Following the April issue of mivision,1 United States optometrist Dr Art Epstein reflects on his experience applying amniotic membranes to recalcitrant and complex anterior eye cases.
Q. We spoke about why we use amniotic membrane and its mechanism of action in the April issue of mivision. Now, drawing on your personal experience, what can you tell Australian eye care practitioners about the use of amniotic membranes that will make them feel more confident about prescribing them in practice?
You know, optometrists are very patientcentric – we care about our patient’s outcomes like they are family. So, it’s probably helpful to know that we’ve been using amniotic membrane extensively and safely for many years.
In the United States, a typical medically focused optometrist, one who services a remote area, an active specialty contact lens practitioner, or a dry eye practitioner, may find use for amniotic membranes as often as several times a week. Others will find that when it rains, it pours – they might have a month when they don’t use any amniotic membrane, then they will use five in quick succession.
The advantage of using a dry membrane is convenience
The advantage of using a dry membrane is convenience. Unlike cryopreserved membrane that requires sub-zero celsius freezing and needs to be defrosted before using, dry is much more flexible. Because it does well in normal temperature storage, you can have a few in the practice for when you need them.2
I would reassure optometrists that there is nothing to fear about prescribing them – there is no downside due to their antiinfective nature; they do not complicate management of infectious keratitis. If you feel reasonably comfortable handling more difficult cases, you will find amniotic membrane is a great tool to add in your armamentarium that enhances patient care.
However, I’d recommend only using them to treat conditions within your comfort zone – if you don’t normally feel comfortable managing a central corneal ulcer, don’t let the availability of amniotic membrane tempt you to try it. Refer on as you would normally.
Q. Would you use amniotic membrane to treat patients with neuropathic dry eye pain but no staining?
This goes back to the homeostasis model of dry eye described by DEWS II. A lot of what goes on on the ocular surface is neurologically controlled.
The BostonSight dry eye centre in the United States, which was responsible for developing the Boston PROSE scleral lens, was started by ophthalmologist Perry Rosenthal. Perry first defined ‘pain that doesn’t make sense’ cases and, since his passing, Pedram Hamra has taken over.
Pedram has further refined these cases, referring to them as either ‘pain without stain’ or ‘pain that can occur with stain’. We know that these occur due to abnormal pain innervation connections.
In the United States, we would treat these cases using Oxervate, a recombinant epithelial nerve factor produced by essentially reprograming E coli to produce human corneal growth factor. The cost can be quite prohibitive at US$40-$60,000 as an orphan drug, but it can be covered by insurance with support by charitable foundations under the right indications for neurotrophic keratitis.
Pedram Hamra looked at the use of amniotic membrane to regenerate damaged nerves with chronic dry eye post LASIK, as well as neurosensory and neuroeffector corneal disease cases. One paper, sponsored by Bio-Tissue, showed nerve regeneration on confocal microscopy with a cryopreserved tissue.3,4
Personally, I have seen some improvement in cases of neuropathic dry eye with the use of amniotic membranes. I have had a case treated with Oxervate that showed complete recovery. I have also prescribed Oxervate and used amniotic membrane treatment as a combined therapy for a lady with severe dry eye symptoms in one eye and mild in the other. We treated the severe dry eye with Oxervate and amniotic membrane treatment and the improvement was so significant that her severe eye became better than her ‘mild’ eye, based on how much her eye had healed.
Q. Currently in Australia, our guidelines for an optometrist suggest we definitely should not debride corneas – our medicolegal coverage does not cover us (at the time of print of this article).* What is involved in corneal debridement and would you debride or not debride before amniotic membrane application?
Some practitioners in the US might remove a large area of corneal epithelium in conditions like recurrent corneal erosion, but I take a more conservative approach and do not debride adherent epithelium before using an amniotic membrane. I do remove any corneal epithelium which is already loose. For example, in the case of a corneal erosion that has almost fully sloughed on its own, I would remove that part of corneal epithelium – but I do not debride for amniotic membrane treatment.
A typical debridement will leave 1mm or 2mm of corneal epithelium at the limbus. Stem cells are, of course, in the crypts adjacent to the limbus – this is where the corneal epithelium will repopulate from. So, a typical corneal epithelium debridement area would cover approximately 10.5mm of the average cornea. Corneal debridement would be to the level where Bowman’s layer appears to glisten. The peripheral epithelium will repopulate and regrow the entire surface of the corneal epithelium, via extending pseudopods. The prime directive of the epithelium is to seal itself to prevent any open wounds and the process is quite impressive.
