Blue Cross Blue Shield RI amniotic membrane Coverage

Coverage and Medical Necessity Criteria

inv-01: Ophthalmic Indications — Covered with Criteria

Human amniotic membrane with or without suture may be considered medically necessary for the following ophthalmic indications when filed with a covered diagnosis:

Ophthalmic Indications List: Coverage allowed for: neurotrophic keratitis; corneal ulcers and melts; corneal perforation; bullous keratopathy; partial limbal stem cell deficiency with extensive diseased tissue; moderate or severe Stevens-Johnson syndrome; persistent epithelial defects; severe dry eye; moderate or severe acute ocular chemical burn.

Filed with covered diagnosis required

inv-02: Ophthalmic Indications — Grafts with suture or glue

Human amniotic membrane with suture or glue may be considered medically necessary for:

Sutured/Glue Grafts: Corneal perforation; pterygium repair.

Filed with covered diagnosis required

inv-03: Diabetic Lower‑Extremity Ulcers — Covered

HAM patches or flowable formulations for nonhealing diabetic lower‑extremity full‑thickness ulcers:

Diabetic LE Ulcers: For nonhealing diabetic lower-extremity full-thickness ulcers, randomized controlled trials and registries for specific HAM products (eg, Affinity, AmnioBand Membrane, Biovance, EpiCord, EpiFix, Grafix) have shown improved wound closure versus standard care or outcomes at least comparable to established advanced wound products; considered to improve net health outcome for these indications.

Specific product evidence cited

inv-04: Lower‑Extremity Ulcers due to Venous Insufficiency — Not Covered / Insufficient Evidence

HAM for venous leg ulcers:

Venous Ulcers: Published RCTs (including trials of EpiFix) and other studies have methodological limitations and inconsistent results; additional well-designed RCTs are needed. Evidence is insufficient to conclude improved net health outcome; not covered/not medically necessary for venous insufficiency ulcers.

Methodologic concerns cited

inv-05: Injectable HAM / Amniotic Fluid for Orthopedic Indications — Not Covered / Insufficient Evidence

Injection of micronized/particulated HAM or amniotic fluid for osteoarthritis and plantar fasciitis:

Orthopedic Injections: Evidence consists of feasibility/pilot studies and interim reports; existing trials are limited in size and follow-up. The evidence is insufficient to determine improved net health outcome; injections of micronized/particulated HAM or amniotic fluid for osteoarthritis or plantar fasciitis are not covered/not medically necessary.

Studies described as preliminary or interim

inv-06: Other Ophthalmic Indications — Mixed / Insufficient Evidence

Various ophthalmic conditions where evidence is limited or mixed:

Neurotrophic Keratitis: RCT evidence (n=30) showed no benefit of sutured HAM compared to tarsorrhaphy or bandage contact lens; evidence insufficient to determine improved net health outcome.

RCT referenced

Corneal Ulcers and Melts: Systematic review of primarily case series and nonrandomized comparative data demonstrate high rates of improvement and some comparative evidence of faster epithelialization; overall high‑quality comparative evidence is limited but findings are supportive in certain contexts.

Systematic review and comparative study cited

Corneal Perforation With Active Inflammation After Transplant: No comparative evidence identified for corneal perforation with active inflammation after transplant; evidence insufficient to determine improved net health outcome.

No comparative trials

inv-07: Moderate or Severe Stevens-Johnson Syndrome

Covered when evidence supports benefit:

Stevens-Johnson syndrome: Moderate or severe Stevens-Johnson syndrome.

RCT (25 patients, 50 eyes) found improved symptoms and function with HAM compared to medical therapy alone; evidence sufficient to determine improvement in net health outcome.

inv-08: Corneal Perforation (when corneal tissue not immediately available)

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

Corneal perforation temporizing therapy: Corneal perforation when corneal tissue is not immediately available.

Sutured HAM may provide temporary coverage; evidence sufficient to determine improvement in net health outcome.

inv-09: Moderate or Severe Acute Ocular Chemical Burns

Not clearly covered — evidence insufficient:

Acute ocular chemical burns: Moderate or severe acute ocular chemical burn.

Three RCTs (total 197 patients) with mixed results; two of three did not show faster epithelial healing and no significant benefit for other outcomes; evidence insufficient.

inv-10: Bullous Keratopathy in Patients Not Candidates for Keratoplasty

Coverage uncertain/palliative use — evidence insufficient:

Bullous keratopathy palliative HAM: Bullous keratopathy in patients who are not candidates for endothelial or penetrating keratoplasty.

RCT found no advantage of sutured HAM over stromal puncture; evidence insufficient to determine improvement in net health outcome.

inv-11: Partial Limbal Stem Cell Deficiency with Extensive Diseased Tissue

Evidence limited; benefit not established:

Partial limbal stem cell deficiency with extensive diseased tissue where selective removal alone is not sufficient.

No comparative trials; some reports of improved visual acuity when HAM used with limbus removal; evidence insufficient.

inv-12: Persistent Epithelial Defects and Ulceration Not Responding to Conservative Therapy

Insufficient evidence for net health outcome improvement:

Persistent epithelial defects and ulceration that do not respond to conservative therapy.

No comparative trials identified; evidence insufficient.

inv-13: Severe Dry Eye with Ocular Surface Damage and Inflammation

Evidence supports benefit:

Severe dry eye with ocular surface damage and inflammation not responding to conservative therapy.

