Medical Device Daily National Editor

The human body is mostly water and the bloodstream acts as an inner sea within this complex aquatic venue, delivering all sorts of necessary stuff to every organ of the body.

Particularly sea-like, because it's particularly salty, according to Elias Greenbaum, PhD, is the eye, an environment containing some extremely complex chemistry.

Greenbaum knows more than a just few things about sea-like salty environments and human eyes.

He is the leader of a team that in 2005 won a Federal Laboratory Consortium Award of Excellence in Technology Transfer for an algal biosensor monitoring technology approach to protection of source waters from chemical attacks.

And in collaboration with Professor Mark Humayun, MD, of the Keck School of Medicine at the University of Southern California (Los Angeles), Greenbaum founded the U.S. Department of Energy's artificial sight program, which is aimed at restoration of sight to people who are blind from age-related macular degeneration and retinitis pigmentosa.

And he developed the initial insights which led to development of the artificial retina Humayun contributing the surgical approaches a project launched in 2004. Now, Second Sight Medical Products (Sylmar, Calilfornia) is working to push the artificial retina device, branded as the Argus II, to commercialization.

"Now, we can piggyback on that [artificial retina] work," Greenbaum told Medical Device Daily, in explaining his ground-level conceptualization of a related technology – a prosthetic device designed to supply a steady flow of oxygen to eyes gradually losing access to that important nutrient and thus leading to blindness.

A corporate fellow and leader of ORNL's Molecular Bioscience & Biotechnology Research Group, Greenbaum has continued his collaboration with Hymayun and other researchers at USC and the University of Tennessee (UT; Knoxville) to develop the concept of what he calls this "smart" eye prosthetic.

The technique uses an implant to provide oxygen to retinal tissues and nerves that are being deprived of oxygen because of restricted blood flow. This condition occurs predominantly in patients with diabetic retinopathy, affecting an estimated 5.5 million people every year.

Greenbaum is lead author of a paper, to be published in the upcoming issue of IEEE Transactions on Biomedical Engineering, describing the concepts and necessary approaches to produce what he terms a "metabolic" prosthetic.

He explained that the procedure involves the implantation of a feedback-controlled three-electrode electrolysis system that stimulates production of oxygen near the retina. The electrodes provide small amounts of current in very short pulses about 200 microseconds.

Greenbaum noted that electrolysis normally results in the production of hydrogen and chlorine, the hydrogen causing no problems but the chlorine being injurious to inner eye chemistry. Dealing with that then is one of the key technical hurdles for developing the oxygen prosthetic.

The electrodes provide repeated "pulsed charge-limited electrolysis" that is "selective," he said. "If you do this [electrolysis] with pulsed currents, you get the oxygen but not the chlorine."

The pulsed currents are delivered by three electrodes and by means of a feedback loop made possible by implanting a "ground" electrode behind the patient's ear the device is able to maintain constant pH in the area being treated. The pulses are delivered wirelessly by a device external to the eye.

Greenbaum said that in general, the goal is to maintain oxygen supply to the eye which tends to be cut off in retinopathy in two ways. After the initial occlusion, the eye creates new but weaker blood vessels which break down or burst, causing leakage and the additional blockage of necessary oxygen.

Animal studies for this prosthetic technique are underway, and Greenbaum told MDD that he and his fellow researchers have developed the detailed plans for producing the necessary device system.

Others involved in this project are Charlene Sanders, Hugh O'Neill and Barbara Evans, all members of ORNL's Chemical Sciences Division.

Funding for this research is provided by DOE's Office of Biological and Environmental Research, the National Academies Keck Foundation Initiatives Smart Prosthetics seed grant program and ORNL's Laboratory Directed Research and Development program.

Meanwhile, development of the artificial retina continues through the efforts of Second Sight.

The company's system consists of a camera, mounted on eyeglasses, that captures an image and sends it to a video processor which induces pulses that the wearer interprets, giving a sense of patterns and images otherwise unavailable to the failed retina. It first developed a 16-electrode system, and the second iteration uses 60 electrodes.

Second Sight late last year reported that it had increased patient enrollment for the Argus II Retinal Implant study of the second-generation Argus II Retinal Implant, for the retinitis pigmentosa applications, throughout clinical trials sites in Europe (MDD, Dec. 4, 2008).

Robert Greenberg, MD, PhD, president/CEO of Second Sight, told MDD that 20 subjects have been implanted in that trial, with the hope of total enrollment completion this year.

He said that with the device, patients with serious blindness are able to do such things as "follow lines on the floor, find windows and doors in a room."

Noting the usual considerable difficulties of predicting FDA regulatory action on the required PMA for the device – because its surgically implanted and providing "active stimulation" to the body Greenberg expressed confidence that the Argus II will reach commercialization in Europe next year.

"It's been challenging," he said. "The biggest challenge was interfacing an electrode array of some size without damaging a tissue [the retina] that is much like a wet piece of tissue paper."

And he said that the continued success shown with the Argus indicates hope for "hundreds of thousands" of people suffering retinitis pigmentosa, with potentially usefulness for treating other eye problems.

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