Amniotic Membrane and Limbal Stem Cell Transplantation for the Treatment of Ocular Conditions - CAM 047HB

The objective of amniotic membrane and limbal stem cell transplantation is to reconstruct damaged ocular surfaces and promote healing of corneal, conjunctival and eyelid tissues after injury due to trauma, disease or surgery.

Severe ocular injuries due to trauma or disease degrade the corneal and limbal epithelium. Often, the epithelial damage is so extensive that the corneal surface cannot regenerate. The injury may not heal, or non-corneal epithelium may migrate from the periphery of the wound, sometimes resulting in pain, scarring, vascularization and loss of sight. Amniotic membrane (AM) has been used on various types of wounds for many years as a biological bandage. It has recently begun to be used for amniotic membrane transplantation (AMT) as a method for reconstructing damaged ocular surfaces, promoting healing following surgical repair of a variety of conditions of the cornea, conjunctiva and eyelid. AM contains an avascular matrix, which inhibits angiogenesis in adjacent tissues, thus minimizing vascularization during ocular healing. It exhibits anti-inflammatory properties and suppresses expression of transforming growth factor-beta (TGF-β) isoforms, minimizing scar tissue during the healing process. In addition, AM does not express histocompatibility antigens, thereby reducing the risk of an immune mediated reaction to the transplanted tissue and decreasing the need for immunosuppressive drugs. The goals of AMT for treatment of ocular conditions are to decrease scarring, reduce inflammation and restore function and appearance. Human amniotic membrane that is obtained from cesarean deliveries is used.

Limbal epithelial stem cells are the primary source of corneal epithelial cell regeneration. Limbal stem cell deficiency (LSCD) can develop in traumatic, immunologic or genetic diseases that affect the ocular surface. LSCD leads to conjunctivalization, with corneal vascularization and opacification and subsequent loss of vision. Limbal stem cell transplantation is a surgical treatment to address LSCD and restore a corneal epithelial phenotype. Based on the source of cells, limbal transplant can be autologous or allogenic.

Amniotic membrane transplantation OR limbal stem cell transplantation may be considered MEDICALLY NECESSARY for the treatment of an ocular disease (e.g., bullous keratopathy, pterygium, Stevens-Johnson syndrome) corneal ulceration or defect, chemical or thermal ocular injury, neurotrophic keratophathy and hereditary aniridia when there is failure, contraindication or intolerance to medical management (e.g., lubricants, artificial tears, topical or systemic steroids, antibiotics, eyelid taping, patching).

Randomized controlled trials and retrospective reviews support amniotic membrane transplantation for multiple ocular issues, including bullous keratopathy, corneal ulceration, ocular burns, pterygium and Stevens-Johnson Syndrome. Studies support the safety and efficacy of AMT. Statisticially significant deceases in symptom scores  and complete epithelialization were reported by Chawla et al., 2010, Chansanti and Horatanaruang, 2005, relating to treatment of bullous keratopathy. Similar findings were found by Fuchsluger et al., 2007, and Chen et al., 2006, Hick et al., 2005, and Khokar et al., 2005, regarding the treatment of corneal ulceration.

Limbal Stem Cell transplantation has been supported in studies related to ocular burns [Rama et al. (2010)] and  pterygium (Kucukerdonmez et al., 2007).  These studies had small patient populations, but showed significant improvement in symptoms for many participants.


