1Pramanik S, Musch DC, Sutphin JE, Farjo AA. Extended long-term outcomes of penetrating keratoplasty for keratoconus. Ophthalmology 2006;113(9):1633-8.

2Maharana PK, Agarwal K, Jhanji V, Vajpayee RB. Deep anterior lamellar keratoplasty for keratoconus: a review. Eye Contact Lens 2014;40(6):382-9.

What is Corneal Cross-Linking?

Cross-linking is a minimally invasive outpatient procedure for the treatment of progressive keratoconus. FDA approved epi-off cross-linking combines the use of prescription eye drops, Photrexa® Viscous (riboflavin 5’-phosphate in 20% dextran ophthalmic solution), Photrexa® (riboflavin 5’-phosphate ophthalmic solution), and ultra-violet A (UVA) light from the KXL® system to create new collagen cross-links and leads to the stiffening of the cornea. The goal of the procedure is to stiffen the cornea to slow or prevent further progression of the condition and preserve your vision.

What Is the Difference Between FDA-Approved & Non-FDA-Approved Cross-Linking?

FDA APPROVED

Epi-Off Cross-Linking

Epi-off cross-linking requires the removal of the epithelium, the outermost layer of the cornea, to assure penetration of the prescription eye drops. This protocol has been rigorously tested and is the only cross-linking procedure approved by the US Food and Drug Administration (FDA) when performed with Photrexa Viscous, Photrexa and the KXL System.

NOT FDA APPROVED

Epi-On Cross-Linking

Epi-on cross-linking is a procedure where the epithelium is left intact. In the U.S., there are currently no epi-on cross-linking procedures that are FDA approved.

Products That Are Not FDA Approved

The use of any drug(s) other than Photrexa® Viscous and Photrexa® or any device other than the KXL® System for corneal cross-linking is not FDA approved, except as part of an investigational new drug (IND) study.

Top Questions to Ask Your Eye Doctor Download PDF

Which Corneal Cross-Linking Procedures Are Currently FDA Approved in the US?

Epi-off cross-linking performed with Photrexa® Drug Formulations, Photrexa® Viscous, Photrexa® and KXL® System is the only cross-linking procedure approved by the FDA.

The FDA approval letters for these cross-linking products can be found here:

FDA-approved cross-linking is performed with drug products that have been rigorously tested and are specifically controlled and manufactured in an FDA-registered facility and in compliance with FDA guidelines.

Corneal Cross-Linking: A New Standard of Care for Progressive Keratoconus

Corneal collagen cross-linking is an innovative therapy that has transformed the treatment of progressive keratoconus. Historically, as many as 1 in 5 patients with progressive keratoconus have required a corneal transplant, with more than half needing multiple transplants within 20 years.1, 2

Photrexa® Viscous, Photrexa® and the KXL® System are the first and only therapeutic products for corneal crosslinking which have been FDA approved to treat progressive keratoconus, offering an effective treatment for patients who had no therapeutic options to limit the progression of this sight-threatening disease. The epi-off cross-linking procedure with Photrexa® Viscous, Photrexa® and the KXL® System is FDA-approved, clinically proven, safe and effective.

As with most procedures, adverse events such as corneal haze can occur, and your doctor should monitor you for risks of infection.

1Pramanik S, Musch DC, Sutphin JE, Farjo AA. Extended long-term outcomes of penetrating keratoplasty for keratoconus. Ophthalmology 2006;113(9):1633-8.

2Maharana PK, Agarwal K, Jhanji V, Vajpayee RB. Deep anterior lamellar keratoplasty for keratoconus: a review. Eye Contact Lens 2014;40(6):382-9.

Is Corneal Cross-Linking Covered by Insurance?

Insurance coverage for FDA approved cross-linking with Photrexa® Viscous, Photrexa® and the KXL® System is now widely available. Greater than 95% of the commercially insured population has access to this potentially sight-protecting treatment. For additional information on insurance coverage and to view the latest list of insurers that are known to have policies that cover cross-linking, visit the Insurance Information page.

View Insurance Information

Which Corneal Cross-Linking Procedures Will My Insurance Cover?