Q. What is your recommendation for managing patient discomfort during amniotic membrane treatment?
It is important to warn them of some initial discomfort – the cryopreserved amniotic membrane is obviously more uncomfortable for patients than the dry membrane – discomfort from a dry amniotic membrane under a bandage contact lens is not that bad.
In some severe cases, I supply the patient with a non-preserved tetracaine or alcaine ampoule and advise them to use it only when absolutely necessary and then as infrequently as possible. This way they know they have control. Never prescribe topical NSAIDs in this situation – they can cause corneal melting.
Generally, the use of preserved anaesthetic is a bad idea in amniotic membrane treatments. Non-preserved anaesthetic is a better choice, and I recommend patients use it very sparingly and only when absolutely necessary to manage extreme pain. I also advise patients to take oral ibuprofen and/or acetaminophen if required.
Q. What techniques do you use to apply the amniotic membrane?
The first is with a speculum:
- Use the speculum to separate the eyelids,
- Place the membrane on the cornea,
- Dry the cornea slightly with a Weck Cel sponge,
- Apply anaesthetic,
- Use the Weck Cel to tamp it down onto the corneal surface,
- Smooth it out, then
- Very carefully place a bandage contact lens on top of the amniotic membrane.
The second technique is without a speculum:
- Take the amniotic membrane and carefully place it on the inside of the bandage contact lens,
- Note that there is a ‘right way up’ for most amniotic membrane – the correct surface has to touch the corneal surface – so follow the manufacturer’s instructions,
- Ensure the amniotic membrane is stuck to the contact lens – while this technique is fraught with difficulty, it is the easier of the two techniques once you get experienced at it, then
- Apply the bandage contact lens to the eye.
If the amniotic membrane is not placed properly on the contact lens, problems may arise. However, if you discover you haven’t applied it to the correct side, don’t change it; it will usually still work.
Q. Should you use amniotic membranes concurrently with topical antibiotics?
While amniotic membranes naturally have protective properties against most microbes, they should strictly be used with topical antibiotics for prophylactic coverage. The less toxic the antibiotic, the better for corneal healing, so in the United States, we prescribe moxifloxacin and the fourth generation fluoroquinolones concurrently with amniotic membrane application.
We also use ciprofloxacin and ofloxacin, which may be accessible options for you in Australia, as they continue to show relatively little antibiotic resistance for microbial keratitis at ophthalmic concentrations.
There are companies that compound and pre-make non-preserved topical antibiotics in the United States, however, antibiotic preservatives cause very little toxicity damage relative to their capacity to heal the cornea, so we don’t bother with non-preserved options. Moxifloxacin is self-preserved.
Q. Finally, based on your experience, do you have any advanced tips to share?
Applying amniotic membrane will always be difficult in the beginning – even when you are more experienced, some amniotic membranes can be so thin that they may curl back, creating challenges during application. If this happens, they will still release healing factors, they may just feel slightly less comfortable for the patient.
As we have more options here in the United States, we try to work with membranes that have some thickness – they will be easier to handle.
Also, it is important to advise the patient not to rub their eyes despite the discomfort – as this will impede corneal healing. The use of amniotic membranes, if adopted, will change the way optometry sees itself in Australia, as it will greatly improve visual outcomes across the board for patients.
FIND OUT MORE
To support best practice of this emerging therapy, the Cornea and Contact Lens Society of Australia will bring together an online webinar and an in-person workshop on prescribing amniotic therapy in July and August 2021. Dr Art Epstein will be one of the guest speakers in this education series.
* Check with Professional Services at Optometry Australia or your current professional indemnity provider. This article is provided as a general guide only and optometrists should take their own precautions on exercising care for their patients.
- Lam M, Epstein A. Amniotic membranes and ocular surface repair – the new frontier. mivision Issue 166, April 2021, P51-53
- www.optometry.org.au/patient_care_management/ australian-optometrists-can-use-placental-tissue-amnioticmembrane- grafts-for-some-ocular-surface-conditions. Note: At the time of writing, access to amniotic membrane requires SAS approval and this process varies for ophthalmologists and optometrists. Ophthalmologists are able to store dry membranes in advance and submit for TGA approval retrospectively and optometrists must obtain approval before each use.
- Morkin MI, Hamrah P. Efficacy of self-retained cryopreserved amniotic membrane for treatment of neuropathic corneal pain. Ocul Surf. 2018 Jan;16(1):132- 138. doi: 10.1016/j.jtos.2017.10.003. Epub 2017 Oct 13. PMID: 29032001; PMCID: PMC5798468.
- John T, Tighe S, Sheha H, et al. Corneal nerve regeneration after self-retained cryopreserved amniotic membrane in dry eye disease. J Ophthalmol. 2017;2017:6404918. doi:10.1155/2017/6404918
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.