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Amniotic Membrane Transplantation for the Ocular Surface

Policy Number: MP-624

Latest Review Date:   February 2020

Category:  Medical                                                               

Policy Grade:  C

POLICY:

Effective for dates of service on or after June 26, 2019:

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™) may be considered medically necessary for any 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

Amniotic membrane transplantation for the treatment of dry eye syndrome and any other conditions not listed above is not medically necessary and is considered investigational.

Effective for dates of service May 6, 2016- June 25, 2019:

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®) may be considered medically necessary for any 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;
  • Following removal of conjunctival lesion(s);
  • Hereditary corneal dystrophies;
  • Neurotrophic keratoconjunctivitis;
  • Ocular burns;
  • Stevens-Johnsons Syndrome;
  • Pterygium;
  • Pseudopterygium

Amniotic membrane transplantation for the treatment of dry eye syndrome and any other conditions not listed above is not medically necessary and is considered investigational.

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 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 5 days of pressure patching, therapeutic contact lens, topical lubricants, and topical antibiotics.

Conservative therapy for corneal ulcers and melts may include 2 days of patching, therapeutic contact lens, and topical antimicrobial agents.

A persistent epithelial defect is one that failed to close completely after 5 days of conservative treatment or has failed to demonstrate a decrease in size after 2 days of conservative treatment. Conservative treatment of a persistent epithelial defect may include 5 days of the following: topical lubricants, topical antibiotics, therapeutic contact lens, or patching.

KEY POINTS:

The most recent literature update was performed through December 20, 2019.

SUMMARY OF EVIDENCE:

Neurotrophic Keratitis with Ocular Surface Damage and Inflammation That Does Not Respond to Conservative Therapy

For individuals who have neurotrophic keratitis with ocular surface damage and inflammation that does not respond to conservative therapy who receive HAM, the evidence includes an RCT. The relevant outcomes are symptoms, morbid events, functional outcomes, and QOL. An RCT of 30 patients showed no benefit of sutured HAM graft compared to tarsorrhaphy or bandage contact lens. Based on clinical input, HAM might be considered for patients who did not respond to conservative therapy. Clinical input indicated that non-sutured HAM in an office setting would be preferred to avoid a delay in treatment associated with scheduling a surgical treatment. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Corneal Ulcers and Melts That Does Not Respond to Initial Medical Therapy

For individuals who have corneal ulcers and melts that does not respond to initial medical therapy who receive HAM, the evidence is limited. The relevant outcomes are symptoms, morbid events, functional outcomes, and QOL. Corneal ulcers and melts are uncommon and variable and RCTs are not expected. Based on clinical input, HAM might be considered for patients who did not respond to conservative therapy. Clinical input indicated that non-sutured HAM in an office setting would be preferred to avoid a delay in treatment associated with scheduling a surgical treatment. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Corneal Perforation When There is Active Inflammation after Corneal Transplant Requiring Adjunctive Treatment

For individuals who have corneal perforation when there is active inflammation after corneal transplant requiring adjunctive treatment who receive HAM, the evidence is limited. The relevant outcomes are symptoms, morbid events, functional outcomes, and QOL. No comparative evidence was identified for this indication. Clinical input supported the use of HAM to reduce inflammation and promote epithelial healing with active inflammation following corneal transplantation. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Bullous Keratopathy as a Palliative Measure in Patients Who are not Candidates for a Curative Treatment (e.g., endothelial or penetrating keratoplasty)

For individuals who have bullous keratopathy and who are not candidates for curative treatment (e.g., endothelial or penetrating keratoplasty) who receive HAM, the evidence includes an RCT. The relevant outcomes are symptoms, morbid events, functional outcomes, and QOL. An RCT found no advantage of sutured HAM over the simpler stromal puncture procedure for the treatment of pain from bullous keratopathy. Based on clinical input, non-sutured HAM could be used as an alternative to stromal puncture. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Partial Limbal Stem Cell Deficiency with Extensive Diseased Tissue Where Selective Removal Alone is not sufficient

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 QOL. No RCTs were identified on HAM for limbal stem cell deficiency. Improvement in visual acuity has been reported for some patients who have received HAM in conjunction with removal of the diseased limbus. Clinical input noted the limitations of performing an RCT and supported the use of HAM for this indication. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Moderate or Severe Stevens - Johnson syndrome

