Corneal cross-linking, or CXL, is a minimally invasive surgical procedure for the treatment of corneal ectasia, a group of conditions in which the cornea—the outermost layer of the eye—thins, weakens, and bulges outward. The procedure, which takes about an hour to complete, strengthens and stiffens the cornea by creating bonds—or cross-links—between collagen fibers (a type of protein) in the cornea.

In 2016, the Food and Drug Administration (FDA) approved the iLink® corneal cross-linking procedure from Glaukos, a medical technology and pharmaceutical company, for the treatment of two types of corneal ectasia: Progressive keratoconus, a condition in which the cornea thins and bulges outward in a cone shape, and corneal ectasia that occurs after undergoing refractive (or laser eye) surgery to improve vision, such as LASIK™. Corneal ectasia is a rare complication of refractive surgery.

Both keratoconus and corneal ectasia after refractive surgery can cause vision problems, including increased nearsightedness and astigmatism (when the cornea is abnormally curved, causing blurred or distorted vision) and a reduction in visual acuity (sharpness of vision). They can also be progressive, meaning that if left untreated, substantial, irreversible vision loss may occur over time. Corneal cross-linking can slow or stop the progression of these conditions, thereby lessening future vision changes and reducing the need for more invasive treatments. For those with keratoconus or corneal ectasia after refractive surgery, it is important to undergo corneal cross-linking as early as possible to stop progression of the condition and to preserve the individual’s sight. A delay in getting the procedure may allow vision to permanently worsen. Additionally, if the condition becomes too advanced, the cornea becomes too thin for cornea cross-linking, and the procedure cannot be done.

Corneal cross-linking is most frequently used to treat keratoconus, a condition in which the cornea (the clear, outermost layer of the eye) becomes thin and weak and bulges outward in a cone shape.

When light reaches the eye, it first passes through the cornea, which helps focus the light on the retina at the back of the eye. The retina then sends signals to the brain, which converts them into images.

Normally, the cornea is dome-shaped. In someone with keratoconus, however, it becomes cone-shaped and bulges outward. The change in the shape of the cornea alters the angles at which light enters the eye. As a result, the cornea does not properly focus light on the retina, resulting in blurred or distorted vision, increased sensitivity to light, and increased nearsightedness. Keratoconus is a progressive condition, meaning it usually gets worse over time. In its advanced stages, it can cause substantial vision loss, as well as pain and discomfort.

It can affect both men and women, and typically develops in the early teenage years through early adulthood and may continue to worsen through a person’s 20s and 30s, after which it stops progressing. In adolescents and young adults, keratoconus presents as a rapidly worsening astigmatism. Patients who see their optometrist and are told that their astigmatism prescription is changing or who cannot see clearly despite a change in glasses prescription should be seen by a cornea specialist.

The cause of keratoconus is unknown, though some risk factors have been identified, including a family history of keratoconus, eye-rubbing, eczema, asthma, and certain medical conditions, such as Down syndrome and Ehlers-Danlos syndrome. Keratoconus affects around 50 to 230 out of every 100,000 people.

Refractive surgery involves using lasers to change the shape of the cornea to correct nearsightedness, farsightedness, and astigmatism. There are several types of refractive surgery, including laser-assisted in situ keratomileusis (LASIK), photorefractive keratectomy (PRK), and small incision lenticule extraction (SMILE). In these procedures, a laser is used to precisely remove a tiny amount of corneal tissue to reshape the cornea, so it better focuses light onto the retina, thereby improving vision.

In rare cases, refractive surgery results in corneal ectasia—the thinning, weakening, and bulging of the cornea. Symptoms include blurred vision, increasing nearsightedness, and astigmatism.

In addition to corneal cross-linking, treatments include:

• Corrective lenses. Eyeglasses may be used to correct vision in mild cases; contact lenses may be used in mild-to-moderate cases.
• Intrastromal corneal ring segments (ICRS) are plastic rings that are inserted in the cornea. They flatten the cornea, reduce astigmatism, and improve visual acuity.
• Photorefractive keratectomy (PRK) involves the use of lasers to reshape the cornea. It is often used in combination with CXL.
• Corneal transplant (keratoplasty) is used to treat people with severe cases of keratoconus or other types of corneal ectasia. In this surgical procedure, the abnormally shaped cornea is replaced with a cornea from a deceased donor. It is often reserved for cases in which other treatment options have been tried but are no longer effective in managing the condition. Corneal transplantation may be an option if keratoconus or corneal ectasia following refractive surgery continue to progress after an individual undergoes a corneal cross-linking procedure. It may also be an option for people who are not good candidates for corneal cross-linking, such as those with a thin cornea, previous herpes infection of the eye, severe scarring or opacification (cloudiness) of the cornea, severe dry eye, or an autoimmune disorder. Around 10% to 15% of people with keratoconus require a corneal transplant.