RCT (n=20) and large case series showed symptom improvement and restoration of corneal surface and nerve for up to 3 months; evidence sufficient to determine improvement in net health outcome.

inv-14: Pterygium Repair When Conjunctival Autograft Not Possible

HAM not superior for recurrence reduction:

Pterygium repair - insufficient autograft tissue: Pterygium repair when there is insufficient healthy tissue to create a conjunctival autograft.

Systematic reviews of RCTs found conjunctival or limbal autograft more effective than HAM in reducing recurrence; evidence insufficient to determine net health benefit for HAM.

inv-15: Repair Following Mohs Micrographic Surgery (facial/hand reconstruction)

Evidence limited and insufficient to establish benefit:

dHACM for Mohs reconstruction: Reconstruction after Mohs micrographic surgery for skin cancer on face/head/neck/dorsal hand using dehydrated human amnion/chorion membrane.

Nonrandomized comparative retrospective study reported less infection and better scar cosmesis with dHACM versus autologous reconstruction but is limited by design; evidence insufficient to determine improvement in net health outcome.

For ophthalmic indications, the policy distinguishes which uses of human amniotic membrane (HAM) are acceptable and which are not. Injection of micronized or particulated HAM and injection of human amniotic fluid are not covered for all indications (including but not limited to osteoarthritis and plantar fasciitis), and all other HAM products and indications not specifically listed as medically necessary are not covered / not medically necessary. This noncoverage language applies across product lines as specified (Medicare Advantage and Commercial Products).

Claims for ophthalmic applications of HAM must be filed with a covered diagnosis from the policy’s ophthalmic indications list to be considered for coverage; uses outside that list are subject to denial as not covered or not medically necessary.

The policy notes that when a conjunctival or limbal autograft is feasible for pterygium repair, HAM is not supported as superior for reducing recurrence. Therefore use of HAM as the primary method for pterygium repair when an autograft is possible is not considered to provide a net health benefit compared with standard autograft techniques.

For Commercial Products, HAM with or without suture for ophthalmic indications not listed as medically necessary in this policy are not medically necessary. Additionally, the policy explicitly states that injections of micronized/particulated HAM and injections of amniotic fluid are considered not medically necessary for all indications under commercial product language.

Several ophthalmic indications are described in the policy as having limited or insufficient evidence to determine an improved net health outcome. Examples include: bullous keratopathy (RCT showed no advantage of sutured HAM over stromal puncture), partial limbal stem cell deficiency (no comparative trials), persistent epithelial defects (no comparative trials), moderate or severe acute ocular chemical burns (three RCTs with mixed results), pterygium repair when autograft feasible (systematic reviews favor autograft for recurrence reduction), and reconstruction after Mohs surgery (limited nonrandomized comparative data).

For these indications the policy concludes that evidence is insufficient to establish that HAM improves net health outcomes, and therefore such uses may be considered not covered or not medically necessary without additional supporting documentation.

Billing and Coding Guidance

Medically necessary HCPCS when paired with listed ICD-10HCPCSCovered

HCPCS codes (see attached list)

HCPCS codes identified in the policy's attached list for amniotic/placental membrane products

Provider Requirements and Billing Actions

Prior Authorization

Prior Authorization Required

Prior Authorization: Not applicable

Prior authorization is not required for these products.

Documentation Required

Verify Member Benefits

Verify member benefits and coverage prior to submission. Benefits may vary between groups and contracts; confirm applicable surgical and not medically necessary/not covered benefits in the member's Benefit Booklet, Evidence of Coverage, or Subscriber Agreement.

Check member-specific benefits and any applicable medical necessity rules before billing.

Background and Scope

Human amniotic membrane (HAM) is the innermost layer of the amniotic sac (amnion and chorion) that is harvested after birth and processed for allograft use. HAM products are cleaned, sterilized, and preserved by cryopreservation or dehydration and may be supplied as patches, grafts, contact‑lens like inserts, or processed into flowable/injectable formulations. HAM contains structural proteins and bioactive factors (for example, collagen, fibronectin, hyaluronic acid, and cytokines) and is considered minimally immunogenic; it is thought to have anti‑inflammatory, antifibrotic, and antimicrobial properties and is used to promote surface healing or provide temporary tissue coverage in various clinical contexts.

Key Definitions

Human amniotic membrane (HAM)

DefinitionHuman amniotic membrane (HAM) consists of the amnion and chorion (innermost layers of the amniotic sac) harvested after birth, cleaned, sterilized, and preserved (cryopreserved or dehydrated) for use as an allograft.

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

FormulationsAvailable as patches/grafts, contact‑lens–like inserts, and suspensions/particulates for topical application or injection.

Biologic propertiesThought to have anti‑inflammatory, antifibrotic, and antimicrobial effects and is minimally immunogenic.

Clinical uses overviewStudied for chronic full‑thickness diabetic lower‑extremity ulcers, venous ulcers, knee osteoarthritis, plantar fasciitis, and multiple ophthalmic conditions.

OpenPayer

Human Amniotic Membrane and Amniotic Fluid Products — Coverage Criteria

Coverage and Medical Necessity Criteria

Billing and Coding Guidance

Provider Requirements and Billing Actions

Background and Scope

Key Definitions