For individuals who have moderate or severe Stevens-Johnson syndrome who receive HAM, the evidence includes an RCT. The relevant outcomes are symptoms, morbid events, functional outcomes, and QOL. The evidence on HAM for the treatment of Stevens-Johnson includes one RCT with 25 patients (50 eyes) that found improved symptoms and function with HAM compared to medical therapy alone. Clinical input indicated that large RCTs are unlikely due to the severity and rarity of the disease, supported the use of HAM for moderate or severe Stevens-Johnson syndrome. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Persistent Epithelial Defects and Ulceration That Do Not Respond to Conservative Therapy

For individuals who have persistent epithelial defects that do not respond to conservative therapy who receive HAM, the evidence is limited. The relevant outcomes are symptoms, morbid events, functional outcomes, and QOL. No RCTs were identified on persistent epithelial defects and ulceration. Clinical input noted the difficulty in conducting RCTs for this indication and supported the use of amniotic membrane for persistent epithelial defects and ulcerations that do not respond to conservative therapy. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Severe Dry Eye with Ocular Surface Damage and Inflammation That Does Not Respond to Conservative Therapy

For individuals who have severe dry eye with ocular surface damage and inflammation that does not respond to conservative therapy, who receive HAM, the evidence includes an RCT and a large case series. The relevant outcomes are symptoms, morbid events, functional outcomes, and QOL. The evidence on HAM for severe dry eye with ocular surface damage and inflammation includes an RCT with 20 patients and a retrospective series of 84 patients (97 eyes). Placement of self-retained HAM for 2 to 11 days reduced symptoms and restored a smooth corneal surface and corneal nerve density for as long as 3 months.

Moderate or Severe Acute Ocular Chemical Burns

For individuals who have moderate or severe acute ocular chemical burn who receive HAM, the evidence includes 3 RCTs. Relevant outcomes are symptoms, morbid events, functional outcomes, and QOL. Evidence includes a total of 197 patients with acute ocular chemical burns who were treated with HAM transplantation plus medical therapy or medical therapy alone. Two of the 3 RCTs did not show a faster rate of epithelial healing, and there was no significant benefit for other outcomes. Clinical input was in support of HAM for acute ocular chemical burn. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Corneal Perforation When Corneal Tissue is not Immediately Available

For individuals who have corneal perforation when corneal tissue is not immediately available who receive sutured HAM, the evidence is limited. The relevant outcomes are symptoms, morbid events, functional outcomes, and QOL. The standard treatment for corneal perforation is corneal transplantation. Based on clinical input, sutured HAM may be used as a temporary measure when corneal tissue is not immediately available. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Pterygium Repair When There is Insufficient Healthy Tissue to Create a Conjunctival Autograft

For individuals who have pterygium repair when there is insufficient healthy tissue to create a conjunctival autograft who receive HAM, the evidence includes RCTs and systematic reviews of RCTs. The relevant outcomes are symptoms, morbid events, functional outcomes, and QOL. Systematic reviews of RCTs have been published that found that conjunctival or limbal autograft is more effective than HAM graft in reducing the rate of pterygium recurrence. Based on clinical input, sutured or glued HAM may be considered when there is insufficient healthy tissue to create a conjunctival autograft (e.g., extensive, double, or recurrent pterygium). The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Clinical Input

In 2019, clinical input was sought to help determine whether the use of human amniotic membrane graft either without or with suture fixation for several ophthalmic conditions would provide a clinically meaningful improvement in net health outcome and whether the use is consistent with generally accepted medical practice.

Respondents

Clinical input was provided by the following specialty societies and physician members identified by a specialty society or clinical health system:

  • American Academy of Ophthalmology (AAO)
  • Mark Latina, MD, Ophthalmology, Tufts University School of Medicine, identified by Massachusetts Society of Eye Physicians and Surgeons

Clinical input provided by the specialty society at an aggregate level is attributed to the specialty society. Clinical input provided by a physician member designated by a specialty society or health system is attributed to the individual physician and is not a statement from the specialty society or health system. Specialty society and physician respondents participating in the Evidence Street® clinical input process provide a review, input, and feedback on topics being evaluated by Evidence Street. However, participation in the clinical input process by a specialty society and/or physician member designated by a specialty society or health system does not imply an endorsement or explicit agreement with the Evidence Opinion published by BCBSA or any Blue Plan.

