For more than 50 years, science has understood that the amniotic membrane, the innermost layer of the human placenta, has powerful anti-inflammatory and antifibrotic properties. And, when it comes to ocular surface surgery, few materials provide the powerful properties of the human amniotic membrane. Amniotic membrane (also called amnion) can significantly improve outcomes for your patients.

The first documented ophthalmological application was in the 1940s, when it was used in the treatment of ocular burns, according to a January/February 2014 article in Survey of Ophthalmology. More than 25 years ago, Juan Batlle, MD, described the use of amniotic membrane as a conjunctival substitute.¹ His research ushered in the modern era of amniotic membrane surgery.

Amniotic membrane is readily available and has a long shelf life. For example, Katena’s amniotic membrane products have a five-year shelf life when packaged and sterilized, while Bio-Tissue’s cryopreserved product shelf life is two years when kept at a temperature range of -112°F to 39°F (-80°C to +4°C), according to the companies.

Amnion come in two forms:

1. Dehydrated. Prepared by removing moisture from the amnion and terminally radiating it to ensure sterility
2. Cryopreserved. Prepared by freezing the hydrated amnion

Whatever the form, the clinical performance of the amniotic membrane is the same. Surgeons should select the form of amniotic membrane they feel best suits their surgical preference.

In this article, I review how amniotic membrane can help patients with pterygium and nonhealing surface defects.

PTERYGIUM SURGERY

Approaches

Amniotic membrane provides significant benefits in pterygium surgery, where a main objective is to prevent recurrence of the pterygium. In general, surgeons have four common approaches:

1. Excision of the pterygium and bare sclera healing
2. Excision and conjunctival autograft
3. Excision and amniotic membrane transplant
4. Excision and conjunctival autograft as well as subconjunctival amniotic membrane transplant

In the bare sclera technique, the surgeon removes the pterygium but does not provide a barrier to pterygium growth. This is an easy technique but does not provide optimal results — various reports indicate recurrence rates ranging from 24% to 89%.^2-4

Results with the conjunctival autograft method are far better, with recurrence rates around 5% in low-risk patients.⁵ After excising the pterygium, the surgeon takes a thin graft from the superior conjunctiva (Figure 1). Once cut free, the graft is laid with its epithelial side against the corneal epithelium and moved nasally toward the limbus at the excision site. Thrombin is applied to the bare sclera and fibrinogen to the back of the graft. When the graft is inverted, these two materials mix for adhesion. The eye is then patched and shielded.

Using amnion

Instead of bare sclera or a conjunctival autograft, the surgeon can use amniotic membrane as a graft. After fully excising the pterygium, the surgeon may place mitomycin 0.025% on small pledgets for one to three minutes in the subconjunctival space surrounding the excision site to reduce recurrence. The pledgets are then removed, and the surgeon rinses the application area copiously with balanced salt solution.

To use the amnion, the surgeon cuts it within its surgical packaging to the appropriate size. The thickness allows ease of placement and for the amnion to remain on the ocular surface for at least several weeks following surgery. Typically a membrane thickness of 35-100 μm is used for this purpose.

The surgeon should make sure to place the amniotic membrane at least a few millimeters beneath the surrounding conjunctival tissue, because the fibroblasts that can lead to pterygium recurrence reside in this area. In this same area, protected from the ocular surface by the remaining conjunctiva, the amnion stays in place for many weeks, exerting its antifibrotic and anti-inflammatory effects long after the patient discontinues eyedrops. Postoperative management is similar to the autograft method.

The amniotic membrane technique provides a number of benefits. First, similar to the conjunctival autograft, the recurrence rate is around 5%.⁶ In addition, this method avoids surgery at a second site to harvest the autograft, which could complicate future glaucoma surgery. What’s more, comfort and the cosmetic appearance, particularly in the early postoperative stage, may be better for the patient.

