Corneal Collagen Cross-linking (CXL)

Corneal Collagen Cross-linking (CXL): a treatment for keratoconus and other ectasias

Corneal collagen cross-linking (CXL) is an outpatient eye procedure that strengthens the cornea if it has been weakened by keratoconus, other corneal diseases, or as a complication of refractive surgery. CXL goes by many names and abbreviations, including cross-linking, corneal cross-linking, corneal collagen cross-linking, C3-R, CCL, CXL and KXL. 

Spectacles and contact lenses can improve vision in keratoconus, but they do not treat the underlying corneal weakness. Therefore, they do not prevent the keratoconus from progressing.  CXL is a minimally invasive procedure that involves applying liquid riboflavin (vitamin B2) to the surface of the eye, followed by treatment with a controlled application of ultraviolet light (UVA), to strengthen the weakened cornea.

The cornea stroma is made up of many long strands of collagen fibres bound together by bonds or anchors. The bonds between these collagen fibres give structural support and strength to the cornea. CXL uses chemicals to form extra anchors, or cross-links, between these collagen fibres. This is currently performed using riboflavin (vitamin B2) and ultraviolet light (UVA). Natural occurring collagen cross-linking has been observed in many different tissues within the body including the cornea, teeth, and bones.

Crosslinking - covalent bonds

Figure 1. Comparison of weaker cornea with keratoconus (left)  and stronger cornea after corneal collagen cross-linking (right).  Note the extra anchors or cross-links between the collagen fibres.

In extensive experimental studies using riboflavin/UVA cross-linking treatments in animal and human eyes, researchers have demonstrated a significant increase in corneal rigidity and strength after CXL. By stiffening the cornea, the progression of keratoconus can be prevented, and in some cases can lead to improvement, with flattening of the cornea.

It is important to understand that CXL treatment is not a cure for keratoconus. Any significant corneal distortion that is present before the treatment is expected to remain after the treatment. The goal of CXL is to halt the progression of the condition. After the treatment, it is expected that people will continue to wear spectacles or contact lenses, although a change in the prescription may be required. By preventing further deterioration in vision and further weakening in the cornea, cross-linking treatment will hopefully reduce the need for corneal transplantation in keratoconus patients.

Who is a candidate for corneal cross-linking (CXL)?

People with progressive keratoconus, other cornea ectasia disease, or ectasia after refractive surgery. CXL is most effective if it can be performed before the cornea has become too irregular in shape and before there is significant vision loss. If applied early, CXL will stabilize the shape of the cornea, resulting in stable vision and an improved ability to wear contact lenses.

When is cross-linking (CXL) not an option?

If the cornea is too thin, less than 400 µm at the thinnest point, then the treatment may cause damage to the deeper layers of the cornea or structures inside the eye. It is important to have corneal thickness measurements done prior to considering the treatment.  

If there is an active ocular disease other than corneal ectasia.

In patients with herpes simplex keratitis, a corneal infection caused by the cold sore virus.

In women who are pregnant.

In patients who have active, uncontrolled eye allergies or an autoimmune disease such as rheumatoid arthritis.

In patients with central corneal scars that significantly affect their vision.

What does corneal cross-linking (CXL) involve?

During your initial eye examination, Dr MacIntyre will measure the thickness of your cornea and perform a mapping of your cornea (called corneal tomography) to determine the severity of the keratoconus. He will also assess your visual acuity and general eye health.  These evaluations are to make sure you are a good candidate for the procedure.  Once you decide to have the procedure, a date for the procedure will be scheduled.  

Only one eye is treated at a time. Usually the more advanced eye is treated first, to ensure it doesn’t progress to a point where CXL is contraindicated. Prior to the CXL procedure, you will be asked to lie down comfortably on a bed.  Anaesthetic eye drops will be given before and throughout the procedure, numbing the surface of the eye, so you will not feel any pain. 

The surface layer of the cornea (the epithelium) is removed and drops of riboflavin are placed onto the eye.  These drops are given for 15 to 30 minutes to allow the riboflavin to fully saturate the cornea.  An ultraviolet light (UVA) is then focused on the eye for 10 to 30 minutes, depending on the strength of the light. Riboflavin drops are placed on the eye during this time and your cornea thickness will be monitored. You will need to lie still during this procedure to keep the UVA light focused. 


Figure 2. The five layers of the cornea.  The epithelium, the most superficial layer, is removed or weakened during CXL.  This allows the riboflavin to soak into the stroma, where the bonds between the collagen fibres will be formed.

At the end of the procedure a soft contact lens is placed in the eye. This contact lens is used as a bandage to allow the epithelium to heal.  It is usually removed several days after the procedure.  You will be given eye drops to use at home, including an antibiotic (to prevent infection), a steroid (to reduce inflammation), and a lubricant (to speed the healing process).  

Where in Melbourne will the corneal cross-linking (CXL) be done?

Dr MacIntyre currently performs CXL at two modern surgical centres in Melbourne: Melbourne Excimer Laser Group in East Melbourne and Manningham Day Procedure Centre in Templestowe Lower.