BCBS Rhode Island amniotic membrane Coverage

inv-01: Nonhealing diabetic lower-extremity ulcers — Covered when ALL of the following are met

Covered when ALL of the following are met

Primary criteria: Treatment of nonhealing diabetic lower-extremity ulcers using human amniotic membrane products may be considered medically necessary when filed with a covered diagnosis.non-healing defined in trials as <20% healing with 2 weeks of standard care

Randomized controlled trials of select HAM/placental products (eg, AmnioBand, Biovance, EpiCord, EpiFix, Grafix) demonstrated improved wound closure versus standard care; evidence sufficient to determine an improvement in net health outcome.

inv-02: Ophthalmic conditions — Ophthalmic indications with mixed evidence

Ophthalmic indications with mixed evidence

Covered ophthalmic indications: Human amniotic membrane (with or without suture) may be considered medically necessary for listed ophthalmic indications when filed with a covered diagnosis (includes neurotrophic keratitis; corneal ulcers and melts; corneal perforation; partial limbal stem cell deficiency with extensive diseased tissue; bullous keratopathy; moderate or severe Stevens-Johnson syndrome; severe ocular surface disease/dry eye; persistent epithelial defects; moderate or severe acute ocular chemical burn; pterygium repair).

Evidence varies by indication: some indications (eg, corneal ulcers/melts; Stevens-Johnson syndrome; severe ocular surface disease) have sufficient evidence, while others (neurotrophic keratitis, bullous keratopathy, some chemical-burn trials) have insufficient or mixed evidence.

inv-03: Lower-extremity ulcers due to venous insufficiency — 1 top-level node

Not established: Use of human amniotic membrane for lower-extremity ulcers due to venous insufficiency is not established; published randomized trials are limited and methodologically inconsistent, and the evidence is insufficient to determine an improvement in net health outcome.

Two multicenter RCTs of EpiFix reported mixed results; interpretation limited by methodological concerns; additional well-designed RCTs needed.

inv-04: Orthopedic injections and micronized/particulate products — 1 top-level node

Not covered / insufficient evidence: Injection of micronized or particulated human amniotic membrane and injection of human amniotic fluid for osteoarthritis, plantar fasciitis, and other orthopedic indications are considered not covered / not medically necessary due to insufficient evidence to determine improvement in net health outcome.

Available evidence includes feasibility and preliminary studies; larger randomized trials are needed.

inv-05: Corneal ulcers and melts — 1 top-level node

Sufficient evidence: Human amniotic membrane for corneal ulcers and melts that do not respond to initial medical therapy has evidence (systematic review and comparative case series) showing high healing rates and improved vision; evidence is sufficient to determine improvement in net health outcome.

Corneal ulcers/melts are uncommon; randomized trials are unlikely; nonrandomized data support use.

inv-06: Stevens-Johnson syndrome — Covered when evidence supports clinically meaningful benefit

Covered when evidence supports clinically meaningful benefit:

Stevens-Johnson syndrome (moderate or severe): Use of human amniotic membrane for moderate or severe Stevens-Johnson syndrome is supported by randomized trial evidence showing improved symptoms and function compared with medical therapy alone; evidence sufficient to determine improvement in net health outcome.RCT (n=25, 50 eyes)

Large RCTs are unlikely due to disease rarity.

inv-07: Severe ocular surface disease / dry eye with ocular surface damage — Covered when evidence supports clinically meaningful benefit

Covered when evidence supports clinically meaningful benefit:

Severe ocular surface disease with inflammation not responding to conservative therapy: Self-retained human amniotic membrane placement (2–11 days) for severe ocular surface disease/dry eye reduced symptoms and restored corneal surface and nerve density for up to 3 months; evidence sufficient to determine improvement in net health outcome.RCT (n=20) plus retrospective series (84 patients, 97 eyes)

Duration of benefit reported up to 3 months.

inv-08: Corneal perforation (temporary coverage) — Covered as a temporizing measure when standard treatment not immediately available

Covered as a temporizing measure when standard treatment not immediately available:

Corneal perforation when corneal tissue not immediately available: Sutured human amniotic membrane may provide temporary coverage of corneal perforation when corneal tissue is not immediately available; evidence supports its use as a temporizing measure.

