Modifiedblue cross blue shield - louisianaPolicy 00325

Corneal collagen cross-linking (CXL) for keratoconus

This policy governs coverage for corneal collagen cross-linking using riboflavin and UVA for progressive keratoconus for members of Blue Cross and Blue Shield of Louisiana and its HMO subsidiary.

Policy Summary

PayerBlue Cross and Blue Shield of Louisiana

PolicyCorneal collagen cross-linking (CXL) for keratoconus

Policy CodePolicy 00325

Change TypeCoverage criteria revisedEpioxa added

Effective Date05/01/2026

Next Review Date02/2027

Key ActionObtain prior authorization showing documented progression within 24 months, age ≥13, and corneal thickness ≥325 microns.

SourceLink

POLICY UPDATE CHANGES

The policy includes coverage consideration for epithelium-on CXL (Epioxa) after its 2025 FDA approval for patients aged 13 and older in conjunction with the O2n System and Boost Goggles.

Updated minimum corneal thickness criterion to ≥325 microns and patient age to ≥13 years for coverage eligibility.

Specifies that CXL is covered for progressive keratoconus when defined progression criteria occur within 24 months.

Revised the coverage statement for corneal cross-linking (CXL) as a treatment of progressive keratoconus by using riboflavin and ultraviolet A and removed the 'When Services Are Eligible for Coverage' section.

Removed requirement that CXL be performed only 'in patients who have failed conservative treatment (e.g., spectacle correction, rigid contact lens)'.

Coverage previously included corneal ectasia after refractive surgery; that phrase was removed and a clarification was added regarding exclusions for correction of refractive errors and complications of non-covered services.

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Coverage Criteria for Corneal Collagen Cross-Linking (CXL)

Coverage: Progressive keratoconus (eligible)

Covered when ALL of the following are met:

Patient selection for CXL: Diagnosis of keratoconus based on keratometry and corneal mapping

Documented progression (within 24 months): Any of the following changes occurred within 24 months: increase ≥1.00 D in steepest keratometry (Kmax or steepest K), OR increase ≥1.00 D in manifest cylinder, OR increase ≥0.50 D in manifest refraction spherical equivalent (MRSE)within 24 months

Age criterion: Age ≥13 years

Corneal thickness ≥325 microns

Prior procedures and healing: No history of previous corneal cross-linking in the eye to be treated or other corneal surgery; no corneal or systemic disease that would interfere with healing (e.g., chemical injury, active infection, delayed epithelial healing)

Allergy/implant status: No hypersensitivity to benzalkonium chloride or any product ingredients; not aphakic or pseudophakic without a UV-blocking intraocular lens

Guideline-based distinctions (epithelium-off vs epithelium-on/CXL plus)

Guideline-based distinctions and recommended contexts:

Epithelium-off (epi-off): Current evidence on safety and efficacy of epithelium-off corneal collagen cross-linking for keratoconus is adequate in quality and quantity; can be used with normal clinical governance, consent and audit.

From summarized guidance in policy.

Epithelium-on (transepithelial, epi-on) and 'CXL plus' (combination) procedures: Current evidence on safety and efficacy is inadequate in quantity and quality; these procedures should only be used with special arrangements for clinical governance, consent, audit or research.

Limited evidence; recommended context is research or special governance per guidance.

Progressive keratoconus

Covered when ALL of the following apply:

Coverage statement: Corneal collagen cross-linking using riboflavin and ultraviolet A is eligible for coverage as a treatment of progressive keratoconus.

Coverage statement revised and approved by Medical Policy committees as documented in policy history.

Investigational — Other indications

Not covered / investigational when ANY of the following apply:

Other indications: Corneal collagen cross-linking using riboflavin and ultraviolet A is considered investigational and not covered for all indications other than progressive keratoconus.

Treatments deemed investigational per policy definitions are not supported as medically necessary.

Corneal collagen cross-linking (CXL) using riboflavin and ultraviolet A is considered investigational for all indications other than progressive keratoconus. Requests for CXL to treat corneal ectasia that is determined to be a complication of refractive surgery will be denied as not a covered benefit when the refractive surgery itself was a non-covered service under the member contract.

The correction of refractive errors of the eye (including but not limited to radial keratotomy and laser refractive surgery) is excluded from coverage under medical benefits for the majority of member contracts; treatment of complications of non-covered services is also excluded. If corneal ectasia is determined to be a complication of refractive surgery, requests for CXL will be reviewed and may be denied per these exclusions.

