History
The amniotic membrane has become a widely used graft in human ophthalmology due to its ability to support ocular surface regeneration. In recent years, its application in veterinary ophthalmology has gained traction, backed by studies demonstrating its clinical value across multiple species. AMNIOVET™ emerged in this context, adapting tissue biotechnology advances to the veterinary field.
ORIGIN AND EVOLUTION IN HUMAN OPHTHALMOLOGY
Biological membranes have been used as grafts for over a century to support tissue repair in cutaneous and mucosal applications.
In particular, the therapeutic use of human placental membranes has a long history.
In 1910, J.W. Davis first described the use of fetal amniotic membrane as a surgical material for skin transplantation.
The amniotic membrane was introduced into human ophthalmology in 1940, when De Röth proposed using it as a biological covering for ocular surface injuries.
Although initial treatments were relatively successful, the clinical use of amniotic membrane declined until the mid-1990s, when Kim and Tseng reintroduced its application through improved processing and preservation methods.
Since then, thousands of ocular procedures involving amniotic membrane have been performed, and over 700 publications have reported on its use.
APPLICATION IN VETERINARY OPHTHALMOLOGY
In veterinary ophthalmology various biological membranes, including equine pericardium, rabbit renal capsule, canine peritoneum, and equine renal capsule, have been explored.
In recent years, inspired by advances in human medicine, the use of amniotic membrane in dogs, cats, and horses has expanded significantly.
The amniotic membrane’s characteristics — including low immunogenicity, biological compatibility, ease of preservation, and cost-effectiveness — have led to its increasing use in multiple medical fields.
There has been growing interest in veterinary ophthalmology, where the amniotic membrane serves as a natural scaffold to support ocular surface repair.
Ocular disorders in dogs, cats, rabbits, and horses have been successfully managed using amniotic membrane grafts, sourced both homologously and heterologously from various species, including canine, porcine, equine, and human.
AMNIOVET™ is the first product on the market processed from bovine amniotic membrane, offering a natural biological scaffold designed for veterinary ophthalmology applications.
Biological characteristics
The amniotic membrane (amnion) consists of a layer of cuboidal epithelial cells, a basement membrane whose composition is structurally similar to that of the conjunctiva, and a stromal matrix that is fully avascular and rich in collagen and mucopolysaccharides, with relatively few cellular elements, primarily macrophages and fibroblasts. This natural composition contributes to the amnion’s low immunogenicity, and the host response to grafted material, if any, is typically minimal.
The supportive properties of the amniotic membrane graft are explained by its histological structure:
- An amniotic epithelium that maintains a stable, continuous surface.
- A basement membrane that acts as a physical scaffold, supporting the orderly organization and attachment of epithelial cells, reinforcing surface stability, and serving as a natural substrate for epithelial coverage while maintaining normal cellular behavior.
These structural properties of the amniotic membrane are associated with the following supportive effects:
- Provides a natural scaffold that assists in maintaining epithelial surface continuity.
- Acts as a protective barrier to help stabilize the ocular surface environment during recovery.
- Supports the natural organization of tissues by maintaining surface integrity.
AMNIOVET™ adapts closely to the defect surface (secured by sutures or adhesives) and, due to its preserved structural architecture, serves as a mechanical covering that protects exposed tissue. The host cells can interact with the preserved extracellular matrix, facilitating tissue coverage and surface organization. The membrane is hydrophilic and naturally absorbs surrounding fluids. During the healing process, the membrane gradually integrates into the tissue environment. General literature suggests that the membrane typically integrates within approximately 14–21 days.
Surgical Applications
The amniotic membrane can be used in a large number of ophthalmologic surgical indications, either as a structural graft, a protective overlay, or a combination of both.
When implanted as a graft (inlay technique), it provides a natural scaffold that covers stromal defects and supports epithelial surface organization.
When applied as a patch (overlay technique), the amniotic membrane functions as a protective covering over the ocular surface, supporting a stable environment favorable for epithelial recovery.
The surgical technique will vary in each case, depending on whether the stromal side is applied to promote integration or the epithelial side is applied for temporary surface coverage.
A single layer or multiple layers of amniotic membrane can be used. In the latter case, an additional layer may be applied to cover the entire corneal surface.
Currently, amniotic membrane transplantation is a surgical procedure with ongoing exploration regarding its full range of indications and applications.