Standard definitive treatment is corneal transplantation; no randomized trials identified for this temporizing use.

inv-09: Acute ocular chemical burns — Not clearly covered due to insufficient evidence

Not clearly covered due to insufficient evidence:

Moderate or severe acute ocular chemical burns: Three randomized trials (total 197 patients) of human amniotic membrane transplantation as adjunct to medical therapy did not demonstrate consistent significant benefit on key outcomes; evidence is insufficient to determine improvement in net health outcome.197 patients across RCTs

Adjunctive HAM plus medical therapy showed no consistent advantage for some outcomes.

inv-10: Insufficient evidence indications — Not covered / insufficient evidence for routine use

Not covered / insufficient evidence for routine use:

Other ocular indications with insufficient evidence: The following ophthalmic indications have insufficient or limited evidence to determine an improvement in net health outcome: corneal perforation with active inflammation after transplant; bullous keratopathy as palliative therapy in patients not candidates for curative treatment; partial limbal stem cell deficiency with extensive diseased tissue; persistent epithelial defects and ulceration not responding to conservative therapy; pterygium repair when sufficient healthy tissue exists for autograft.No comparative trials or RCTs, or RCTs with negative/no advantage

Evidence described as limited or insufficient; conjunctival/limbal autograft preferred over HAM for pterygium recurrence reduction.

inv-11: Mohs surgery reconstruction (dHACM) — Conditional/limited evidence in wound reconstruction

Conditional/limited evidence in wound reconstruction:

Repair following Mohs micrographic surgery using dHACM: A retrospective comparative study (propensity-score matched, 143 patients) found fewer infections and better scar outcomes with dHACM versus autologous repair after Mohs surgery; evidence is limited by retrospective design and is insufficient to definitively determine improved net health outcome.143 propensity-score matched patients

Well-designed prospective studies are needed.

All other human amniotic membrane products and indications not specifically listed as covered in this policy are not covered / not medically necessary. Examples include, but are not limited to, treatment of lower-extremity ulcers due to venous insufficiency and repair following Mohs micrographic surgery. This reflects the policy determination that the available evidence is insufficient to demonstrate an improvement in net health outcome for those indications.

For pterygium repair, systematic reviews of randomized trials have found that a conjunctival or limbal autograft is more effective than human amniotic membrane (HAM) in reducing recurrence. When autograft tissue is feasible, an autograft is the preferred technique and HAM is not favored as the primary repair method.

This policy is provided for informational purposes and does not guarantee payment. Benefits and eligibility are determined by the member's subscriber agreement, member certificate, and/or employer agreement, which supersede the provisions of this policy. Providers should verify member-specific coverage and billing rules with the payer prior to providing services.

Injection of micronized or particulated human amniotic membrane formulations and injection of human amniotic fluid for intra-articular or soft-tissue indications (including, but not limited to, osteoarthritis and plantar fasciitis) are not covered / considered not medically necessary because the evidence is insufficient to demonstrate an improvement in net health outcome.

There are several ocular indications for which the evidence is insufficient to determine that HAM improves net health outcomes. Examples include: bullous keratopathy (an RCT showed no advantage of sutured HAM over stromal puncture), persistent epithelial defects or ulceration (no comparative trials identified), and certain studies of moderate to severe acute ocular chemical burns (three RCTs, total n=197, showed no consistent significant benefit on key outcomes). Additionally, for pterygium repair when autograft is feasible, HAM is inferior to autograft for reducing recurrence. For these indications, the evidence is limited or mixed and is considered insufficient to support routine coverage.

Provider Requirements and Billing Actions

Note

Benefits may vary by contract

Benefits may vary by contract. Providers must refer to the member's contract (Benefit Booklet, Evidence of Coverage, or Subscriber Agreement) to determine applicable surgery benefits, covered services, and non-covered benefits before delivering services.

Verify member-specific benefits and eligibility with the provider call center prior to treatment or scheduling.
If services are determined to be not medically necessary or are non-covered benefits, the provider may not bill the member unless the member has been informed and has agreed in writing in advance to assume financial responsibility; refer to the provider participation agreement for details.

Billing Rule

Coding and filing requirements

Claims must be filed with the HCPCS codes identified in the attached list and must be paired with the corresponding ICD-10 diagnosis codes from the attached list. Use the appropriate HCPCS/ICD-10 pairings when submitting claims; failure to pair codes as required may result in claim denial.

Use the HCPCS codes from the attached list only when billed with the matching ICD-10 diagnosis codes from the attached list.
Ensure documentation supports the billed codes and the medical necessity for the service.

Documentation Required

Billing documentation

Use the HCPCS codes identified in the attached list only when accompanied by the matching ICD-10 diagnosis codes from the attached list. Include supporting clinical documentation with the claim to substantiate the diagnosis and the medical necessity of the service.

