Corneal collagen cross-linking (CXL)

How Does CXL Work?

The corneal collagen cross-linking (CXL) procedure relies on a combination of riboflavin (vitamin B2) eye drops and controlled exposure to ultraviolet (UV) light.

Here's how it works:

1. Riboflavin Application: The eye is prepared by applying riboflavin drops to the cornea. The transparent outer layer of the cornea (epithelium) may be removed to allow for better penetration of the riboflavin.
2. UV Light Activation: Once the riboflavin has sufficiently penetrated the corneal tissue, the cornea is exposed to UV-A light (365 nm wavelength). The riboflavin then reacts with the UV light, leading to the formation of bonds between the various molecules in the corneal stroma (collagen, proteoglycans, etc.), a process called cross-linking.
3. Stabilization and Strengthening: These new bonds reinforce the corneal structure, thereby reducing the likelihood of it continuing to thin and deform.

What Are the Different Types of CXL?

There are two main types of corneal collagen cross-linking (CXL) procedures:

• Epithelium-Off Cross-linking (Epi-Off): The outer layer of the cornea (epithelium) is removed to allow for better absorption of riboflavin. This method is the most studied and has demonstrated high efficacy.
• Epithelium-On Cross-linking (Epi-On) or Transepithelial: The corneal epithelium is left intact to reduce patient discomfort and accelerate healing. However, this approach may result in less riboflavin absorption, and its efficacy might be slightly lower than that of the Epi-Off method.

What Are the Benefits of CXL?

CXL can slow down, or even halt, the progression of keratoconus, thereby helping to prevent further vision deterioration.

In many cases, CXL can help avoid a corneal transplant by stabilizing the cornea early enough.

Compared to other surgical options, CXL is a minimally invasive procedure with a relatively short recovery time and few complications.

What are the possible combinations with other procedures?

Corneal collagen cross-linking (CXL) can be combined with other procedures to optimize results and improve the management of patients with keratoconus or other corneal ectasias.

1- CXL + Synthetic Intracorneal Ring Segments (ICRS) or Biological Intracorneal Ring Segments (CAIRS)

Goal: To reduce irregular astigmatism and improve corneal shape.

Principle: Synthetic or biological rings are inserted into the corneal stroma to flatten its curvature and improve the regularity of the corneal dome. CXL is then performed to stabilize the corneal structure.

​Order of procedures: The segments are inserted first, immediately followed by CXL.

​2- CXL + excimer laser (topography-guided transPTK/PRK)

Goal: To improve visual quality by reducing corneal surface irregularities.

Principle: An excimer laser-assisted photorefractive keratectomy such as topography-guided (trans)PRK (or wavefront-guided) is performed to smooth the cornea and improve visual acuity. CXL is then performed to stabilize the corneal structure.

Indications: Patients with a sufficiently thick cornea and significant irregularities limiting vision even with glasses.

Order of procedures: Laser remodeling is performed first, immediately followed by CXL.

3- CXL + Implantable Contact Lenses (ICL)

Goal: To correct residual myopia and/or astigmatism after keratoconus stabilization.

Principle: A phakic intraocular lens (such as an ICL implant) is inserted into the eye to improve vision without altering the cornea.

Order of procedures: CXL is performed first to stabilize the cornea, and the implant is placed several months later, once corneal topography has stabilized.

4- CXL + Scleral or Hybrid Contact Lenses

Goal: Optimize visual correction after keratoconus stabilization.

Principle: After CXL, patients can wear scleral or hybrid lenses, which compensate for corneal irregularities by creating a regular optical surface.

Procedure Order: CXL is performed first, followed by a lens fitting a few weeks later.

What are the risks of CXL?

Corneal collagen cross-linking (CXL) is generally a safe and effective procedure, but like any medical intervention, it carries certain risks and side effects.

1- Postoperative Pain and Discomfort

• Discomfort decreases after epithelial healing (3 to 5 days).
• A bandage contact lens is applied to the cornea at the end of the procedure to reduce discomfort while the epithelium heals. ‍

2- Corneal Opacities and Haze

• An inflammatory corneal haze (opacity) can appear after CXL, temporarily affecting vision.
• It is often transient but can persist for several months in some cases.
• The application of mitomycin C (MMC) after CXL combined with PRK can help reduce this risk.
• In cases of persistent scars, there are now eye drops (losartan) which in many cases allow them to fade or even disappear completely.

3- Transient Reduction in Vision

• Some patients experience a temporary decrease in visual acuity after the procedure, due to transient corneal changes and postoperative inflammation.
• Visual improvement generally takes several weeks to several months.‍

4- Corneal Infection and Ulceration

• Although rare, a corneal infection can occur, especially if epithelial healing is delayed.
• Corneal ulceration can lead to a loss of transparency and decreased vision, requiring further treatment.‍

5- Treatment Failure or Keratoconus Progression

• While CXL is effective in stabilizing the cornea in most cases, some patients may experience keratoconus progression despite treatment.
• In such cases, a repeat CXL or other complementary management (intracorneal segments, corneal transplant, etc.) may be necessary.