ModifiedCentenePolicy N/A

Concert Genetic Testing: Eye Disorders

Defines medical necessity and investigational determinations for genetic testing related to inherited eye disorders (macular degeneration, inherited retinal dystrophies, and other genetically associated eye conditions) for Centene-affiliated plans.

Policy Summary

PayerCentene

PolicyConcert Genetic Testing: Eye Disorders

Policy CodePolicy N/A

Change TypeCoding and criteria updatesremovals and renames

Effective DateN/A

Next Review DateN/A

Key ActionDo not include CPT 81406 when submitting prior authorization for the Fulgent Genetics macular degeneration test; ensure panels include RPE65 and document pathogenic RPE65 variants and phase when required.

SourceLink

POLICY UPDATE CHANGES

Macular Degeneration: Removed CPT code 81406 from Fulgent Genetics test in Policy Reference Table and within criteria; Updated access date for online reference.

Inherited Retinal Dystrophies Multigene Panel Analysis: Updated access date for online reference and added/clarified panel coding (includes 81434, 81404, 81406, 81408, 81479 depending on test).

Other Covered Eye Disorders: Removed 'Retinitis Pigmentosa' from the disorders list (covered under Inherited Retinal Dystrophies Multigene Panel Analysis).

Inherited Retinal Dystrophies Multigene Panel Analysis criteria set name changed (formerly 'RPE65 Sequencing and/or Deletion/Duplication Analysis') and clinical criteria updated to align with guidelines.

CPT code 81406 removed from Fulgent Genetics test in Policy Reference Table and within macular degeneration criteria.

Glaucoma criteria retired due to rarity of testing (low order and claim volume).

~500genes identified that contribute to inherited eye diseases

1/3proportion of human diseases that may affect the eyes

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81404,81406,81408,81434,81479CPT codes referenced

V1.2025policy version

removed 81406coding change

Coverage Criteria

Macular Degeneration - Investigational

Genetic testing for macular degeneration is excluded from medical necessity and is considered investigational.

Macular Degeneration Testing Stance: Genetic testing for macular degeneration (81404, 81408, 81479, 81599, 0205U) is considered investigational.

Inherited Retinal Dystrophies Multigene Panel - Medically Necessary (ALL conditions)

Medically necessary when ALL of the following criteria are met:

Inherited Retinal Dystrophies panel criteria: A. The member/enrollee has findings consistent with one of the following: 1) Rod-cone degeneration (e.g., retinitis pigmentosa), OR 2) Cone-rod degeneration (e.g., achromatopsia), OR 3) Chorioretinal degeneration, OR 4) Macular dystrophy; AND B. The test includes, at a minimum, the RPE65 gene.

Test codes referenced: 81404, 81406, 81408, 81434, 81479

Inherited Retinal Dystrophies - Investigational Uses

Investigational for indications not specified as medically necessary:

Investigational uses: Genetic testing for inherited retinal dystrophies via a multigene panel (81404, 81406, 81408, 81434, 81479) is considered investigational for all other indications not specified in the medically necessary criteria.

Other Covered Eye Disorders - Medically Necessary (ALL conditions)

Medically necessary when ALL of the following are met:

Other covered disorders criteria: Genetic testing to establish or confirm one of the listed eye disorders to guide management is medically necessary when the member demonstrates clinical features consistent with the disorder (examples include: Duane syndrome; familial exudative vitreoretinopathy; aniridia; X-linked congenital retinoschisis; presenile cataracts).

Clinical features references: GeneReviews, OMIM, National Library of Medicine, Genetics Home Reference, or other scholarly sources.

Updated Criteria Actions — policy changes and criteria set actions affecting coverage

Policy updates, retirements, and coding actions affecting coverage:

Inherited Retinal Dystrophies: Criteria set renamed to 'Inherited Retinal Dystrophies Multigene Panel Analysis' (formerly 'RPE65 Sequencing and/or Deletion/Duplication Analysis'); clinical criteria updated to align with guidelines.

Supports consolidation of retinitis pigmentosa under this criteria set.

Glaucoma Testing: Glaucoma criteria set retired due to rarity of testing (low order volume and low claim volume).

