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Cryopreserved amniotic membrane excels at healing ocular surface wounds

Optometry Times JournalDigital edition: January 2022
Volume 14
Issue 01

With its anti-infective, anti-inflammatory, and regenerative properties, this versatile therapeutic should be in your toolbox.

Amniotic membrane (AM) tissue is an excellent option for rapidly and effectively treating a variety of corneal and ocular surface conditions.

This versatile therapeutic falls well within optometry’s vast scope of practice, and I have found that it is a vital tool to have at hand when an anti-infective, anti-inflammatory, or wound-healing intervention is indicated.

Greg Caldwell

Why amniotic membrane?

Despite its longstanding use in eye care, many optometrists are still unfamiliar with AM as a viable therapeutic option. AM tissue was first described as a biological dressing for the management of conjunctival defect in 1940.1

Today, the AM tissue used to treat corneal and ocular surface disorders is derived from placental tissue obtained during elective cesarean deliveries. However, not all AM tissue used for these indications is the same.

Two types of AM are available for ocular use: cryopreserved and dehydrated. Both come in a variety of tissue thicknesses and sizes, but the critical distinction lies in how they are preserved.

Related: How to address dry eye in the challenging cornea

Cryopreserved AM (CAM) is kept frozen until shortly before use. Dehydrated AM (DAM) is stored at room temperature and rehydrated just before use. The preservation process is intrinsic to the capabilities of these grafts in daily clinical practice.

The cryopreservation process allows CAM to retain a matrix of natural growth factors. CAM’s HC‑HA/PTX3 matrix is composed of heavy chain peptide covalently conjugated with high molecular weight hyaluronic acid that is noncovalently conjugated with pentraxin 3.

This combination is responsible for anti-inflammatory and regenerative healing properties that are maintained in cryopreservation but lost in dehydration.2-6

Whereas CAM has anti-inflammatory, antiscarring, and antiangiogenesis properties—which are designated by the FDA—DAM products have no formal medical designation from the FDA, and their only indication is for wound coverage.7

CASE STUDY: A 68-year-old White woman was referred for persistent keratitis OS and failure on multiple medications:

CASE STUDY: A 68-year-old White woman was referred for persistent keratitis OS and failure on multiple medications. Click to read here!

Pictured: Infectious keratitis before application of Prokera Slim.

Critical distinctions

There are several DAM products available, including AmbioDisk (IOP Ophthalmics/Katena) and BioDOptix (Derma Sciences). But there is only 1 CAM, and that is Prokera/AmnioGraft (Bio-Tissue).

Optometrists sometimes consider DAM a more appealing option because of its lower cost and because they erroneously assume that all commercially available AM tissue is the same.

This is why it is critical to understand that CAM and DAM are different. They are distinguished by cost and capability and—in at least 1 instance—contraindication.

Although the cost of DAM is lower, it is capable of less. In addition to being an anti-inflammatory, CAM promotes limbal stem cell expansion, cellular migration, and epithelialization, and it expedites recovery, suppresses pain, and reduces fibrovascular ingrowth and neovascularization.6-10

Those properties are not associated with DAM.6 Unlike CAM, DAM is contraindicated in cases of infectious keratitis, which is clearly stated on the package insert. This means that AM would have to be cryopreserved if used for patients with herpes simplex or bacterial infectious keratitis.

Related: Corneal keratometry and corneal astigmatism changes after surgery for acquired ptosis

I have tried a variety of dehydrated AM products, but due to the cryopreserved biologics in CAM and their associated capabilities, I now use CAM exclusively. It’s a matter of understanding that with DAM you get wound coverage, but with CAM you get wound healing.6

Clinical applications

Whereas AM grafts once relied on sutures and were relegated to the operating room, AM grafts now can be easily applied in the office setting. Cryopreserved Prokera is a sutureless graft delivered via a self-containing conformer ring that helps maintain its placement.

I use Prokera to treat recurrent corneal erosion (RCE), epithelial basement membrane (EBMD), persistent epithelial defects, chemical burns of the ocular surface, corneal epithelial defects such as those associated with bullous or band keratopathy, keratitis, and corneal ulcers, among other things. More than 20 of my patients with RCE have avoided phototherapeutic keratectomy because of successful treatment with Prokera.

I previously used CAM for only the worst cases—filamentary keratitis, neurotrophic ulcers, and superficial punctate keratitis that wouldn’t resolve. But now I use CAM to treat conditions such as RCE, infectious keratitis, and moderate to severe dry eye disease with great success.

CASE STUDY: A 68-year-old White woman was referred for persistent keratitis OS and failure on multiple medications.

CASE STUDY: A 68-year-old White woman was referred for persistent keratitis OS and failure on multiple medications. Click to read more!

Pictured: The eye 6 days after application of Prokera Slim. (All figures courtesy of Greg Caldwell, OD, FAAO)

It’s an ideal intervention in these cases because it heals the cornea and the ocular surface, and it has been shown to restore nerve function.8 So instead of waiting for the nerves to die off and then trying to bring sensation back, I introduce CAM earlier in the process to circumvent potential enervation.

When a patient presents with persistent keratitis and is at risk for scarring and vision loss, Prokera is my go-to treatment.

These patients have not healed despite previous treatment with a gamut of traditional therapies such as cyclosporine (Restasis), lifitegrast ophthalmic solution (Xiidra), prednisolone acetate ophthalmic suspension 1%, loteprednol etabonate ophthalmic suspension 0.5% (Lotemax), and cyclosporine ophthalmic solution (Cequa).

