Name of Blue Advantage Policy: Amniotic Membrane Transplantation for the Ocular Surface Policy #: 624 Latest Review Date: February 2021 Category: Medical Policy Grade: C BACKGROUND: Blue Advantage medical policy does not conflict with Local Coverage Determinations (LCDs), Local Medical Review Policies (LMRPs) or National Coverage Determinations (NCDs) or with coverage provisions in Medicare manuals, instructions or operational policy letters. In order to be covered by Blue Advantage the service shall be reasonable and necessary under Title XVIII of the Social Security Act, Section 1862(a)(1)(A). The service is considered reasonable and necessary if it is determined that the service is: 1. Safe and effective; 2. Not experimental or investigational*; 3. Appropriate, including duration and frequency that is considered appropriate for the service, in terms of whether it is: • Furnished in accordance with accepted standards of medical practice for the diagnosis or treatment of the patient’s condition or to improve the function of a malformed body member; • Furnished in a setting appropriate to the patient’s medical needs and condition; • Ordered and furnished by qualified personnel; • One that meets, but does not exceed, the patient’s medical need; and • At least as beneficial as an existing and available medically appropriate alternative. *Routine costs of qualifying clinical trial services with dates of service on or after September 19, 2000 which meet the requirements of the Clinical Trials NCD are considered reasonable and necessary by Medicare. Providers should bill Original Medicare for covered services that are related to clinical trials that meet Medicare requirements (Refer to Medicare National Coverage Determinations Manual, Chapter 1, Section 310 and Medicare Claims Processing Manual Chapter 32, Sections 69.0-69.11). Page 1 of 15 Proprietary Information of Blue Cross and Blue Shield of Alabama An Independent Licensee of the Blue Cross and Blue Shield Association Blue Advantage Medical Policy #624 POLICY: Effective for dates of service on or after June 26, 2019: Blue Advantage will treat amniotic membrane transplantation for the treatment of corneal conditions refractory to conventional treatment using grafts that are fixated using sutures, glue fixation, secured under a bandage contact lens, self-contained or unfixated (e.g., Prokera®, AmbioDisk™) as a covered benefit for coverage for the following conditions: • Absence of iris; • Bullous keratopathy; • Conjunctivochalasis; • Corneal degeneration; • Corneal ectasia, corneal staphyloma, descemetocele or other corneal deformity; • Corneal ulceration or defect; • Corneal disorder due to contact lens or recurrent erosion of cornea; • Corneal perforation when there is active inflammation after corneal transplant requiring adjunctive treatment; • Following removal of conjunctival lesion(s); • Hereditary corneal dystrophies; • Neurotrophic keratoconjunctivitis; • Ocular burns; • Stevens-Johnsons Syndrome; • Partial limbal stem cell deficiency with extensive diseased tissue where selective removal alone is not sufficient; • Persistent Epithelial defects that do not respond to conservative therapy; • Pterygium; • Pseudopterygium Blue Advantage will treat amniotic membrane transplantation for the treatment of dry eye syndrome and any other conditions not listed above as a non-covered benefit and as investigational. Effective for dates of service on and after May 6, 2016 and prior to June 26, 2019: Blue Advantage will treat amniotic membrane transplantation for the treatment of corneal conditions refractory to conventional treatment using grafts that are fixated using sutures, glue fixation, secured under a bandage contact lens, self-contained or unfixated (e.g., Prokera®) as a covered benefit for coverage for the following conditions: • Absence of iris; • Bullous keratopathy; • Conjunctivochalasis; • Corneal degeneration; • Corneal ectasia, corneal staphyloma, descemetocele or other corneal deformity; • Corneal ulceration or defect; Page 2 of 15 Proprietary Information of Blue Cross and Blue Shield of Alabama An Independent Licensee of the Blue Cross and Blue Shield Association Blue Advantage Medical Policy #624 • Corneal disorder due to contact lens or recurrent erosion of cornea; • Following removal of conjunctival lesion(s); • Hereditary corneal dystrophies; • Neurotrophic keratoconjunctivitis; • Ocular burns; • Stevens-Johnsons Syndrome; • Pterygium; • Pseudopterygium Blue Advantage will treat amniotic membrane transplantation for the treatment of dry eye syndrome and any other