The use of amniotic membrane in wound care has been part of clinical practice for over a century, with its first use in ophthalmology reported in the 1940s.1 Following World War II, when the need for innovation in wound care was critical, the use of amniotic membrane in healthcare proliferated.
However, historically there have been multiple significant barriers to its widespread adoption by ophthalmologists, optometrists, opticians and other optics professionals in eye care.
What is amniotic membrane and how can it be used in wider eye care?
Amniotic membrane holds significant therapeutic promise in a wide range of medical fields due to its natural healing properties. A waste product of birth, amniotic membrane possesses unique structural and rich biological attributes that can provide an environment that is conducive to natural healing and recovery.
The raw tissue is ethically collected under fully informed consent from pregnant women due to undergo elective caesarean section. The tissue makes up the innermost layer of the placental sac, which is closest to the baby in the womb. One of the thinnest membranes in the human body, this tissue is composed of five layers; the epithelium; basement membrane; compact layer; fibroblast layer; and spongy layer.
Amniotic membrane functions to protect and nurture the developing foetus during pregnancy, where it reduces the risk of infection, prevents injury and subsequent foetal scarring, and protects the baby from being rejected by the mother’s own immune defences.
Due to the nature of its role and unlike other tissues in the body, amniotic membrane’s structure and rich collection of bioactive proteins allows the tissue to support natural healing, prevent development of inflammation, minimise adhesions and limit scar formation.
Due to these properties, the use of amniotic membrane in supporting healing in areas across the body, and in multiple conditions, has been extensively researched. It has become a standard for care of chronic wounds, and in ophthalmology it has become a standard intervention in the management of corneal defects.
In recent years, studies have shown the clinical efficacy of amniotic membrane in stimulating natural healing by promoting epithelialisation while suppressing inflammation, angiogenesis and scarring.2
This has led to the conclusion that amniotic membrane may not only facilitate ocular healing during reconstruction procedures, but also support the stabilisation and recovery of the eye’s surface in cases such as acute chemical burns, persistent corneal epithelial defects and corneal ulcers.3
However, its use has previously been restricted due to limitations associated with storage, preservation and the requirement for surgical application in ophthalmology.
The historic use of amniotic membrane in eye care
The first professional to perform a human amniotic membrane transplantation in medicine was John Staige Davis, who used the tissue to provide skin substitutes for treating open wounds in 1910.4
In the 1940s, de Rotth described the first clinical use of fresh amniotic membrane in ophthalmology as a substrate for the management of conjunctival defects.5 Despite these developments, amniotic membrane remained under the radar in the management of eye conditions until the mid-1990s, when Dr Scheffer CG Tseng and JC Kim reported the use of amniotic membrane for ocular surface transplantation in a rabbit limbal stem cell deficiency model when more clinicians began to take note.6
A short while later, in 1997, Tseng founded BioTissue, which was the first company to introduce the use of cryopreserved amniotic membrane tissue for clinical application. Dr Tseng was highly prolific and progressive in his research and publication of the benefits of amniotic membrane as a treatment in ophthalmology.
However, there were limitations in the extent to which this original presentation of amniotic membrane could be used by professionals in eye care, as the tissue needed to be surgically grafted onto the surface of the eye to keep it in place to support natural wound healing. The issue of retaining the tissue on the surface of the eye led to inconsistencies in how it was applied – for example some clinicians used sutures while others used glue.
Storage limitations also presented a barrier to the widespread use of amniotic membrane. Originally the only suitable preservation method was cryopreservation where the tissue was stored frozen at -80°C. This meant the tissue was subject to costly cold chain logistics and storage requirements, significantly limiting accessibility at the point of care.
The limitations discussed above meant that the resurgence in interest in the use of amniotic membrane declined and led to the tissue becoming a treatment of last resort for use in the treatment of severe disease.
How can research lead to mass adoption of amniotic membrane?
There has long been a debate regarding how amniotic membrane works. For example, one dogma is that it acts as a simple biological scaffold, while later research has shown that the tissue preserves rich and diverse biochemical makeup that supports improved healing and surface regeneration.
In the early 2000s, I started my research at University of Nottingham’s ophthalmology department, investigating how amniotic membrane may work. We started to understand its unique properties and how we could overcome conventional barriers to its use, for example, through the discovery and development of unique preservation and storage processes.
