Medical Policy: 02.01.60
Original Effective Date: March 2018
Reviewed: March 2021
Revised: March 2021
This policy contains information which is clinical in nature. The policy is not medical advice. The information in this policy is used by Wellmark to make determinations whether medical treatment is covered under the terms of a Wellmark member's health benefit plan. Physicians and other health care providers are responsible for medical advice and treatment. If you have specific health care needs, you should consult an appropriate health care professional. If you would like to request an accessible version of this document, please contact customer service at 800-524-9242.
Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.
This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.
There are many products available using amnion, chorion, amniotic fluid, and umbilical cord that are being studied for the treatment of a variety of conditions. Frequently this is referred to as human amniotic membrane (HAM) by grafting or by injection. Human amniotic membrane (HAM) consists of 2 conjoined layers, the amnion and chorion, and forms the innermost lining of the amniotic sac or placenta. When prepared for use, the membrane is harvested immediately after birth, cleaned, sterilized, and either cryopreserved or dehydrated.
Conditions being studied include chronic full thickness diabetic lower extremity ulcers, venous ulcers, knee osteoarthritis, plantar fasciitis, tendonitis, cartilage damage, for alleviation of pain and stiffness, and for ophthalmic surface disorders.
When administered by injection human amniotic tissue is micronized, or reduced in particle size to a form that can be suspended in liquid. Multiple products are available for injection. They include AmnioFix® Injectable (MiMedx), Amnio Restore™, Clarix® Flo and Neox® Flo (Amniox), AmnioMatrix® (Derma Sciences), AmnioPro™ (Human Regenerative Technologies), and AmnioGen™ (US Biologix). Amniotic fluid products that are cryopreserved and contain living cells include AmnioVisc™ (previously named AmnioClear® LCT from Liventa Bioscience) and OrthoFlo™ (MiMedx). PalinGen® Flow and Sport Flow™ (Amnio ReGen Solutions) contains cryopreserved amniotic fluid and cryofractured amniotic membrane. ReNu™ (NuTech Medical) is composed of a human amniotic membrane suspension along with amniotic fluid derived cells.
Amniotic membrane extract may be combined with umbilical cord (UC) blood as another type of amniotic membrane-derived solution. Drops made from amniotic fluid, reconstituted dehydrated amnion or morselized amniotic tissue will soon be available in the United States.
HAM graft that is fixated by sutures or glue or secured under a bandage contact lens is an established treatment for disorders for the corneal surface. Non-fixated amniotic patch within a flexible ring that is inserted like a contact lens has more recently been investigated for the treatment of corneal and ocular surface disorders.
Currently, two main types of amniotic membrane (AM) are commercially available for in-office use: cryopreserved and dehydrated. Both types come in a variety of tissue thicknesses and sizes, depending on clinical needs.
Cryopreserved AM. Cryopreservation of AM involves slow freezing at –80°C using DMEM/glycerol preservation media to allow for slow-rate freezing without ice formation. This preservation technique retains the extracellular matrix components, such as heavy-chain hyaluronic acids, growth factors, fibronectin, and collagen, all of which promote anti-inflammatory effects and healing. The tissue is stored in a –80°C freezer and brought to room temperature when needed for use.
ProKera (BioTissue) is a cryopreserved form of AM in which the membrane is secured around a polycarbonate ring or an elastomeric band. It requires no assembly and is inserted into the eye in a manner similar to contact lens placement. This form of AM has been cleared by the FDA as a class II medical device, and product claims approved by the FDA include protective, wound healing, and anti-inflammatory effects.
Dehydrated AM. Dehydrated AM is preserved using vacuum with low temperature heat to retain devitalized cellular components. FDA-approved claims for this type of AM are limited to wound coverage. Unlike cryopreserved tissue, dehydrated AM is kept at room temperature, but it must be rehydrated for clinical use.
AmbioDisk™ (IOP Ophthalmics) is a processed, dehydrated, sterilized human amniotic membrane tissue graft intended for overlay use on the ocular surface to treat nonhealing epithelial defects, neurotrophic ulcerations, corneal erosions, acute chemical/thermal burns, or postinfectious keratitis. AmbioDisk is commercially available for in-office use; it is applied directly to the ocular surface and covered with an overlying bandage contact lens.
AmnioClip (FORTECH GmbH) is a ring designed to hold the amniotic membrane in the eye without sutures or glue fixation. A mounting device is used to secure the amniotic membrane within the AmnioClip. The AmnioClip currently has CE approval in Europe but is not approved for use in the United States.
Not applicable.
For information on amniotic membranes for use as skin substitutes see medical policy 02.01.17 Bio-Engineered Skin and Soft Tissue Substitutes
Injections of micronized or particulated human amniotic membrane is considered investigational for all indications.
Injections of human amniotic fluid is considered investigational for all indications.
Additional trials, which will have a larger sample sizes and longer follow-up, are needed to permit conclusions on the effect of this treatment. The evidence is insufficient to determine the effects of the technology on health outcomes.
FDA approved human amniotic membrane grafts with or without sutures (e.g. AmnioGraft®, Prokera, AmbioDisk™) for the treatment of ophthalmic indications are considered medically necessary for the following conditions:
Amniotic membrane grafts are considered investigational for the treatment of all other ophthalmic conditions including but not limited to:
Amniotic Serum Drops/Umbilical Cord Serum Drops (e.g. Regener-Eyes, Genesis) are considered investigational.
Traditionally, amniotic membrane has been sutured onto the eye for a variety of ocular surface disorders. There is a belief that using stitches allows the membranes to stay in contact with the affected surfaces longer. Amniotic membrane typically dissolves over a period of one or two weeks. Results from 2 recent RCTs have suggested benefit, but the studies are at high or uncertain risk of bias due to unequal baseline scores and the lack of masking (blinding). Additional study in a larger number of subjects is needed to demonstrate consistent effects. The Prokera device is novel by having a ring around the c-HAM allograft that allows it to be inserted under topical anesthesia similar to insertion of a contact lens, allowing for more widespread use.
For individuals who have partial limbal stem cell deficiency with extensive diseased tissue where selective removal alone is not sufficient who receive HAM, the evidence is limited. The relevant outcomes are symptoms, morbid events, functional outcomes, and quality of life. No RCTs were identified on HAM for limbal stem cell deficiency. A recent RCT on the use of amniotic membrane for ocular burns showed no significant difference in time to epithelial healing or in visual acuity versus medical therapy alone. The value of amniotic membrane for this condition has not shown improved net health outcomes. Although Clinical input supported HAM in cases of severe dry eye with ocular surface damage and inflammation that does not respond to conservative therapy, currently the evidence is insufficient to determine that the technology results in a meaningful improvement in net health outcomes over conventional treatment. In scenarios of superficial keratitis caused by both bacteria and viruses there is no treatment needed, as recovery usually occurs within weeks.
To report provider services, use appropriate CPT* codes, Alpha Numeric (HCPCS level 2) codes, Revenue codes and / or diagnosis codes.
Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc. They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.
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