May 2017

 

COVER FEATURE

 

Treating the cornea before cataract surgery
Optimizing the ocular surface with amniotic membrane therapy


by Liz Hillman EyeWorld Staff Writer

   





Appropriate use of an amniotic membrane product in pre-operative ocular surface optimization prior to refractive cataract surgery. Significant EBMD detrimental to accurate pre-operative biometry and lens selection (top). A superficial keratectomy with placement of Prokera for 3 days (middle) produced quality healing without haze or scar (bottom) allowing candidacy for and accurate selection of a presbyopia-correcting IOL.
Source (all): Neel R. Desai, MD

Amniotic membrane is known to contain healing properties

For more than 70 years, amniotic membrane has been used in various ophthalmic conditions for its healing properties. Within the last few years it has become a tool in ocular surface optimization prior to cataract surgery, especially as premium IOLs require the most accurate of measurements to meet high patient expectations.
According to the 2003 article “Human amniotic membrane transplantation: Past, present, and future,” amniotic membrane, the innermost layer of the placenta, was originally used in skin transplants to treat burns and ulcers.1 It later was used for various indications in other areas of medicine to promote healing. A. DeRöth began using fetal membranes—chorion and amniotic membranes—in ophthalmology in 1940 to treat symblepharon. A. Sorsby and H.M. Symons were the first, according to this article, to use the amniotic membrane without the chorion to treat eyes with chemical burns and saw “rapid recovery with few complications.”
“In surgical applications of the human amniotic membrane to the ocular surface, the transplanted amniotic membrane is known to facilitate ocular surface healing with minimal inflammation and scarring. The surface healing effect of amniotic membrane may be caused by several factors,” according to this article, which explained that these factors include the amniotic membrane’s basement membrane facilitating migration, differentiation, adhesion, and longevity of epithelial cells. The composition of amniotic basement membrane is also similar to the conjunctiva in collagen and laminin structures, which can also help adhere and anchor epithelial cells, in particular to the stroma. The article also stated that amniotic membrane contains antiangiogentic and anti-inflammatory proteins and is known to inhibit fibrosis.
As Rahman et al. put it during a session of the Cambridge Ophthalmological Symposium in 2008, “the consensus is that [amniotic membrane] acts as a substrate or scaffold for host cells to populate and thus facilitate healing and repair.”2
Both Rahman et al. and Vlasov et al.3 wrote that the exact mechanism of action of amniotic membrane to promote healing on the ocular surface is not fully known. What’s more, Rahman et al. stated that while individual cases and series might tout the success of amniotic membrane, this is “not substantiated in the few published randomized controlled trials.”2 Vlasov et al.’s prospective nonrandomized control trial published in 2016 involving PRK patients found that while amniotic membrane helped speed corneal repeithelialzation, it did not do so faster than a bandage contact lens.3 Visual outcomes, clarity, and optical quality were also similar between the amniotic membrane and bandage contact lens groups.
Paolin et al., on the other hand, wrote that the “benefits and safety features of [amniotic membrane] in ocular disorders are evident, based on long term data analysis of these procedures,” which included epithelial ulceration, pterygium, keratitis, glaucoma, and bullous keratopathy.4

Who to use amniotic membrane on?

