Eyeworld

EW GLAUCOMA 32 by Tony Realini, M.D. Introperative bleeding: nanotechnology to the rescue? T he eye is a highly vascular- ized organ, and bleeding is a common complication in many ophthalmic surgical procedures. For some proce- dures, intraoperative bleeding is just a nuisance. But for others, bleeding can adversely affect the outcome of the procedure. "In glaucoma surgery, blood is bad," said Robert Fechtner, M.D., director, Glaucoma Divison, Insti- tute of Ophthalmology and Visual Science, New Jersey Medical School, University of Medicine & Dentistry of New Jersey, Newark. Post-op filtra- tion of aqueous depends on care- fully modulated wound healing, he said. "Blood in the operative field in- troduces pro-healing factors. For most filtering procedures, we don't want a lot of bleeding at the sclera- conjunctiva interface." Our current approach to intra- operative bleeding might even make matters worse. "Currently our pri- mary approach to hemostasis in- volves electrocautery," he explained. "Cautery is tissue destructive and al- most certainly incites an inflamma- tory reaction, which in turn promotes an undesirable healing re- sponse in filtered eyes. We try to use minimal cautery, of course, but even gentle cautery is likely to have some detrimental effect on wound heal- ing." "A method of achieving hemo- stasis without cautery would be highly desirable," Dr. Fechtner said. Nano solution Scientists may have invented just such a method. Rutledge Ellis- Behnke, Ph.D., associate director, Technology Transfer Office, Univer- sity of Hong Kong, and research af- filiate, Brain and Cognitive Sciences Department, Massachusetts Institute of Technology, Cambridge, Mass., re- cently described a novel nanotech- nology solution to the problem of intraoperative bleeding. His team has developed a small self-assem- bling nanoparticle that aggregates when applied to the ocular surface and achieves hemostasis without clotting or stimulating an immune reaction. "The nanomolecule is a small peptide, just a string of amino acids about 5 nanometers long," Dr. Ellis- Behnke explained. "It's a self-assem- bling material. When it comes into contact with the ocular surface, these small nanopeptide molecules aggregate and seal the leaking blood vessel without inducing clotting and without causing an inflammatory re- action." The nanoparticles are packaged in a gel much like viscoelastic mate- rial and can be delivered via cannula directly to areas of active bleeding. The material forms a scaffold around the injured vessel and supports new cells as they grow in and repair the vessel, he said. "Complete hemosta- tis is achieved within 15 seconds, and when you wipe away the excess material, the vessel does not re- bleed," Dr. Ellis-Behnke said. "It's a completely different way of thinking about healing," he said. Wide applications The hemostasis nanomolecule was initially developed to promote heal- ing of neuronal tissues following brain and spinal cord injury, Dr. Ellis-Behnke explained. "We've demonstrated the return of func- tional vision following complete transaction of the optic tract of a rat using this same material," he said. In the same way that it creates a scaf- fold for vessel repair, it provides a supportive scaffold for neuronal re- pair, he said. "In the process of conducting those and other studies involving the central nervous system, we noted incidentally that bleeding stopped very rapidly in the areas where the material was applied," he added. To be effective on the ocular sur- face, his team had to modify the molecule somewhat. "You have to tailor the backbone of the material to the nature of the tissue to which it is being applied," he explained. In addition to hemostasis, the molecule could be easily adapted to provide transient sealing of clear corneal wounds following cataract surgery. "This would help to main- tain intraocular pressure and prevent the ingress of germs in a post-opera- tive eye until the cornea could heal itself," he said. Dr. Fechtner found these prelim- inary results encouraging. "We are already familiar with the concept of a molecular medical device through our widespread use of viscoelastic agents," he said. "The potential for hemostasis without inflammation or clotting is very appealing for filtra- tion surgery. The demonstrations presented here are dramatic." He envisioned other potential uses for the technology. "I can imag- ine that it would become popular with our vitreoretinal colleagues as well. If it works intraocularly, it could be a tremendously useful ad- junct to operations such as the peel- ing of diabetic membranes from the posterior pole. Those lesions are typ- ically highly vascular, and the proce- dures are often complicated by bleeding and limited by the extent to which bleeding occurs. The abil- ity to quickly achieve hemostatis in that setting, without any damage to the surrounding tissues, would be very helpful." Safety Although still being tested in animal models, initial efficacy and safety re- sults are encouraging. "Given that the nanomolecule stops bleeding, one concern might be that, should it achieve systemic access, it could pro- mote intravascular thrombosis," Dr. Fechtner said. In fact, that doesn't seem to be the case. "The nanoparticles assem- ble on the outside of the vessel but break up once inside the vessel," Dr. Ellis-Behnke said. "We've injected up to 100 cc of this material into the systemic circulation of a rat and ob- served no evidence of stroke or other adverse events." He added that the nanoparticles are cleared in urine within a few days. The technology has been licensed and is undergoing further clinical development, he said. EW Editors' note: Drs. Fechtner and Ellis- Behnke did not indicate any financial interests related to their comments. Contact information Ellis-Behnke: rutledg@mit.edu Fechtner: fechtner@umdnj.edu January 2011 A video print taken during a laser Doppler measurement with the Canon Laser Blood Flowmeter CLBF 100 instrument; the nano solution may provide surgeons with a hemostasis solution without relying on cautery Source: Gilbert T. Feke, Ph.D.

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