Natural Protection

In comparison to some medications that can result in immense feelings of discomfort for patients suffering from dry eye disease (DED), the use of amniotic membranes has been shown to heal various forms of corneal disease and DED without causing extensive ocular surface damage.

Amniotic membrane transplants (AMTs) promote healing through upregulated expression of several growth factors, including EGF and PDGF-B (1), and also play a prominent role in reducing inflammation by switching macrophage phenotypes from a pro-inflammatory M1 state to an M2 anti-inflammatory state (2). Other prominent effects that help promote healing in corneal disorders include anti-microbial activity and the ability to inhibit matrix metalloproteinases.

In addition to causing dryness, several diseases, including glaucoma, may cause a deficiency in limbal stem cells due to mechanical deterioration and denervation of the ocular surface. It is believed that the deficiency of stem cells may be readily augmented through the use of amniotic membranes, which contain placental derived tissue, rich in stem cells.

Currently, two main forms of AMTs are available on the market and used broadly by ophthalmologists for treating ocular surface disease: cryopreserved or dehydrated.

Although a more complex process, previous studies have indicated that cryopreservation is effective at maintaining both the quantity and activity of biological signaling proteins found within the amniotic tissue (3). Several of the most important components that are maintained via cryopreservation include heavy chain hyaluronic acid, which is complexed with Pentraxin 3, collagen, fibronectin, and growth factors (4). One notable drawback of cryopreserved amniotic membranes is that they carry a high monetary cost because of their strict storage requirements (5).

Dehydrated amniotic membranes are certainly a cheaper alternative to their cryopreserved counterparts – primarily because they can be stored at room temperature; however, studies have also shown that dehydrated amniotic membranes are less effective at maintaining the availability and activity of important biological factors that influence healing and tissue regeneration (6).

For Joshua Cohen, both cryopreserved and dehydrated amniotic membranes are an integral part of his treatment regimen at the Cohen Laser & Vision Center in Boca Raton, FL. He believes that AMTs can be a powerful tool for treating many forms of corneal disease. As a third-year medical student who is interested in becoming an ophthalmologist, I had the opportunity to sit down with Cohen to discuss the use of AMTs in his clinical practice.

What are the most common clinical indications that qualify a patient for an amniotic membrane transplant?
 

Amniotic membranes are a very useful tool for patients who are experiencing slow healing or non-healing epithelial keratopathy of the cornea. The most classic indications would be a neurotrophic keratitis or non-healing ulcer, which is typically caused by a herpetic infection of the eye or prior surgery or trauma. AMTs can also be used for patients who have poorly controlled dry eye disease and a history of a muted response to traditional treatment options. We also employ AMT after superficial keratectomy to accelerate healing after corneal debridement for a variety of conditions, including Salzmann nodules. Additionally, glaucoma patients who are unable to be weaned off topical therapies and experiencing corneal decompensation may also benefit from AMTs.

Once you decide that the use of an AMT is appropriate, how do you decide which type of AMT to use?
 

For patients who have mild to moderate corneal disease, we will start with a dehydrated membrane. If that initial treatment doesn’t work, we will jump to a cryopreserved membrane. If the patient has significant disease, a very large defect, or if we are concerned that the patient may be rubbing their eye to the point of dislodging the contact lens, we will go straight to a cryopreserved membrane.

Is the insertion process the same for both dehydrated and cryopreserved membranes?
 

For a dehydrated AMT, we’ll start by prepping the eye with a topical anesthetic, such as proparacaine, and we may also use a drop of dilute 5% beta-iodine if we are treating an infectious ulcer. While a technician holds the patient’s eyelids open, I place an AMT onto the patient’s cornea using a set of jeweler’s forceps. We will use a 10–12 mm graft depending on the size of the defect. A bandage contact lens is then placed over the top. We will leave the contact lens on the eye for one week, providing the patient with a topical antibiotic and possibly a steroid, depending on the underlying etiology of their disease.

For a cryopreserved membrane, we most commonly use a Prokera Slim due to accessibility and patient comfort. To prep the eye, we do a fairly aggressive irrigation of the membrane with a sterile BSS solution. Insertion of the membrane is done in a similar manner, but the cryopreserved membrane must be inserted with a specific orientation. After we insert the membrane, we often take a piece of tape, 4–7mm, and tape the upper-lid to keep the lid partially closed. This is done to prevent the membrane from popping out. The patient will receive antibiotic drops and will be brought back in one week.

Have you noticed any differences in patient tolerability or clinical outcomes between patients who have received cryopreserved versus dehydrated membranes?
 

I think that patients find the dehydrated amniotic membranes more comfortable overall because they only require the use of a soft contact lens. Therefore, they are not as irritating around the rim of the eye when compared with cryopreserved membranes. For patients with smaller orbits or recessed adnexal structure, the dehydrated is typically more suitable. Contrarily, for patients with irregular corneas, such as those who have keratoconus or significant scarring, a cryopreserved amniotic membrane may be helpful because it provides more support and covers a wider area along the periphery of the cornea.

Overall, we have found success with both. I wouldn’t say that either is perfect. If I had to only choose only one, I think cryopreserved membranes offer high patient satisfaction and can treat more severe diseases.

I imagine many patients have not heard of an AMT… Have you had any difficulty proposing this treatment to prospective patients? And how do you help to manage their expectations?
 

Proposing the use of a membrane can sometimes be a challenging discussion to have; treatments that involve human tissue can sometimes be off-putting to patients. It is important to remind patients that this tissue is cultured from human placentas that have been donated and designated for this purpose, and that no fetal tissue is involved. This can help patients overcome any ethical concerns that they may have.

As far as expectations go, I always tell patients that this is one ingredient in their treatment regimen and that it may not be the be-all-end-all – but oftentimes it is. It is important to explain that the treatment itself can be discomforting and may worsen vision temporarily. We always have to counsel patients to expect blurriness for the first week. It is important for patients to know that they may not notice improvement until the membrane is removed. Even after the membrane is removed they may not be fully healed, in which case we can discuss re-applying the AMT or converting to other medical therapies.

Will AMTs become a more popular treatment option in the future – and do you have any concerns about this treatment overall?
 

I think it’s important for doctors and patients to have an awareness of AMTs in the back of their mind. They should know that there may be a solution that has a short duration of therapy but can have a long-lasting beneficial impact. AMTs may also offset the burden of additional drops or therapies that can be overwhelming for patients, especially in the glaucoma population.

That said, I would also offer a word of caution: we do not want to overuse these products. Patients can get good relief with conventional therapies. The cost of overusing AMTs could ultimately decrease patient accessibility and reimbursement moving forward. Therefore, being judicious with AMTs is critical – knowing the right time to use an AMT is the real art of this particular procedure. Ultimately though, I think that they’re easy to use, very helpful, and it is fortunate that most patients can access this tool financially. The AMT is an invaluable intervention that has allowed patients to find the road to recovery when nothing else has worked for them.

For comment, please email [email protected] or call 561-702-6124.