In the first of a two part article, Margaret Lam and leading US optometrist, Dr Art Epstein, discuss amniotic membranes for the management of complex ocular conditions.
Amniotic membranes have been effectively used in medical applications since 1910, however it has only been in recent decades that they have been applied to ocular surface repair in Europe and the United States; and in recent years that we have begun to apply them in Australia. The unique characteristics of an amniotic membrane make them ideally suited to repairing ocular tissues in conditions where there has been significant pathophysiology.
The use of amniotic membranes will change the way optometry sees itself in Australia…
Figure 1. Dense SPK due to severe dry eye.
UNIQUE CHARACTERISTICS
In all mammalian species, embryos are held in a sac made up of a foetal membrane. The outermost layer of this sac is called the chorion, the innermost is called the amnion, and, inside, the sac is filled with amniotic fluid.
The amnion itself is avascular, which as we know, is what gives its unique immune privilege, much like the eye. The amnion has three layers: the epithelium, the basement membrane, and the stroma:
- The epithelium has non-differentiated epithelial cells, which allow it to be used for corneal or conjunctival (or other mucous membrane) reconstruction.
- The basement membrane has laminin and fibronectin, which improve epithelial cell migration and strengthen adhesions on the basal cells. The basement membrane also has growth factors and cytokines, which help prevent epithelial apoptosis. This is the location where epithelial cell differentiation occurs.
- The stroma has anti-inflammatory and anti-angiogenic proteins, which inhibit inflammation, corneal neovascularisation and scarring.
As a result of their structure, the eye and the embryo are two rare immune-privileged sites in the body with protective effects to reduce inflammation. The amnion plays a critical role to protect the embryo from an immune response and amniotic membranes have an incredible capacity to repair the ocular surface.
Over a long Zoom discussion, I asked Dr Art Epstein to share his experiences working with amniotic membranes and offer his best pearls on their use in managing more recalcitrant and complex anterior eye cases.
Figure 2. Corneal erosion.
Q. How did you first start working with amniotic membranes?
Many years ago, I started working closely with ophthalmology in a hospital clinic setting which allowed me to care for patients with quite complex cases. Most recently, I have been working in Phoenix, Arizona, in a tertiary subspecialty optometry clinic. We manage dry eye, retinal disease (medical retina) and complex anterior eye cases. With COVID, we have certainly been managing even more unusual and complex cases, and these have given us the ability to extend our care and expertise. In the case of dry eye disease, we are increasingly realising that, as per findings in DEWS II, dry eye is a ‘wiring’ problem.
Specifically, I mean that the significance of homeostasis comes to the fore as a primary cause of dry eye disease. The cornea has more nerve endings than any other part in the body and, being heavily innervated, it is constantly transmitting information about the ocular surface environment. By using an amniotic membrane, one likely mechanism of treating a patient’s dry eye disease is by improving the information the cornea transmits to the central control areas of the brain.
Q. You’ve described the use of amniotic membranes as the single most significant advancement for optometry in recent years, can you explain why?
Naturally, I am a fixer – I can’t stand to see things broken. The greatest frustration for the cornea and contact lens community, both in ophthalmology and optometry, is something that is unfixable. For example, when you are managing a central corneal ulcer you know that even once healed, your patient will have corneal scarring and significantly reduced best corrected vision. And, in addition to that, there also can be a cosmetic impact.
The application of amniotic membrane will stimulate normal regrowth in recurrent corneal erosion and epithelial membrane basement dystrophy (EMBD) with a recurrent corneal erosion component
Back in the 1980s, we were seeing a lot of corneal ulcers. Although we had finally developed decent topical antibiotics – such as second-generation fluoroquinolones which were effective against pseudomonas – and we had even started using fortified antibiotics such as tobramycin and a gram positive targeting cefazolin, we would still end up with significant corneal scarring that was impeding vision.
At this time, Dr Scheffer Tseng published an article about a new holistic way of looking at the ocular surface environment and ‘the unified theory of dry eye’. In his article, Dr Tseng wrote about the integrity, and use, of amniotic membranes to restore normal corneal function. Although there had been scattered reports from Europe of using placental tissue and umbilical cord tissue, he was the first to recognise the potential for amniotic membrane to restore normal corneal function and reroute physiology back in the right direction.
Also at the time, Dr Tseng’s company Bio-Tissue was using cryopreserved amniotic membrane tissue that could be sutured in place or placed, using a rigid ring in the Prokera, which held the amniotic membrane in place to improve corneal healing.
While this was happening, I had a patient with corneal stem cell failure and phototherapeutic keratectomy (PTK). Her corneal epithelium had been replaced with conjunctival tissue that was extensively scarred. I contacted Dr Tseng about my patient, and with the use of an amniotic membrane, she recovered significantly. I met Dr Tseng years later when we copresented at a conference; surprisingly he remembered the case quite vividly.
The early use of amniotic membranes to heal corneal ulcers is particularly effective.
For instance, without applying amniotic membrane, a patient with a large central corneal ulcer would normally be left with a best corrected vision of around 6/60. With amniotic membrane application, we can expect an improvement in final visual acuity, in many cases, to 6/6 with almost no visible scarring on microscopy.
The worst part of our job is to have to explain to a patient that they are going to live with permanent loss of vision, and have a resultant, giant white opacified leucoma.
Having the ability to fix a patient’s vision by capturing the essence of normal physiology and applying it to cases of pathophysiology is incredibly empowering and rewarding – as a technique, it’s probably the most significant development I’ve seen during my career.
