CurrentBlue Cross Blue Shield - MassachusettsPolicy N/A

Human amniotic/chorionic membrane (HAM/dHACM/placental allografts) clinical indications

This part of the medical policy reviews evidence for multiple indications of human amniotic/chorionic membrane and amniotic fluid–derived products (ocular, wound, orthopedic, dermatologic) and reports which indications have sufficient evidence of net health benefit versus insufficient evidence.

Policy Summary

PayerBlue Cross Blue Shield - Massachusetts

PolicyHuman amniotic/chorionic membrane (HAM/dHACM/placental allografts) clinical indications

Policy CodePolicy N/A

Change TypeLiterature update; coding clarifications; product list updated

Effective DateJan 1, 1970

Next Review Date

Key ActionDocument the specific clinical indication and prior conservative therapy failure where applicable, and obtain payer authorization per coding/prior-authorization guidance.

POLICY UPDATE CHANGES

Annual policy review with literature updates through January 3, 2024 and February 21, 2025.

Coding information clarified on multiple dates including 10/2025, 9/2025, 7/2025, and earlier entries.

3Indications with sufficient evidence

8Indications with insufficient evidence

MultipleCoding clarification events

Overview: This policy part reviews use of human amniotic/chorionic membrane and related placental/amnion products (HAM/dHACM and amniotic fluid–derived products) across ocular, wound, orthopedic, and dermatologic indications. Coverage stance is mixed: some specific indications are considered medically necessary while many others are investigational/insufficient per the evidence summaries. The subject of the policy is Human amniotic/chorionic membrane (HAM/dHACM/placental allografts) for multiple clinical indications.

Evidence scope note: The review covers randomized controlled trials, systematic reviews, and case series across ophthalmic, wound, orthopedic, and dermatologic uses. Certain ophthalmic and wound indications have stronger supporting evidence (see sufficiency conclusions below), whereas many orthopedic and other indications have limited or preliminary data. Overall, the policy identifies 3 indications with sufficient evidence and 8 indications with insufficient evidence in this section, reflecting variable evidence strength across the different clinical areas.

Key evidence highlights and definitions (brief)

Corneal ulcers/melts (systematic review)Healing in 97% of patients; vision improved in 53% of eyes

Stevens–Johnson syndrome (RCT)RCT (25 patients, 50 eyes) showed improved symptoms and function with HAM vs medical therapy alone

Severe dry eye evidenceRCT (20 patients) and retrospective series (84 patients, 97 eyes): self‑retained HAM reduced symptoms and restored corneal surface and nerve density up to 3 months

Corneal perforation temporary coverageHAM may provide temporary coverage when corneal tissue is not immediately available (no comparative trials)

Neurotrophic keratitis RCTRCT (n=30) showed no benefit of sutured HAM versus tarsorrhaphy or bandage contact lens

Moderate/severe acute ocular chemical burnsThree RCTs (total n=197) with mixed results; two RCTs did not show faster epithelial healing

DefinitionsHAM = human amniotic membrane (amnion/chorion composite, cryopreserved or dehydrated); dHACM = dehydrated human amnion/chorion membrane allograft

Pterygium repair noteSystematic reviews: conjunctival or limbal autograft more effective than HAM in reducing recurrence

Medical-Necessity Criteria and Coverage Conclusions

Osteoarthritis (knee) - Coverage conclusion

Evidence summary and coverage determination:

Injection of suspension or particulate formulation of human amniotic membrane (HAM) or amniotic fluid for knee osteoarthritis

Evidence includes feasibility/pilot study; additional larger RCTs needed

Coverage determination: Insufficient evidence to determine improvement in net health outcome

Not proven medically necessary based on current evidence

Plantar fasciitis - Coverage conclusion

Evidence summary and coverage determination:

Injection of amniotic membrane (micronized injectable-HAM) for plantar fasciitis

One larger (N=145) patient-blinded comparison showed greater pain and function improvement vs placebo; report is interim with 12-month results pending