Their condition may be the result of contact lens use or multiple medications, or they may have had a prior infectious process that transitioned into a cornea that will not heal.

Related: Contact lens overwear leads to short-term, long-term consequences

As healing occurs with Prokera, the inlay membrane dissolves, and in the majority of cases, there is no need for a second application. In some infectious keratitis and severe EBMD cases, a second Prokera application is called for when the disease causes the wound to reopen or the infection is so bad that it dissolves the membrane in 1 to 2 days.

After debriding the wound in RCE, I reapply Prokera. After approximately 5 days, the inlay membrane dissolves, the patient returns to my office for ring removal, and I place a bandage contact lens for 30 days.

This is the same protocol that I follow for a first episode of RCE treated with CAM. The majority of patients with RCE respond sufficiently to 1 CAM treatment, but it helps to know that a second application may be necessary.

Optometrists who are wary about venturing into AM use should keep in mind that if a patient presents with a condition that could benefit from CAM, they should consider referring that patient to an optometrist rather than automatically considering an ophthalmologist.

There are plenty of optometrists who are experienced in placing Prokera as well as many who are eager to gain experience, and they would welcome the opportunity to treat your patient.

One of the reasons that I have heard optometrists say they shy away from CAM is they are under the impression that there is significant discomfort associated with the Prokera conformer ring. In my experience, that is not the case.

Some patients experience temporary discomfort, but I find that if they are made aware of the potential for mild to moderate discomfort, and they know what to expect, they invariably are not troubled by it.

Often with this treatment I can help these patients gain some visual acuity, and once the Prokera treatment is complete and they are seeing better, the temporary discomfort is quickly forgotten.

Related: Guideline redefines amniotic membrane’s role in ocular surface disease

I want optometrists to know that this is a relatively easy procedure with a short learning curve, and it is no more difficult than placing a contact lens once the proper technique is learned.

Many of my peers who are comfortable using CAM reserve it for bacterial ulcers, infectious keratitis, and dry eye. I cannot emphasize enough how effective Prokera is for conditions such as RCE and limbal stem cell burnout.

When I explain to patients that the cornea will heal on its own if they avoid contact lens wear for a year, or I can add steroids and maybe rehabilitate the limbal cells in 6 months, or I can use a regenerative therapy with growth factors to heal the cornea much faster, they are typically excited about the prospect of Prokera.


Optometrists have lobbied too hard and too long for the right to provide therapeutic treatments to our patients for us to eschew any opportunities. AM treatment is one of those opportunities, and cryopreserved AM treatment, in particular, is a critical tool for us to have in our armamentarium.

In-office application of sutureless, self-retaining CAM is no more difficult than placement of various types of contact lenses, and we owe it to our patients to help them avoid surgery while achieving excellent outcomes whenever possible.


1. de Rötth A. Plastic repair of conjunctival defects with fetal membranes. Arch Ophthalmol. 1940;23(3):522-525. doi:10.1001/archopht.1940.00860130586006

2. Tseng SCG. HC-HA/PTX3 Purified from amniotic membrane as novel regenerative matrix: insight into relationship between inflammation and regeneration. Invest Ophthalmol Vis Sci. 2016;57(5):ORSFh1-8. doi:10.1167/iovs.15-17637

3. Jirsova K, Jones GLA. Amniotic membrane in ophthalmology: properties, preparation, storage and indications for grafting-a review. Cell Tissue Bank. 2017;18(2):193-204. doi:10.1007/s10561-017-9618-5

4. Röck T, Bartz-Schmidt KU, Landenberger J, Bramkamp M, Röck D. Amniotic membrane transplantation in reconstructive and regenerative ophthalmology. Ann Transplant. 2018;23:160-165. doi:10.12659/AOT.906856

5. Watson CT, Breden F. The immunoglobulin heavy chain locus: genetic variation, missing data, and implications for human disease. Genes Immun. 2012;13(5):363-373. doi:10.1038/gene.2012.12

6. Cooke M, Tan EK, Mandrycky C, He H, O’Connell J, Tseng SC. Comparison of cryopreserved amniotic membrane and umbilical cord tissue with dehydrated amniotic membrane/ chorion tissue. J Wound Care. 2014;23(10):465-474, 476. doi:10.12968/jowc.2014.23.10.465

7. Mcgaughy AG, Gupta PK. In-office use of amniotic membrane. EyeNet. February 2015. Accessed November 23, 2021. https://www.aao.org/ eyenet/article/in-office-use-of-amniotic-membrane

8. John T, Tighe S, Sheha H, et al. Corneal nerve regeneration after self-retained cryopreserved amniotic membrane in dry eye disease. J Ophthalmol. Published online August 15, 2017. doi:10.1155/2017/6404918

9. Morkin MI, Hamrah P. Efficacy of self-retained cryopreserved amniotic membrane for treatment of neuropathic corneal pain. Ocul Surf. 2018;16(1):132-138. doi:10.1016/j.jtos.2017.10.003

10. Pachigolla G, Prasher P, Di Pascuale MA, McCulley JP, McHenry JG, Mootha VV. Evaluation of the role of ProKera in the management of ocular surface and orbital disorders. Eye Contact Lens. 2009;35(4):172-175. doi:10.1097/ICL.0b013e3181a66a12

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