Generally, insurance does not typically cover products and procedures that have not received FDA approval. As an example, the Blue Cross and Blue Shield Association’s Technology Evaluation Center (Premera BCBS Technology Review) lists as part of their new technology evaluation criteria:

“1. The technology must have final approval from the appropriate governmental regulatory bodies.”

The only FDA-approved products for cross-linking are from Avedro and performed epi-off. Many insurance policies have detail about the fact that the epi-off procedure is the only FDA approved treatment for progressive keratoconus that is being covered, while epi-on is not. See the examples below from Aetna, Cigna, and other insurance coverage policies.

Aetna

“Aetna considers epithelium-off photochemical collagen cross-linkage using riboflavin and ultraviolet A medically necessary for keratoconus and keratectasia.

Aetna considers epithelium-on (transepithelial) collagen cross-linkage experimental and investigational for keratoconus, keratectasia, and all other indications.”

Cigna

“Conventional, epithelium-off, corneal collagen crosslinking (C-CXL) using an FDA approved drug/device system (e.g., Photrexa® Viscous or Photrexa® with the KXL® System) is considered medically necessary for the treatment of progressive keratoconus and corneal ectasia following refractive surgery.”

BCBS of MA

“Currently, the only CXL treatment approved by the Food and Drug Administration (FDA) is the epithelium-off method. There are no FDA-approved CXL treatments using the epithelium-on method.”

Moda Health

“Moda Health considers corneal collagen cross-linking (CXL) medically necessary if the requested procedure is for epithelium-off photochemical collagen cross-linkage using riboflavin (Avedro’s Photrexa) and ultraviolet A.”

SelectHealth

“SelectHealth covers epithelium-off corneal cross-linking once per lifetime if the following criteria are met: The medicine used is Photrexa Viscous/Photrexa with the KXL device.”

If I Receive Cross-Linking as Part of a Clinical Study, Will It Be Covered by My Insurance?

As previously stated, only FDA approved procedures are typically covered by insurance. However, generally clinical studies of investigational procedures are offered to the patient at no cost.

Below are some helpful resources on clinical trials in the U.S.:

National Keratoconus Foundation: About Clinical Trials

Even Clinical Trials Can Be Fake Now: Here’s How to Spot One

What Can I Expect During the Corneal Cross-Linking Procedure?

  • After numbing drops are applied, the epithelium (the thin layer on the surface of the cornea) is gently removed.
  • Photrexa® Viscous (riboflavin 5’-phosphate in 20% dextran ophthalmic solution) eye drops will be applied to the cornea for at least 30 min;
  • Depending on the thickness of your cornea, Photrexa® (riboflavin 5’-phosphate ophthalmic solution) drops may also be required.
  • The cornea is then exposed to UV light for 30 minutes while additional Photrexa Viscous drops are applied.

Cross-Linking Procedure FAQs

What is ultra-violet A (UVA) light?

UVA is one of the three types of invisible light rays given off by the sun (together with ultra-violet B and ultra-violet C) and is the weakest of the three.

Does corneal cross-linking require removal of the epithelium?

Yes, your doctor will apply topical anesthesia to numb the eye prior to the removal of the epithelium. This process helps to prepare your eye so that the drug can penetrate the tissue of the cornea to have an effective cross-linking procedure.

Will I need to be out of my contact lenses for this process?

Yes. Typically, patients are asked by their doctor to stop wearing hard contact lenses prior to surgery for a period of several weeks. Once treated, patients will not be allowed back into contact lenses for 1 month.

Am I awake during the procedure?

Yes, typically you will be awake during the treatment. You may be given a medication to help you relax and numbing anesthetic drops.

How long does the treatment take?

The actual procedure takes about an hour, but you will be at the office for approximately two hours to allow sufficient time for preparation and recovery before you return to the comfort of your own home.

Does it hurt?

There is some discomfort during immediate recovery but usually not during the treatment. Immediately following treatment, a bandage contact lens is placed on the surface of the eye to protect the newly treated area. After the numbing drops wear off, there is some discomfort, often described as a gritty, burning sensation managed with Tylenol and artificial tears. If pain is severe, oral narcotic medications may be used.

What Can I Expect After the Corneal Cross-Linking Procedure?