In human ophthalmology, amniotic membrane has been used successfully to support ocular surface management in cases of:
- Corneal burns – chemical and physical
- Pterygium
- Large conjunctival defects
- Symblepharon / fornix reconstruction
- Persistent corneal epithelial defects
- Limbal stem cell deficiency
- Strabismus surgery
- Glaucoma surgery (in filtering bleb repair)
- Stevens-Johnson Syndrome
- Bullous keratopathy (to alleviate surface discomfort when keratoplasty is not possible)
On the other hand, some limitations in the use and effectiveness of amniotic membrane transplantation have also been identified: in the absence of an adequate tear film, the graft may fail to restore the ocular surface; and in the presence of a strong inflammatory activity, the membrane may be resorbed more rapidly, both in graft-type implants and overlay applications.
In veterinary ophthalmology, various studies have described the use of amniotic membrane transplantation in cases of corneal ulcers, keratomalacia, dermoids, bullous keratopathy, corneal perforations, excision of corneal-limbal tumors in dogs and horses, and symblepharon or corneal sequestration in felines.
BIBLIOGRAPHY
HUMAN MEDICINE
- DeRoth A., Plastic repair of conjunctival defects with fetal membrane. Arch Ophthalmol 1940;23:522-25
- Bourne G., The Fœtal Membranes. Postgrad Med J. 1962 Apr;38(438):193–201.
- Kim JCI, Tseng SCG., Transplantation of preserved human amniotic membrane for surface reconstruction in severely damaged rabbit corneas. Cornea 1995;14:473-84.
- Zee SH, Tseng SCG., Amniotic membrane transplantation for persistent epithelial defects with ulceration. Am J Ophthalmol 1997;123:303-12.
- Tseng SC, Prabhasawat P, Barton K, Gray T, Meller D., Amniotic membrane transplantation with or without limbal allografts for corneal surface reconstruction in patients with limbal stem cell deficiency. Archives of ophthalmology. 1998;116(4):431.
- Blanco AA, Pillai CT, Dua HS., Amniotic membrane transplantation for ocular surface reconstruction. Br J Ophthalmol 1999;83:399-402.
- Tseng SCG, Li D-Q, Ma X., Suppression of transforming growth factor‐beta isoforms, TGF‐β receptor type II, and myofibroblast differentiation in cultured human corneal and limbal fibroblasts by amniotic membrane matrix. Journal of Cellular Physiology. 1999 Jun 1;179(3):325–35.
- Lee S-B, Li D-Q, Tan DT, Meller D, Tseng SC., Suppression of TGF-ß signaling in both normal conjunctival fibroblasts and pterygial body fibroblasts by amniotic membrane. Current eye research. 2000;20(4):325–34.
- Meller D. et al., Amniotic membrane transplantation for acute chemical or thermal burns. Ophthalmology 2000;107:980-90.
- Hui-Kang D, See LC, Zian SB, Tsai RJF., Amniotic membrane graft for primary pterygium: Comparison with conjunctival autograft and topical Mitomycin C treatment. British Journal of Ophthalmology 2000;84:973-78.
- Kim JS, Kim JC, Na BK, Jeong JM, Song CY., Amniotic membrane patching promotes healing and inhibits proteinase activity on wound healing following acute corneal alkali burn. Exp. Eye Res. 2000 Mar;70(3):329–37.
- Solomon A., Suppression of interleukin 1alpha and interleukin 1beta in human limbal epithelial cells cultured on the amniotic membrane stromal matrix. British Journal of Ophthalmology. 2001 Apr 1;85(4):444–9.
- Sippel KC, Ma JJK, Foster CS., Amniotic membrane surgery. Curr Opin Ophthalmol 2001;12:269-81.
- Prabhasawat P, Tesavibul N, Komolsuradej W., Single and multilayer amniotic membrane transplantation for persistent corneal epithelial defect with and without stromal thinning and perforation. Br J Ophthalmol. 2001;85(12):1455–63.
- Baum J., Amniotic membrane transplantation: Why is it effective? Cornea. 2002;21(4):339–41.
- Tseng SCG, Tsubota K., Amniotic membrane transplantation for ocular surface reconstruction. In: Holland EJ, Marris M J, editors. Ocular Surface Diseases: Medical and Surgical Management. New York: springer-Verlag; 2002. p226-31.
- Madhavan HN, Priya K, Malathi J, Joseph PR., Preparation of amniotic membrane for ocular surface reconstruction. Ophthalmology practice. 2002; 50 (3),227-31.
- Solomon A. et al., Amniotic membrane grafts for nontraumatic corneal perforations, descemetoceles, and deep ulcers. Ophthalmology. 2002 Apr;109(4):694–703.
