The biological bandage is an emerging option for keratitis, recurrent corneal erosions and more.
June 1, 2013
Inflammation, the first sign of wound healing, is also the hallmark of all ocular surface diseases. Uncontrolled inflammation leads to chronic pain and discomfort/irritation, delayed healing, more tissue damage and vision-threatening complications such as corneal scarring and haze. Thus, effective control of inflammation is an important strategy to promote healing.
In the past, our armamentarium mostly consisted of topical anti-inflammatory drugs, bandage contact lenses and, in some instances, immunosuppressive agents. While largely successful, these treatments may not always resolve the patient’s condition.
In these instances, use of amniotic membrane represents an option for treatment and regenerating corneal and conjunctival tissue. Here, I will discuss the role of amniotic membrane, the innermost layer of the placenta, in treating ocular inflammation.
Amniotic Tissue and Wound Healing
Investigators have described transplantation of amniotic tissue, harvested and preserved following delivery of a newborn by C-section, as one of the major new developments in surgery of the ocular surface.1
The unique cryopreservation method of AmnioGraft and ProKera (Bio-Tissue, Doral, Fla.) allows for greater retention of the membrane’s structural, physiological and biochemical properties responsible for its dramatic healing and easier handling intraoperatively. A dehydrated preservation process, as is used with other types of amniotic membrane, devitalizes and denatures these properties, yielding a graft devoid of active factors and that is hard to handle. Cryopreserved amniotic membrane consists mainly of four components: epidermal growth factor; keratocyte growth factor; structural proteins, such as laminin and type VII collagen; and several neurotropic substances.1 The key mechanisms of amniotic membrane in wound healing are:1,2
The ProKera bandage allows the ocular surface to retain its biomechanical healing properties.
As a result, cryopreserved amniotic membrane relieves symptoms, promotes re-epithelialization and suppresses stromal inflammation, angiogenesis and scarring.1-3
Sutureless Amniotic Membrane
A sutureless form of amniotic membrane, ProKera, is a biological corneal bandage. This class II medical device is composed of cryopreserved amniotic membrane clipped into a thermoplastic ring set. It is FDA approved for corneal and limbal defects and scarring due to various etiologies. A 16-mm thermoplastic ring placed beneath the upper and lower lids holds the membrane in place and in direct contact with the affected area on the cornea.4
The amniotic corneal bandage has some advantages over an amniotic membrane allograft. The former can be inserted in the office rather than the operating room, and it requires no sutures. I’ve found that it allows for earlier treatment and, in many cases, quicker resolution of the signs and symptoms of corneal inflammation.5
Common indications for the biological corneal bandage include herpes simplex keratitis, microbial keratitis, filamentary keratitis, dry eye syndrome, recurrent corneal erosions and Salzmann’s nodular degeneration. Additional indications include corneal abrasions, scarring and erosions, chemical burns, corneal defects, partial limbal stem cell deficiencies, high-risk corneal transplants and Stevens–Johnson syndrome.
For Infectious Keratitis and Dry Eye
To achieve the greatest success with ProKera, one must first always treat the underlying disease process. When treating infectious keratitis with the amniotic membrane, I scrape the cornea to identify the specific pathogen, start fortified antibiotics, then use the graft as an adjunct treatment to enhance healing and reduce pain.
If the patient has exposure, you must perform a temporary tarsorrhaphy once the membrane is in place. This may be done by applying a Tegaderm (3M, St. Paul, Minn.) film dressing to the temporal aspect of the upper and lower eyelid, or, in more severe cases I like to use 6-0 prolene on a curved needle to temporarily suture the temporal aspect of the lids together, using a slip-knot technique for easier viewing of the patient’s eye during slit-lamp examination. For the patient with dry eye, ProKera is appropriate only after standard treatments, such as artificial tears, punctal plugs and Restasis (cyclosporine, Allergan, Irvine, Calif.) have failed.
