Medical Policy: 07.01.72
Original Effective Date: September 2016
Reviewed: September 2018
Revised: September 2018
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This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.
Corneal cross-linking (CXL) is an in-office eye procedure that is said to strengthen or stabilize the cornea if it's been weakened by keratoconus, other corneal disease, or a complication of LASIK surgery. During the procedure, riboflavin is applied to the epithelized or de-epithelialized cornea followed by exposure to UV light. Using riboflavin as a photosensitizer and ultraviolet-A (UVA) to increase the formation of intra and interfibrillar covalent bonds by photosensitized oxidation thus, resulting in a measureable stiffening of corneal tissue. This treatment has also been used to treat infectious corneal ulcers and in combination with other treatments, such as intracorneal ring segment implantation.
Alternative and brand names for the procedure include corneal crosslinking, corneal collagen crosslinking, C3-R, CCL and KXL.
The only method that currently has FDA approval (as of the printing of this edition) utilizes an instrument manufactured by Avedro, Inc. (Waltham, MA) to deliver ultraviolet light and eye drops containing vitamin B2 (riboflavin). The treatment involves removing the central epithelium (the outermost layer of the cornea) to assure penetration of the eye drops. This is called the ‘epi-off’ or epithelium-off method and is the standard CXL method.
Eye surgeons are testing CXL protocols that do not require disturbing the epithelium (‘epi-on’). These treatments have yet not been shown to be as effective as the epi-off method and have yet to be FDA approved
In review: The two basic types of corneal cross-linking are:
The expected result is that the progression of keratoconus stops or is slowed. CXL does not reverse keratoconus changes that have already occurred. That is why this procedure is recommended for those who are recently diagnosed and whose keratoconus is progressing. The procedure is less impactful for those who are no longer experiencing vision changes due to keratoconus.
The initial treatment for keratoconus often consists of hard contact lenses. A variety of kerato-refractive procedures have also been attempted, broadly divided into subtractive and additive techniques. Subtractive techniques include photorefractive keratectomy or laser in situ keratomileusis (LASIK), although generally, results of these techniques have been poor. Penetrating keratoplasty (ie, corneal grafting) is the last line of treatment. About 20% of patients with keratoconus will require corneal transplantation. All of these treatments attempt to improve the refractive errors, but are not disease-modifying.
None of the currently available treatment options for keratoconus reverse the progression of disease and corneal transplantation is the only option available when functional vision can no longer be achieved.
According to the Global Consensus on Keratoconus and Ectatic Diseases: abnormal posterior ectasia, abnormal corneal thickness distribution and clinical noninflammatory corneal thinning must be present for a diagnosis of keratoconus. “Ectasia progression” is defined by a consistent change in at least two of the following parameters:
Criteria used to establish keratoconus progression in cross-linking clinical trials:
In 2013 NICE issued an Interventional Procedure Guideline (IPG 466).
The IPG stratifies their recommendations for corneal CXL as follows: “Most of the published evidence on photochemical corneal collagen cross-linkage (CXL) using riboflavin and ultraviolet A (UVA) for keratoconus and keratectasia relates to the technique known as 'epithelium-off' CXL'. 'Epithelium-on (transepithelial) CXL' is a more recent technique and less evidence is available on its safety and efficacy. Either procedure (epithelium-off or epithelium-on CXL) can be combined with other interventions, and the evidence base for these combination procedures (known as 'CXL-plus') is also limited. Therefore, different recommendations apply to the variants of this procedure, as follows:
In 2016, the FDA approved Avedro’s cross-linking system for progressive keratoconus. The approval was unique, as it is a combination drug and device approval. The approval includes Avedro's Photrexa Viscous and Photrexa, which are riboflavin solutions used with the KXL System during the procedure.
The Cornea Research Foundation of America contributed to the recent USA Food and Drug Administration (FDA) approval of cross-linking for halting or slowing the progression of keratoconus and corneal ectasia after prior refractive surgery. They enrolled patients in the first USA clinical trials, which began in 2008, and the results of those studies led to the FDA determination that cross-linking is a safe and effective treatment.
Corneal cross-linking involves administering riboflavin (vitamin B2) eye drops and UVA light in carefully selected parameters that strengthen the front layers of the cornea (clear covering of the eye) and avoid damage to the back part of the eye.
Corneal collagen cross-linking using riboflavin and ultraviolet light with the epithelial off procedure may be considered medically necessary as a one-time treatment of progressive keratoconus in those 14-65 years old.
Progressive keratoconus is defined as 1 or more of the following:
AND when the following criteria are met:
Corneal collagen cross-linking is considered investigational for any other indication including when combined with a second refractive procedure or in disease that does not have evidence of progression.
Corneal collagen cross-linking using the epithelial on procedure is considered investigational
Collagen cross-linking treatment is not a cure for keratoconus, rather, it aims to slow or even halt the progression of the condition. The main aim of this treatment is to arrest progression of keratoconus, and thereby prevent further deterioration in vision and the need for corneal transplantation. Patients over the age of 40, are unlikely to progress but should be monitored for documented progression.
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