Billing documentation must include clinical notes, operative reports (if applicable), and any imaging or pathology results that support the diagnosis and treatment.
Injection of micronized or particulated human amniotic membrane and injection of human amniotic fluid are considered not covered / not medically necessary for many indications; do not bill covered HCPCS for these non-covered services.
For ophthalmic pterygium repair, document why conjunctival or limbal autograft is not feasible when HAM is used (insufficient healthy tissue), as evidence indicates autograft is preferred to reduce recurrence.

Prior Authorization

Verify coverage prior to treatment

Providers should verify coverage and authorization requirements prior to providing treatment. This policy is informational and not a guarantee of payment; verify member-specific coverage with the provider call center and obtain any required authorizations or approvals before delivering services.

Prior authorization: Not applicable to this policy unless specified by the member's contract—confirm with the member's plan.
Benefits and eligibility are determined by the member's subscriber agreement or employer agreement; these documents supersede this medical policy.

Denial Risk

Member billing and denial risk

Services determined to be not medically necessary or services that are medically necessary but considered non-covered benefits under the member's contract may result in denial and potential billing liability to the provider. Providers should obtain member benefit confirmation and written member consent if proceeding with non-covered services.

If a claim is denied as not medically necessary or non-covered, the provider may be financially responsible unless written member acceptance was obtained in advance.
Contact the provider call center for member-specific benefit details and to discuss potential appeals or medical necessity review processes.

Documentation Required

Preferred primary technique before HAM

For ophthalmic pterygium repair, evidence shows conjunctival or limbal autograft is more effective than HAM in reducing recurrence. Providers should use conjunctival or limbal autograft as the preferred primary technique when feasible and document clinical justification when HAM is selected because insufficient healthy tissue exists for autograft.

Document intraoperative findings that demonstrate insufficient healthy conjunctival tissue to create an autograft when billing for HAM in pterygium repair.
Include rationale and supporting clinical notes with the claim to substantiate the choice of HAM over autograft.

Definitions

Human amniotic membrane (HAM) — definition and forms

DefinitionTwo conjoined placental layers (amnion and chorion) harvested after birth, cleaned, sterilized, and preserved (cryopreserved or dehydrated) for use as an allograft

CompositionContains collagen, fibronectin, hyaluronic acid, growth factors, cytokines, and anti-inflammatory proteins (eg, interleukin-1 receptor antagonist)

FormsPrepared as patches (grafts) or as suspensions/particulates/flowable formulations for topical application or injection

Biologic propertiesReported anti-inflammatory, antifibroblastic, antimicrobial properties and considered nonimmunogenic

Clinical uses (context)Used as grafts/patches for corneal surface disorders and investigated for chronic diabetic lower‑extremity ulcers, venous ulcers, orthopedic and ophthalmic indications

Amniotic fluid — definition and context as injectable biologic

DefinitionFluid surrounding the fetus containing proteins, carbohydrates, peptides, amino acids, enzymes, hormones, pigments, and fetal cells

Composition relevanceContains components similar to synovial fluid (eg, hyaluronan, lubricants, cholesterol, cytokines) under evaluation for joint therapies

Clinical contextHuman (and bovine) amniotic fluid and amniotic fluid–derived cells have been investigated since the early 20th century as injectable biologics for osteoarthritis and plantar fasciitis

Mode of useEvaluated for intra-articular injection or as biologic cell–derived therapies in orthopedic indications

Self-retained cryopreserved amniotic membrane — definition and retention details

DefinitionA cryopreserved form of HAM designed for placement on the ocular surface without sutures (self-retained), often using a conforming device or ring

Retention durationReported short-term retention on the ocular surface for approximately 2 to 11 days

Clinical effects observedPlacement for 2–11 days reduced symptoms and restored a smooth corneal surface and corneal nerve density for up to about 3 months

Evidence baseSupported by an RCT (n=20) and a retrospective series (84 patients, 97 eyes) demonstrating symptomatic and structural improvements

Amniotic membrane transplantation — surgical or sutureless placement definition

DefinitionSurgical or sutureless placement of amniotic membrane on the ocular surface as an adjunctive therapy for severe ocular surface disease, corneal ulcers, chemical injuries, and related indications

Delivery methodsMay be sutured to the ocular surface (graft) or placed sutureless (self-retained devices) depending on indication and product

PurposeUsed to provide temporary coverage, promote epithelial healing, reduce inflammation, and support corneal surface reconstruction

Evidence noteUsed in RCTs and nonrandomized studies for acute severe chemical injury and corneal ulcers; evidence strength varies by indication

OpenPayer

Human Amniotic Membrane and Amniotic Fluid Therapies — Coverage Criteria

Coverage and Medical Necessity Criteria

Codes and Billing Information

Provider Requirements and Billing Actions

Background and Clinical Context

Definitions