Coverage determination: Insufficient evidence to determine improvement in net health outcome

Ophthalmic conditions - General

Coverage determination varies by specific ophthalmic indication:

Neurotrophic keratitis with ocular surface damage and inflammation not responding to conservative therapy: RCT (n=30) showed no benefit of sutured HAM versus tarsorrhaphy or bandage contact lens

Insufficient evidence to determine improvement in net health outcome

Corneal ulcers and melts not responding to initial medical therapy: Systematic review of case series and nonrandomized comparative study; healing in 97% and improved vision in 53% in review; one retrospective comparative study showed more rapid epithelialization with self-retained HAM

Evidence sufficient to determine HAM results in improvement in net health outcome

Corneal perforation with active inflammation after corneal transplant requiring adjunctive treatment: No comparative evidence identified

Insufficient evidence to determine improvement in net health outcome

Bullous keratopathy as palliative measure for patients not candidates for curative treatment: RCT found no advantage of sutured HAM

Pterygium repair

Coverage determination when insufficient healthy tissue to create conjunctival autograft:

Use of HAM for pterygium repair when insufficient tissue for conjunctival autograft

Systematic reviews of RCTs show conjunctival or limbal autograft more effective than HAM in reducing recurrence

Coverage determination: Insufficient evidence to determine improvement in net health outcome

Repair following Mohs micrographic surgery (face/head/neck/dorsal hand)

Coverage determination for use of human amnion/chorion membrane:

Use of dehydrated human amnion/chorion membrane (dHACM, e.g., Epifix) for same-day reconstruction after Mohs surgery

Retrospective comparative study (143 propensity-score matched pairs) showed less infection and better scar cosmesis with dHACM vs autologous repair; limited by retrospective design

Coverage determination: Insufficient evidence to determine improvement in net health outcome

Provider Actions / Authorization & Documentation

Prior Authorization

Prior authorization implication

Policy history and coding notes indicate prior authorization and coding clarifications over multiple effective dates. Providers should obtain authorization per payer processes and reference applicable effective dates (for example, 9/1/2025 and 1/1/2025). Coding clarification events are recorded repeatedly in the policy history; confirm current billing/coding requirements with the payer before submission.

Obtain prior authorization per payer processes for HAM products when required.
Reference policy effective dates and coding clarification entries (examples: effective 9/1/2025 and 1/1/2025).
Be aware the policy history documents multiple coding clarification events across dates (e.g., 1/1/2025, 7/2025, 9/2025, 10/2025).

Documentation Required

Indication-specific documentation

Document the specific clinical indication and prior conservative therapy failure where applicable, and support use with trial evidence or rationale summarized in the policy. For diabetic lower‑extremity ulcers, indicate nonhealing status per the policy definition where relevant (less than 20% decrease in wound area with standard wound care for at least 2 weeks). Cite trial evidence or rationale from the policy to justify medical necessity.

Specify the clinical indication (e.g., corneal ulcer, Stevens‑Johnson syndrome, nonhealing diabetic lower‑extremity ulcer).
Document failure of appropriate conservative therapy when required by the indication (policy lists conservative therapy durations/steps for ophthalmic indications and defines nonhealing diabetic ulcer criteria).
Reference relevant trial evidence or rationale summarized in the policy to support the request (e.g., RCTs and systematic reviews for ophthalmic and diabetic ulcer indications).

Coding

No specific codes listed in this document partmixed

No codes listed

Changes and coding: Recent policy edits clarified coding and updated literature through February 21, 2025; NuShield was added to the medically necessary list for nonhealing diabetic lower‑extremity ulcers and AmnioExcel was previously added. The policy history documents multiple coding clarification entries (including 10/2025, 9/2025, 7/2025 and earlier) and effective dates (for example, effective 9/1/2025 and 1/1/2025).

