Stage 3 Dry Eye Treatments: Amniotic Membrane Grafts

Part 2 of a four-part Q&A series about advanced dry eye disease treatments.

By Abby Gillogly Harsch, OD, and Nicole Stout, OD; with Richard B. Mangan, OD

Patients with dry eye disease (DED) who have been treated with artificial tears, warm compresses, omega-3 fatty acid supplements, and prescription medication without relief of symptoms likely fit into the category of stage 3 DED. Stage 3 is defined by significant corneal staining and limitations of lifestyle activities as a result of discomfort.1 Treatments for patients with stage 3 DED may include one or more of the following: autologous serum (which was covered in part 1 of this series; see the box at the end of this article), amniotic membrane (AM) transplantation, punctal cautery, and scleral contact lenses.

We interviewed experts in the field about common questions that arise when use of these advanced treatment options for stage 3 DED is considered. In this installment, Doug Devries, OD, and Chris Wroten, OD, joined us to discuss the use of AM grafts. AM tissue is available in both cryopreserved and dehydrated forms and is often utilized clinically for nonhealing ocular surface defects.

—Abby Gillogly Harsch, OD, and Nicole Stout, OD

In what type of DED patient would an AM graft be most beneficial?

Douglas Devries, OD: I utilize AM grafts for patients who continue to have unresolved keratitis every time I examine them despite advanced treatment for DED, which means that the cornea is recalcitrant to healing. This is when I have found cryopreserved AM to be useful.

Chris Wroten, OD: I use AM in patients with severe DED that has significantly compromised the epithelium and/or underlying corneal tissues, or in those who have had symptoms recalcitrant to other traditional DED treatments.

What is your recommended follow-up schedule for patients treated with AM?

Dr. Devries: I schedule the patient to return in 4 to 7 days.

Dr. Wroten: I ask the patient to return 1 week after initial AM graft placement, then as indicated based on resolution of signs and symptoms, and as appropriate based on other concurrent treatments being used.

In what time frame do you expect patients to notice improvement of their symptoms with this treatment?

Dr. Devries: Of course, when the AM graft is on, the cornea begins to heal, but I really see continued improvement 2 to 3 weeks after the membrane has dissolved.

Dr. Wroten: Many patients experience symptomatic improvement within 1 to 2 weeks of initial AM application. If clinical signs and/or symptoms persist, a second course of AM therapy may be beneficial. If there is no definitive improvement in signs or symptoms after initial AM therapy, however, I would be hesitant to apply additional AM grafts.

What are the clinical contraindications for use of AM?

Dr. Devries: Allergies to ciprofloxacin or amphotercin B are contraindications to the use of cryopreserved AM. Patients who have had glaucoma filtering surgery are also contraindicated.

Dr. Wroten: Obviously, it is imperative to adequately treat the infection first, before using AM, in patients with infectious keratitis. Depending on the AM used, in cases of severe ocular surface inflammation, it may also be prudent to initiate antiinflammatory pharmacologic treatment first. Additionally, graft intolerance, allergy to any components of the preservation media used for the AM (eg, ciprofloxacin and amphotericin B in Prokera [Bio-Tissue]), and prior glaucoma filtering surgeries are potential contraindications for AM use.

What are the risks and complications for patients treated with AM?

Dr. Devries: With any amniotic tissue, there may be some discomfort and a decrease in visual acuity in the treated eye when the AM is in place.

Dr. Wroten: In addition to foreign body sensation and blurred vision when the AM is in place, there is also the risk of contamination of the AM if it is not handled properly prior to and during insertion. Additionally, extensive precautions are taken during AM harvesting to ensure donor tissues are free of infectious diseases, but there is a risk of transmission if harvesting and preservation protocols were ever violated.

What is the most common positive or negative feedback you have received from patients treated with AM?

Dr. Devries: The most common negative feedback is the blur created during the treatment and the foreign body sensation. The most common positive feedback is how good the patient’s eye feels after the treatment.

Dr. Wroten: Positive feedback includes clinical improvement in conjunctival injection, increased clarity of vision after absorption, and—just as important to patients—a significant reduction in ocular discomfort and other traditional symptoms of DED. The most common patient complaints are foreign body sensation and blurred vision after application of the AM.

What clinical pearls can you share regarding this treatment method?

Dr. Devries: Patients with stage 3 DED are just looking for help and improvement, so they need education that this is a biologic that will help them heal themselves. Taping can help to center the AM graft when cryopreserved Prokera is used. Dry membranes must be placed with the proper side down on the cornea.

Dr. Wroten: AM therapies are still a relatively new area for our profession, but they have been used in other areas of medicine successfully for many years. They are not difficult to apply, so, when it is clinically appropriate to use them for patients, don’t be shy about trying AM. Numerous online videos and educational tools from various manufacturers are available to assist practitioners looking to use this technology for the first time.