  1. Chandra A, Maurya OP, Reddy B, Kumar G, Pandey K, Bhaduri G. Amniotic membrane transplantation in ocular surface disorders. J Indian Med Assoc. 2005 Jul;103(7):364-6, 368.
  2. Chansanti O, Horatanaruang O. The results of amniotic membrane transplantation for symptomatic bullous keratopathy. J Med Assoc Thai. 2005 Nov;88 Suppl 9:S57.
  3. Chawla B, Sharma N, Tandon R, Kalaivani M, Titiyal JS, Vajpayee RB. Comparative evaluation of phototherapeutic keratectomy and amniotic membrane transplantation for management of symptomatic chronic bullous keratopathy. Cornea. 2010 Sep;29(9):976-9.
  4. Chen HC, Tan HY, Hsiao CH, Huang SC, Lin KK, Ma DH. Amniotic membrane transplantation for persistent corneal ulcers and perforations in acute fungal keratitis. Cornea. 2006 Jun;25(5):564-72.
  5. Fuchsluger T, Tuerkeli E, Westekemper H, Esser J, Steuhl KP, Meller D. Rate of epithelialisation and re-operations in corneal ulcers treated with amniotic membrane transplantation combined with botulinum toxin-induced ptosis. Graefes Arch Clin Exp Ophthalmol. 2007 Jul;245(7):955-64.
  6. Gomes JA, Romano A, Santos MS, Dua HS. Amniotic membrane use in ophthalmology. Curr Opin Ophthalmol. 2005 Aug;16(4):233-40.
  7. Gomes JA, Santos MS, Ventura AS, Donato WB, Cunha MC, Hofling-Lima AL. Amniotic membrane with living related corneal limbal/conjunctival allograft for ocular surface reconstruction in Stevens-Johnson syndrome. Arch Ophthalmol. 2003 Oct;121(10):1369-74.
  8. Hick S, Demers PE, Brunette I, La C, Mabon M, Duchesne B. Amniotic membrane transplantation and fibrin glue in the management of corneal ulcers and perforations: a review of 33 cases. Cornea. 2005 May;24(4):369-77.
  9. Küçükerdönmez C, Akova YA, Altinörs DD. Comparison of conjunctival autograft with amniotic membrane transplantation for pterygium surgery: surgical and cosmetic outcome. Cornea. 2007 May;26(4):407-13.
  10. Rama P, Matuska S, Paganoni G, Spinelli A, De Luca M, Pellegrini G. Limbal stem-cell therapy and long-term corneal regeneration. N Engl J Med. 2010 Jul 8;363(2):147-55.
  11. Hayes Online, Inc. Amniotic membrane transplantation for treatment of ocular conditions. August 2001, archived 1/1/2007.
  12. Nakamura T, Yoshitani M, Rigby H, et al. Sterilized, freeze-dried amniotic membrane: a useful substrate for ocular surface reconstruction. Invest Ophthalmol Vis Sci. 2004 Jan; 45(1): 93-9.
  13. Figueiredo F, Amniotic membrane transplantation in ophthalmology. Ophthalmic Research Network.
  14. Koizumi N, Kinoshita S. Ocular surface reconstruction, amniotic membrane and cultivated epithelial cells from the limbus. British Journal of Ophthalmology 2003;87:1437-1439.
  15. Shay E, Kheirkhah A, Liang L, Sheha H, Gregory DG, Tseng SC. Amniotic membrane transplantation as a new therapy for the acute ocular manifestations of Stevens-Johnson syndrome and toxic epidermal necrolysis. Surv Ophthalmol. 2009 Nov-Dec;54(6):686-96. Epub 2009 Aug 21.
  16. Müller M, Meltendorf C, Mirshahi A, Kohnen T. [Use of multilayer amniotic membrane as first therapy for penetrating corneal ulcers]. Klin Monatsbl Augenheilkd. 2009 Aug;226(8):640-4.
  17. Said DG, Nubile M, Alomar T, Hopkinson A, Gray T, Lowe J, Dua HS. Histologic features of transplanted amniotic membrane: implications for corneal wound healing. Ophthalmology. 2009 Jul;116(7):1287-95. Epub 2009 May 17.
  18. Yoon KC, Im SK, Kim JC, Yoon KW, Choi SK. Prognosis of paraquat-induced ocular surface injury: therapeutic effect of amniotic membrane transplantation. Cornea. 2009 Jun;28(5):520-3. Cornea. 2009 Jun;28(5):520-3.
  19. Yidiz EH, Nurozler AB, Ozkan Aksoy N, Altiparmak UE, Onat M, Karaguzel H. Amniotic membrane transplantation: indications and results. Wur J Ophthalmol. 2008 Sep-Oct, 18(5): 685-90.

Coding Section

Codes Number Description
CPT 65778

Placement of amniotic membrane on the ocular surface; without sutures


Placement of amniotic membrane on the ocular surface; single layer, sutured


Ocular surface reconstruction; amniotic membrane transplantation, multiple layers

  65781 Ocular surface reconstruction; limbal stem cell allograft (e.g., cadaveric or living donor)
  65782 Ocular surface reconstruction; limbal conjunctival autograft (includes obtaining graft)
HCPCS V2790 Amniotic membrane for surgical reconstruction, per procedure
ICD-9 Diagnosis 370.00-370.06 

Corneal ulcer 

  370.35 Neurotrophic keratoconjunctivitis 
  371.23 Bullous keratopathy 
  371.42 Recurrent erosion of cornea
  371.50-371.58 Hereditary corneal dystrophies 
  371.82  Corneal disorder due to contact lens 




  695.10-695.19 Erythema multiforme [Stevens-Johnson syndrome] 
  940.0-940.9  Burn confined to eye and adnexa 
  941.02  Burn of face, head, and neck, unspecified degree, eye (with other parts of face, head, and neck) 
  941.12  Burn of face, head, and neck, erythema [first degree], eye (with other parts face head and neck) 
  941.22  Burn of face, head, and neck, blisters, epidermal loss [second degree], eye (with other parts of face head and neck) 
  941.32  Burn of face, head, and neck, full-thickness skin loss [third degree nos], eye (with other parts of face head and neck) 
  941.42  Burn of face, head, and neck, deep necrosis of underlying tissues [deep third degree], without mention of loss of a body part, eye (with other parts of face head and neck) 
  941.52  Burn of face, head, and neck, deep necrosis of underlying tissues [deep third degree], with loss of a body part, eye (with other parts of face head and neck) 
ICD-10-CM (effective 10/01/15)  H11.01-H11.069 




  H16.001-H16.049  Corneal ulcer 
  H16.061-H16.079  Mycotic and perforated corneal ulcer 
  H16.231-H16.239  Neurotrophic keratoconjunctivitis 

Bullous keratopathy 

  H18.43  Other calcerous corneal degeneration 

Corneal dystrophy 


Erosion of cornea 

  L12.30  Acquired epidermolysis bullosa, unspecified 
  L12.31  Epidermolysis bullosa due to drug 

Other acquired epidermolysis bullosa 

  L51.0-L51.9  Erythema multiforme [Stevens-Johnson syndrome] 
  T26.00XA-T26.92XA Burn of eye and around eye 

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.  

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross Blue Shield Association technology assessment program (TEC) and other nonaffiliated technology evaluation centers, reference to federal regulations, other plan medical policies and accredited national guidelines.

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