Provider billing guidance: Because the policy lists many HCPCS/Q‑codes and CPT entries for informational purposes and coding has been clarified on multiple dates, providers should consult payer‑specific billing guidance, fee schedules, and prior‑authorization requirements to confirm the exact CPT/HCPCS/NDC codes, billing instructions, and reimbursement rules applicable to a given product and service.

Background and Evidence Context

Background and evidence scope: The policy review encompassed randomized controlled trials, systematic reviews, and case series evaluating HAM, dHACM, and related placental/amnion products delivered as patches, sutured grafts, self‑retained devices, or injectable formulations across ophthalmic, wound, orthopedic, and reconstructive indications.

Variation in evidence strength: Evidence strength varied by indication. For chronic nonhealing diabetic lower‑extremity ulcers and some wound applications, multiple RCTs and registries support improved wound closure and were judged sufficient for benefit. Several ophthalmic indications have mixed results: some (eg, corneal ulcers/melts; Stevens‑Johnson syndrome; severe dry eye; temporary use for corneal perforation when tissue unavailable) have stronger supporting data, while many ophthalmic conditions (eg, neurotrophic keratitis, bullous keratopathy, chemical burns, persistent epithelial defects, pterygium repair alternatives) have limited, mixed, or insufficient comparative evidence.

Feasibility of RCTs: The background notes many ophthalmic conditions are uncommon or severe, limiting the feasibility of large RCTs; where rarity or severity make large randomized trials unlikely, high‑quality case series and smaller RCTs were considered in the assessment.

Brief evidence — trial sizes and outcomes

Systematic review (corneal ulcers/melts)Healing in 97% of patients; vision improved in 53% of eyes

Stevens–Johnson syndrome (RCT)RCT with 25 patients (50 eyes): HAM improved symptoms and function vs medical therapy alone

Severe dry eye (evidence)RCT (20 pts) and retrospective series (84 pts, 97 eyes): self‑retained cryopreserved HAM reduced symptoms and restored corneal nerve density for up to 3 months

Corneal perforation (post‑transplant)No comparative evidence identified for active inflammation after corneal transplant; evidence insufficient

Neurotrophic keratitis (RCT)RCT of 30 patients: no benefit of sutured HAM vs tarsorrhaphy or bandage contact lens

Acute ocular chemical burns (RCTs)Three RCTs, total n=197; mixed results; two RCTs did not show faster epithelial healing

Bullous keratopathyRCT found no advantage of sutured HAM as palliative measure

Pterygium repairSystematic reviews of RCTs: conjunctival/limbal autograft superior to HAM for reducing recurrence

Diabetic lower‑extremity ulcers (policy and trials)Multiple RCTs support several HAM/dHACM products as medically necessary for nonhealing diabetic foot ulcers (defined as <20% area reduction after ≥2 weeks of standard care)

Revision History

9/2025annual_review_and_update

Annual policy review: Policy updated with literature review through February 21, 2025; references added; NuShield added to medically necessary policy statement for treatment of nonhealing diabetic lower-extremity ulcers; coding clarified. Effective 9/1/2025.

02/21/2025literature_reviewLatest

Literature review through February 21, 2025 performed to update policy evidence and references.

1/3/2024annual_review

Annual policy review with literature updates through January 3, 2024; AmnioExcel added to the list of medically necessary products for the treatment of nonhealing diabetic lower-extremity ulcers. Effective 1/1/2025.

10/2025coding_clarification

Coding information clarified (policy history notes clarification of coding information in 10/2025).

7/2025coding_clarification

Coding information clarified (policy history notes clarification of coding information in 7/2025).

4/2025policy_entry

Policy history includes an entry for 4/2025 (non-substantive entry).

1/2025annual_review

Annual policy review entry listed for 1/2025 as part of policy history (coding clarified and literature updates noted elsewhere).

OpenPayer

Human amniotic/chorionic membrane (HAM/dHACM/placental allografts) clinical indications

Coverage Summary

Medical-Necessity Criteria and Coverage Conclusions

Provider Actions / Authorization & Documentation

Coding

Background and Evidence Context

Revision History