What specific patient education should be undertaken before treatment with AM?

Dr. Devries: Patients definitely need to know about the decrease in visual acuity and the feeling of a foreign body in the eye.

Dr. Wroten: As always, setting appropriate and realistic expectations for patients regarding what they will experience during and after AM therapy is important. This includes letting patients know the temporary symptoms they may encounter and that reduction in DED symptoms may take a few weeks to be realized.

What are the pros and cons of cryopreserved AM versus dehydrated AM for DED treatment?

Dr. Devries: My clinical experience has shown greater efficacy with cryopreserved AM rather than dehydrated AM. Patients, however, will usually tolerate a dry AM with a contact lens over it a bit better than they will tolerate the 22-mm ring.

Dr. Wroten: I have more clinical experience with cryopreserved AM and find them to be slightly quicker and easier to apply, but both work well. The dry AM grafts are sometimes more comfortable for patients.

How long should a patient expect to be on this treatment regimen?

Dr. Devries: Typically, 4 to 7 days. However, if the patient has severe disease, he or she might require repeated applications of AM.

Dr. Wroten: I have not performed serial AM treatments for stage 3 DED beyond one or two applications, with each application lasting approximately 1 week (or until the AM has largely been absorbed).

Do repeated AM treatments have an additive effect? How do you determine if a patient will benefit from a repeated AM graft?

Dr. Devries: Yes, no question about it—repeated treatments have an additive effect. How much effect depends on the severity of the DED, and how the patient responds to it.

Dr. Wroten: Yes. If there is at least some improvement in clinical signs and symptoms after the initial AM graft, consider additional applications.

What is the maximum number of times you can use AM grafts in a given patient?

Dr. Devries: There is no limit other than what the clinical healing course reveals regarding efficacy.

Dr. Wroten: I agree. Theoretically, there’s no limit, but, again, if there’s no improvement in clinical signs and symptoms after the first or second AM treatment, I would not proceed with additional treatments.

What are the symptoms and signs of patient intolerance to AM or to the apparatus used to hold the membrane in place?

Dr. Devries: A patient with an allergic reaction will have diffuse chemosis. The patient can have the membrane fall out or simply not tolerate the foreign body sensation.

Dr. Wroten: Agreed. Foreign body sensation and/or an increase in ocular surface inflammation.

In a patient whose AM graft does not dissolve in the expected time frame, is there a maximum duration that it can be left in the eye safely?

Dr. Devries: An AM graft is going to have a diminishing return, but I have left cryopreserved AM on for 2 weeks or more and patients tolerated it and healed well.

Dr. Wroten: Theoretically, there is no maximum duration, but, if the AM is not dissolved within 10 to 14 days, I would remove it and use other therapies.

Do you typically recommend that patients continue frequent use of artificial tears in addition to AM treatment?

Dr. Devries: You should not really stop any previous treatments after the membrane is off because these patients are already established as having severe DED. During the course of treatment, I still have them use artificial tears.

Dr. Wroten: Yes, I think it’s critical to keep the AM moist, and artificial tears seem to help with absorption and patient comfort.

In severe DED patients with compromised corneal epithelium, do you recommend an antibiotic drop for prophylaxis?

Dr. Devries: I use an antibiotic, but only if I would have otherwise used an antibiotic if I were not putting the AM graft on.

Dr. Wroten: I agree. I would only use a topical antibiotic with AM if it was warranted to do so without the AM, as well.

1. Behrens A, Doyle JJ, Stern L, et al; Dysfunctional Tear Syndrome Study Group. Dysfunctional tear syndrome: a Delphi approach to treatment recommendations. Cornea. 2006;25(8):900-907.

From the BMC Archive

Stage 3 Dry Eye Treatments: Autologous Serum

By Abby Gillogly Harsch, OD, and Nicole Stout, OD; with Richard B. Mangan, OD Advanced Ocular Care Volume 8, Issue 4

Series Editor Richard B. Mangan, OD, FAAO
• clinical faculty, Department of Ophthalmology, University of Colorado in Boulder, Colo.
• financial disclosure: none relevant

Abby Gillogly Harsch, OD, FSLS
• optometrist, Nittany Eye Associates, State College, Pa.
• financial disclosure: none relevant

Nicole Stout, OD
• clinical instructor, University of Waterloo School of Optometry and Vision Science, Waterloo, Ontario, Canada
• financial disclosure: none relevant

Douglas Devries, OD
• cofounder, Eye Care Associates of Nevada, Sparks, Nev.
• financial disclosure: none relevant

Chris Wroten, OD, Diplomate, ABO
• chief operating officer and partner, Bond-Wroten Eye Clinics, Hammond, La.
• financial disclosure: none relevant