Retirement may affect coverage for tests previously covered under that criteria set.

Macular Degeneration Testing: CPT code 81406 removed from Fulgent Genetics test listing and criteria for macular degeneration.

Coding update; impacts billed codes and prior authorization submissions.

Genetic testing for macular degeneration is investigational. The policy lists common test codes associated with macular degeneration testing as 81404, 81408, 81479, 81599, and 0205U, and these uses are excluded from medical necessity determinations for this indication.

The condition Retinitis Pigmentosa has been removed from the "Other Covered Eye Disorders" list and is now addressed under the Inherited Retinal Dystrophies Multigene Panel Analysis criteria set. This consolidation aligns retinitis pigmentosa with the broader inherited retinal dystrophies criteria and clinical requirements.

Rationale: Genetic testing for macular degeneration is considered investigational due to limited clinical utility and insufficient evidence that testing improves health outcomes or guides management for typical age-related macular degeneration. As a result, testing intended to predict risk or guide treatment decisions for AMD is excluded from medical necessity.

Coding and Billing

Macular Degeneration - example/common CPT codesCPT

81479	Unlisted molecular pathology procedure (listed as common CPT for macular degeneration and other tests in table)
81599	Unlisted category III or IV (listed as common CPT for macular degeneration)
0205U	Proprietary molecular test (listed for Vita Risk)
81404	CPT for molecular multigene panel (listed for macular degeneration and IRD panels)

Inherited Retinal Dystrophies - multigene panel CPT codesCPTCovered

81434	Targeted genomic sequence analysis = Inherited retinal dystrophies multigene panel (listed)
81406	CPT code referenced in IRD panel group (appears in older/referenced listings; later removed for specific vendor)
81408	CPT code referenced for multigene panel

Example ICD-10 codes referencedICD-10

H35.30	Macular degeneration, unspecified
H35.3110	Nonexudative age-related macular degeneration, right eye

Other Covered Eye Disorders - CPT rangeCPT

81400-81408

Range of molecular pathology CPT codes referenced for Other Covered Eye Disorders

Removed/Updated CPT CodesCPTNot Covered

81406

CPT code previously listed for Fulgent Genetics test (removed)

Provider Actions and Requirements

Denial Risk

Retired/Removed criteria risk

Retired criteria (example: glaucoma) have been removed from the active clinical criteria. Submissions using retired or removed criteria may be denied. Providers should verify they are using the current criteria set and code list before submitting prior authorization requests or claims.

Check policy version and effective date before submission.
Do not submit tests under retired criteria sets (may cause claim denials).

Documentation Required

RPE65 documentation requirements

Documentation must confirm pathogenic or likely pathogenic variant(s) in RPE65 when genetic testing is used to establish a diagnosis. By definition, pathogenic/likely pathogenic variants must be present in both copies of RPE65 to establish biallelic RPE65-mediated inherited retinal dystrophy. Include the laboratory report showing variant classification (pathogenic/likely pathogenic) and gene-level interpretation.

Background

Background: Age-related macular degeneration (AMD) is a multifactorial condition and a leading cause of central vision loss in older adults. Because AMD results from a combination of genetic and environmental factors and genetic findings have limited clinical utility to alter routine management for typical AMD, the policy classifies genetic testing for macular degeneration as investigational and not medically necessary for most presentations.

Definitions

Age-related Macular Degeneration (AMD) definition

DefinitionAge-related Macular Degeneration (AMD) is the leading cause of blindness and irreversible vision loss among older adults (greater than age 65 years).

Typical onsetPrimarily affects adults older than 65 years, causing central vision loss.

Clinical utility noteGenetic testing for AMD is characterized in the policy as investigational due to limited evidence of improved health outcomes.

Retinal dystrophies (RDs) definition

DefinitionRetinal dystrophies (RDs) are degenerative diseases of the retina with marked clinical and genetic heterogeneity; vision impairment may vary from poor peripheral or night vision to complete blindness, and severity usually increases with age.