Combination method

The fourth method involves the combined use of conjunctival autograft and placement of amniotic membrane in the subconjunctival space surrounding the excision site (Figure 2). This is used mostly for high-risk patients, including those with larger or inflamed pterygia or ptergyia that are likely to recur, especially pterygia that have been previously excised.

After excising the pterygium, the surgeon harvests a conjunctival autograft, leaving it attached at the limbus. Then, the surgeon opens the potential space beneath the surrounding subconjunctiva and cuts the amniotic membrane in a C-shape configuration to conform to the shape of the surrounding tissue. This graft is then tucked into the subconjunctival space. Here, thinner amnion is used, about 35-50 μm, which is ideal for cutting and handling and allows it to remain quietly in the subconjunctival space for many months after surgery.

It is not essential to keep all sides of the amnion with its basement membrane side up. In this case, the amnion is used mostly as a depot of anti-inflammatory activity, so its orientation does not matter quite as much. Then, the conjunctival autograft is placed identically as discussed earlier.

With this technique, one study showed a recurrence rate of about 1% without the use of mitomycin.⁵

NONHEALING SURFACE DEFECTS

A variety of uses

Beside its use in pterygium surgery, amniotic membrane can aid patients with nonhealing surface defects, especially those patients with difficult defects.

Causes of the neurotropic cornea that underlies the nonhealing surface defects include rheumatoid arthritis, dry eye with chronic, vision-threatening epithelial defects, herpes simplex and herpes zoster.

By healing the surface defect quickly, the surgeon can help the patient avoid infection and potential impaired vision. For the patient who has failure to heal with eye drops, surgeons can proceed quickly to amniotic membrane instead of continuing the drops. In these cases, amniotic membrane provides a barrier to friction, separating the eyelid from the cornea. It also provides antifibrotic and anti-inflammatory effects that permit tissue healing.

Forms

For nonhealing surface defects, self-retaining amniotic membrane is most useful. Two forms are most commonly used.

The first form is a circular disk of dehydrated amniotic membrane that is placed on the eye with a soft contact lens. This holds the amnion in place, usually for at least two weeks, until the amnion eventually dissolves. This particular application is unique to Katena’s AmbioDisk.

The second is a cryopreserved amnion, which is wet. It is delivered to the eye on a plastic ring that is tucked into the eyelid and is larger than the cornea.

Both the contact lens and plastic ring need to be removed after epithelial healing is complete.

ESTABLISHED SUCCESS

Amniotic membrane usage is a well-established technology that has applications in pterygium and nonhealing defects of the cornea.

While historically the purview of cornea specialists, any general ophthalmologist who treats advanced ocular surface disease should be familiar with amniotic membrane. OM

REFERENCES

1. Batlle JF, Perdomo FJ. Placental membranes as a conjunctival substitute. Ophthalmol. 1993;100:A107.
2. Sebban A, Hirst LW. Treatment of pterygia in Queensland. Aust N Z J Ophthalmol. 1991;19:123-127.
3. Chen PP, Ariyasu RG, Kaza MD, et al. A randomized trial comparing mitomycin C and conjunctival autograft after excision of primary pterygium. Am J Ophthalmol. 1995;120:151-160.
4. Jaros PA, DeLuise VP. Pingueculae and pterygia. Surv Ophthalmol. 1988;33:41-49.
5. Shusko A, Hovanesian JA. Pterygium excision with conjunctival autograft and subconjunctival amniotic membrane as antirecurrence agents. Can J Ophthalmol. 2016;51:412-416.
6. Hovanesian JA, Starr CE, Vroman DT, et al. Surgical techniques and adjuvants for the management of primary and recurrent pterygia. J Cataract Refract Surg. 2017;43:405-419.

About the Author

John A. Hovanesian, MD, FACS, is a specialist in cataract, refractive and corneal surgery at Harvard Eye Associates in Laguna Hills, Calif. He is also a member of the clinical faculty at UCLA Jules Stein Eye Institute in Los Angeles, Calif.

Disclosure: Dr. Hovanesian is the medical director at Katena.