December 2012




Bonding with LASIK: New adhesive could improve safety

by Maxine Lipner Senior EyeWorld Contributing Writer

Innovative glue shows promise

Did you know that if someone who has LASIK gets hit with a tennis ball or an automobile air bag, the flap comes right open, even though it may be several years after the operation?

While most of the time the LASIK flap continues to lay smoothly in place without any issues for the patient, blunt-force trauma from something as mundane as a misfired ball or Frisbee can change that. After surgery, the LASIK flap unfortunately remains forever vulnerable to dislocation, according to Gary Conrad, Ph.D., University Distinguished Professor, Division of Biology, Kansas State University, Manhattan, Kan. "People thought that the LASIK flap was self-sealing, but in fact it's just like a wet piece of Saran Wrap on a wet windshield, held there beautifully by surface tension," Dr. Conrad said. Until now, a flap dislodged by trauma, with dirt likely flying everywhere, almost inevitably called for transplant. However, a new glue mixture developed by researchers in Dr. Conrad's lab may help to immobilize the flap and offset this risk, he thinks.

Results published in the June issue of Investigative Ophthalmology & Visual Science (IOVS) highlighted the glue's ability to bind with the corneal surface. A second paper, published in the September issue of IOVS, focused on the molecular mechanisms at work here. The lead author of both, Stacy Littlechild, a recent bachelor's degree graduate in biology, began working in Dr. Conrad's lab as a "dishwasher" before undertaking the project. Ms. Littlechild's idea for the glue grew out of other work being done in the lab on changes on the surface of the cornea that occur after LASIK. Dr. Conrad explained: "I had colleagues who said, 'Did you know that if someone who has LASIK gets hit with a tennis ball or an automobile air bag, the flap comes right open, even though it may be several years after the operation?'" He agreed to take a look at potential causes of the unnervingly easy flap dislocations.

A practical notion

With this research swirling around her, Ms. Littlechild began to wonder why someone didn't secure the vulnerable flap in place with glue. "Without my knowing, she was rummaging around in the literature looking for a biological glue and she stumbled upon one," Dr. Conrad recalled. "It was based on the use of fibrinogen."

The glue indeed appears promising for the purpose of LASIK. "It doesn't create an opaque glue layer," he said. "It apparently looks transparent, and it becomes very strong."

A core component of this is the blood protein fibrinogen. "Maybe other proteins would work equally well, but this was a component of another glue from a paper that was published previously, so it seemed like a reasonable place to start," Dr. Conrad said. The fibrinogen is mixed with a saline solution and forms a strong, sticky solution on its own, he explained. However, if riboflavin is also included, UV light can then be used to activate this, thereby enhancing bonding. The UV light used here is the same as that used in tanning salons, Dr. Conrad noted, adding that in the presence of riboflavin this results in permanent crosslinking. "If riboflavin is present and you shine UV light on it for the standard 30 minutes, then not only do you get the beginning kind of binding, but you get an irreversible covalent bonding," Dr. Conrad said. The fibrinogen bonds to the abundant collagen in the cornea.

The strongest bond

While the thinking is that this could be used to secure LASIK flaps to ensure that they are not vulnerable to dislocation, it has never been used in a LASIK case. Thus far, lab investigators have been joining two animal corneas together stroma-to-stroma to create the rough equivalent of a LASIK flap. To this, different compositions of glue were tested to see which ones were best by measuring the force required to separate the two layers. Investigators determined that the strongest mixtures were those that combined the use of fibrinogen, riboflavin, and UVA. The other three adhesive combinations, which included fibrinogen and riboflavin, fibrinogen and UVA, and then riboflavin and UVA, resulted in approximately the same amount of adhesion, Dr. Conrad noted. "However, if you put all three of those things togetherfibrinogen, riboflavin, and UVAthen you get a degree of adhesion that is almost three times that," he said.

Although the glue has not yet been used in humans, its characteristics are promising. Investigators also found that it appears to be transparent. "The riboflavin is a bright yellow that shows up in the photographs that we took of these corneas, but after 1 hour that yellow has gone away," Dr. Conrad said. "It diffuses away, and we assume that it would also diffuse away in the eye of an animal or a patient." He admitted, however, that this remains unproven.

While the thinking is to apply this to LASIK flaps during surgery, Dr. Conrad sees any number of other potential applications. It is not as though this was only designed to work in the cornea, he pointed out. "Any time there's a flap of tissue or a hole needs closing, this fibrinogen glue would be worth considering," he said. "If you mix in riboflavin along with the fibrinogen and then expose the incision or hole to the UV light for 30 minutes, that's going to make a tougher bond."

Although Dr. Conrad has no plans to study the glue further, he is happy to have this in his experimental arsenal. "It's always on the tool rack as something that we could use," he said. "We have a variety of experimental things that we're doing, studying the development of the normal eye embryonically, and we would like to be able to transfer a piece of tissue somewhere else so that glue we might end up using very heavily." Either with the riboflavin and UVA or without it, this is effective glue, he contended. "It's simply one more gadget in the tool box of possible experimental techniques," Dr. Conrad concluded.

Editors' note: Dr. Conrad has no financial interests related to this article.

Contact information

Conrad: 785- 532-6662,