Corneal cross-linking, sometimes referred to as corneal collagen cross-linking, is a minimally invasive surgical procedure that stiffens and strengthens the cornea. It is used to treat conditions such as keratoconus and corneal ectasia following refractive surgery in which the cornea thins, weakens, and bulges outward, causing a wide range of vision problems.

Corneal cross-linking strengthens the cornea and makes it more rigid by creating bonds—or cross-links—between collagen fibers in the cornea. (Collagen is the principal component of the cornea. It plays an important role in providing strength and maintaining the shape of the cornea.)

By strengthening and stiffening the cornea, corneal cross-linking can slow or stop the progression of keratoconus and corneal ectasia after refractive surgery.

The FDA has approved a corneal cross-linking treatment called iLink® (see below for details on the procedure) for the treatment of two conditions:

• Progressive keratoconus
• Corneal ectasia following refractive surgery.

While other cross-linking procedures may be offered by some health care providers, iLink® is the only FDA-approved treatment.

The iLink treatment involves two types of riboflavin (vitamin B2) eyedrops (called Photrexa® Viscous and Photrexa®) and the Glaukos KXL® system, which supplies ultraviolet (UV) light.

Before the procedure begins, patients are given anesthetic eyedrops to numb the eye. Patients remain awake during the procedure, but the numbing eyedrops minimize discomfort and pain. They may also be given medication to help them relax during the procedure.

Using a blunt metal spatula or a soft brush, the doctor then removes the topmost layer (about 50 microns) of the epithelium, the outermost layer of the cornea. (Because this procedure involves the removal of the topmost layer of the epithelium, it is known as an “epithelium-off” or “epi-off” procedure. There are other corneal cross-linking protocols known as “epithelium-on” or “epi-on” that do not involve the removal of the epithelium. These other protocols are not FDA-approved.)

Next, the doctor adds drops of Photrexa Viscous to the eye. The riboflavin solution soaks the eye for about 30 minutes. (Removing the topmost layer of the epithelium helps the riboflavin solution penetrate the corneal tissue.) For people with a cornea that is under 400 microns thick, the doctor will add drops of Photrexa. This solution causes the cornea to swell, thereby increasing its thickness.

The eye is then exposed to ultraviolet (UV) light for 30 minutes using the Glaukos KXL System. Photrexa viscous drops are added to the eye every two minutes during the UV exposure period. The procedure takes about an hour to complete.

The application of riboflavin solution followed by exposure of the eye to UV radiation leads to the formation of bonds—or cross-links—between collagen molecules in the cornea.

Corneal cross-linking is an outpatient procedure, meaning people can go home the same day. After undergoing a corneal cross-linking procedure, patients may need to wear a bandage contact lens, a special type of contact lens that is worn temporarily to protect the cornea while it heals. They may also be advised to wear an eye patch or shield to protect the eye. Patients will need to use antibiotic and anti-inflammatory eyedrops as directed by their doctor to prevent infection and reduce inflammation.

Following the procedure, the treated eye may feel gritty, have a burning sensation, or be more sensitive to light than usual. Patients should avoid rubbing their eyes after the procedure. Over-the-counter pain medications may help manage any discomfort and sunglasses may help reduce light sensitivity. The discomfort will resolve on its own in the days following the procedure.

Vision is often blurry after the procedure but typically resolves on its own within a week or two.

Patients should see their ophthalmologist for regular check-ups to monitor their recovery.

Complications of corneal cross-linking may include the following:

• Corneal opacity (sometimes called corneal haze, in which the cornea becomes cloudy or hazy; it is usually temporary)
• Corneal epithelial defects (when the epithelium fails to heal properly after the procedure)
• Corneal inflammation
• Corneal striae (fine lines on the cornea)
• Eye pain
• Reduced visual acuity
• Blurred vision
• Dry eye
• Light sensitivity (photophobia)

Most of the above complications are usually temporary and often resolve within a year or less after the procedure.

Corneal cross-linking has been used to treat keratoconus and other types of corneal ectasia for many years. The procedure can be used to treat children, adolescents, and adults. While it is not a cure for keratoconus or corneal ectasia, it can slow or halt the progression of these conditions.

Though outcomes vary based on a number of factors, the majority of studies have found a success rate of over 90% in stabilizing the progression of keratoconus. The procedure can also halt the progression of corneal ectasia following refractive surgery. Slowing or stopping the progression of keratoconus and other corneal ectasias can reduce future changes in vision and may also reduce the need for more invasive treatments, such as corneal transplants. Other studies have found that corneal cross-linking may improve visual acuity in people with keratoconus and other types of corneal ectasia, though most people who undergo the procedure still need to wear glasses or contact lenses to improve their vision.

For people with keratoconus or corneal ectasia after refractive surgery, early diagnosis and treatment with corneal cross-linking are important to stopping the progression of the condition before it affects vision.

This article was medically reviewed by Yvonne Wang, MD, a Yale Medicine ophthalmologist who specializes in cataract and corneal surgery.