crosslinking is primarily used to treat corneal conus(keratoconus from Greek kerato – horn, Latin conus – cone) – a specific form of astigmatism in which the cornea of the eye bulges forward in the shape of a cone. The procedure is also used to treat transparent marginal corneal degeneration(keratotorus: Pellucid Marginal Degeneration PMD). Unlike corneal cone, PMD is not always associated with central corneal thinning, but rather with thickening and stiffening of the corneal edge (corneal thickening).

Unfortunately, thickening also leads to irregular corneal steepness, which often leads to PMD being mistaken for corneal cone. In many cases of keratotorus (PMD), astigmatism can still be well corrected with glasses. This may be due to the fact that in the case of PMD, the center of the cornea is probably not “diseased” – it is only distorted by the warping of the corneal edge. Meanwhile, with corneal cone, the curvature of the cornea is much more irregular and therefore cannot be corrected with glasses.

In the case of keratotorus (PMD), treatment currently involves UV crosslinking of the cornea. The cornea should be stabilized in such a way as to neutralize the “pulling effect” of the corneal edges relative to the center of the cornea. Also in the case of keratoconus (corneal cone), stabilization of the cornea by crosslinking has proven effective in stopping the progressive process of corneal bulging.

The earlier keratoconus (corneal cone) or keratotorus (PMD) is detected, the better it can be dealt with and achieve truly satisfactory treatment progress for the patient. Since collagen crosslinking is a very low-risk procedure with a high chance of success, it is recommended to start treatment with this method as early as possible. If the frequent change of glasses or contact lenses can be explained by corneal changes visible on topographic examination – which slows down or prevents the selection of glasses or contact lenses – it is worth considering crosslinking.

Crosslinking vs corneal transplantation

Until recently, the only correct treatment for advanced
corneal cone
was considered its transplantation. However, it is not a simple procedure, and there is also a risk of graft rejection. The long healing process means that significant improvement in vision is only achieved after two years. Since corneal transplants are also used in young patients with progressive corneal cone, this always involves high demands on the transplant. Meanwhile, CLX does not require such deep intervention in the structure of the eye or the use of foreign material. Cross-linking the cornea allows it to stabilize and halt the progression of the disease.

To be able to perform crosslinking the cornea should be at least 400 µm thick. If the corneal thickness is below the minimum value, endothelial damage cannot be ruled out. Corrected vision with glasses or contact lenses should not be less than 0.3.

What corneal crosslinking looks like – Epi-Off and Epi-On method

During crosslinking of the eye’s cornea, individual fibers of the corneal connective tissue are joined together by UV light and the light-sensitive vitamin B2 (riboflavin). This mechanically stabilizes and strengthens the cornea, stopping the process of progressive deformation and deterioration of vision. The procedure is performed on an outpatient basis. The patient gets local anesthesia, in the form of an injection or application of special eye drops, and his eyelids are immobilized for the operation.


In the classic cross-linking method (Epi-Off), the surgeon removes the upper protective layer of the cornea, as the epithelium provides protection from UV rays – if the protective layer were not removed, riboflavin would not be able to penetrate the corneal epithelium and enter the stroma – and administers 0.1% riboflavin drops every two minutes. This process takes about half an hour.


In the transepithelial method (Epi-On), it is not necessary to scrape the surface, i.e. remove the upper protective layer of the cornea. This method uses iontophoresis crosslinking: with the help of an iontophoresis applicator electrode, riboflavin diffuses much faster through the intact epithelium into the corneal stroma than with the usual Epi-on crosslinking procedure. This means that the process takes much less time (about 15 minutes in total). Because the epithelium remains intact, there is no corneal opacity after the procedure, no infection and no deterioration of vision. However, these drawbacks can be seen from time to time after the standard Epi-off procedure. The depth of penetration by this method is estimated at approx. 150 µm.

The surface of the eye is thus irradiated with a UV-A light source for 10 to a maximum of 30 minutes, depending on the treatment protocol chosen for the patient. During this time, the cornea is “saturated” with riboflavin, which acts as the so-called “corneal”. Photosensitizer and absorbs UV radiation. Illumination puts riboflavin in the cornea into an excited state, triggering a photochemical process that produces oxygen radicals. Oxygen radicals cause interactions with collagen in the cornea, forming bridges between collagen molecules. More than 90% of UV light is absorbed by the cornea, so there is no danger to the lens or retina of the body.

The effect of the two methods (Epi-Off and Epi-On) is comparable because crosslinking in both methods occurs only in the upper layers of the cornea. The depth of penetration of riboflavin in the lower layers of the cornea does not seem to matter much. A penetration depth of 150 µm appears to be sufficient for the intended effect.

If the cornea is thinner than the recommended 400 µm, administration of hypotonic riboflavin may cause corneal swelling, but cross-linking will still be possible. UV light exposure during crosslinking of the eye’s cornea (about 10 minutes) then takes place over an area of about 8 to 9 cm². The distance between the UV light and the cornea and the intensity of the beam are chosen so that the areas under the cornea are not damaged. The doctor continuously monitors the thickness of the cornea while performing the cross-linking. The corneal surface is then rinsed. Including preparation, the entire procedure takes about. two hours. Crosslinking increases the density of collagen in the tissue, thereby increasing the stability and thickness of the cornea.

Management after cross linking procedure

Immediately after the procedure, the eye is painful and hypersensitive to light. The doctor recommends antibiotics and steroid drops. As part of the dressing and protection, the patient wears soft contact lenses for several days. Until the epithelial healing process is complete, various side effects, such as burning and watery eyes, may occur during the first two months. After successful eye treatment, the patient can return to hard contact lenses. As a rule, with CLX of the cornea of the eye, the desired goal of stabilization is achieved after the first treatment.

Corneal cross-linking of the eye is usually a very safe method that does not cause any serious side effects. Compared to corneal transplantation, it is also much cheaper. No serious complications associated with corneal crosslinking, such as damage to the retina or lens of the eye, have been observed to date. The complication rate of the procedure is less than 3%. None of the cases previously treated with corneal crosslinking also had a subsequent need for a corneal transplant. 98-99% of eyes previously treated with CLX achieved the desired corneal stabilization.

Experience has shown that many patients with keratotorus (PMD) can receive optical supplies with implantable contact lenses for permanent ametropia correction after about 6 months of UV cross-linking. In patients with corneal cone, due to the greater irregularity of the corneal curvature, contact lenses with stable dimensions or alternatively corneal ring segments (ICRS) are more suitable for optical treatment.

Can you stop wearing glasses after cross-linking surgery

After the crosslinking procedure, astigmatism is often much more regular than before. In this way, PMD patients in particular achieve good visual acuity under spectacle correction. There is also a chance to permanently correct vision by implanting implantable contact lenses made of biocompatible collagen (EVO VISIAN ICL).

Implantation should occur no sooner than 6 months after cross-linking, as the cornea may still change during this time. A combination of transepithelial crosslinking and ICL has already succeeded in freeing some patients from glasses and contact lenses.

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