Dr Blair Lonsberry
MS OD MEd FAAO
Clinic Director and Professor of Optometry, Pacific University Oregon USA
Amniotic membranes (AM) have been used clinically for more than 60 years; however, a non-surgical application of these membranes for the management of many ocular pathologies was not available until the mid 1990s.1 Since that time, the popularity of AM has grown dramatically due to their ability to help speed healing and encourage regeneration of ocular tissues.
AM can be used in the form of a graft or as a patch. It can be sutured or sutureless. When using AM as a graft, it is intended to act as a scaffold for epithelial cells to grow. It is considered to be a biological bandage when used as a patch.2
The AM is derived from the inner portion of foetal membranes. Foetal membranes consist of two layers. The outer layer of the foetal membrane is the chorion, which is vascular and in contact with the uterine wall. The inner membrane is the amnion, which is avascular and is in contact with amniotic fluids.
AM are derived from the inner layer of the foetal membranes and consist of three different layers: the epithelium, basement membrane and stroma which further consists of three contiguous but distinct layers: the inner compact layer, middle fibroblast layer and the outermost spongy layer.3,4
The amniotic tissue that is used in the development of AM is retrieved from donors undergoing elective caesarean section and who have been previously screened serologically for potentially communicable diseases including human immunodeficiency virus, hepatitis B and C viruses and syphilis.
The maternal donor is recommended to have repeated serological testing at six months to confirm the absence of any communicable diseases before the tissue is released for transplant.
The placenta is washed with antibiotics (covering gram +/-) and antifungal agents. A blunt dissection separates the amnion from the chorion, and the amnion is preserved via either cryopreservation or in a dry de-epithelialised form.
The cryopreserved AM has to be stored frozen and removed prior to installation to warm to room temperature. The dry de-epithelialised form can be stored at room temperature for two to five years and has to be rehydrated prior to use.3
Figure 1. Top: corneal staining after debridement of area affected by a recurrent corneal erosion (RCE). Bottom: cornea after treatment with a Prokera Slim AM for seven days. Image: BioTissue
Amniotic membranes promote epithelialisation, decrease inflammation and scarring, prevent new blood vessel growth, improve patient comfort by reducing pain and potentially have antimicrobial properties.2,4
The AM acts as a mechanical barrier similar to a therapeutic contact lens, increasing patient comfort and promoting epithelial regeneration by shielding a damaged cornea from the frictional forces of a blink.2 The basement membrane of the AM is similar to the conjunctival/cornea and provides a suitable substrate for promoting re-epithelialisation.
Regenerating corneal epithelium makes AM particularly useful for non-healing or persistent wounds, and is thought to occur from a combination of facilitating epithelial cell migration, reinforcing basal epithelial cell adhesion, promotion of epithelial cell differentiation and prevention of apoptosis.2
AM possess foetal hyaluronic acid, which helps to suppress the production of corneal, conjunctival and limbal fibroblasts, thus reducing scarring.3 Pro-inflammatory mediators are suppressed/down regulated by the stromal layer of the AM helping to reduce inflammation and aiding in reducing scar formation.2 Several anti-angiogenic factors are produced, which reduces new blood vessel growth and scarring.
Antimicrobial properties of AM are debatable. Some researchers propose antimicrobial activity from antimicrobial factors found in amniotic fluid and that the graft acts as a barrier to infection.3
Figure 2A. Patient presented with an infectious central corneal ulcer. Patient was treated and was left with a sterile ulcer. After seven days of non-healing, Prokera Slim was applied for seven days due to risk of central scarring. Image: BioTissue
Figure 2B. Resulting cornea shows no scarring. Image: BioTissue
Three different types of AMs have been developed: permanent surgical grafts, dehydrated sutureless grafts and cryopreserved sutureless grafts.3
• Permanent surgical grafts
Corneal surgeons use surgical grafts when a more permanent graft needs to be sutured onto the host tissue and will later dissolve. This is commonly used during conjunctival reconstruction surgeries such as pterygium resection.
• Dehydrated sutureless grafts
Dehydrated sutureless grafts consist of a flat disc of tissue without a stabilising outer ring and require more finesse and dexterity during application. A lid speculum is required for applying the AM to the cornea, which is then smoothed and centred over the involved area.5 A bandage contact lens is applied over the top of the AM. Special care must be taken when removing the lid speculum in order to not disrupt the graft by bumping it or the contact lens.5 Two of the most common dehydrated sutureless grafts are the AmbioDisk (IOP Ophthalmics)5 and BioDOptix (BioD).6
• Cryopreserved sutureless grafts
The Prokera amniotic membrane is an example of a cryopreserved sutureless graft. These AM grafts are fastened within an ophthalmic conformer ring that is then applied over the cornea with the conformer ring resting on the sclera.7 Prokera AMs come in three thicknesses: Prokera Slim (~100 microns thick), Prokera and Prokera Plus (~200 microns thick). The recommended thickness is based on the severity of the corneal defect being treated (the more severe the condition, the thicker the AM must be).