PRACTICE GUIDELINES AND POSITION STATEMENTS:

Tear Film and Ocular Surface Society

The Tear Film and Ocular Surface Society (2017) published the DEWS [Dry Eye Workshop] II management and therapy report. The report evaluated the evidence on treatments for dry eye and provided a treatment algorithm for dry eye disease management. The full report is available at:

https://www.tearfilm.org/dettreports-tfos_dews_ii_report/32_30/eng/

U.S. PREVENTIVE SERVICES TASK FORCE RECOMMENDATIONS

Not applicable.

KEY WORDS:

Absence of iris; Amniotic membrane transplantation; AMT; dry eye syndrome; keratopathy; bullous keratopathy; conjunctivochalasis; corneal degeneration; corneal ectasia; corneal staphyloma; descemetocele; other corneal deformity; corneal ulceration; corneal defect; corneal disorder due to contact lens or recurrent erosion of cornea; conjunctival lesion removal; hereditary corneal dystrophies; neurotrophic keratoconjunctivitis; ocular burns; pterygium; pseudopterygium; Stevens-Johnsons Syndrome; SJS; Prokera

APPROVED BY GOVERNING BODIES:

The U.S. Food and Drug Administration regulates human cells and tissues intended for implantation, transplantation, or infusion through the Center for Biologics Evaluation and Research, under Code of Federal Regulation (CFR) title 21, parts 1270 and 1271. Human amniotic membrane products and amniotic fluid products are included in these regulations.

In 2017, the FDA published clarification of what is considered minimal manipulation and homologous use for human cells, tissues, and cellular and tissue-based products(HCT/Ps).

HCT/Ps are defined as human cells or tissues that are intended for implantation, transplantation, infusion, or transfer into a human recipient. If an HCT/P does not meet the criteria below and does not qualify for any of the stated exceptions, the HCT/P will be regulated as a drug, device,and/or biological product and applicable regulations and premarket review will be required.

An HCT/P is regulated solely under section 361 of the PHS Act and 21 CFR Part 1271 if it meets all of the following criteria:

"1) The HCT/P is minimally manipulated;

2) The HCT/P is intended for homologous use only, as reflected by the labeling, advertising, or other indications of the manufacturer’s objective intent;

3) The manufacture of the HCT/P does not involve the combination of the cells or tissues with another article, except for water, crystalloids, or a sterilizing, preserving, or storage agent, provided that the addition of water, crystalloids, or the sterilizing, preserving, or storage agent does not raise new clinical safety concerns with respect to the HCT/P; and

4) Either:

i) The HCT/P does not have a systemic effect and is not dependent upon the metabolic activity of living cells for its primary function; or

ii) The HCT/P has a systemic effect or is dependent upon the metabolic activity of living cells for its primary function, and:

a) Is for autologous use;

b) Is for allogeneic use in a first-degree or second-degree blood relative; or

c) Is for reproductive use."

The guidance provides the following specific examples of homologous and non-homologous use for amniotic membrane:

"a. Amniotic membrane is used for bone tissue replacement to support bone regeneration following surgery to repair or replace bone defects. This is not a homologous use because bone regeneration is not a basic function of amniotic membrane.

b. An amniotic membrane product is used for wound healing and/or to reduce scarring and inflammation. This is not homologous use because wound healing and reduction of scarring and inflammation are not basic functions of amniotic membrane.

c. An amniotic membrane product is applied to the surface of the eye to cover or offer protection from the surrounding environment in ocular repair and reconstruction procedures. This is homologous use because serving as a covering and offering protection from the surrounding environment are basic functions of amniotic membrane."

FDA noted the intention to exercise enforcement discretion for the next 36 months after publication of the guidance.

In 2003, Prokera™ was cleared for marketing by FDA through the 510(k) process for the ophthalmic conformer that incorporates amniotic membrane (K032104). FDA determined that this device was substantially equivalent to the Symblepharon Ring. The Prokera™ device is intended “for use in eyes in which the ocular surface cells have been damaged, or underlying stroma is inflamed and scarred.”

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.

