Definition & Overview

Corneal cross-linking is a medical procedure that strengthens the collagen bonds in the cornea to halt the progression of keratoconus, a degenerative eye disorder caused by structural changes in the cornea.

The cornea is the transparent part of the eye located in its front most part. It refracts incoming light and helps in focusing objects. It covers the iris, pupil, and the anterior chamber of the eye. It is composed of several layers though it contains no blood vessels and gets oxygen directly through the air, which is dissolved in tears and diffused all over the cornea.

The corneal cross-linking procedure was primarily developed to halt the progression of corneal diseases but not necessarily cure it. One example is keratoconus, a type of disease that thins the cornea causing it to bulge out and form a cone-like shape. The pressure in the eye causes it to protrude, leading to reduced vision acuity. Corneal cross-linking refers to the ability of collagen fibrils to bond with other fibrils. In healthy eyes, this process occurs naturally as one matures and is enhanced through the process of glycation and oxidation.

There are generally two types of corneal cross-linking -- one that involves the removal of a thin layer of epithelium (epithelial-off crosslinking) to allow the penetration of riboflavin or vitamin B2 while the other technique involves a longer process but leaves the epithelial layer intact (epithelial-on crosslinking).

Who Should Undergo and Expected Results

Corneal cross-linking benefits patients diagnosed with:

  • Keratoconus - Patients with keratoconus (preferably aged 10-35 years) may be able to reverse the bulging appearance of the cornea with the help of corneal cross-linking before it becomes too irregular. This procedure is often indicated for those who can no longer perform daily, normal activities like driving, reading, or even watching television due to reduced visual acuity. The procedure may be considered as a combined therapy that involves implanting corneal inserts and as means of stabilising and reshaping the cornea in advanced stages of keratoconus.

  • Pellucid marginal degeneration - This condition is quite similar to keratoconus but involves the thinning of the peripheral and inferior parts of the cornea.

  • Terrien’s marginal degeneration - This is the thinning of the peripheral corneal stroma leading to a high degree of against-the-rule astigmatism. The condition is uncommon and is associated with corneal neovascularisation and lipid deposition.

  • Corneal ulcers – This is an eye condition typically caused by infection. Cornea cross-linking is indicated only if the condition has been unresponsive to antibiotic medications. A corneal ulcer is quite painful and the patient experiences reduced vision with eye discharge. The corneal part may also appear red.

  • Ectasia - There are rare instances in which patients who underwent LASIK procedure develop ectasia or the thinning of the cornea. Corneal cross-linking can address this condition and halt vision loss.
    As for the expected results, corneal cross-linking using epithelial-off method is found to be quite effective in improving the shape of the cornea. Patients often found that their visual acuity has improved after the procedure, with no major complications. Most can resume normal, daily activities a few weeks after the procedure.

How is the Procedure Performed?

The procedure starts with the administration of anesthetic drops to ensure patient comfort. If the ophthalmologist opts to perform epithelial-off crosslinking, the epithelial layer will be removed and a lid speculum is placed over the affected eye. After removing the thin layer, riboflavin drops are administered at specific time intervals. A blue filter is then used to determine if enough amount of riboflavin has penetrated the anterior chamber of the eye. The next step involves positioning the patient under the UV light for several minutes to activate the drops. The other technique, epithelial-on crosslinking, is performed basically the same way but does not involve the removal of the epithelial layer. Instead, the patient is placed in a reclining position and riboflavin drops are started right away. The eyes are then evaluated to ensure that the cornea has received sufficient amount of riboflavin. Following the procedure, some patients may opt to undergo another operation called photorefractive keratomy that flattens the bulging cornea.

The whole procedure takes about 60 to 90 minutes and the patient is advised to wear a bandage contact lens for several days to protect the affected eye. Antibiotic drops are also prescribed to help prevent the development of infection.

A study conducted to compare the effectiveness of the two techniques found that 94.4% of patients diagnosed with progressive keratoconus and have undergone the epithelial-off method did not experience worsening of the disease whereas only 66per cent of patients in the epithelial-on group experienced the same results.

Possible Risks and Complications

Although considered a safe and straightforward procedure, corneal cross-linking has risks and can lead to possible complications. These include:

  • Infection - Removing the thin layer of epithelium can expose the cornea to infection, though this rarely occurs. There are some instances of microbial infection following corneal cross-linking, but these are attributed to improper hygiene and inadequate eye care following the procedure .
  • Corneal haze - Some patients develop corneal haze a year or two following the procedure. In some instances, the procedure can lead to the loss of keratocytes, causing vision problems.
  • Damage to nearby parts – This risk is mainly attributed to UV irradiation and occurs if the UV machine used is not handled correctly .
  • Keratoconic progression - Since this procedure is only meant to halt the progression of corneal diseases, the patient may experience keratoconic progression after a significant time has passed following corneal cross-linking. This is typical in older patients.

  • Central stromal scars - There are also reports of central stromal scars after the procedure.


  • Agarwal, Amar; Jacob, Soosan (August 10, 2014). "Contact lens-assisted cross-linking treats corneal ectatic disorders in thin corneas". Ocular Surgery News U.S. Edition.

  • Abbondanza, M; Abdolrahimzadeh, B; Guidobaldi, M (January 2016). "[Combined Corneal Collagen Cross-linking and Mini Asymmetric Radial Keratotomy for the Treatment of Keratoconus].". Acta Medica International 3 (1): 63–68.doi:10.5530/ami.2016.1.1

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