Crosslinking: Information & Crosslinking Specialists

Crosslinking is a safe and successful routine procedure for stabilizing the cornea. Doctors use it in particular to treat progressive keratoconus.

This stabilization is achieved through a photochemical process. When exposed to UV light, the B2 vitamin riboflavin is activated, releasing oxygen radicals. These radicals bond the carbon and nitrogen groups of the cornea’s collagen fibers together. This is therefore also referred to as cross-linking of the cornea. A dense network is formed that stabilizes the cornea.

The riboflavin used also absorbs UV light, thereby protecting deeper layers of the cornea.

The cost of corneal cross-linking amounts to several hundred euros. In most cases, health insurance will cover the costs.

Approximately 40,000 people in Germany suffer from keratoconus. This is a specific form of corneal curvature in which the cornea bulges forward in a cone-shaped manner.

The causes of the disease are largely unknown. Since keratoconus tends to run in families, a genetic predisposition is suspected. Other possible causes include

• enzyme abnormalities in the epithelium, the outer layer of the cornea, 
• metabolic disorders, and
• infections

.

The disease often develops at an early age. It can manifest during puberty, but most commonly by the age of 30. For young patients in particular, corneal cross-linking may therefore be an alternative to previous treatment approaches.

In keratoconus, the cornea bulges forward in a cone-shaped manner © Zarina Lukash | AdobeStock

The most common form of keratoconus is the so-called “Forme Fruste” or silent form. In the majority of cases, it can be corrected with corrective eyewear and does not require further intervention.

However, if the condition develops very early on, keratoconus often progresses. In other words, the condition worsens. In such cases, glasses are initially recommended to correct the visual impairment. Rigid gas-permeable contact lenses, which do not exert additional pressure on the damaged cornea, can also provide relief.

As a surgical option, corneal cross-linking can be a viable alternative even in the early stages of the disease.

However, if the bulging of the cornea continues to increase, the cornea becomes thinner and may rupture or scar.

Visual acuity is permanently impaired, and the deterioration continues despite the use of glasses or contact lenses. The perception of

• halos,
• rings of light—which appear particularly around lamps and other light sources—as well as
• shadows or streaks

can be further signs of keratoconus.

Initially, keratoconus affects only one eye, but as the disease progresses, it spreads to the other eye. Especially in advanced stages, cross-linking plays a significant role in treatment.

In the early stages of the disease, keratoconus can only be reliably diagnosed using medical technology. In addition to a general ophthalmological examination, the doctor employs various methods. The goal is to accurately measure the cornea and precisely determine its thickness. This is also important for subsequent crosslinking, as certain conditions must be met for the treatment to be successful.

Various measurement techniques are used to diagnose keratoconus and to assess the feasibility of crosslinking. Progressive keratoconus can be detected by an increase in corneal refractive power of approximately one diopter over the course of one year.

Using a so-called Scheimpflug camera, the treating physician can capture the topography of the cornea. Based on the contour lines, the physician calculates the curvature of the corneal surface. A Pentacam also allows for the measurement of corneal thickness and radii of curvature.

Both procedures take only a moment and are completely painless.

An assessment based on eyeglass prescription is less reliable. Previous findings should not replace a medically sound diagnosis before beginning cross-linking.

Although the technology allows for early detection, keratoconus is often not diagnosed until it is already quite advanced. By then, it is often clearly visible even without corrective lenses.

A cure is not yet possible. However, the progression of the disease can be halted.

The progression of the disease varies from patient to patient. In about 20 percent of cases, the bulging and scarring of the cornea progress to a very advanced stage. Conventional visual aids and custom-made contact lenses are no longer effective at this point. They cannot stay in place and fall out of the eye.

Until now, corneal transplantation was considered the preferred surgical option for advanced-stage keratoconus. However, this form of treatment carries significant risks.

For example, there is no guarantee that the patient will tolerate the donor cornea. Furthermore, the healing process usually takes quite a long time. Unlike with crosslinking, a significant improvement in vision does not occur until up to two years later.

Corneal transplantation is also often performed on young patients, which places high demands on the graft. Crosslinking, on the other hand, does not require major surgery or the use of foreign materials.

Crosslinking now offers a gentle and promising alternative. The goal of corneal cross-linking is to stabilize the cornea. Correcting refractive errors is not the primary objective. However, it is now clear that in many cases, cross-linking causes the curvature of the cornea to decrease slightly. This also improves vision.