BENEFIT APPLICATION:

Coverage is subject to member’s specific benefits.  Group specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply.

FEP: Special benefit consideration may apply. Refer to member’s benefit plan. FEP does not consider investigational if FDA approved and will be reviewed for medical necessity.

CURRENT CODING:

CPT Codes:

65778    Placement of amniotic membrane on the ocular surface; without sutures
65779   ; single layer, sutured
65780 Ocular surface reconstruction; amniotic membrane transplantation, multiple layers

REFERENCES:

  1. Arora R, Mehta D, and Jain V. Amniotic membrane transplantation in acute chemical burns. Eye. 2005; 19:273-78.
  2. Bouchard CS, John T. Amniotic membrane transplantation in the management of severe ocular surface disease: indications and outcomes. Ocul Surf. Jul 2004; 2(3):201-211.
  3. Bouchard CS, John TT. Amniotic membrane transplantation in the management of severe ocular surface disease: indications and outcomes. Ocul Surf. 2007 Jan; 12;2(3).
  4. Chansanti O, Horatanaruang O. The results of amniotic membrane transplantation for symptomatic bullous keratopathy. J Med Assoc Thai. 2005; 88 Suppl 9:557-S62.
  5. Chen Z, Yan J, Yang H, et al. Amniotic membrane transplantation for conjunctival tumor. Yan, Ke. Xue, Bao.  2003; 19(3): 165-7.
  6. Cheng AM, Zhao D, Chen R, et al. Accelerated restoration of ocular surface health in dry eye disease by self-retained cryopreserved amniotic membrane. Ocul Surf. Jan 2016; 14(1):56-63.
  7. Clare G, Suleman H, Bunce C, et al. Amniotic membrane transplantation for acute ocular burns. Cochrane Database Syst Rev. 2012;9:CD009379.
  8. Clearfield E, Muthappan V, Wang X, et al. Conjunctival autograft for pterygium. Cochrane Database Syst Rev. Feb 11 2016; 2:CD011349.
  9. Dalla Pg, Ghirlando A, Busato F, et al. Reconstruction of conjunctiva with amniotic membrane after excision of large conjunctival melanoma: a long-term study. Eur J Opthalmol. 2005; 15(4): 446-50.
  10. Duchesne B, Tahi H, Galand A. Use of human fibrin glue and amniotic membrane transplant in corneal perforation.  Cornea. 2001; 20(2): 230-32.
  11. Food and Drug Administration. 510(k) Summary: ProKeraTM Bio-Tissue Inc. (K032104). 2003; https://www.accessdata.fda.gov/cdrh_docs/pdf3/K032104.pdf. Accessed January 26, 2018.
  12. Georgiadis NS, Terzidou CD.  Epiphora caused by conjunctivochalasis: treatment with transplantation of preserved amniotic membrane. Cornea. 2001; 20: 619-21.
  13. Gregory DG. Treatment of acute Stevens-Johnson syndrome and toxic epidermal necrolysis using amniotic membrane: A review of 10 consecutive cases. Opthalmology. 2011; 118(5):908-14.
  14. Hanada K, Shimazaki J, Shimmura S, et al. Multilayered amniotic membrane transplantation for severe ulceration of the cornea and sclera. Am J Ophthalmol. 2001; 131(3): 324-31.
  15. Hick S, Demers PE, Brunette I, et al. Amniotic membrane transplantation and fibrin glue in the management of corneal ulcers and perforation: a review of 33 cases. Cornea 2005; 24(4): 369-77.
  16. Honavar S, Bansai A, Sangwan V, et al. Amniotic membrane transplantation for ocular surface reconstruction in Stevens-Johnson syndrome. Ophthalmology. 2000; 107(5):975-79.
  17. Jain S, Rastogi A. Evaluation of the outcome of amniotic membrane transplantation for ocular surface reconstruction in symblepharon. Eye. 2004; 18(12): 1251-57.
  18. John TT, Tighe S, Sheha H, et al. Corneal nerve regeneration after self-retained cryopreserved amniotic membrane in dry eye disease. J Ophthalmol. Aug 15 2017; 2017:6404918.
  19. John TT, Tighe S, Sheha H, et al. Corneal nerve regeneration after self-retained cryopreserved amniotic membrane in dry eye disease. J Ophthalmol, 2017 Sep 13;2017:6404918.