Evaluating The Evidence
Various trials have shown that amniotic membrane—both as a graft or bandage — can successfully treat several of the aforementioned conditions. Among the most notable:
■ Ocular surface disease. Among 65 patients with different ocular surface diseases, one series reported that amniotic membrane transplants led to a reduction of pain, redness photophobia and inflammation with few complications.3
■ Varied corneal diseases and dystrophies. Researchers reviewed charts of 108 patients who underwent amniotic membrane transplantation (AMT) for nontraumatic corneal perforation, persistent epithelial defect, aphakic/pseudophakic bullous keratopathy, infectious ulcer resistant to treatment, necrotizing keratitis secondary to endophthalmitis or caustic injury.6 They found the mean survival of corneal integrity was similar in all groups, leading them to conclude that AMT is a successful adjunct in achieving corneal epitheliazation.
■ Conjunctival disorders. A trial evaluated 105 patients with corneal disorders and 25 patients with conjunctival disorders who underwent AMT and found that the cornea healed satisfactorily in 85.7% of the corneal group, and determined the success rate of conjunctival group to be 92%.7
■ Chemical and thermal injuries. Investigators analyzed AMT in 53 patients (53 eyes) with corneal ulceration and limbal deficiency following chemical and thermal injuries. They found the graft helped stop ulceration and promote corneal epithelialization in patients with severe chemical or thermal eye injuries.8
■ Stevens-Johnson syndrome and toxic epidermal necrolysis. Researchers at Loyola University in Maywood, Ill., found that early use of AMT prevents severe vision loss in these patients.9 A retrospective chart review of 128 patients admitted to the center’s Burn Intensive Care Unit found that one of 23 eyes with moderate or severe presentation treated with early amniotic membrane transplant had a poor outcome within three months vs. 8 of 23 eyes (34.8%) that were medically managed.
■ Noninfectious corneal ulceration and stromal thinning. Investigators used multiple layers of amniotic membrane in 22 consecutive patients (22 eyes) refractory to medical treatment, with a successful result in 20 eyes (91%).10 Mean preoperative residual stromal thickness at the ulcer bed was 222 μm, while mean total corneal thickness (including the amniotic membrane layers) was 623 μm at day one postoperatively. The findings illustrated that multiple layers of amniotic membrane can integrate into the corneal stroma, leading to increased corneal thickness.
I usually have the patient present for follow-up within three days after membrane placement. I confirm the ring is well centered, the patient is comfortable and no exposure keratopathy is present. I typically leave the biological bandage in for 7-14 days. If it has not melted by this time, I will remove it.
When to Use a Graft
While I typically use amniotic membrane for corneal pathology, I will opt for the AmnioGraft amniotic membrane allograft for other anterior segment disorders. The amniotic membrane graft offers the same regenerative effects as ProKera, but it can cover a larger surface. For example, a graft is indicated to prevent recurrence of pterygium as well as to decrease or prevent scarring of the corneal tissue, and help promote healing of the ocular surface. The graft is also indicated for conjunctivochalasis refractory to treatment with topical medications.
I typically use the inlay technique, debriding the wound and then suturing or gluing the amniotic membrane with the epithelium/basement membrane side facing outward. This allows epithelial cells on the cornea to migrate onto the amniotic membrane and the wound to begin closing.1 Deep defects, such as corneal ulcers, may require multiple layers. The membrane becomes incorporated into the cornea permanently.
In another technique, the onlay technique, the surgeon places a large amniotic membrane on the cornea as a temporary patch that typically detaches from the corneal surface after one to two weeks.1
Whenever I use a graft, I always see the patient at day one postoperatively, at one week and at one or two weeks to monitor healing. During this period, I look for the tissue to melt and become incorporated into the ocular surface.
AMT in Treating Infectious Keratitis
A number of trials and reports have documented the efficacy of amniotic membrane in treating varied forms of infectious keratitis. One study compared 14 eyes with Pseudomonas that underwent AMT group to 11 eyes in controls found the former exhibited less pain and earlier healing of corneal epithelial defects, while the sizes of corneal opacities and neovascularization were similar.11 The AMT group reported better uncorrected visual acuity.