After the Procedure

  • You should not rub your eyes for the first five days after the procedure.
  • You may notice a sensitivity to light and have a foreign body sensation. You may also experience discomfort in the treated eye and sunglasses may help with light sensitivity.
  • If you experience severe pain in the eye or any sudden decrease in vision, you should contact your physician immediately.
  • If your bandage contact lens from the day of treatment falls out or becomes dislodged, you should not replace it and contact your physician immediately.
  • Ulcerative keratitis, a potentially serious eye infection, can occur. Your doctor should monitor defects in the outermost corneal layer of the eye for resolution. The most common ocular side effect is haze. For the full list of potential side effects, see Prescribing Info.

What results can I expect from corneal cross-linking?

  • Clinical trials demonstrated that cross-linking is effective at slowing or halting the progression of keratoconus.
    In the study, patients who did not undergo cross-linking continued to progress, while patients who did undergo cross-linking did not progress.
  • The goal of the procedure is to preserve vision. Cross-linking is not intended to eliminate or reduce dependence on refractive correction.
  • Ulcerative keratitis, a potentially serious eye infection, can occur. Your doctor should monitor defects in the outermost corneal layer of the eye for resolution. The most common ocular side effect is haze. For the full list of potential side effects, see Prescribing Info.

Can anyone tell by my appearance that I have had cross-linking?

No. There is no change in the appearance of your eyes following cross-linking.

Questions Regarding Insurance Coverage?

ARCH Can Help!

Epithelium-off cross-linking with Avedro’s Photrexa® Viscous (riboflavin 5’-phosphate sodium in 20% dextran ophthalmic solution) and Photrexa® (riboflavin 5’-phosphate sodium ophthalmic solution) in conjunction with the KXL System is the only cross-linking procedure that has been approved by the FDA.

Insurance coverage for FDA approved cross-linking is now widely available. Greater than 95% of the commercially insured population has access to this potentially sight-protecting treatment.

If you have questions about coverage, visit LivingWithKC.com/Insurance for the latest list of insurance companies covering cross-linking and links to their policies. In addition, ask your doctor to consult with your insurance company to determine coverage. Each patient’s insurance situation is unique. If your insurance hasn’t posted a coverage policy, it may not mean that they do not cover the procedure. You can also speak with your doctor about filing an appeal. Depending on your situation, an appeal may be done before or after treatment. You may also want to discuss financing options with your doctor.

Contact your insurance company directly and ask to speak to the benefits representative.

If you are having issues getting your insurance to cover cross-linking, the Avedro Reimbursement Customer Hub (ARCH) Program can help. Our program provides insurance support for the FDA-approved procedure using Avedro’s drug and device.

The full-service end-to-end program is designed for providers and their patients who are seeking access and reimbursement for cross-linking. An ARCH representative can discuss your options with you and help you find a solution.

ARCH works directly with the doctor’s office and insurance company to help facilitate the insurance reimbursement process. Prior to getting the procedure, confirm with your doctor that they are performing Avedro’s FDA approved cross-linking procedure. You can find a list of physicians who are familiar with the cross-linking procedure using our locator tool.

Phone 1-844-528-3311
Email info@avedroARCH.com
Hours 9am – 8pm ET, Monday – Friday

The information provided is for informational purposes only and represents no statement, promise, or guarantee by Avedro concerning levels of reimbursement, payment or charges. Codes are supplied for informational purposes only and represent no statement, promise, or guarantee by Avedro that these codes will be appropriate or that reimbursement will be made. Information provided is not intended to increase or maximize reimbursement by any payor.

Is Cross-Linking Right for Me?

Ask your doctor. Patients who have been diagnosed with progressive keratoconus should ask their doctor whether they may be an appropriate candidate for corneal cross-linking.

Ask Your Doctor If She/He Is Performing FDA Approved Cross-Linking

Photrexa Viscous (riboflavin 5′-phosphate in 20% dextran ophthalmic solution) & Photrexa (riboflavin 5′-phosphate ophthalmic solution) are:

  • The only FDA-approved riboflavin ophthalmic solution drugs
  • Supported with published, FDA reviewed, clinical data
  • Manufactured in a world-class FDA registered facility
  • Manufactured in compliance with FDA guidelines
  • Highest quality, controlled manufacturing process

Don’t be afraid to ask your doctor what device he/she uses for cross-linking and whether the procedure is FDA-approved or investigational.

MA-00687C