Although there are many indications for amniotic membrane use, when it comes to preparing the ocular surface prior to cataract surgery, Neel Desai, MD, director, Cornea and Refractive Surgery Eye Institute of West Florida, Tampa Bay, Florida, said candidates for cryopreserved amniotic membrane fall into two categories: (1) those with mild but visually significant ocular surface disease such as severe dry eye syndrome or mild to moderate keratitis or (2) those with severe ocular surface disease such as severe keratitis, epithelial basement membrane dystrophy, or Salzmann’s nodular degeneration.
“In the first cases, placement of a PROKERA biological bandage [Bio-Tissue, Doral, Florida] alone may provide a potent anti-inflammatory effect to quiet acute phase ocular surface inflammatory enough to obtain more accurate biometry,” Dr. Desai said. “However, in the second cases, wherein the ocular surface disease has topographically altered the surface and precluded accurate biometric analysis, a superficial keratectomy followed by placement of a PROKERA graft is indicated.”
Kendall Donaldson, MD, medical director, Bascom Palmer Eye Institute, Plantation, Florida, and Preeya Gupta, MD, assistant professor of ophthalmology, cornea and refractive surgery, Duke University Eye Center, Durham, North Carolina, also said they would use amniotic membrane for these indications to optimize the ocular surface prior to cataract surgery.
Dr. Donaldson said amniotic membrane has really taken hold within the last 5 years as multifocal and toric IOL technologies have demanded optimization of the ocular surface for positive patient outcomes.
“If we have a patient who has severe dry eye, anterior basement membrane, corneal dystrophy, or Salzmann’s degeneration, those patients make excellent candidates for ocular surface optimization with amniotic membrane,” Dr. Donaldson said. “For the patients that have anterior basement membrane dystrophy and the patients who have Salzmann’s degeneration, those patients are often undergoing superficial keratectomy 4–6 weeks before cataract surgery, so when we do a superficial keratectomy, I find the amniotic membranes can be a useful tool to supplement healing when we do that minor procedure to optimize their ocular surface. It can also be used with severe dry eye patients who have a lot of punctate epitheliopathy.… [In these cases, it] can help heal the surface and make the topography more regular making axis and power calculations more accurate.”

When to use it?

While biologics like amniotic membrane can be a powerful tool, Dr. Desai said they are “not an end-all-be-all panacea.”
“Since ocular surface disease is typically seen as a chronic condition, all available modalities for treating the underlying contributors to ocular surface disease must be instituted simultaneously. Since many of these treatments take time to perform and work before I can rationally proceed to a refractive cataract surgery, I often find myself counseling patients that due to co-existing problems, I want to do things not the fast way, but rather the right way,” he said.
Treatments Drs. Desai and Gupta consider prior to or in conjunction with amniotic membrane, depending on the patient’s pathology, include artificial tears, immunomodulators (e.g., steroids, cyclosporine, lifitegrast), nutraceuticals, and warm compresses. If the patient has meibomian gland disease, ocular rosacea, or evaporative tear deficiency, Drs. Desai and Gupta advise LipiFlow (TearScience, Morrisville, North Carolina) coupled with Intense Pulsed Light (IPL) therapy.
Dr. Gupta said she’ll treat ocular surface inflammation with topical therapies first, but if the condition doesn’t improve with that treatment, she’s apt to turn to amniotic membrane as a next resort.  
“One caveat is in patients in whom I am looking for a relatively rapid response—often [amniotic membrane] can rapidly restore the surface, but you will often still need to treat the underlying dry eye for long-term control,” Dr. Gupta said.
Dr. Donaldson, who started using amniotic membrane in the operating room in residency, later employing it in the office setting, at Bascom Palmer where Scheffer Tseng, MD, PhD, founder of Bio-Tissue, was then a faculty member, expressed a similar sentiment.
“If they’re already on several treatments and already maximized their medical regimen, then I would move on to this,” she said. “A lot of times, they don’t want to wait that long for their cataract surgery and they just say, ‘Let’s do everything I can now to move this forward as quickly as possible,’ and then I would recommend going forward with the PROKERA. You have to have that conversation with the patient to see how aggressive they want to be and how quickly they want to move forward.”
According to Dr. Desai, caution must be exercised when using amniotic membrane in the presence of infectious keratitis prior to a response to antimicrobial therapy or in cases where a yet-undiagnosed ocular or systemic condition is the underlying etiology for the apparent ocular surface disease.
According to Paolin et al.’s evaluation of data from more than 5,000 amniotic membrane patches over a 12-year period from a tissue bank, there were no adverse reactions reported, “confirming the high safety margin assured by this therapy.”4

What kinds of amniotic membrane products are there?

