Amniotic Membrane and Amniotic Fluid Injections for Ophthalmic Indications
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Defines coverage and medical necessity criteria for human amniotic membrane grafts and states investigational status for injections of amniotic fluid and particulated amniotic membrane for ophthalmic indications; applies to BCBS North Carolina providers and members.
No material clinical or coverage changes in this revision.
Coverage and Medical Necessity Criteria
Initial Therapy Coverage
Covered when the following indication-specific criteria are met
HAM graft indications
- Neurotrophic keratitis with ocular surface damage and inflammation that does not respond to conservative therapy (see Policy Guidelines).conservative therapy failed
See Policy Guidelines for examples of conservative therapy duration and modalities.
- Corneal ulcers and melts that do not respond to initial conservative therapy (see Policy Guidelines).conservative therapy failed
- Corneal perforation with active inflammation after corneal transplant: Corneal perforation when there is active inflammation after corneal transplant requiring adjunctive treatment.
Sutured or glued HAM may be used when indicated.
- Bullous keratopathy (palliative): Bullous keratopathy as a palliative measure in patients who are not candidates for curative treatment (eg, endothelial or penetrating keratoplasty).
- Partial limbal stem cell deficiency with extensive diseased tissue where selective removal alone is not sufficient.
- Moderate or severe Stevens-Johnson syndrome.
- Persistent epithelial defects that do not respond to conservative therapy (see Policy Guidelines).conservative therapy failed
- Severe dry eye (DEWS 3 or 4) with ocular surface damage and inflammation that remains symptomatic after Steps 1, 2, and 3 of the dry eye disease management algorithm (see Policy Guidelines).failed steps 1-3 of TFOS/DEWS management algorithm
Placement of self-retained HAM for 2–11 days has been associated with symptom reduction and surface restoration in trials and series.
- Moderate or severe acute ocular chemical burn.
- Use with suture or glue (specific situations): Human amniotic membrane grafts with suture or glue may be considered medically necessary for: corneal perforation when corneal tissue is not immediately available; and pterygium repair when there is insufficient healthy tissue to create a conjunctival autograft.
Not Medically Necessary / Investigational
For wound and burn indications, see related policy 'Skin and Soft Tissue Substitutes.'
When Covered (selected ophthalmic indications)
Covered when evidence and clinical input support HAM use for the following ophthalmic conditions:
Clinical input supported use and evidence judged sufficient to determine meaningful improvement in net health outcome.
Relevant outcomes include symptoms, morbid events, functional outcomes, and QOL.
Standard treatment remains corneal transplantation.
Evidence includes RCTs and systematic reviews; clinical input supports selective use.
When Not Covered / Investigational
Not covered or investigational uses explicitly stated in policy history and guidelines:
This position is reiterated in policy history and reference sections.
See policy history entries (2016–2018) for prior statements and coding updates.
This policy addresses the use of human amniotic membrane (HAM) grafts and injections of amniotic-derived products specifically for ophthalmic indications. This policy does not address use of amniotic products for wounds or burns; those indications are handled under a related policy (see "Skin and Soft Tissue Substitutes"). Providers should refer to the separate wound/burn policy for coverage criteria and coding when treating non‑ophthalmic wounds or burns. (See also the policy history noting prior cross‑references and coding changes.)
Injection of micronized or particulated human amniotic membrane is classified as investigational for all indications. The policy explicitly lists micronized/particulated HAM injections as investigational and excludes them from coverage for ophthalmic and non‑ophthalmic uses (for example, osteoarthritis and plantar fasciitis). Historical policy history entries reiterate this investigational stance and document its inclusion since policy inception.
The policy distinguishes between particulate/injectable HAM products and HAM grafts or self‑retained HAM devices: while certain HAM grafts or self‑retained HAM products may be considered medically necessary for specified ophthalmic indications, micronized/particulated HAM injections remain investigational and are not covered.
Injection of human amniotic fluid is considered investigational for all indications and is not covered. The policy explicitly states that injectable amniotic fluid products are investigational across indications, and this exclusion has been reiterated in the policy language and history.
Because amniotic fluid is being investigated for injectable therapeutic use but lacks sufficient evidence for safety and effectiveness in ophthalmic indications, claims for injections of human amniotic fluid should be treated as investigational and not reimbursed under this policy.
Billing, Codes, and Related Guidance
| Prokera® | Self-retained amniotic membrane graft (example product referenced) |
| AmbioDisk™ | Amniotic membrane graft (example product referenced) |
Provider Responsibilities, Prior Authorization, and Documentation
Prior authorization recommended for HAM grafts
Human amniotic membrane grafts (eg, Prokera®, AmbioDisk™) may be considered medically necessary for specified ophthalmic indications; providers should obtain prior authorization per BCBSNC requirements and verify benefit coverage before performing these procedures.
Attempt and document required conservative therapies and durations
The policy requires specific conservative therapy attempts and minimum durations for several indications before considering HAM grafts; document that conservative therapy failed per the policy thresholds.
- Neurotrophic keratitis: example conservative therapy includes 5 days of pressure patching, therapeutic contact lens, topical lubricants, and topical antibiotics
- Corneal ulcers/melts: initial conservative therapy may include 2 days of patching, therapeutic contact lens, and topical antimicrobials
- Persistent epithelial defect: failed to close after 5 days of conservative treatment or no decrease after 2 days
Include indication-specific clinical rationale with requests
When submitting requests or performing procedures, include indication-specific details and a concise clinical rationale tied to the policy’s covered indications to support medical necessity determinations.
- State the specific covered indication (eg, neurotrophic keratitis, severe DEWS 3–4, corneal perforation)
- Explain why conservative therapy was inadequate or why HAM is required (eg, corneal tissue unavailable, insufficient conjunctiva for autograft)
Verify member benefits before applying policy
Verify member benefits and refer to the Member's Benefit Booklet for availability of benefits prior to applying this policy; member benefit design may affect coverage.
Provide complete medical necessity documentation when records are requested
When medical records are requested for medical necessity review, include all specific clinical information needed (eg, prior conservative treatments, durations, response) — letters of support alone are not sufficient unless they contain all required details.
- Include documentation of prior conservative therapies and duration
- Include clinical findings supporting the covered indication and reason HAM is needed
- Letters of support may be helpful but must include all specific information required for determination
Avoid nonlisted indications — investigational status
Use of amniotic membrane grafts for ophthalmic indications not specifically listed as medically necessary in this policy will be considered investigational and may be denied.
Medical records may be requested and codes do not ensure payment
BCBSNC may request medical records to determine medical necessity; the presence of a listed code does not guarantee reimbursement.
Clinical Background and Rationale
Human amniotic membrane (HAM) is the innermost lining of the amniotic sac composed of the amnion and chorion that is harvested after birth and processed (eg, cryopreserved or dehydrated) for use as an allograft. HAM contains collagen, fibronectin, hyaluronic acid, growth factors, cytokines, and anti-inflammatory proteins (for example, interleukin‑1 receptor antagonist) and has been reported to have anti‑inflammatory, antifibroblastic, and antimicrobial properties. HAM is considered largely nonimmunogenic, and processed products retain regenerative potential; these biological properties underlie the clinical use of HAM as grafts or patches for ocular surface disorders.
Definitions
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