In another study, investigators in France found that early AMT combined with topical corticosteroids in severe BK provided immediate pain relief and allows epithelial healing.12
In a prospective noncomparative case series, 12 patients with severe bacterial keratitis received maximal topical antibiotics, then underwent amniotic membrane transplant at 48 hours. They reported a significant decrease in pain score, and achieved epithelial healing within eight to 45 days.
Use AM Early
Perhaps the most significant take-home message I can offer based on these studies and my own clinical experience is that early use of amniotic tissues is key in treating severe ocular inflammation rather than waiting until the patient has a chronic anterior segment problem that has lingered without improvement. Earlier use means less likelihood of scarring and less likelihood of irreversible chronic changes in the eye. OM
1. Meller D, Pauklin M, Thomasen H, Westekemper H, Steuhl KP. Amniotic membrane transplantation in the human eye. Dtsch Arztebl Int. 2011;108:243-248.
2. Liu J, Sheha H, Fu Y, et al. Update on amniotic membrane transplantation. Expert Rev Ophthalmol. 2010 5:645-661.
3. Thatte S. Amniotic membrane transplantation: an option for ocular surface disorders. Oman J Ophthalmol. 2011;5:67-72.
4. Trattler WB. Promoting corneal wound healing. Cat Refrac Surg Today. 2012;July:(insert)1-4.
5. Sheha H, Liang L, Li J, Tseng SC. Sutureless amniotic membrane transplantation for severe bacterial keratitis. Cornea. 2009;28:1118-1123.
6. Yildiz EH, Nurozler AB, Ozkan Aksoy N, Altiparmak UE, Onat M, Karaguzel H. Amniotic membrane transplantation: indications and results. Eur J Ophthalmol. 2008;18:685-690.
7. Celik T, Katircioglu YA, Singar E, et al. Clinical outcomes of amniotic membrane transplantation in patients with corneal and conjunctival disorders. Semin Ophthalmol. 2013;28:41-45.
8. Iakimenko SA, Buznyk OI, Rymgayllo-Jankowska B. Amniotic membrane transplantation in treatment of persistent corneal ulceration after severe chemical and thermal eye injuries. Eur J Ophthalmol. 2013 [Epub ahead of print].
9. Hsu M, Jayaram A, Verner R, Lin A, Bouchard C. Indications and outcomes of amniotic membrane transplantation in the management of acute Stevens-Johnson syndrome and toxic epidermal necrolysis: a case-control study. Cornea. 2012;31:1394-1402.
10. Nubile M, Dua HS, Lanzini M et al. In vivo analysis of stromal integration of multilayer amniotic membrane transplantation in corneal ulcers. Am J Ophthalmol. 2011;151:809-822.
11. Barequet IS, Habot-Wilner Z, Keller N, et al. Effect of amniotic membrane transplantation on the healing of bacterial keratitis. Invest Ophthalmol Vis Sci. 2008 Jan;49:163-167.
12. Gicquel JJ, Bejjani RA, Ellies P, Mercié M, Dighiero P. Amniotic membrane transplantation in severe bacterial keratitis. Cornea. 2007;26:27-33.
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What is PROKERA®?
June 22, 2012
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Living-Tissue Devices Helps Heal Wounds
March 6, 2012
At first glance, the patient pool that could benefit from this cutting-edge corneal wound-and-healing treatment might seem shallow.
But consider that a leading cause of corneal ulcers is sleeping in contact lenses - even those FDA-approved for round-the-clock wear, says Mary Davidian, M.D., founder and medical director of Highland Ophthalmology Associates in New Windsor - and that potential pool soars.
"I get some of the worst cases referred to me, caused by extremely virulent bacteria sometimes resulting in nonhealing corneal defects and significant scarring," says Davidian, a corneal specialist.
"Amniotic tissue from the internal layer of the placenta has been used for many years in eye surgery because of its anti-inflammatory, wound-healing and wound-repair properties," she says. "But it was first only available in pieces that had to be cut to size in an operating room and stitched or attached with an ocular 'glue.' "
Now, amniotic membrane, called ProKera, is available - not unlike a contact lens - secured between two flexible rings and in individual-use packaging.