Prokera Slim is for mild-to-moderate indications such as recurrent corneal erosions,8 Prokera is for moderate-to-severe indications such as neurotrophic epithelial defect and Prokera Plus is for very severe indications such as chemical burns. For most indications, the Prokera Slim is used as it provides more comfort to the patient.7
A new Prokera AM has just been released, called Prokera Clear, which has a 6-mm trephinated circle in the centre of the membrane to allow some visual function and is indicated for patients who have a more peripheral inflammatory condition, for example, keratoconjunctivitis sicca.9
Ophthalmic indications for AM include a broad spectrum of ocular surface disorders which ultimately result in damage to the ocular surface cells, underlying stromal inflammation or any condition that leads to permanent scarring affecting the patient’s vision.4 Some of these include recurrent corneal erosion,10 corneal sequelae of severe dry eye syndrome, neurotrophic ulcer, persistent corneal epithelial defect, chemical and thermal burn, Salzmann’s nodular degeneration, acute Stevens Johnson Syndrome,11 microbial ulcers, herpes simplex keratitis and herpes zoster keratitis.2,3,4
An AM may be used at any point to treat these conditions and replace the use of a therapeutic contact lens, which provides only a mechanical barrier. A therapeutic contact lens will provide patient comfort but it has no effect on scar inhibition.12 A clinician should strongly consider an AM over a bandage contact lens in any corneal condition that has trouble healing on its own or may result in corneal scarring, such as in a central corneal ulcer. If a patient is currently taking adjunct pharmaceutical therapy, it is important they continue, especially when an active infection is present.
There are two groups of patients for whom the use of these membranes would be contraindicated: patients with glaucoma drainage devices or filtering blebs. Other contraindications specific to Prokera include patient allergies to ciprofloxacin or amphotericin B.8
AM are becoming more commonly used in the treatment and management of ocular surface disorders. As the conditions that are successfully treated with the use of AM become more understood, the role of the optometrist in the use of these treatment options will increase and be more commonplace.
1. Ilic D, Vicovac L, Nikolic M, & Lazic Ilic E. (). Human amniotic membrane grafts in therapy of chronic non-healing wounds. Brit Med Bulletin 2016; 117: 1: 59-67.
2. Chavez-Garcia C, Jimenez-Corona A, Graue-Hernandez EO, et al. Ophthalmic indications of amniotic membrane transplantation in Mexico: an eight years Amniotic Membrane Bank experience. Cell Tissue Banking 2016; 17: 2: 261-268.
3. Malhotra C, Jain AK. Human amniotic membrane transplantation: Different modalities of its use in ophthalmology. World J Transplantation 2014; 4: 2: 111-121.
4. Paolin A, Cogliati E, Trojan D, et al. Amniotic membranes in ophthalmology: long term data on transplantation outcomes. Cell Tissue Banking 2016; 17: 1: 51-58.
5. AmbioDisk: Product Insert/Instructions for Use. https://www.iopinc.com/wp-content/uploads/2012/05/AmbioDisk_Product_Insert_May_2012.pdf.
6. BioDOptic amniotic sutureless membrane. http://www.biodlogics.com/technology/biod-optix. Accessed July 24, 2016.
7. Suri K, Kosker M, Raber IM, et al. Sutureless amniotic membrane Prokera for ocular surface disorders: short-term results. Eye Contact Lens 2013; 39: 5: 341-347.
8. Prokera Slim Product Insert. Bio-Tissue website: www.biotissue.com/downloads/prokera-slim-insert_PI-BT-004E_V1.pdf. Accessed July 24, 2016.
9. Prokera Products. http://www.biotissue.com/products/prokera/prokera-indications.aspx. Accessed July 24, 2016.
10. Managan R. Stopping corneal erosion: with amniotic membranes. Review of Optometry; October 2014.
11. Ma KN, Thanos A, Chodosh J, Shah AS, Mantagos IS. A novel technique for amniotic membrane transplantation in patients with acute Stevens-Johnson syndrome. Ocular Surface 2016; 14: 1: 31-36.
12. Kent HD, Cohen EJ, Laibson PR, et al. Microbial keratitis and corneal ulceration associated with therapeutic soft contact lenses. CLAO J 1990; 16: 49-52.