April 01, 2003
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Amniotic membrane can prevent ocular damage from toxic epidermal necrolysis

Close follow-up is needed following surgery to ensure the ocular surface remains covered during the acute inflammatory process.

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Clinical photographs of patient with toxic epidermal necrolysis (TEN).

Reprinted with permission from Ophthalmology. Copyright 2002, Elsevier Science Inc.

TINLEY PARK, Ill. — Transplantation of amniotic membrane during acute toxic epidermal necrolysis can prevent eyelid adhesion and damage to conjunctival and ocular surfaces, a surgeon here reported.

Toxic epidermal necrolysis is a type of autoimmune disorder af-fecting mucus membranes of the body, usually with severe ocular involvement.

According to Thomas John, MD, a clinical associate professor at Loyola University Medical Center here, it is a potentially blinding disease, and patients with ocular involvement will often lose vision over time. If not treated effectively, patients will also have other ongoing ocular problems, such as severe dry eye, entropion, corneal clouding and corneal ulceration.

Dr. John and colleagues reported two pediatric cases in which amniotic membrane transplant effectively prevented severe vision loss. Their report was published in the journal Ophthalmology.

“We feel this treatment … is extensive because we are lining the entire ocular surface and anchoring it to the eyelid inferiorly and superiorly, passing sutures through the full thickness of the eyelid. Then we tie it on the surface,” he said.

Dr. John said, based on their results, he would recommend amniotic membrane transplantation as the treatment of choice during the acute phase of the disease. Close follow-up is also needed to ensure the ocular surfaces remain covered because the disease process may cause the amniotic membrane to melt.

Whole ocular surface

According to Dr. John, the classic treatment for the ocular complications of acute toxic epidermal necrolysis involves the ophthalmologist using a glass rod to break the adhesions between the eyelids and the globe. The glass rod is used because it has a smooth, nonabrasive surface. This is repeatedly performed while the patient recovers from the attack, usually in the intensive care unit of a hos-pital. Lubricating eye drops or ointments are also used to coat the ocular surface.

“What they are doing in a sense is just temporarily breaking these adhesions. They are really not doing anything for the long-term prognosis of the individual because the tissues will continue to get damaged by the disease process,” Dr. John said.

“You will end up, even though you broke the adhesions like that, with permanent adhesions called symblepharon, ankyloblepharon and fornix foreshortening,” he said.

“It does not alter the long-term prognosis, which is very poor in this disease process. This is a potentially blinding disease.”

Dr. John performed a transplant on a 6-year-old boy who developed epidermal necrolysis following oral administration of Septra (trimethoprim, sulfamethoxazole, Glaxo Wellcome). At the time of surgery, Dr. John said, he had been using amniotic membrane for various other ocular diseases and was confident the glass rod would not help the patient’s vision or prevent ocular surface damage from the disease process.

Amniotic membrane was used to line the entire ocular surface and the eyelids. Dr. John said the cornea itself is not involved in the acute phase, and only the cornea was left exposed. The amniotic membrane prevented tissue adhesion and damage to the conjunctival tissue by the disease process.

Dr. John said this is the first report of the use of human amniotic membrane transplantation in acute toxic epidermal necrolysis and the first use of human amniotic membrane on the external eyelid surfaces and eyelid margins.


Schematic representation of human amniotic membrane transplantation onto the ocular surface and the inner surface of the lower eyelid.


The amniotic membrane is attached to the bulbar surface with multiple interrupted vicryl sutures, and the cornea is exposed.

Surgical intervention

According to the report, in the surgery a large donor segment of human amniotic membrane was placed on the ocular surface. The inferior margin was anchored to the inner surface of the everted lower eyelid, close to the lid margin. It was further attached beyond the inferior fornix and onto the bulbar conjunctiva.

The amniotic membrane was also draped onto the ocular surface and attached to completely cover the ocular surface. It was attached to the inner surface and the margin of the upper eyelid. The membrane over the cornea was removed, leaving the cornea exposed.

According to the report, strips of amniotic membrane were also used to cover the ulcerated eyelid margins on all four eyes described in the journal article. All four eyelids were additionally devoid of skin, which left the underlying tissues and musculature exposed. Segmental amniotic membrane transplants were performed on all four eyelids. A bandage contact lens was placed following surgery.

According to the report, the 6-year-old patient had no symblepharon and good ocular surface wetting 36 months following bilateral surgery. After about 4 to 5 years follow-up, Dr. John said the patient retained 20/20 uncorrected visual acuity.

The second patient, an 8-year-old girl, was 20/30 in her right eye and 20/40 in her left eye at 34 months postop.


Human amniotic membrane strip graft application to the eyelid margins.


Diagrammatic representation of human amniotic membrane transplantation to the skin on the external eyelid surfaces of the upper and lower eyelids.

Immediate intervention

Dr. John said immediate, early intervention is needed to prevent vision loss and damage to the ocular surface.

“If you don’t go in immediately in the acute phase, and you wait, the results are already stacked against you because the disease process has damaged the conjunctival tissue and the ocular surface,” he said.

It is possible to intervene at a later date and try to repair the adhesions, he said. However, the basic function of the conjunctiva and the lacrimal glands will be compromised and the patient will continue to have severe dry eye and associated problems.

“I would say it would be best if the surgical intervention is done less than 14 days after onset, preferably 7 to 10 days maximum. If you intervene after 2 weeks you can do it, but you have already compromised ocular surface tissues,” he said.

Dr. John noted that close follow-up is necessary following the amniotic membrane transplant to ensure the ocular surface remains covered throughout the entire acute inflammatory process. Only when the eye becomes quiet is the membrane no longer necessary.

“During the acute phase … the minimum would be about 3 weeks or longer that you will be following the patient,” he said.

It may be necessary to perform multiple transplants during the follow-up because the inflammatory process may dissolve the transplanted amniotic membrane, he said. If such a case occurs, additional layers of membrane may be needed.

“We had to do the amniotic membrane grafts multiple times because he had a severe reaction and the membrane began melting. We had to place new membrane,” he said.

Amniotic membrane availability

Amniotic membrane is generally available in three forms.

In developing countries, fresh amniotic membrane is preferred because of easier availability and the prohibitive cost of commercially prepared samples.

In the United States, amniotic membrane is commercially available in two forms: preserved-frozen or freeze-dried.

Preserved-frozen samples require storage in deep freezers at –80° C and need to be thawed before use.

Freeze-dried samples can be stored at room temperature and require rehydration with balanced salt solution.

For Your Information:
  • Thomas John, MD, can be reached at 7060 Centennial Dr., Suite 103, Tinley Park, IL 60477; (708) 429-2223; fax: (630) 325-5304; e-mail: cornea999@aol.com.
Reference:
  • John T, Foulks GN. Amniotic membrane in the surgical management of acute toxic epidermal necrolysis. Ophthalmology. 2002;109:351-360.