Clinical spectrum

Revision History

2024-11material_revisionLatest

Multiple material updates: Removed CPT code 81406 from the Fulgent Genetics test listing and within macular degeneration criteria; renamed and updated the Inherited Retinal Dystrophies criteria set to 'Inherited Retinal Dystrophies Multigene Panel Analysis' with clinical criteria alignment; removed 'Retinitis Pigmentosa' from Other Covered Eye Disorders and consolidated it under the inherited retinal dystrophies criteria; updated reference access dates and GeneReviews copyright dates.

2024-04approval

Approval noted with semi-annual review and updated title to reflect V1.2025; included coding and reference-table updates and minor rewording for clarity.

Policy Summary

PayerCentene

PolicyConcert Genetic Testing: Eye Disorders

Policy CodePolicy N/A

Change TypeCoding and criteria updatesremovals and renames

Effective DateN/A

Next Review DateN/A

SourceLink

On This Page

Include lab report with variant classification (pathogenic or likely pathogenic).

Document clinical correlation with vision loss consistent with inherited retinal dystrophy.

Documentation Required

Phase confirmation requirement

When two pathogenic or likely pathogenic RPE65 variants are detected, the phase (trans vs. cis) must be confirmed because standard next-generation sequencing or Sanger sequencing may not resolve configuration. Additional testing or family studies demonstrating variants in trans are required to establish biallelic disease.

If two RPE65 variants are reported, provide additional documentation confirming trans configuration (e.g., parental testing, long-read sequencing, or other phase-resolving methods).
If phase cannot be established, the diagnosis of biallelic RPE65-mediated disease is not confirmed for coverage determination.

Note

Supporting references

Cite relevant guideline and reference sources in submissions and include clinical findings that support medical necessity. Key references include AAO and GeneReviews guidance, FDA approval information for RPE65-related therapy, and society guidance on genetic testing for macular degeneration and inherited retinal degenerations.

American Academy of Ophthalmology Guidelines on Clinical Assessments of Patients with Inherited Retinal Degenerations (AAO)
GeneReviews (RPE65 and inherited eye disease summaries)
FDA approval letter for LUXTURNA and relevant society guidance (e.g., ASRS Genetics Task Force)
Document the clinical findings (e.g., rod-cone or cone-rod degeneration, macular dystrophy, chorioretinal degeneration) in the medical record and include with the request.

Ranges from night-vision or peripheral vision loss (e.g., retinitis pigmentosa) to severe, progressive vision loss and blindness.

Genetic heterogeneityMultiple genes contribute to RDs; phenotypes and inheritance patterns are variable.

RPE65 definition

Gene descriptionRPE65 encodes a retinal isomerase (retinal pigment epithelium-specific protein 65-kD) expressed in the retinal pigment epithelium responsible for regeneration of 11-cis-retinol in the visual cycle.

Clinical significancePathogenic biallelic variants in RPE65 cause RPE65-mediated inherited retinal dystrophy and are required for consideration of gene therapy (e.g., voretigene neparvovec/Luxturna).

Testing implicationPolicy requires documentation of pathogenic or likely pathogenic RPE65 variants and confirmation of phase (trans vs cis) when two variants are detected.

Gene therapy definition

DefinitionGene therapy is a treatment that changes the expression of genes to treat disease, for example by replacing or inactivating a nonfunctioning gene or introducing a new gene, typically delivered via a vector such as a virus.

ExampleVoretigene neparvovec (Luxturna) is an FDA-approved gene therapy for RPE65-mediated inherited retinal dystrophy (referenced in policy references).

MechanismAlters gene expression in target cells to restore or modify biological function relevant to disease management.

Genetic reference resources — GeneReviews and OMIM

GeneReviewsGeneReviews is a curated, peer-reviewed resource for clinically relevant information on genetic conditions referenced by the policy (GeneReviews [Internet], University of Washington).

OMIMOnline Mendelian Inheritance in Man (OMIM) is a comprehensive catalog of human genes and genetic phenotypes cited as a policy reference (https://omim.org/).

Use in policyBoth GeneReviews and OMIM are cited as evidentiary sources to support clinical alignment and testing decisions for inherited eye disorders.