Surgery

A look at the basics of Corneal cross-linking

An understanding of this procedure from the clinician’s point of view can help you know your role.

J. James Thimons, OD FAAO, Fairfield, Conn.

The “epi-off” method of collagen corneal cross-linking is illustrated here.

Though keratoconus treatment challenges clinicians, corneal cross-linking (CXL), a procedure not yet fully approved by the FDA, opens the door for patients to obtain comfortable and functional vision. With keratoconus, a progressive eye disease that thins the cornea, the normally round cornea begins to bulge into a cone-like shape. Previously, doctors were limited to palliative intervention during the early phases of the disease, advanced contact lens technologies in the mid-stages and surgical intervention in late-presenting cases.

Procedure

The underlying principles behind CXL involve the utilization of riboflavin (vitamin B2) in a special mixture, along with highly focused ultraviolet light at 370 nm. This combination in the corneal stroma creates a reactive oxide, which structurally enhances the collagen matrix and strengthens the eye to allow the cessation of progression of thinning and forward coning of the corneal surface.

Riboflavin is administered every two minutes until there is full corneal saturation and riboflavin “flare” in the anterior chamber is achieved upon physical assessment by the clinician at the slit lamp. In most patients, this is typically 30 to 40 minutes, but can take longer in some patients, especially, younger individuals due to the fact that the corneal matrix is more difficult for the riboflavin to penetrate. Several iterations of the riboflavin formula exist, but most clinicians are using a dextran-free version that has better penetration characteristics.

Methods

The procedure can be applied in multiple ways. The concept of epithelial removal (epi-off cross-linking), versus epi-on, has resulted in some controversy and has been addressed in clinical trials. It is also currently under review in the Avedro clinical trials. A separate trial, the CXLUSA clinical trial, is evaluating epi-on crosslinking with the largest collection of epi-on cases to date. Data support both interventions to be efficacious, with the difference in outcomes based primarily on the management of the epithelial wound healing in epi-off patients, and the relatively small, but real risk of complications related to infectious disease in that treatment modality.

Candidates

CXL is best applied to the keratoconic patient in the early phases of the disease state. Typically, the patient’s corneal thickness should be greater than 400 microns, and minimal (if any) scarring is preferable, though not preclusive.

Other factors enter into the decision-making process, including age and previous surgical interventions such as RK, PK, LASIK and PRK.

Post-operative care

The patient’s post-operative course is predicated on which of the two interventions, epi-off or epi-on, is selected.

Slit-lamp photo of riboflavin loading during epi-on CXL shows good saturation.

If epi-off is utilized, the patient is typically placed in a bandage contact lens, and topical antibiotics and anti-inflammatory agents are used, much like in post-PRK management. In my experience, the wound healing may last up to seven days — slightly slower than a PRK treatment. Additionally, patient discomfort can be notable.

In the epi-on treatment group, a bandage lens is placed at the time of the procedure. Topical antibiotics (for several days) and steroids (taper over several weeks) are used. The bandage contact lens can be removed the first day post-op, and the patient can return to normal activities in several days.

In most cases, because the vision of the patient is not optimal with correction prior to the procedure, acuity is minimally affected and not a noticeable part of the postoperative course.

Potential complications

Complications are predominantly directed towards the epi-off treatment protocol, and they involve delays in wound healing, microbial keratitis, and stromal haze development. Epi-on patients experience minimal, if any, complications, though some experience noticeable corneal haze.

Following an epi-on procedure, most patients can reinstitute soft lenses, combination and piggy-back fits within one week. For more complex interventions, 10 to 14 days of hybrid lens wear is usually recommended.

For the epi-off group, I recommend 14 days for hard lens wear, three to four weeks for complex lens wear and four to six weeks for hybrid lenses. This is due in part to the epithelial re-modeling after the procedure and the potential for a recurrent erosion-like presentation if the cornea is manipulated significantly early in postoperative course.

Effects

The potential for CXL in clinical practice is unrivaled in anterior segment therapy. For the first time, we have the ability to change the arc of the disease state as it impacts our patients, produce a cessation of progression, and improve their visual welfare. CXL stabilizes the disease state and typically provides little change in refractive error.

Concurrent technologies

Other techniques can be used simultaneously with the CXL procedure. These include PRK, Intacs and a resurrection of conductive keratoplasty. The impact of these additional elements is less predictable than traditional refractive outcomes.

It’s important to counsel patients as to the potential for long-term success and visual rehabilitation. The concern with the implantation of the Intacs is the potential for complications relative to microbial keratitis. While these are not common, they present significant challenges when they occur. For most patients, the microbial keratitis, because it is based in the channel in which the Intacs have been implanted, needs to be cultured and subsequently treated aggressively with topical antibiotic therapy. OP

J. James Thimons, OD, FAAO, practices in Fairfield, Conn. He is director of the Center for Keratoconus and Crosslinking. In addition, he is adjunct clinical professor at the Illinois College of Optometry and Pacific College of Optometry.