We had a clear understanding of the beneficial properties contained in amniotic membrane and its potential uses, however, its drawbacks were well-known at the time. My research led me to discover that cryopreservation, (usually storing the tissue at around -80°C), is not a sophisticated method of preservation and can lead to degradation of the tissue’s integrity and a reduction in its beneficial properties. There were also, of course, significant cost and logistical issues with storage and transportation of cryopreserved tissue.
Amniotic membrane has a composition similar to the layers of the cornea, however, it can be challenging to maintain its natural integrity due to the tissue being difficult to process and store without inducing damage. For example, during my research I found that cryopreservation creates ice crystals, which can damage the integrity of the tissue.
Looking under an electron microscope, we discovered that after thawing and washing the membrane following cryopreservation the damage caused by these crystals had an adverse impact on the beneficial properties of the tissue.
Cryopreservation also led to inconsistent efficacy, as every amniotic membrane needed thawing and washing which introduced variability. Our research highlighted that the understanding of the effects of processing on the tissue was very limited.
Next generation amniotic membrane technology
My research led us to developing new preservation and storage methods that transformed the quality and usability of amniotic membrane, opening up the potential to treat a wider range of patients much earlier in the care pathway.
This focus on new storage and processing methods allowed amniotic membrane to be delicately dehydrated, shipped and stably stored at room temperature. This not only ensures the natural barrier function benefits of the amniotic membrane are retained but gives healthcare professionals the option to use it in their clinical practice as specialist equipment is not required to be able to store it correctly.
Currently, the management of eye conditions is a relatively reactive pathway with the treatment of the majority of conditions escalating as they become more severe. This can lead to more protracted, expensive and complex treatment solutions.
The deployment of innovative solutions, like amniotic membrane, can support a more proactive pathway where potential concerns are identified and treated before they become severe.
Amniotic membrane may prove to be valuable in preventative care, potentially saving resources and yielding better patient outcomes through earlier intervention and reducing the risk of disease progression. For example, the complexity and funding requirements for surgery has meant that it previously was not possible for patients with superficial ocular diseases to be treated with amniotic membrane.
Our innovations mean that this is no longer the case and now patients can be treated with amnion earlier following their diagnosis.
Alongside understanding preservation and storage methods, my research also focused on developing new methods of transplanting
amniotic membrane onto the surface of the eye without the need for surgery.
This led to the development of a unique specialised bandage contact lens, which enables the loading and application of amniotic membrane onto the eye in a straightforward four-to-six-minute procedure, eliminating the need for surgery.
This has led to a recent resurgence in the clinical deployment of amniotic membrane, particularly in an outpatient setting. Not only have innovations, such as this specialised bandage contact lens, made amniotic membrane a more accessible and affordable option for professionals, but non-surgical interventions also enable greater consistency in each procedure.
This therefore supports healthcare professionals in developing a wider understanding of the benefits of amniotic membrane as we are seeing consistent results and a significant number of successful treatments across multiple patients.
The amniotic membrane developed during my research can be used in the management of multiple ocular surface indications including epithelial injury, inflammation, corneal pain and potentially fibrosis. Innovative methods of application that allow for suture-free transplantation enable amniotic membrane to be applied as a temporary onlay (patch), which acts as a biological bandage. This protects wounds, physically prevents inflammation, adhesion development and supports pain management whilst facilitating tissue recovery.
The main objective in the use of amniotic membrane in the treatment of eye conditions is to expedite natural healing and reduce the development and progression of inflammation and fibrosis to avoid scarring.
This, of course, means that amniotic membrane can now be considered for a multitude of conditions including recurrent corneal erosions, superficial inflammatory conditions, and moderate-to-severe dry eye disease, which traditionally would be excluded from the benefits of amniotic membrane transplantation.
I hope that as more professionals become aware of the potential uses and benefits of amniotic membrane, we will see a widespread adoption of this therapeutic option in primary care settings, enhancing patient care.
What can amniotic membrane do for opticians and their patients?
