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Corneal collagen cross-linking (CXL) is a photochemical procedure being evaluated as a method to stabilize the cornea in patients with progressive keratectasia such as keratoconus and pellucid marginal degeneration. CXL may also have anti-edematous and antimicrobial properties.
Corneal CXL is performed with the photosensitizer riboflavin (vitamin B2) and ultraviolet A (UV-A) irradiation. A common CXL protocol removes about 8 mm of the central corneal epithelium under topical anesthesia to allow better diffusion of the photosensitizer riboflavin into the stroma. Following de-epithelialization, a solution with riboflavin is applied to the cornea (every 1-3 minutes for 30 minutes) until the stroma is completely penetrated. The cornea is then irradiated for 30 minutes with 370 nm UV-A, a maximal wavelength for absorption by riboflavin, while the riboflavin continues to be applied. The interaction of riboflavin and UV-A causes the formation of reactive oxygen species, leading to additional covalent bonds (cross-linking) between collagen molecules, resulting in stiffening of the cornea. Theoretically, by using a homogeneous light source and absorption by riboflavin, the structures beyond a 400 micron thick stroma (endothelium, anterior chamber, iris, lens, and retina) are not exposed to a UV dose that is above the cytotoxic threshold.
CXL is being evaluated primarily for corneal stabilization in patients with progressive corneal thinning, such as keratoconus. CXL may also have anti-edematous and antimicrobial properties.
Keratoconus is a bilateral dystrophy that is characterized by progressive ectasia (paracentral steepening and stromal thinning) that impairs visual acuity. While frequently diagnosed at a young age, the progression of keratoconus is variable. Initial treatment often consists of hard contact lenses. A variety of keratorefractive 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. Implantation of intrastromal corneal ring segments (see Implantation of Intrastromal Corneal Ring Segments medical policy) is an additive technique in which the implants are intended to reinforce the cornea, prevent further deterioration, and potentially obviate the need for penetrating keratoplasty. Penetrating keratoplasty (i.e., 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. In contrast, corneal CXL has the potential to slow the progression of disease.
Pellucid marginal degeneration is a noninflammatory progressive degenerative disease, typically characterized by bilateral peripheral thinning (ectasia) of the inferior cornea. Deterioration of functional vision results from the irregular astigmatism induced by asymmetric distortion of the cornea, and visual acuity typically cannot be restored by using spherocylindrical lenses. Rigid gas permeable contact lenses may be used to treat pellucid marginal degeneration. Intrastromal ring segment implantation, crescentic lamellar keratoplasty, penetrating keratoplasty, and corneal wedge excision have also been proposed as treatments.
No UV-A devices for treatment of keratoconus are currently approved by the U.S Food and Drug Administration. A search of clinicaltrials.gov shows ongoing Phase III safety and efficacy trials of UV-A Illumination Systems by Topcon Medical (VEGA) and Avedro Inc. (KXL or UV-X). The U.S. Food and Drug Administration (FDA) has granted Avedro a priority review of their new drug application (NDA) for the riboflavin ophthalmic solution/KXL II™ system as an orphan drug (<200,000 individuals affected in the U.S.). If approved, Avedro would have 7 years of market exclusivity in the U.S. In October 2015, Avedro resubmitted its NDA to FDA. The KXL II™ System is currently approved for use in Europe.
Related policies are –
Corneal collagen cross-linking is considered investigational for all indications.
The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.
Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.
POLICY HISTORY07/19/2012: Approved by Medical Policy Advisory Committee.
05/08/2013: Policy reviewed; no changes.
07/03/2014: Policy reviewed; description updated regarding devices. Added Corneal Topography/Computer-Assisted Photokeratoscopy as a related policy. Policy statement unchanged.
07/13/2015: Code Reference section updated for ICD-10.
10/30/2015: Policy description updated. Policy statement unchanged. Investigative definition updated in policy guidelines section.
05/27/2016: Policy number added.
07/11/2016: Policy description updated regarding devices. Policy statement unchanged. Code Reference section updated to add CPT code 0402T.
SOURCE(S)Blue Cross Blue Shield Association policy # 9.03.28
CODE REFERENCEThis may not be a comprehensive list of procedure codes applicable to this policy.