There are two major types of amniotic membrane: cryopreserved and dehydrated. Sutured surgical grafts have become less common in ophthalmology in favor of the former unsutured varieties.
“Unfortunately, there is the false impression that all amniotic membranes are the same in their characteristics, qualities, and efficacy,” Dr. Desai said. “It would be more accurate to view the amniotic membrane as a carrier for the pertinent biological factors producing the anti-inflammatory, anti-fibrotic, and pro-healing effects.”
“Cryopreservation allows retention of PTX-3 and the high-molecular weight HC-HA complexes, whereas dehydration processes denature these key molecules and render them largely undetectable in many of the dehydrated membranes where, instead, proinflammatory low-molecular weight complexes remain,” he added.
Both Drs. Gupta and Desai said they prefer cryopreserved amniotic membrane because it has both anti-inflammatory effects as well as a barrier function. PROKERA’s cryopreserved amniotic membrane, which is held in place by a polymethyl methacrylate (PMMA) ring, is the only one approved by the U.S. Food and Drug Administration as a wound-healing corneal bandage. PROKERA also comes in a Slim version and a thicker Plus version, which is longer lasting.
Dr. Gupta said some patients might not tolerate PROKERA’s PMMA ring and in these cases, dehydrated amniotic grafts can work well, being placed on the ocular surface and covered with a bandage contact lens. Dr. Desai explained further that PROKERA might be contraindicated in patients with filtering glaucoma blebs, for example. IOP Ophthalmics (Costa Mesa, California) has several dehydrated amniotic membrane products.
Dr. Donaldson said most of her patients tolerate the PROKERA Slim well, but she explained that she aids in this tolerance with a taped tarsorrhaphy.
“We’re not taping the eye shut, it just makes the upper lid slightly ptotic so that it droops enough that the blink is incomplete,” Dr. Donaldson said. “It’s very rare now that I have a patient not tolerate it. But, of course, it looks like they have a droopy lid, so you do have to warn them ahead of time.”
Patients also need to be warned that they will experience decreased vision with PROKERA, but Dr. Donaldson pointed out that Bio-Tissue now offers PROKERA Clear. The PROKERA Clear may be very useful in a monocular patient that cannot afford to compromise vision in their only eye. The central portion of the PROKERA Clear is devoid of amniotic membrane to preserve vision. If a patient won’t tolerate PROKERA because of the ring, Dr. Donaldson said she’ll use another form of bandaged contact lens, though it won’t be as therapeutic.

When to take measurements?

While amniotic membrane products lead to “rapid re-epithelialization without scarring or haze” in a week or less, Dr. Desai said, it can take up to 4 weeks for the epithelial remodeling to complete. The physicians interviewed for this article varied slightly on when they would take measurements for IOL power calculations. Dr. Desai said biometry could be completed a month after “Prokeratectomy,” while Dr. Donaldson said she’d wait 3–4 weeks, and Dr. Gupta said she would wait at least 6 weeks, especially in the setting of prior epithelial defects, to allow epithelial remodeling to take place, checking measurements serially to make sure keratometry values were stable before proceeding with surgery.
Dr. Donaldson also noted that after having the amniotic membrane product applied for a week, she directs her patients to then continue their prior ocular surface regimen, which might include artificial tears and other medical therapy.
Putting amniotic membrane in the context of the bigger picture, Dr. Donaldson said cataract surgery requires a partnership with the patient in order to achieve our very best outcomes.
“They have to understand that cataract surgery is a once-in-a-lifetime experience per eye, and we need to make the investment in time and effort to choose the best IOL possible,” she said. “We want to do everything we can in our power to optimize the surface and optimize the choice of lens that’s going into their eye because it’s going to last forever. Once you create this partnership with the patient, they don’t get frustrated with taking the extra time to do this…Fortunately, with all the technology—the imaging technology, the therapeutic technology, and the diagnostic technology—that we have nowadays, we can use those things to help patients understand better so that they can take part in this treatment process to make their cataract surgery outcomes the best possible.”

Editors’ note: The physicians interviewed have financial interests with Bio-Tissue.

References

1. Thomas J. Human amniotic membrane transplantation: Past, present, and future. Ophthalmol Clin N Am. 2003.16:43–65.
2. Rahman I, et al. Amniotic membrane in ophthalmology: Indications and limitations. Cambridge Ophthalmological Symposium. Eye. 2009;23: 1954–61.
3. Vlasov A, et al. Sutureless cryopreserved amniotic membrane graft and wound healing after photorefractive keratectomy. J Cataract Refract Surg. 2016;42:435–43.
4. Paolin A, et al. Amniotic membranes in ophthalmology: Long term data on transplantation outcomes. Cell Tissue Bank. 2016;17:51–8.

Contact information

Desai
: desaivision@hotmail.com
Donaldson: KDonaldson@med.miami.edu
Gupta: preeya.gupta@duke.edu