No operating room necessary
"I can now use this product in the office, rather than having to take patients to the operating room," says Davidian of the more than 50 patients on which she has. "The device is removed from the sterile packet and irrigated. Then the flexible ring is placed on the sclera, or white, of the eye. This allows the amniotic tissue to be positioned on the cornea to assist in healing."
ProKera is useful in not only treating nonhealing corneal abrasions and ulcers but also chemical burns, high-risk corneal transplants, Stevens-Johnson syndrome and many other ocular-surface conditions, she says. The natural biological properties stimulate the growth of ocular tissue while decreasing inflammation. There is typically less scarring and pain, although, because it is semi-opaque, there is a temporary decrease in vision.
"The patient will experience a stinging when it first goes in, which generally resolves in a few minutes," she says. "Because right now there is only one ring size - but different-size eyes - I do not allow the patients to leave the office until I ensure the ring will remain centered. Occasionally, I have to perform a tarsorrhaphy - a temporary partial closure of the lid - to keep it in place.
"The amniotic tissue usually dissolves in 10-14 days, giving off healing and anti-inflammatory factors in the process that assist with corneal surface regeneration. The more highly inflamed the eye, the faster it melts," Davidian says. "If not sooner, after 30 days, the ring is removed."
Educating other doctors
Davidian is just one of a handful of doctors in the Hudson Valley using this product, and she has been asked by the manufacturer to assist in educating other doctors in its use.
"This is a wonderful adjunctive therapy in difficult corneal cases that are not healing properly," she says. "I think of it as a magic Band-Aid that, in some cases, can provide an alternative to having to perform ocular surgery."
Additional research is also being done in the use of amniotic membrane in the areas of spinal, disc and joint-repair surgeries.
August 17, 2011
The eye's cornea, too, is sharing the new-technology spotlight with the retina.
Mary E. Davidian, M.D., a fellowship-trained cornea specialist, refractive surgeon and medical director of Highland Ophthalmology Associates in New Windsor, explains.
Just a few weeks ago, Davidian saw a patient with a disease called Fuch's corneal dystrophy. Fuch's dystrophy, in which the cornea's endothelial, or fluid-pumping, cells are damaged, is the reason for about 80 percent of all corneal transplants. It is an inherited disease.
The job of the endothelial cells, which make up the posterior layer of the cornea, is to pump excess fluid out, thereby keeping the cornea tissue clear. When they are not working properly, the overhydrated cells cloud vision.
"Sometimes, especially if there is already some damage to endothelial cells, the cornea can decompensate further when a patient has cataract surgery, which in and of itself is a form of trauma to the eye," Davidian says.
This is what happened to a patient of hers; he was told by his general ophthalmologist that there was nothing that could be done to improve his cloudy vision.
"He is now seeing 20/40," says Davidian - thanks to a new procedure called DSAEK (Descemet's Stripping Automated Endothelial Keratoplasty) that, as one of the few cornea specialists in the region, she is performing.
"It's not magic, and it doesn't always work," she says. "But when it does, it's amazing."
When the corneal cells become swollen and cloudy because the pumping cells are not functioning properly, the only previous option was a full-thickness cornea transplant, Davidian says. A mini-circular cookie cutter of sorts, called a trephine, is used to excise 80 percent of the cornea. A similar-size graft is taken from the donor. Fine sutures are used to stitch the donated cornea into place.
"There's a long healing period (with full-thickness corneal transplants); in older patients, sometimes longer than a year," says Davidian.
Stitches cannot be removed until scar tissue starts to form, which also can result in significant astigmatism, or an irregular curvature of the cornea.
'Clearer vision faster'
With state-of-the-art DSAEK, however, a tiny incision is used to allow the selective removal of the back (endothelial) cells of the diseased cornea. Similarly, the same selective cells are removed from the healthy donor, folded in half and slipped into the tiny incision.
"Air is injected to float the donor button up and make it stick," says Davidian. "There are, on average, three stitches placed peripherally that typically do not induce astigmatism. The wound is stronger and, therefore, resistant to future trauma. Most importantly to the patient, there is clearer vision faster."
