Corneal Collagen Crosslinking


Keratoconus is, by definition, a deteriorating, non-inflammatory, disease of the eye. The eye forms a conical, cone shaped cornea, caused by structural changes within the cornea which cause it to thin and stretch.

Keratoconus is, however, somewhat of a mystery. Although it can affect all ethnic groups, there is a higher incidence in certain parts of the world due to genetic factors - Finland and New Zealand being two such places. It is certainly found to run in particular families and higher numbers of cases are also reported in people with downs syndrome. Millions of pounds have been put into researching this disease, however it is still unclear what causes it.

Characteristics And Stages Of The Disease

Keratoconus almost always develops asymmetrically (i.e. after being diagnosed in the first eye, five years later diagnosis of the second occurs). The onset is around adolescence, progressing as people reach their twenties or thirties. Very seldom does keratoconus develop after forty. Occasionally children as young as eight are diagnosed with the disease.

In early stages, vision will start blurring, fluctuating over a number of months, lending the patient to change lens prescriptions more frequently. The more progressive the disease becomes, the more likely correcting contact lenses, and perhaps eventually, rigid gas permeable contact lenses will be required.

Normally, keratoconus will sporadically progress over 10 to 20 years, and may halt at any stage from mild to severe. In advanced cases, the descemet's membrane can rupture as a result of extreme bulging of the cornea, and in extreme cases an emergency corneal transplant is necessary to save the eye.

Treatments Past And Present

Although somewhat barbaric by today's standards, 19th Century surgeons used treatments such as fine hooks to pull on the iris. Inserted through the cornea this elongated the pupil into a slit like the eyes of a cat. Chemical cauterisation was also used - by applying a solution of silver nitrate using a pressure dressing this effectively moulded the cornea back into shape. Today's treatments are, however, far less invasive and include rigid gas permeable contact lenses, corneal transplant and collagen cross-linking.

The Rise Of A New Procedure

Corneal Collagen Crosslinking

As the number of corneal collagen cross-linking procedures performed each year continue to rise, many people with keratoconus are compelled to find out just what this relatively new treatment has to offer.

In order that the cornea stays strong, layers and layers of collagen (which is what the cornea is made up of) are arranged in regular patterns and knitted together with collagen fibres. These collagen layers are called the 'stromal lamellae. As a keratoconus sufferer has far less of these collagen fibrils and they lose their ability to link, this results in the bulging of the cornea. Collagen cross-linking treatment strengthens the cornea by creating more cross-linking fibres. The procedure utilises riboflavin (which is actually vitamin B2 drops) and a specialised UV light.

Treatments Used In Conjunction With Collagen Cross-linking

INTACS is a treatment used in addition to cross-linking for suffers who can be intolerant of contact lenses. INTACS are micro thin inserts designed to bring the cornea back to its normal shape. These are placed within the circumference of the cornea, are not visible and cannot be felt. In extreme cases of keratoconus, the newer INTACS SK would be the option. INTACS and cross-linking can therefore be used together to achieve the best visual result.

Traditional Collagen Cross-linking (CXL) Vs. Transepithelial Collagen Cross-linking (C3R)

The more traditional approach favours removal of the epithelium by creating an 'intralisk flap' which can be lifted to allow the riboflavin solution to be applied to the stromal layer. The flap can be replaced and exposure to UVA can follow. Riboflavin solutions have almost never been able to penetrate the epithelium, removal being the only option. With C3R, the development of new riboflavin solutions enables surgeons to make numerous small perforations in the epithelium, enabling the riboflavin to soak - then UVA exposure intermittently. Removal of the epithelium is not necessary. Some surgeons argue C3R is less efficient resulting in patients having to have additional treatments in two or three years; others claim that CXL is more painful for the patient and recovery time is slower.

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Who Makes A Good Candidate For Treatment?

  • Ideally, the patient should have a corneal thickness of 400 microns or more. Corneal cross-linking is not recommended for anyone whose cornea is too thin or too scarred.
  • It would be a first choice therapy for patients with progressive keratoconus aged around 26 years, however most under the age of 35 years are eligible.
  • Those who develop keratoconus under the age of 18 will find that the progression of the disease is far faster. They do not make good candidates for this treatment as the severity of their condition often results in the need for a corneal transplant.

What To Expect During The Procedure

When it comes to treatment, there are two types of corneal cross-linking; epi-on and epi-off.


With this method, the 'epi', representing the epithelium (the surface layer of the cornea) is not removed. The surgeon will numb the eye with a topical anesthetic agent in the form of drops. A riboflavin solution will then be used to soak the eye. The solution permeates the epithelium and a special UV light is applied to react with the solution. It is a painless, 30 minute procedure and both eyes can be treated at the same time.


As the name suggests, here the epithelium is removed, which naturally makes for a far more invasive treatment. Again, numbing eye drops are used before the epithelium is carefully scraped away with surgical instruments. The riboflavin then soaks the eye for 30 minutes (being re-applied every 3 minutes) after which UV light exposure completes the procedure. This is a more painful operation and because the epithelium is removed, healing is assisted by giving the patient a course of antibiotics and steroid eye drops.

What To Expect After The Operation

Patients can expect to be put on antibiotics and be asked to used anti-inflammatory drops on their eyes for a few weeks. They will have to wear a contact lens bandage for a couple of days. Surgeons place a small single stitch in the cornea and this is not removed until around three months later, enabling the shape of the cornea to stabilise. The cornea must be stable before contact lenses or glasses can be worn.

Depending on which technique is chosen, patients might feel mild, moderate or severe pain. If the epithelium is not removed, then hazy vision and a 'foreign body' sensation might be all a patient experiences. This will clear up after 24 hours. However, should the epithelium be removed, moderate to severe pain can last up to a week, and vision might be blurry for 1 to 12 weeks. Light sensitivity may also cause problems for a few patients, usually returning to normal within a month.

A Successful New Treatment

Corneal collagen cross-linking is a developing treatment, reducing the need, in many instances, for sufferers of keratoconus to undergo a corneal transplant. Indeed, those who undergo successful treatment can expect a re-shaped, strengthened cornea and improved vision within approximately 3 months.

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