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Corneal Crosslinking CxL

Corneal Collagen Crosslinking with Riboflavin (CxL) for keratoconus, ectasia, or unstable RK.

Image of diagram showing how light is redirected into an eye with an irregular cornea.
Keratoconus and ectasia create an irregular cornea that can be treated with Intacs inserts and/or CxL.


Image of ultraviolet light being introduced to the corneas after being protected with Riboflavin.
UVA light is applied in precise amounts using a specialized goggle with LED lights.


Diagram of parallel lines connected with few vertical lines to illustrate anchors holding layers of the cornea.
The theory behind CxL treatment is that the fibrils of the keratoconus cornea lose their ability to link to each other.


Diagram of parallel lines connected with many vertical lines to illustrate increase in anchors holding layers of the cornea after CxL.
CxL treatment causes more cross-linking of the fibrils, making the cornea stronger.


Image of topographical map showing keratoconus.
The image shows a map of an eye with keratoconus. The off-center red and yellow area shows the forward bulging due to keratoconus.


Image of Intacs held on a fingertip.
Intacs are tiny plastic rings surgically added to the cornea.


Image of topographical map showing keratoconus resolved with CxL.
CxL and Intacs can resolve a significant amout of keratoconus and corneal instability.


A developing keratoconus and keratectasia treatment is Corneal Collagen Crosslinking with Riboflavin (CxL), that has been proven outside of the US to strengthen a weakened corneal structure. US Food and Drug Administration CxL studies in the United States were halted in June 2010 for reasons that do not relate to efficacy. Several doctors currently provide CxL as an off-label use of Riboflavin (vitamin B2). Several US study groups continue to measure the efficacy of CxL. For more information, visit CxL Clinical Studies.

Increase Tissue Anchors

This method works by increasing collagen crosslinking, which are the natural "anchors" within the cornea. These anchors are responsible for preventing the cornea from bulging out and becoming steep and irregular, consequence of advanced keratoconus.


Keratectasia occurs when the integrity of the cornea is compromised during surgery such as Lasik. Studies have shown that a health cornea will remain stable if at least 250 microns of corneal tissue remains untouched. Ectasia occurs when the cornea is health or too little cornea remains untouched. Ectasia presents as symptoms of progressive refractive error as the cornea bulges forward due to intraocular pressure within the eye. Ectasia is largely preventable in Lasik, Bladeless Lasik, PRK, LASEK, and Epi-Lasik surgery by diligent evaluation of the health of the eye and amount of tissue to be removed during refractive surgery, however ectasia may occur absent other know indicators.

CxL treats refractive surgery induced ectasia by strengthening the cornea and effectively making it stiffer to withstand the intraocular pressure associated with forward movement of the cornea.

Quick In-Office Procedure

The 30-minute corneal crosslinking treatment is performed in the doctor's office. During the treatment, custom-made Riboflavin eye drops are applied to the cornea, which is then activated by ultraviolet light. This amazingly simple process has been shown in laboratory and clinical studies to increase the amount of collagen cross-linking in the cornea and strengthen the cornea. In published European studies, such treatments were proven safe and effective in patients.


Keratoconus is a disease of the cornea that makes the cornea become weak and may gradually bulge outward. Most often, this bulging is in the lower half of the cornea and first presents as astigmatism, however not all astigmatism is due to keratoconus. In mild or early stages of keratoconus (forme fruste keratoconus), eyeglasses may correct the astigmatic vision.

The abnormal curvature of the cornea due to keratoconus changes the cornea's refractive error producing moderate to severe blurriness of vision. As keratoconus advances, rigid gas-permeable (RGP) contact lenses maybe the only non-surgical way to achieve clear vision. If keratoconus continues to advance, scarring of the central cornea may occur.

Approximately half of keratoconus patients have no negative lifestyle effects beyond corrective lenses. The cornea stabilizes after a few years without ever causing severe vision problems. For others, the only resolution to keratoconus has been PKP, with a long healing period and unpredictable refractive error. Even after corneal transplant PKP, keratoconus can reoccur in the new donor cornea. Fortunately, there are two new methods to treat keratoconus that are much less invasive than a corneal transplant.

CxL for Keratoconus

European and US clinical studies have shown that CxL reduces the progression of Keratoconus and in some cases reduced the forward vaulting by strengthening the corneal tissue.