Claims for CXL that are related to the correction of refractive error or to complications of refractive procedures should be carefully evaluated. When the etiology of ectasia is linked to a prior refractive surgery (a commonly excluded benefit), coverage is not provided and the request may be denied consistent with member contract exclusions.

Experience with epithelium-on (transepithelial) CXL has been limited historically and long-term visual acuity outcomes were previously lacking. The policy notes the limited evidence base for epi-on approaches; however, newer products (for example, the FDA‑cleared Epioxa kit) have recent trial data summarized in their prescribing information and are reflected in the policy updates.

Evidence remains inadequate to confirm equivalence of epithelium-on (transepithelial) CXL to standard epithelium-off CXL, and evidence is likewise insufficient to support routine use of combination or 'CXL plus' procedures. The policy follows guidance that these variants should be limited to research settings or used only where special arrangements for governance, consent and audit are in place.

Treatments and indications that meet the policy definition of investigational are not supported as medically necessary under this policy. Based on available evidence and defined policy criteria, CXL uses outside the covered indication of progressive keratoconus are classified as investigational and therefore not covered.

Coding and Clinical Thresholds

Epioxa kit NDCNDCCovered

NDC 25357-024-01

Epithelium-on Cross-linking Kit (Epioxa HD 0.239% + Epioxa 0.177% + System Treatment Activation Card)

CPT codesCPT

0402T	CPT code listed for services associated with this policy
66999	CPT - Unlisted procedure, anterior segment

HCPCS codesHCPCS

J2787	HCPCS code listed for services associated with this policy
J3490	HCPCS miscellaneous — added effective 03/01/2026

ICD-10 Diagnosis CodesICD-10

All Related Diagnoses

ICD-10 diagnosis codes associated with corneal conditions

inv-15: Progression measurement window — within 24 months

Progression measurement windowChanges defining progression must have occurred within 24 months

Documentation requirementDocument progression using keratometry and corneal mapping records spanning the 24-month window

Relation to eligibilityProgression within 24 months is required in addition to age and corneal thickness criteria for coverage

inv-16: Keratometry / refraction progression thresholds — Kmax/steep K ≥1.00 D; manifest cylinder ≥1.00 D; MRSE ≥0.50 D

Keratometry (Kmax/steep K)Increase ≥1.00 diopter (D) in the steepest keratometry measurement (Kmax or steepest K)

Provider Actions, Prior Authorization, and Documentation Requirements

Prior Authorization

Prior authorization required

Prior authorization is required for corneal collagen cross-linking (CXL). Submit documentation demonstrating the patient meets all patient selection criteria for progressive keratoconus (diagnosis by keratometry and corneal mapping; documented progression within 24 months; age ≥13 years; corneal thickness ≥325 microns; no prior CXL or other corneal surgery in the eye to be treated; no corneal/systemic conditions interfering with healing; no hypersensitivity to product ingredients; not aphakic/pseudophakic without a UV-blocking IOL).

Required: documentation of diagnosis by keratometry and corneal mapping
Required: objective evidence of progression within 24 months (see progression criteria)

Prior Authorization

Establish etiology of ectasia for prior authorization

When requesting prior authorization for ectasia, the provider must establish the etiology. If corneal ectasia is determined to be a complication of prior refractive surgery that was a non-covered service under the member contract, the request will be denied as not a covered benefit. Evaluate and document surgical history to determine whether ectasia is post-refractive.

Background and Evidence Context

Keratoconus is a progressive, noninflammatory corneal dystrophy characterized by corneal thinning and steepening that leads to irregular astigmatism and decreased vision. It typically presents in adolescence or young adulthood and can progress over months to years; approximately 20% of affected patients may ultimately require corneal transplantation for advanced disease. Corneal collagen cross-linking is intended to stiffen the cornea and slow or halt progression, with two main procedural approaches described: epithelium-off (standard) techniques and epithelium-on (transepithelial) variants.

Definitions

inv-32: Epithelium-off (epi-off) — definition and notes

DefinitionEpithelium-off (epi-off): central corneal epithelium (~8 mm) is removed to allow riboflavin penetration prior to UVA irradiation

Procedure notesAfter de-epithelialization, riboflavin is applied (every 1–3 minutes for ~30 minutes) and cornea irradiated with UVA 370 nm to induce cross-linking

Evidence contextHistorically the primary FDA‑approved method with an adequate evidence base for keratoconus

inv-33: Epithelium-on (epi-on) — definition and notes

DefinitionEpithelium-on (epi-on / transepithelial): the corneal epithelium is left intact (or partially disrupted) and riboflavin loading time is longer; may use different riboflavin formulations and supplemental oxygen or devices

Regulatory note

Revision History and Policy Changes

2026-02-11Committee approvalLatest

Medical Policy Implementation Committee approved revisions including removal of the 'When Services Are Eligible for Coverage' section and revision of the coverage statement for corneal cross-linking as a treatment of progressive keratoconus.

