Medical necessity required; RPE65 testing required prior to Luxturna

Genetic testing for ophthalmologic conditions is covered only when medical necessity criteria are met; for retinal dystrophy, documentation that RPE65 testing was performed is required prior to treatment with voretigene neparvovec (Luxturna).

• Coverage applies when: (1) clinical signs of an inherited retinal degeneration warrant single-gene or multi-gene panel testing; (2) clinical findings suggest another ophthalmologic disorder with a known causative gene where identification of a variant will affect management; (3) RPE65 testing is required prior to Luxturna and must be documented.

Applicable CPT service codes (inclusion ≠ guarantee of payment)

Use the listed CPT codes when submitting claims for genetic testing services; inclusion in the policy’s billing/coding list does not guarantee reimbursement and prior authorization or medical necessity review may be required.

• Applicable service codes: 81401, 81404, 81405, 81406, 81408, 81415, 81416, 81417, 81425, 81426, 81434, 81479

Step therapy: Not applicable

No step therapy requirements are described in this policy for genetic testing of ophthalmologic conditions.

Testing strategy: prefer specific tests; reserve WES/WGS for research/tertiary settings

Order the most specific genetic test(s) appropriate to the patient’s clinical findings and avoid unnecessary parallel or broad testing strategies; reserve massively parallel approaches (WES/WGS) for research or tertiary care settings.

• Avoid unnecessary parallel testing—choose targeted single-gene or multi-gene panels when clinical findings indicate a specific diagnosis.
• Restrict whole-exome sequencing (WES) and whole-genome sequencing (WGS) to research studies at tertiary care facilities, not routine clinical use.

Clinical indication and RPE65 documentation required

Document clinical signs consistent with an inherited retinal degeneration or other ophthalmologic disorder with a known causative gene, and for retinal dystrophy document that RPE65 testing was performed when applicable; documentation must demonstrate that identification of a variant will affect clinical management.

• Clinical findings that support IRD (see policy Note 1) or other gene-associated ophthalmologic disorder.
• Explicit documentation that RPE65 testing was performed for patients being considered for Luxturna.

Medical records and supporting documentation requirements

When BCBSNC requests medical records for a medical necessity determination, include all specific information needed; letters of support or explanation alone are not sufficient unless they contain the required clinical details.

• Provide full medical records documenting clinical findings, test results, and rationale showing how genetic test results will affect management.
• Letters of support may be useful but are not sufficient unless they include all specific information needed to determine medical necessity.

Denial risk: WES/WGS investigational (not covered)

Requests for whole exome sequencing (WES) or whole genome sequencing (WGS) for ophthalmologic conditions will be denied as investigational; these broad sequencing strategies are not covered for routine clinical applications.

• WES/WGS considered investigational for all clinical applications in ophthalmologic conditions.
• Reserve WES/WGS for research studies at tertiary care facilities per guidance.

Denial risk: AMD genetic testing investigational

Genetic testing for age-related macular degeneration (AMD) is considered investigational and will be denied for clinical applications; routine genotyping for complex disorders like AMD should be confined to research studies.

• AMD genetic testing is excluded (investigational) for all clinical applications.
• Avoid routine genetic testing for genetically complex disorders until genotype-specific management is proven beneficial.

Documentation may be requested — omission may trigger denial

BCBSNC may request medical records to determine medical necessity; failure to provide the specific information requested may result in denial of coverage.

• When records are requested, include clinical findings, test reports, and documentation showing how results will affect management.