conditions not listed above as a non-covered benefit and as investigational. Blue Advantage does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. Blue Advantage administers benefits based on the members' contract and medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination. DESCRIPTION OF PROCEDURE OR SERVICE: The outermost layer of the cornea, the clear layer of the eye, has a surface that is composed of an epithelium, a thin layer of stratified squamous cells. The corneal epithelium has the ability to rapidly regenerate and this regeneration relies on stem cells located in the limbal epithelium (the junction zone between the corneal and conjunctival epithelia). Corneal epithelial defects are a focal loss of the corneal epithelium. Persistent corneal epithelial defects refractory to conventional treatment remain a therapeutic challenge, often requiring surgical intervention. Symptoms associated with these defects can include pain, photophobia, tearing and a sensation of a foreign body in the eye. Corneal defects can be caused by: • Corneal dryness and systemic disorders leading to corneal dryness (e.g., Sjogren’s syndrome, Vitamin A deficiency, dry eye syndrome and thyroid eye disease) • Deficiency of the limbal cells or failure to regenerate epithelial cells • Ultraviolet burns (e.g., prolonged sun exposure off reflective surfaces, welding) • Exposure of eye (e.g., neurotrophic diseases causing incomplete eyelid closure, proptosis, restrictive eyelid diseases) • Mechanical trauma of the cornea (e.g., chemical exposure, foreign body in the lid/fornices/trichiasis/distichiasis, contact lens overuse, fingernail scratch) Amniotic membrane transplantation (AMT) has been proposed as a treatment of ocular conditions. AMT is also being investigated for use in the restructuring of damaged ocular surfaces and as an aid in the healing of damaged ocular tissues. Ocular injuries due to trauma or Page 3 of 15 Proprietary Information of Blue Cross and Blue Shield of Alabama An Independent Licensee of the Blue Cross and Blue Shield Association Blue Advantage Medical Policy #624 disease damage the cornea and limbal epithelium. The corneal surface cannot regenerate if the damage to the epithelium is extensive. This results in ulcerations and loss of tissue to the extent of stem cell deficiency. This ulceration often fails to heal normally and can lead to vision loss. Amniotic membrane-covered surfaces are reported to induce rapid re-epithelialization in as little as 2 to 4 weeks, resulting in a smooth, wettable surface, with reduced inflammation, vascularization and scarring. This, in turn, allows for successful surface reconstruction. Human Amniotic Membrane Human amniotic membrane (HAM) consists of two conjoined layers, the amnion and chorion, and forms the innermost lining of the placenta. When prepared for use as an allograft, the membrane is harvested immediately after birth, cleaned, sterilized, and either cryopreserved or dehydrated. Many products available using amnion, chorion, amniotic fluid, and umbilical cord are being studied for the treatment of a variety of conditions, including ophthalmic conditions. Fresh amniotic membrane contains collagen, fibronectin, and hyaluronic acid, along with a combination of growth factors, cytokines, and anti-inflammatory proteins such as interleukin-1 receptor antagonist. There is evidence that the tissue has anti-inflammatory, antifibroblastic, and antimicrobial properties. HAM is considered nonimmunogenic and has not been observed to cause substantial immune response. It is believed that these properties are retained in cryopreserved HAM and dehydrated HAM products, resulting in a readily available tissue with regenerative potential. In support, one dehydrated HAM product has been shown to elute growth factors into saline and stimulate the migration of mesenchymal stem cells, both in vitro and in vivo. Use of a HAM graft, which is fixated by sutures, is an established treatment for disorders of the corneal surface, including neurotrophic keratitis, corneal ulcers and melts, following pterygium repair, Stevens-Johnson syndrome, and persistent epithelial defects. Amniotic membrane products that are inserted like a contact lens have more recently been investigated for the treatment of corneal and ocular surface disorders. Conservative therapy for neurotrophic keratitis may include five days of pressure patching, therapeutic contact lens, topical lubricants, and topical antibiotics. Conservative therapy for corneal ulcers and melts may include two days of patching, therapeutic contact lens, and