BCBS Rhode Island amniotic membrane Coverage

Coverage Criteria

Medically necessary ophthalmic HAM indications

Covered when filed with a covered diagnosis (Medicare Advantage Plans and Commercial Products):

HAM grafts with or without suture (ophthalmic): Human amniotic membrane with or without suture may be considered medically necessary 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; or moderate or severe acute ocular chemical burn.

Apply when filed with a covered diagnosis; Medicare Advantage and Commercial Products.

HAM grafts with suture or glue (ophthalmic): Human amniotic membrane with suture or glue may be considered medically necessary for: corneal perforation; or pterygium repair.

Apply when filed with a covered diagnosis; Medicare Advantage and Commercial Products.

Diabetic lower‑extremity ulcers — ALL criteria required

Covered when ALL of the following are met:

Nonhealing diabetic lower‑extremity ulcers: Treatment of nonhealing diabetic lower‑extremity ulcers with specified HAM products (patch or flowable formulations such as Affinity, AmnioBand Membrane; Biovance, EpiCord, EpiFix, Grafix) may be considered medically necessary based on randomized controlled trials showing improved wound closure versus standard care or outcomes at least as good as established advanced wound care products.

Supported by RCTs and multicenter registries as described in the evidence review.

Not medically necessary / Insufficient evidence indications

Not covered / not medically necessary when ANY of the following apply:

Injection formulations (micronized/particulates) and amniotic fluid injections: Injection of micronized or particulated human amniotic membrane and injection of human amniotic fluid is not covered/not medically necessary for all indications (including but not limited to osteoarthritis and plantar fasciitis) due to insufficient evidence.

Applies to Medicare Advantage and Commercial Products.

Other HAM products and indications not listed as covered: All other human amniotic membrane products and indications not explicitly listed as medically necessary are considered not covered or not medically necessary (examples cited include lower‑extremity ulcers due to venous insufficiency and repair following Mohs micrographic surgery).

Evidence insufficient to determine improvement in net health outcome.

Lower‑extremity venous insufficiency ulcers: Evidence for HAM in lower‑extremity ulcers due to venous insufficiency is insufficient; available RCTs are mixed and methodological concerns limit interpretation.

Additional well‑designed RCTs needed.

Corneal ulcers and melts — coverage node

Corneal ulcers and melts: Use of human amniotic membrane for corneal ulcers and melts that do not respond to initial medical therapy is considered to improve net health outcome based on systematic review and comparative data demonstrating high rates of improvement and epithelialization.

Evidence sufficient per systematic review and comparative studies.

Bullous keratopathy (palliative) — coverage node

Use of HAM for bullous keratopathy as palliative treatment

Bullous keratopathy (palliative): For patients with bullous keratopathy who are not candidates for curative treatment (eg, endothelial or penetrating keratoplasty), an RCT found no advantage of sutured HAM over stromal puncture; evidence is insufficient to determine improvement in pain or net health outcome for palliative use.

Insufficient evidence to conclude benefit.

Partial limbal stem cell deficiency — coverage node

Use of HAM when selective removal is not sufficient

Partial limbal stem cell deficiency: For partial limbal stem cell deficiency with extensive diseased tissue where selective removal alone is not sufficient, evidence is limited; no comparative trials were identified and reported visual improvement in some cases does not establish net health benefit.

Evidence insufficient to determine improvement in net health outcome.

Stevens-Johnson syndrome — coverage node

Moderate or severe Stevens-Johnson syndrome

Stevens-Johnson syndrome: Randomized trial evidence (25 patients, 50 eyes) showed improved symptoms and function with HAM compared with medical therapy alone; the evidence is sufficient to determine an improvement in net health outcome for moderate or severe Stevens-Johnson syndrome.

Small RCT supports benefit.

Persistent epithelial defects and ulceration — coverage node

Persistent epithelial defects and ulceration not responding to conservative therapy

Persistent epithelial defects/ulceration: For persistent epithelial defects and ulceration that do not respond to conservative therapy, no comparative trials were identified; evidence is limited and insufficient to determine that HAM improves net health outcome.

Insufficient evidence.

Severe dry eye — coverage node

Severe dry eye with ocular surface damage/inflammation unresponsive to conservative therapy

Severe dry eye: For severe dry eye with ocular surface damage and inflammation not responsive to conservative therapy, randomized trial and large case series evidence (RCT and retrospective series) showed symptom reduction and corneal surface restoration for up to 3 months with self‑retained HAM; evidence is sufficient to determine improvement in net health outcome.

Supports coverage in appropriate patients.

Acute ocular chemical burns — coverage node

Moderate or severe acute ocular chemical burns

Acute ocular chemical burns: For moderate or severe acute ocular chemical burns, three RCTs (total 197 patients) evaluated HAM plus medical therapy versus medical therapy alone; two of three trials did not show faster epithelial healing and no significant benefit for other outcomes, and overall evidence is insufficient to determine improvement in net health outcome.

Mixed RCT results; evidence insufficient.

Corneal perforation — coverage node

Corneal perforation when corneal tissue not immediately available

Corneal perforation (temporary coverage): When corneal perforation occurs and corneal transplant tissue is not immediately available, sutured human amniotic membrane may provide temporary coverage; evidence is sufficient to determine improvement in net health outcome as a temporary measure, although corneal transplantation remains the standard treatment.

Temporary/palliative use supported when tissue unavailable.