Because air, and not stitches, is used to make the transplant adhere, the donor cornea might not stick and Davidian says, despite the refinements in the procedure since 1998, researchers still don't understand why.
"We may have to inject another air bubble or repeat the procedure, and it may work the second time," she says.
However, there are virtually no suture-related complications, such as the risk of infection or popping and loosening a stitch, even in a repeat procedure.
Davidian says she's doing this surgery more and more frequently - on about 20 patients so far - and she sees about two patients a week with Fuch's dystrophy.
In patients who have had success with a full-cornea transplant, DSAEK can be used if the endothelial cells slack off the down the road.
For more information please call us at (845) 562-0138.
August 19, 2009
"Cataracts are the leading cause of visual loss in Americans 65 and older," says Mary Davidian, M.D., founder and medical director of Highland Ophthalmology Associates in New Windsor.
But there's good news: Cataracts are very treatable.
To increase awareness, Highland Ophthalmology is offering free cataract screenings in its new, full-service vision center during August, which is Cataract Awareness Month.
GO Healthy asked Davidian for an overview on symptoms, causes and treatments.
Q. What is a cataract?
A. A cataract, like a wrinkle, is part of the natural aging process. If we live long enough, we'll have both wrinkles and cataracts.
Some people begin to wrinkle earlier than others, based on factors such as smoking, unprotected sun exposure and genetics.
It's the same with the many types of cataracts. Genetics play a role in how quickly they'll develop. The sun can also hasten their development, as can the use of certain medications such as prednisone, or eye injury or surgery. There are congenital cataracts as well, meaning the person is born with them, although this condition is not common.
Q. Can anything be done to prevent cataracts?
A. Wearing sunglasses with ultraviolet light protection when outdoors, eating a healthy diet rich in antioxidants and avoiding smoking might help stave off the development of cataracts. Regular visits to your eye-care professional will help detect cataracts early in their development.
Q. What are the symptoms of cataracts?
A. Decreased, cloudy or blurry vision is a common complaint. Colors don't seem as bright, and there might be double vision. Eyeglass and contact lens prescriptions might be changed frequently. People also might notice that they need more illumination to perform daily tasks such as reading, and there can be more sensitivity to light in general.
Many people are unable to drive at night because the glare of headlights is unbearable. That is because cataracts are typically not homogenous or a uniform level of clouding across the lens; rather, there are usually spokes of opacification that disburse the light in patterns.
Q. What is the treatment for cataracts?
A. Right now, there is no medication to prevent cataracts or to decrease their density. When the decrease in vision is such that daily activities are limited, then surgery is the only course of action available. Contrary to popular belief, lasers are not used to remove cataracts. The most modern method available utilizes ultrasound, and is called phacoemulsification.
Q. How is the surgery performed?
A. The technology has really advanced in the last decade or so to minimize side effects and maximize results.
Small, approximately 3mm self-healing incisions are made. The small probe of the phacoemulsification machine is inserted into the eye, which breaks up the lens into tiny pieces that are essentially vacuumed up while irrigating the fluid-filled anterior chamber of the eye.
Next, a foldable lens is inserted through that small incision and implanted. The implant opens and is positioned on the lens capsule.
Q. What type of lens is implanted?
A. Each patient is measured to determine the appropriate lens power for his eye. The goal is to get the patient as close to 20/20 vision as possible. Most patients who wore distance glasses before cataract surgery may not need to wear any distance correction after cataract surgery. This is because much of their previous eyeglass power can be incorporated into the implant that goes in their eye. If a monofocal lens implant is used, glasses will generally still be required for reading.
If the patient desires minimal to no dependence on glasses at all, then new generation multifocal lenses may be considered. These lenses have rings of different powers for distance, near and intermediate ranges. The brain learns to focus on the proper ring for each range to bring objects into focus. It's similar to having a progressive lens in the eye.
Barring any unforeseen complications, many patients return for follow-up care the next day with outstanding vision.
Q. What are the potential side effects?
A. All surgical procedures carry the potential for risks. Because there is an incision, however small, there is always a risk for infection or bleeding.