As a general rule, the earlier crosslinking of the cornea is started, the better the outcome for the patient. Very young patients, in particular, can benefit from crosslinking treatment.

The visual acuity corrected with glasses or contact lenses should not be less than 0.3.

The cornea should have a thickness of at least 400 µm. This is the only way to ensure the highest possible absorption of UV radiation by the B vitamin riboflavin. If the corneal thickness falls below the minimum value, damage to the endothelium cannot be ruled out, even with this otherwise very safe procedure.

Other factors that can adversely affect the success of crosslinking treatment include, for example,

• a curvature of more than 55 diopters,
• advanced age,
• pre-existing corneal scarring,
• pregnancy,
• eye infections, or
• epithelial disorders.

The eye does not need to be opened for crosslinking, and the procedure can be performed on an outpatient basis.

First, the eye is desensitized to pain by administering eye drops one drop at a time. An eyelid speculum is typically used to keep the eyes open. The doctor then ablates the cornea from above. This is necessary because the epithelium provides a certain degree of protection against UV rays. Otherwise, the vitamin riboflavin would not be able to penetrate the corneal epithelium and reach the stroma.

After the epithelium has been removed, B-vitamin-based drops are administered into the patient’s eyes. A 0.1 percent riboflavin solution is used at intervals of about two minutes. This procedure takes about half an hour.

If the cornea is thinner than the recommended 400 µm, administering hypotonic riboflavin may cause the cornea to swell. Cross-linking is then still possible.

UV light irradiation during corneal cross-linking is then performed over an area of approximately 8 to 9 cm². The areas beneath the cornea must not be damaged during this process. For this reason, the distance between the UV light and the cornea, as well as the intensity of the beam, are adjusted accordingly. This treatment takes about half an hour.

During this time, the vitamin continues to be instilled every two minutes. The doctor will also continuously monitor the thickness of the cornea while the crosslinking is being performed. Afterward, the surface of the cornea is rinsed.

Including preparation, the crosslinking procedure takes less than two hours.

Immediately after crosslinking, some discomfort is unavoidable. The removed epithelium needs time to heal. Anti-inflammatory antibiotics and steroids are administered as eye drops as needed for about one to two weeks following the procedure.

Following crosslinking, the patient must wear a bandage contact lens for a few days. Until the epithelial healing process is complete, various side effects—such as a sensation of the eyes rubbing or tearing—may occur during the first two months. Dry eyes and sensitivity to light are more common after crosslinking.

Mild clouding of the anterior stroma is also likely as a result of the procedure following corneal cross-linking, but this typically resolves within a few months. The eye will also remain red for about two weeks following corneal cross-linking.

These symptoms are normal and harmless following corneal cross-linking treatment. Regular use of the prescribed medications and artificial tears can alleviate the discomfort associated with corneal cross-linking.

After successful treatment, the patient can resume wearing hard contact lenses. This not only improves visual acuity but also significantly enhances quality of life.

As a rule, the first cross-linking treatment is already successful and can sufficiently stabilize the cornea. This is typically followed by regular follow-up examinations of the cornea. The ophthalmologist checks the corneal topography and visual acuity initially on a daily basis, then every three months, and later every six months.

In some cases, it is also possible to combine crosslinking with ring implantation. This can both halt the progressive course of the disease and achieve significant improvements in vision.

In ring implantation, individual rings are inserted into the deeper segments of the cornea. The degree of correction is influenced by the length and thickness of the rings. The rings are implanted using a high-precision laser.

However, this combination should only be performed if, in addition to progressive keratoconus, the patient also has an intolerance to contact lenses.

Crosslinking is generally a very safe procedure with few side effects. Compared to corneal transplantation, crosslinking is also significantly more cost-effective.

Serious complications, such as damage to the retina or the lens of the eye, have not been reported to date. The complication rate for the procedure is less than 3 percent. These complications following crosslinking are essentially limited to

• delayed wound healing or
• scarring, both of which are treatable.

Infections occur very rarely following corneal cross-linking.

No permanent damage resulting from cross-linking has been observed to date. Nor has a corneal transplant been necessary in any of the cases treated so far.

In 98 to 99 percent of the crosslinking procedures performed, the desired stabilization of the cornea was achieved.