Pterygium repair — coverage node when autograft not feasible

Pterygium repair when insufficient healthy tissue to create conjunctival autograft

Pterygium repair: For pterygium repair when there is insufficient healthy tissue to create a conjunctival autograft, randomized trials and systematic reviews indicate conjunctival or limbal autograft is more effective than HAM; HAM may be used when autograft is not feasible but is less effective.

Autograft preferred when feasible; HAM considered when autograft not possible.

Mohs reconstruction — same-day reconstruction on specified locations

Same-day reconstruction after Mohs surgery on head/face/neck/dorsal hand

Mohs reconstruction with dHACM: For same-day reconstruction after Mohs micrographic surgery on the head, face, neck, or dorsal hand, a retrospective propensity‑matched study (N=143) comparing dehydrated human amniotic/chorionic membrane (dHACM, EpiFix) to autologous repair reported fewer complications and better cosmetic outcomes with dHACM, but limitations of the retrospective design mean evidence is insufficient to determine net health outcome improvement.

Suggestive results from retrospective study; prospective studies lacking.

Injection of micronized or particulated human amniotic membrane and injection of human amniotic fluid are not covered / not medically necessary for all indications. This exclusion applies to Medicare Advantage Plans and Commercial Products and includes, but is not limited to, orthopedic indications such as knee osteoarthritis and plantar fasciitis. The policy states these injection-based formulations are considered not covered or not medically necessary because the evidence is insufficient to demonstrate an improvement in net health outcome.

For pterygium repair, the evidence from randomized trials and systematic reviews favors conjunctival or limbal autograft over human amniotic membrane (HAM). When sufficient healthy conjunctival or limbal tissue exists to create an autograft, the autograft is the preferred technique; HAM should be reserved for cases where autograft is not feasible due to insufficient donor tissue.

Human amniotic membrane products and amniotic fluid injections for indications not explicitly listed as medically necessary in this policy are considered not medically necessary due to insufficient evidence. Examples include treatment of lower‑extremity ulcers due to venous insufficiency, injection-based treatments for knee osteoarthritis, and injections for plantar fasciitis. The cited trials for venous ulcers and the limited pilot or interim studies for osteoarthritis and plantar fasciitis do not provide sufficient, consistent evidence to support coverage.

Operationally, HAM use for ophthalmic indications is managed by indication-specific coverage determinations. Covered ophthalmic uses are limited to the indications enumerated in the policy (for example, corneal ulcers/melts, corneal perforation, neurotrophic keratitis, Stevens‑Johnson syndrome, severe dry eye, and others) and claims should be filed with a corresponding covered diagnosis. Some ophthalmic applications are considered palliative or temporary (eg, sutured HAM for corneal perforation when donor corneal tissue is not immediately available), while others require prior failure of conservative therapy (eg, persistent epithelial defects or severe dry eye unresponsive to standard measures). For conditions where selective removal or a simpler procedure is standard (for example, partial limbal stem cell deficiency where selective removal may suffice, or bullous keratopathy where stromal puncture may be adequate), HAM is considered only when those approaches are not adequate; evidence for many of these uses is limited and may not meet medical necessity without supporting documentation. Additionally, coding and claims pairing rules in the policy require that HCPCS codes be filed with appropriate ICD‑10 diagnoses to be considered medically necessary.

Coding

Medically necessary HCPCS when paired with specified ICD-10HCPCSCovered

HCPCS codes (see attached list)

HCPCS codes identified in the attached list are considered medically necessary when filed with the specified ICD-10 diagnosis codes in the attached list.

Provider Actions and Requirements

Prior Authorization

Prior authorization is not required for these products under this policy.

Billing Rule

Coding / Claims Pairing Requirement

The HCPCS codes identified in the attached code list are considered medically necessary only when filed with one of the ICD-10 diagnosis codes included in the attached list. Claims submitted with HCPCS codes without an accompanying covered ICD-10 diagnosis listed as allowable in the provider attachment may be denied as not medically necessary.

HCPCS-to-ICD-10 pairing required — file both procedure code and an allowed diagnosis code from the attached list.

Background and Rationale

Human amniotic membrane (HAM) is derived from placental tissues and consists of the amnion and chorion layers. HAM products are processed and supplied in multiple formats, including cryopreserved and dehydrated allografts, and are available as patches or grafts that may be sutured or self‑retained, as well as in particulate, suspension, or flowable formulations. HAM contains structural proteins (eg, collagen, fibronectin), hyaluronic acid, cytokines, and anti‑inflammatory proteins, and is generally described as nonimmunogenic. Amniotic fluid, the fluid surrounding the fetus, contains proteins, peptides, enzymes and other factors and has been investigated as an injectable therapy for orthopedic indications; however, evidence for such uses is currently insufficient.

Definitions

Human amniotic membrane (HAM) — definition

DefinitionHuman amniotic membrane (HAM) consists of two conjoined layers, the amnion and chorion, harvested after birth, cleaned, sterilized, and prepared as cryopreserved or dehydrated allografts.

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

PropertiesConsidered nonimmunogenic with anti‑inflammatory, antifibroblastic, antimicrobial properties and regenerative potential retained after processing.

FormulationsAvailable as patches for wound cover, suspensions or particulates for topical or injectable use, and connective tissue extracts/flowable preparations.

Clinical uses (context)Studied 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 therapies — coverage criteria (ophthalmic and other indications)

Coverage Criteria

Coding

Provider Actions and Requirements

Background and Rationale

Definitions