  20. Kaufman SC, Jacobs DS, Lee WB, et al. Options and adjuvants in surgery for pterygium: a report by the American Academy of Ophthalmology. Ophthalmology. Jan 2013; 120(1):201-208.
  21. Kheirkhah A, Blanco G, Casas V, et al. Surgical strategies for fornix reconstruction based on symblepharon severity. Am J Ophthalmol. 2008; 146(2): 266-75.
  22. Kheirkhah A, Casas V, Blanco G, et al. Amniotic membrane transplantation with fibrin glue for conjunctivochalasis. Am J Ophthalmol. 2007; 144(2): 311-13.
  23. Kheirkhah A, Casas V, Esquenazi S, et al. New surgical approach for superior conjunctivochalasis. Cornea.  2007; 26(6): 685-91.
  24. Kheirkhah A, Johnson DA, Paranjpe DR, et al. Temporary sutureless amniotic membrane patch for acute alkaline burns. Arch Ophthalmol. 2008; 126:1059-66.
  25. Khokhar S, Natung T, Sony P, et al. Amniotic membrane transplantation in refractory neurotrophic corneal ulcers: a randomized, controlled clinical trial. Cornea. Aug 2005; 24(6):654-660.
  26. Khokhar S, Natung T, Sony P, et al. Amniotic membrane transplantation in refractory neurotrophic corneal ulcers: a randomized, controlled clinical trial. Cornea, 2005 Jul 15;24(6).
  27. Kim HK, Park HS. Fibrin glue-assisted augmented amniotic membrane transplantation for the treatment of large noninfectious corneal perforations. Cornea. 2009; 28(2): 170-76.
  28. Kobayashi A, Shirao Y, Yoshita T, et al. Temporary amniotic membrane patching for acute chemical burns. Eye. 2003; 17: 149-58.
  29. Liu J, Li L, Li X. Effectiveness of Cryopreserved Amniotic Membrane Transplantation in Corneal Ulceration: A Meta-Analysis. Cornea. 2019 Apr;38(4).
  30. McDonald MB, Sheha H, Tighe S, et al. Treatment outcomes in the Dry Eye Amniotic Membrane (DREAM) study. Clin Ophthalmol. 2018 Apr 9;12:677-681.
  31. Meller D, Maskin SL, Pires RTF, et al. Amniotic membrane transplantation for symptomatic conjunctivochalasis refractory to medical treatments. Cornea. 2000; 19(6):796-803.
  32. Meller D, Pires R, Mack R, et al. Amniotic membrane transplantation for acute chemical or thermal burns. Ophthalmology. 2000; 107: 980-90.
  33. Pachigolla G, Prasher P, Di Pascuale MA, et al. Evaluation of the role of ProKera in the management of ocular surface and orbital disorders. Eye Contact Lens. 2009; 35(4):172-175
  34. Paridaens D, Beekhuis H, van Den Bosch W, et al. Amniotic membrane transplantation in the management of conjunctival malignant melanoma and primary acquired melanosis with atypia. Br J Ophthalmol. 2001; 85: 658-61.
  35. Paris Fdos S, Goncalves ED, Campos MS, et al. Amniotic membrane transplantation versus anterior stromal puncture in bullous keratopathy: a comparative study. Br J Ophthalmol. Aug 2013; 97(8):980-984.
  36. Parolini O, Soncini M, Evangelista M, et al. Amniotic membrane and amniotic fluid-derived cells: potential tools for regenerative medicine? Regen Med. Mar 2009;4(2):275-291.
  37. Prabhasawat P, Tesavibul N, Prakairungthong N, et al. Efficacy of amniotic membrane patching for acute chemical and thermal ocular burns. J Med Assoc Thal. 2007; 90: 319-26.
  38. Rodriguez-Ares MT, Tourino R, Lopez-Valladares MJ, et al. Multilayer amniotic membrane transplantation in the treatment of corneal perforations. Cornea. 2004; 23(6): 577-83.
  39. Sharma N, Thenarasun SA, Kaur M, et al. Adjuvant role of amniotic membrane transplantation in acute ocular stevens-johnson syndrome: a randomized control trial. Ophthalmology. Mar 2016; 123(3):484-491.
  40. Shay E, Kheirkhah A, Liang L, et al. Amniotic membrane transplantation as a new therapy for the acute ocular manifestations of Stevens-Johnson syndrome and toxic epidermal necrolysis. Surv Ophthalmol. 2009; 54(6):686-96.
  41. Shimberg M, Wadsworth K. The use of amniotic-fluid concentrate in orthopaedic conditions. J Bone Joint Surg. 1938;20(I):167-177.
