Corneal Crosslinking for Keratoconus
and LASIK Complications
Corneal collagen crosslinking (CXL) was developed in 1998 by Theo Seiler, MD, and has been shown in numerous clinical trials to strengthen the eye's clear surface (cornea) through the application of riboflavin, a form of vitamin-B2, followed by treatment with ultraviolet A (UV-A) light.
The two basic types of corneal crosslinking are:
- Epithelium off, which means the thin layer covering the eye's surface is removed, allowing for faster penetration with liquid riboflavin.
- Transepithelial corneal crosslinking (epithelium on) is where the corneal epithelial surface is left intact, which requires a longer riboflavin loading time.
Crosslinking with riboflavin and UV-A light has proven to be a first-line treatment for people with eye conditions such as keratoconus, pellucid marginal degeneration and corneal weakness (ectasia) after LASIK.
While crosslinking is used in virtually every country around the world, it is still in the FDA approval process in the United States. Both Avedro and Topcon are working to get their brands of riboflavin drops and UV light sources approved by the FDA. As well, many other single-center and multicenter clinical trials are evaluating CXL in the U.S.
The aim of corneal crosslinking is to strengthen the cornea by increasing the number of "anchors" that bond collagen fibers together. (Diagram: Boxer Wachler Vision Institute)
Corneal crosslinking can also be used in combination with other technologies, with the goal of improving the visual results more rapidly. Tiny plastic inserts known as Intacs, which are surgically implanted within the cornea, have been shown to work well with crosslinking. Surface laser vision correction guided by corneal topography has also proven to be a useful technology.
Another technology, currently under development, uses microwave energy to flatten the cornea, and this may one day prove to be effective when combined with crosslinking.
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Who Are the Best Candidates for Corneal Crosslinking?
Multiple systems for corneal crosslinking have received approval in Europe. Since these systems are widely available there, the goal is to identify patients with corneal ectactic disorders such as keratoconus or pellucid marginal degeneration early in the disease process and treat them before they develop significant vision loss from ectasia.
Once they have received crosslinking, in most cases their corneal shape will either remain stable or actually improve. This can provide patients with improved visual acuity and improved ability to wear contact lenses.
Other potential applications of corneal crosslinking include the treatment of corneal ulcers that are non-responsive to topical antibiotics. Studies have found that the combination of riboflavin plus the UV light can be effective for eradicating a variety of corneal infections.
Some surgeons have also reported reasonable results in improving the stability of the cornea in people who have undergone radial keratotomy, an incisional refractive procedure from the 1980s and 1990s. Crosslinking appears to work best for those who are experiencing daily fluctuations in their vision.
People who are considering vision correction procedures such as LASIK also might eventually be pre-treated with corneal crosslinking to strengthen the eye's surface before undergoing an excimer laser ablation that reshapes the cornea.
What To Expect During and After a Corneal Crosslinking Procedure
During preliminary examinations, your eye doctor will measure the thickness of your cornea and make sure you are a good candidate for the procedure. You also will need to have a routine eye exam to assess your visual acuity and general eye health. And your doctor will perform mapping of your cornea (called corneal topography) to determine the level of your eye condition.
Layers of the cornea. Corneal crosslinking strengthens bonds in the stroma of the cornea, which is the layer from which tissue is removed during LASIK surgery.
The crosslinking procedure takes 60 to 90 minutes in most cases. If you are receiving epithelial-off crosslinking, your surgeon will place you in a reclining position and remove the epithelial layer from your cornea. Riboflavin eye drops will then be placed.
If you are receiving epithelial-on crosslinking, you are placed in a reclining position, and riboflavin drops are started. After enough time has passed (depending on the technique), the surgeon will evaluate your eye to ensure that the cornea has sufficient riboflavin present.
The corneal thickness will be checked, and then the UV light will be applied for up to 30 minutes.
In some cases, a bandage contact lens will be placed. Topical antibiotic and anti-inflammatory drops will be prescribed.
With both epithelial-off and epithelial-on CXL, studies have found that 99 percent of patients will remain stable or achieve improvement in the corneal shape, which is highly significant for people with progressive keratoconus that otherwise might lead to blindness.
Epithelium-Off Vs. Transepithelial Corneal Crosslinking
One of the big questions that some clinicians are researching is whether transepithelial CXL can provide similar results to crosslinking procedures where the epithelium has been removed.
In Europe, a special riboflavin formulation has been developed that helps facilitate transepithelial CXL, called Ricolin TE. In the United States, investigators are evaluating the effectiveness of transepithelial CXL, and to date these researchers have reported visual results that are similar to those of epithelial-off CXL.*
The advantages of transepithelial CXL are reduced risks of infection, corneal haze and delays in epithelial healing. While outcomes with epithelial-off CXL tend to be significantly better in younger candidates than in people older than 35**, this difference does not appear to be an issue with transepithelial CXL.*** Transepithelial CXL also allows for quicker visual recovery and less discomfort.
Current Status of Clinical Trials for Corneal Crosslinking
Current clinical trials in the United States include:
- Epithelial-off CXL for progressive keratoconus, sponsored by Avedro.
- Epithelial-off CXL for keratoconus and ectasia, sponsored by Topcon Medical Systems.
- Multicenter epithelial-on CXL study conducted by the CXL-USA Study Group.
If you are interested in participating in a U.S. clinical trial, visit our access page for the clinical trials database operated by the National Institutes of Health, and type in a search for corneal crosslinking.
Information displayed there will show you where research sites are located and if investigators are still actively recruiting candidates.
You should be prepared to pay from $2,500 to $4,000 per eye for the crosslinking procedure. It is not covered by insurance, because it is still considered investigational in the United States.
***Evaluation of epithelial-on corneal collagen crosslinking in patients ages 35 or older. E-Poster 101325, International Society of Refractive Surgery Annual Meeting, October 2011.
Collagen corneal cross linking. Presentation by Ramon Naranjo-Tackman, MD, at Cornea Day 2011 sponsored by the American Society of Cataract and Refractive Surgery. March 2011.
Corneal collagen crosslinking: promises and problems. British Journal of Ophthalmology. December 2010.
**Complication and failure rates after corneal crosslinking Journal of Cataract & Refractive Surgery. August 2009.
Marilyn Haddrill also contributed to this article.
[Page updated May 2015]