- King A.E. et al., The novel antimicrobial peptide β3-defensin is produced by the amnion: A possible role of the fetal membranes in innate immunity of the amniotic cavity. American Journal of Obstetrics & Gynecology. 2004 Nov;191(5):1678–87.
- Ahn J-I et al., A comparison of lyophilized amniotic membrane with cryopreserved amniotic membrane for the reconstruction of rabbit corneal epithelium. Biotechnology and Bioprocess Engineering. 2005; 10(3):262–9.
- Antimicrobials by Human Placenta and Fetal Membranes. Placenta. 2007. Feb; 28(2–3):161–9.
- Georgiadis NS, Ziakas NG, Boboridis KG, Terzidou C, Mikropoulos DG., Cryopreserved amniotic membrane transplantation for the management of symptomatic bullous keratopathy. Clinical & Experimental Ophthalmology. 2008;36(2):130–5.
- Liu J, Sheha H, Fu Y, Liang L, Tseng SC., Update on amniotic membrane transplantation. Expert Rev Ophthalmol. 2010 Oct;5(5):645–61.
- Riau AK, Beuerman RW, Lim LS, Mehta JS., Preservation, sterilization and de-epithelialization of human amniotic membrane for use in ocular surface reconstruction. Biomaterials. 2010 Jan;31(2):216–25.
- Hsu M, Jayaram A, Verner R, Lin A, Bouchard C., Indications and Outcomes of Amniotic Membrane Transplantation in the Management of Acute Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis. Cornea. 2012 Dec;31(12):1394–402.
VETERINARY MEDICINE
- Barros P.S.M. et al., The use of xenologous amniotic membrane to repair canine corneal perforation created by penetrating keratectomy. Vet Ophthalmology 1(2-3):119-123 (1998).
- Barros P.S.M. et al., Amniotic membrane transplantation for the reconstruction of the ocular surface in three cases. Veterinary Ophthalmology 8:3, 189–192. (2005)
- Lassaline Mary E. et al., Equine amniotic membrane transplantation for corneal ulceration and keratomalacia in three horses. Veterinary Ophthalmology 8:5, 311–317. (2005)
- Ollivier F.J. et al., Amniotic membrane transplantation for corneal surface reconstruction after excision of corneolimbal squamous cell carcinomas in nine horses. Veterinary Ophthalmology 9:6, 404–413. (2006)
- Tsuzuki K, Yamashita K, Izumisawa Y, Kotani T., Microstructure and glycosaminoglycan ratio of canine cornea after reconstructive transplantation with glycerin-preserved porcine amniotic membranes. Veterinary Ophthalmology 11, 4, 222–227. (2008)
- Plummer C.E. et al., The use of amniotic membrane transplantation for ocular surface reconstruction: a review and series of equine clinical cases (2002-2008). Veterinary Ophthalmology 12, Suppl 1, 17-24. (2009)
- Kalpravidh M, Tuntivanich P, Vongsakul S, Sirivaidyapong S., Canine amniotic membrane transplantation for corneal reconstruction after the excision of dermoids in dogs. Vet Res Commun. Dec;33 (8):1003-12 (2009)
- Wichayacoop T. et al., Anti-inflammatory effects of topical supernatant from human amniotic membrane cell culture on canine deep corneal ulcer after human amniotic membrane transplantation. Veterinary Ophthalmology 12, 1, 28–35. (2009)
- Kim JY. et al., Effect of bovine freeze-dried amniotic membrane (Amnisite-BATM)on uncomplicated canine corneal erosion. Veterinary Ophthalmology 12, 1, 36-42. (2009)
- Soo Choi UI. et al., Successful treatment of an unusually large corneal epithelial inclusion cyst using equine amniotic membrane in a dog. Vet Ophthalmology 13, 2, 122–125 (2010)
- Barachetti L, Giudice C, Mortellaro C.M., Amniotic membrane transplantation for the treatment of feline corneal sequestrum: pilot study. Vet Ophthalmology 13, 5, 326-330. (2010)
- Huguet E. et al., The use of human amniotic membrane for corneal reparation in dogs: preliminary results. Proceeding ESVO Meeting 2011. Prague, Czech Republic.
- Huguet E, Sanz F, Vergara J, Díaz-Delgado C., Human amniotic membrane graft fixed with corneal adhesive for the treatment of feline corneal secuestrum: 2 clinical cases. Proceeding ECVO Congress 2013. Barcelona, Spain.
- Kang M, Choi S, Cho Lee AR., Effect of freeze dried bovine amniotic membrane extract on full thickness wound healing. Arch Pharm Res. Apr;36(4):472-8 (2013)