The ophthalmology service in the NHS has the second-highest waiting list with 630,000 people and is the busiest outpatient service.7 If you read the front pages of the UK’s national newspapers in December 2023, you would have likely seen headlines such as ‘Eye patients pay for private treatment - or risk going blind in NHS backlog’.8
With the Independent reporting that one patient had to pay £3,000 for emergency eye procedure or risk going blind due to a three-week NHS wait, it is clear that, as an industry, we need to work together to do what we can to deliver more accessible and effective interventions.9
The key to improving this situation lies in the development of and access to innovative and clinically proven technological solutions that can allow care pathways to be optimised so that care can be delivered effectively.
When it comes to the taxpayer, longer waiting lists and services under pressure can create a significant economic burden. According to recent research, getting people off waiting lists could bring benefits equivalent to £73bn between 2023 and 2027.10
While the case for reducing waiting lists for non-emergency treatment, such as ophthalmology, has historically been made with reference to human cost, there are significant and diverse economic benefits for tackling this backlog.
With the UK ophthalmology NHS services under serious pressure, and the added awareness of the huge impact on our economy, if we do not get waiting lists under control, it might seem like a losing battle. However, the more innovative therapeutic solutions that become available to opticians and other primary care professionals to help their patients living with a range of conditions, the easier it will be to reduce burdens on multiple stakeholders.
For example, amniotic membrane can integrate easily into clinical practice and be delivered profitably as part of existing services in a community setting. In the longer-term, this will take the pressure off scarce NHS resources, allowing secondary-based care to reduce the current ophthalmology waiting list by focusing on patients who can only be treated in a hospital setting.
While the use of any human tissue in a medical setting leads to a perceived risk, for example, through the transmissions of diseases, there has never been a reported case of amniotic membrane transmitting an infectious disease to a patient.
Reasons for this include extremely stringent donor selection and manufacturing processes, and donor and tissue testing, which is heavily regulated and minimises the risk of pathogens being introduced to the tissue, particularly in the Western world.
The natural properties of amniotic membrane are also thought to contribute to reducing this risk. Amniotic membrane has no blood supply, which in other human tissue can be a key carrier for infection, it is also inherently immune-privileged due to its role in protecting the foetus during pregnancy, and the tissue is reported to possess natural anti-microbial/viral qualities.11
While opticians, ophthalmologists, optometrists and other eye care professionals should be aware of the risk when using a human tissue in their practice, the exceptional safety profile of amniotic membrane as a transplant material means that the risks are minimal.
In the case of severe dry eye disease, the current pharmaceutical-based standard of care requires long-term use before a real benefit can be seen and may be associated with significant side effects. Amniotic membrane, on the other hand, often provides a rapid benefit following a single application.
In a recent study, where patients were treated with sutureless amniotic membrane-derived dry matrix to manage persistent corneal epithelial defects, 63% of the eyes showed complete healing with an average treatment length recorded as 22.4±12.3 days.
If more opticians and other eye care professionals become aware of the benefits of amniotic membrane and begin to include it as a treatment option in their practice, this could have a transformational effect on the overall eye care landscape in the UK.
A reduced need for surgery combined with an easily preserved, stored and transported tissue that can be used in the prevention, as well as the intervention, of a range of ocular conditions could lead to significant health economic benefits for multiple stakeholders.
- Dr Andrew Hopkinson is chief scientific officer and founder at NuVision Biotherapies, which develops and provides a selection of products derived from amniotic membrane, including Omnigen, a wound dressing and grafting material from amniotic membrane, and OmniLenz, a bandage contact lens.
References
- Dawiec G, Niemczyk W, Wiench R, Niemczyk S, Skaba D. Introduction to amniotic membranes in maxillofacial surgery—A scoping review. Medicina (Kaunas) [Internet]. 2024 [cited 2024 May 1];60(4):663. Available from: http://dx.doi.org/10.3390/medicina60040663
- McQuilling JP, Vines JB, Mowry KC. In vitro assessment of a novel, hypothermically stored amniotic membrane for use in a chronic wound environment. Int Wound J [Internet]. 2017 [cited 2024 May 1];14(6):993–1005. Available from: https://pubmed.ncbi.nlm.nih.gov/28370981/
- Röck T, Bartz-Schmidt KU, Landenberger J, Bramkamp M, Röck D. Amniotic membrane transplantation in reconstructive and regenerative ophthalmology. Ann Transplant [Internet]. 2018 [cited 2024 May 1];23:160–5. Available from: http://dx.doi.org/10.12659/aot.906856