The use of amniotic membranes will change the way optometry sees itself in Australia, as it will improve outcomes across the board for patients.
Figure 3. Exposure due to poor lid apposition.
Q. What indications are there for amniotic membranes?
The application of amniotic membrane is indicated for any potential corneal pathophysiology that is not healing well; so for corneal ulcers and potentially for persistent non-healing peripheral corneal ulcers.
Amniotic membrane will help with dry eye with recalcitrant dense superficial punctate keratitis, and it will generally help patients with autoimmune and systemic inflammatory conditions associated with dry eye.
The application of amniotic membrane will stimulate normal regrowth in recurrent corneal erosion and epithelial membrane basement dystrophy (EMBD) with a recurrent corneal erosion component. Before application, any loose epithelial tissue should be removed. An outcome of 6/6 vision can be expected following treatment.
Q. Should you use it early on in a disease case?
Amniotic membrane is quite fascinating and can be a life-changing therapy for many patients. You can use the membrane early on – almost immediately – and it works almost like magic. That is not an easy thing for a clinician to say. The amniotic membrane releases its growth factors immediately and, as it was designed to protect and nurture survival of the foetus, it also has some antimicrobial activity (we’ll talk more on an appropriate prescribing protocol and antibiotic regimen to prescribe in the July issue of mivision).
Q. What is the difference between dehydrated and cryopreserved amniotic membranes?
In the US, we have both cryopreserved and a variety of dehydrated membranes, also known as dry membranes.
In Australia, Designs for Vision supplies AmnioTek (ISP Surgical), a dehydrated amniotic membrane.
In my experience, the cryopreserved membrane, while less comfortable for the patient, is a bit more powerful for its efficacy, because they capture a higher order and create more flow of growth factors. However, all amniotic membrane types can be very helpful.
Cryopreserved amniotic membranes are held in a ‘sheet’, are similar to the shape of a scleral lens, are applied with a hard ring, and come in contact with the upper eyelid. Cryopreserved amniotic membranes are unique to Dr Scheffer Tseng’s company, Bio-tissue, and are not currently available in Australia.
A dry amniotic membrane is much more comfortable for a patient than a cryopreserved amniotic membrane, as there is no hard ring and it is applied with a soft bandage contact lens.
The performance of the dry amniotic membrane will depend on how the process captures the active elements of the membrane – you may be lucky in Australia as the processing may capture many of the active elements.
Q. What is the difference between clinical performance of cryopreserved vs dry amniotic membranes?
In my experience, while dry are perhaps slightly less effective than cryopreserved amniotic membranes, both are effective. Dry does have the advantage of being significantly more comfortable for the patient.
For example, in the case of recurrent corneal erosions (RCEs), a cryopreserved membrane will usually heal with complete corneal clarity and no corneal scarring.
In comparison, dry amniotic membranes, again depending on how the process captures the active elements, will heal with slightly more glare and slightly more haze.
With a cryopreserved membrane, the amniotic membrane sits suspended by the retaining ring, in contact with the cornea, and the faster the healing, the faster the membrane dissolves. The ring is all that is left once it has fully healed.
A dry amniotic membrane is always placed under a bandage contact lens, which impedes tear flow and the active exchange of elements from the membrane. Like the cryopreserved membrane, as the eye heals, the membrane dissolves.
Sometimes with dry amniotic membrane, a second application may be necessary if the issue hasn’t fully resolved, for example, in the case of recalcitrant superficial punctate keratitis (SPK). However, further applications are not appropriate – if the case remains unresolved after the second application, consider the use of a therapeutic anti-inflammatory agent or another course of treatment.
In the July issue of mivision we will return to Margaret Lam’s conversation with Dr Art Epstein, who will share his procedural techniques for successful application of amitotic membrane.
Dr Margaret Lam is the National President of the Cornea and Contact Lens Society of Australia, a National Director of Optometry Australia and a Director of Optometry NSW/ACT. She teaches at the School of Optometry at UNSW as an Adjunct Senior Lecturer and works as the Head of Optometry Services for George and Matilda Eyecare.
Dr Arthur B. Epstein, OD, FAAO is a native New Yorker who grew up in the Bronx, NY. He received an O.D. degree from the State University of New York, State College of Optometry where he also was the college’s first resident in ocular disease. After relocating to Phoenix, Dr Epstein co-founded Phoenix Eye Care, PLLC. He heads the practice’s Dry Eye – Ocular Surface Disease Centre – The Dry Eye Centre of Arizona and serves as its Director of Clinical Research. Active in the profession, Dr Epstein is a fellow of the American Academy of Optometry and is a Distinguished Practitioner of the National Academies of Practice. He is a Diplomate of the American Board of Certification in Medical Optometry, a member of the American and Arizona Optometric Associations and Past-Chair of the AOA Contact Lens & Cornea Section. Dr Epstein is a prolific author who has published many hundreds of articles, scientific papers, and book chapters. He is a contributing editor for Review of Optometry and executive editor of Review of Cornea and Contact Lenses. He founded and serves as chief medical editor of Optometric Physician, the first and most widely read E-Journal in eye care. Dr Epstein is a reviewer for numerous clinical and scientific journals. A sought-after speaker, he has presented more than 1,250 invited lectures on a variety of topics nationally and in more than 50 countries across the globe. He especially enjoys his visits to Australia and New Zealand.