  42. Snyder RJ, Shimozaki K, Tallis A, et al. A prospective, randomized, multicenter, controlled evaluation of the use of dehydrated amniotic membrane allograft compared to standard of care for the closure of chronic diabetic foot ulcer. Wounds. Mar 2016;28(3):70-77. 
  43. Solomon A, Espana EM, Tseng SCG. Amniotic membrane transplantation for reconstruction of the conjunctival fornices. Opthalmology. 2003; 110:93-100.
  44. Solomon A, Meller D, Prabhasawat P, et al. Amniotic membrane grafts for nontraumatic corneal perforations, descemetoceles, and deep ulcers. Ophthalmology. 2002; 109(4):694-703.
  45. Sridhar MS, Bansal AK, Sangwan VS, et al. Amniotic membrane transplantation in acute chemical and thermal injury. Am J Ophthalmol. 2000; 130: 134-37.
  46. Srinivas S, Mavrikakis E, Jenkins C. Amniotic membrane transplantation for painful bullous keratopathy. Eur J Ophthalmol. 2007; 17(1):7-10.
  47. Suri K, Kosker M, Raber I, et al. Sutureless Amniotic Membrane ProKera for Ocular Surface Disorders. Short-Term Results. Eye Contact Lens. 2013;39:341-347
  48. Tamhane A, Vajpayee RB, Biswas NR, et al. Evaluation of amniotic membrane transplantation as an adjunct to medical therapy as compared with medical therapy alone in acute ocular burns. Ophthalmology. 2005; 112: 1963-69.
  49. Tandon R, Gupta N, Kalaivani M, et al. Amniotic membrane transplantation as an adjunct to medical therapy in acute ocular burns. Br J Ophthalmol. 2011; 95(2): 199-204.
  50. Tseng SCG, Prabhasawat P, Lee S-H. Amniotic membrane transplantation for conjunctival surface reconstruction. Am J Ophthalmol. 1997; 124: 765-74.
  51. U.S. Food and Drug Administration. Regulatory Considerations for Human Cells, Tissues, and Cellular and Tissue-Based Products: Minimal Manipulation and Homologous Use Guidance for Industry and Food and Drug Administration Staff. 2017 https://www.regulations.gov/document?D=FDA-2017-D-6146-0003 Accessed January 13, 2020
  52. Vlasov A, Sia RK, Ryan DS, et al. Sutureless cryopreserved amniotic membrane graft and wound healing after photorefractive keratectomy. J Cataract Refract Surg. Mar 2016; 42(3):435-443.

POLICY HISTORY:

Medical Policy Group, February 2016 (6):  Newly adopted policy.

Medical Policy Administration Committee, March 2016

Available for comment March 4 through May 5, 2016

Medical Policy Group, May 2016 (3): Updated literature review and clarified/expanded policy statement indications; updated Key Words & References

Medical Policy Administration Committee, May 2016

Medical Policy Panel, May 2017

Medical Policy Group, July 2017 (3): 2017 Updates on Description, Key Points, Governing Bodies, Key Words & References; clarified policy statements with types of grafts approved to coincide with coding and moved regulatory language to Governing Bodies section – no change in intent

Medical Policy Panel, February 2018

Medical Policy Group, March 2018 (3):  2018 Updates to Key Points & References; no change in policy statements

Medical Policy Panel February 2019

Medical Policy Group, June 2019 (6) Updates to Description, Key Points, Practice Guidelines and References. Policy statement updated to include coverage for :Partial limbal stem cell deficiency, Persistent Epithelial defects and corneal perforation after corneal transplant.

Medical Policy Panel, February 2020

Medical Policy Group, February 2020 (6): Updates to Key Points, Governing Bodies and References.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan 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. The plan administers benefits based on the member’s contract and corporate 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.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.