If there is underlying pathology, such as glaucoma or macular degeneration, because the cataract is superimposed on those conditions, the patient might not get optimum results. However, there is generally a noted improvement in vision, despite these conditions, when the cataract is removed.
Q. Who can perform cataract surgery?
A. While an optometrist, or eye doctor, will frequently make the diagnosis, only an ophthalmologist, who is also a surgeon, can perform the surgery. Cataract surgery is not an in-office procedure; it must be done at an ambulatory surgical facility or hospital, but is generally conducted on an outpatient basis, with the patient returning home shortly after the procedure. The cost of surgery is covered by major medical insurances.
For more information please call us at (845) 562-0138.
By Deborah J. Botti, Mid-Hudson Senior Gazette
Did you know that fair-skinned people are at higher risk for macular degeneration, and that cataracts will affect everyone if they live long enough? It's impossible for even the most educated consumer to keep abreast of every new revelation or advance in technology. That's why there are specialists.
And Dr. Mary E. Davidian, who founded Highland Ophthalmology Associates in Newburgh a decade ago, wants it known that a patient needn't travel to Manhattan to ensure state-of-the-art care and cutting-edge technology. Davidian and her staff bring Manhattan to Mid-Hudson.
Davidian is a board-certified medical doctor and fellowship trained cornea specialist and refractive surgeon. She's on staff at the New York Eye and Ear Infirmary in Manhattan, where she also teaches residents. That affiliation, coupled with her participation in ophthalmologic societies, connects her with those in the vanguard.
Dr. Thien (Tim) Huynh, joined the group last July. He received his fellowship training in glaucoma at the Mount Sinai School of Medicine in New York City and specializes in the early detection and treatment of that disease.
Add to the mix two optometrists qualified in primary eye care and an optician, who crafts glasses and cuts lenses, and the result is an all-care practice that can diagnose and treat just about every visual/eye abnormality. "We offer the full spectrum of eye care right here at home," Davidian says.
And here's an eye on what you need to know.
Cataracts are a clouding of the natural lens, resulting in blurry vision. "They're a normal part of the aging process," Davidian says, putting anyone age 60 or older at risk. Steroid use, eye trauma and diabetes can also increase their likelihood.
Years ago, the complication rate from cataract surgery was high, Davidian says, so doctors often held off surgery until the cataract was "ripe", meaning the patient was legally blind. "Today, an ultrasound probe is inserted through a tiny self-healing incision and used to break the cataract into small pieces, allowing for a quicker recovery time," she says. "A lens is then implanted."
Single power and newer multifocal lenses are available, meaning they have multiple powers to address distance and near vision - and everything in between.
Glaucoma, or high pressure in the eye, results when the normal eye fluid does not drain properly. Left untreated, blindness results. "A person can have perfect blood pressure and abnomal eye pressure," says Huynh. "There are no symptoms, no pain or discomfort." Once diagnosed, the disease cannot be reversed. The treatment goal is to prevent progression. Oftentimes the new breed of eye drops are successful. If not, Huynh might perform delicate microsurgery called a trabeculectomy, which allows fluid to drain through a microscopic hole. Another option is the insertion of a tiny filtering tube between the cornea and the iris.
Macular degeneration is the degeneration of the macula, or the central part of the retina. Those with that lack of pigment - in the skin and in the eyes - are more susceptible. Studies indicate that wearing sunglasses and taking antioxidants are helpful.
Macular degeneration can be categorized "wet" or "dry". Wet means blood vessels are leaking, causing a dramatic decrease in vision. There has been success with injections that cause the regression of the vessels. "In this case, we make the diagnosis and set the patient up with one of our retina colleagues," Davidian says.
The cornea is the clear front that covers the iris and pupil. Scars or swelling can cause the cornea to distort light, resulting in glare or blurred vision. Inherited dystrophies, trauma and infections (sometimes caused by sleeping in contact lenses) can affect the cornea. A corneal transplant is considered when vision or swelling cannot be corrected, giving patients the chance of improved sight.
For optimum eye health, annual exams are crucial, the doctors say.