Intacs for Keratoconus

An established treatment for keratoconus is Intacs. Intacs are a medical device approved by the FDA for the correction of 1.00 to 3.00 diopters of myopia (nearsighted, shortsighted) and virtually no astigmatism. Intacs inserts are the only refractive surgery procedure that adds structural integrity to the cornea. This unique attribute made Intacs an ideal treatment for keratoconus.

Intacs are clear small semicircular plastic rings of various thickness that are inserted within the cornea at its outer edges. Insertion of these rings flatten the central area of the cornea and correct myopic refractive error. A major advantage of Intacs is that no tissue is removed and there is no ablation or incision across the visual axis.

Intacs surgery is not truly reversible because of the incision, but the Intacs can be completely removed or exchanged for a different size. Intacs inserts cannot be felt by the patient and are no more visible than a contact lens. After insertion and healing, Intacs require no maintenance.

The placement of Intacs inserts remodels and reinforces the cornea, eliminating some or all of the irregularities caused by keratoconus. Follow-up visits will be required to monitor the healing process and to evaluate the visual benefits of the procedure. Even after a successful Intacs procedure for keratoconus, glasses or contacts may be required, however Intacs have been shown to improve vision and reduce or stop the progression of keratoconus, thereby saving the patient from needing PKP.

Intacs have been approved for the treatment of keratoconus by the FDA under a Humanitarian Device Exemption (HDE) Humanitarian Use Devices (HUDs) are medical devices specially designated by the FDA for use in the treatment of fewer than 4000 patients per year with rare medical conditions.

CxL and Intacs

Corneal crosslinking treatments can be combined with Intacs to flatten the keratoconus cone even more than with Intacs alone. In these cases, corneal crosslinking treatments stabilize keratoconus from getting worse as well as help the Intacs reverse the keratoconus steepening that had already occurred.

Looking For Best Lasik Surgeon?

If you are ready to choose a doctor to be evaluated for conventional or custom wavefront Lasik, Bladeless Lasik, PRK, or any refractive surgery procedure, we recommend you consider a doctor who has been evaluated and certified by the USAEyes nonprofit organization. Locate a USAEyes Evaluated & Certified Lasik Doctor.

Personalized Answers

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Recent Corneal Crosslinking CxL Medical Journal Articles...

Riboflavin-UV-A Crosslinking for Fixation of Biosynthetic Corneal Collagen Implants.

Cornea. 2015 Mar 12;

Authors: Wand K, Neuhann R, Ullmann A, Plank K, Baumann M, Ritter R, Griffith M, Lohmann CP, Kobuch K

PURPOSE: To evaluate riboflavin-UV-A crosslinking as an alternative suture-free fixation method for biosynthetic corneal collagen implants.
METHODS: A range of cell-free corneal implants consisting of recombinant human collagen type III were examined. In vitro, the implants were crosslinked with different riboflavin solutions and irradiations. Ex vivo, the biosynthetic corneal implants were placed on the anterior cornea of porcine and rabbit eyes after performing deep anterior lamellar keratoplasty with a trephine, femtosecond laser, or excimer laser. UV-A crosslinking was performed with isotonic or hypotonic riboflavin at either standard or rapid procedure. The corneas were excised, fixed in PFA 4%, and embedded in paraffin. Crosslinking effects on the implants and the adhesion between implant and corneal bed were evaluated by slit-lamp biomicroscopy, optical coherence tomography (OCT) images, and histologically.
RESULTS: After the crosslinking procedure, the implants showed different degrees of thinning. The accuracy of cutting the corneal bed was highest with the excimer laser. Good adhesion of the implant in the corneal bed could be demonstrated in OCT images. This was more accurate in porcine eyes than in rabbit eyes. Histologically, crosslinks between implant and corneal stroma were demonstrated. There was no difference between standard and rapid crosslinking procedures.
CONCLUSIONS: Riboflavin-UV-A crosslinking as a fixation method for biosynthetic corneal collagen implants was demonstrated to be promising. It can reduce suture-related complications such as haze formation and surface irregularity. Stability of the implants, especially shrinkage after riboflavin-UV-A crosslinking, needs to be further evaluated. Biostability, integration, and long-term outcome are further evaluated in in vivo animal experiments.

PMID: 25768385 [PubMed - as supplied by publisher]


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