2026-02-05Committee review

Medical Policy Committee reviewed the policy prior to implementation committee approval.

2025-12-01

Policy Summary

PayerBlue Cross and Blue Shield of Louisiana

PolicyCorneal collagen cross-linking (CXL) for keratoconus

Policy CodePolicy 00325

Change TypeCoverage criteria revisedEpioxa added

Effective Date05/01/2026

Next Review Date02/2027

Key ActionObtain prior authorization showing documented progression within 24 months, age ≥13, and corneal thickness ≥325 microns.

SourceLink

On This Page

Denial Risk

Refractive surgery exclusion risk

The correction of refractive errors and many refractive surgery procedures are excluded from coverage on most member contracts. Treatment of complications from non-covered refractive surgery is also excluded. If corneal ectasia is judged to be a complication of non-covered refractive surgery, CXL requests will be denied as not a covered benefit.

Refractive surgery history must be documented
Denial risk when ectasia is complication of non-covered refractive surgery

Denial Risk

Exclusion risk for post-refractive surgery complications

Claims will be denied when the treated condition is a complication of a refractive surgery that is a non-covered service under the member's contract. Providers must document whether the ectasia is spontaneous keratoconus versus post-refractive ectasia; lack of documentation of spontaneous etiology when refractive surgery occurred may result in denial.

If ectasia is secondary to non-covered refractive surgery → not covered (deny)

Documentation Required

Required documentation to demonstrate progression

Documentation must include objective evidence of progression. Acceptable documentation: serial keratometry (Kmax or steepest K) and corneal topography/tomography demonstrating one or more of the progression criteria within 24 months. Include dates and numeric values to show change.

Progression documented within 24 months by ANY of: ≥1.00 D increase in steepest K (Kmax); ≥1.00 D increase in manifest cylinder; ≥0.50 D increase in MRSE
Include pre- and post-measurement dates and values; corneal mapping/topography images/reports recommended

Documentation Required

Governance and consent for epithelium-on or combination procedures

Epithelium-on (transepithelial) CXL and combination CXL procedures have limited evidence. Use of these variants should occur only with special arrangements for clinical governance, informed consent, and audit (or in the context of research). Document rationale, informed consent discussing limited evidence and alternative options, and any local governance approvals.

Epithelium-on CXL and CXL-plus procedures require special governance/consent
Document informed consent addressing limited evidence and risks

Note

Initial management expectation

Initial management of keratoconus is commonly conservative (eg, spectacles, rigid contact lenses). CXL is considered when objective progression criteria are met. Prior authorization should reflect that conservative measures were considered as clinically appropriate but CXL is indicated based on documented progression rather than a mandatory failure of conservative treatment.

No requirement to demonstrate failed conservative treatment for authorization (step-therapy removed)
CXL authorization based on documented progression per policy criteria

Step Therapy

Step considerations for epithelium-on or repeat CXL

Evidence for epithelium-on CXL and for repeat CXL is limited. If proposing epithelium-on or repeat procedures, document clinical rationale, prior treatment details, and anticipated benefit. Where evidence is limited, consider use of special arrangements or case-by-case review.

For repeat CXL: document prior CXL details, interval, and objective evidence of further progression
For epithelium-on: document why transepithelial approach is chosen and acknowledge limited long-term efficacy data

Step Therapy

Step therapy status — no failure requirement

There is no step-therapy requirement for CXL in this policy — the prior requirement to fail conservative treatment (eg, spectacles, rigid contact lenses) has been removed. Authorization decisions are based on the coverage criteria and documented progression rather than mandatory prior failure of conservative therapies.

Do not submit documentation requiring prior 'failure' of conservative treatment for coverage determination
Authorization should focus on meeting progression and eligibility criteria

inv-35: epithelium-on (transepithelial) corneal collagen cross-linking — definition and evidence note

DefinitionEpithelium-on (transepithelial) corneal collagen cross-linking: variant that leaves the epithelium intact (or partially disrupted) and uses modified riboflavin formulations/loading

Evidence noteEvidence for transepithelial (epi-on) CXL is limited; long-term efficacy compared with epi-off is unclear and use should be with special governance/audit or research arrangements per guidance

Regulatory updateEpioxa (epi-on product) received FDA approval in 2025; market availability anticipated Q1 2026