Joseph F. Rizzo III, MD presentation at the White House Conference 2004

White House/VA Conference
Emerging Technologies in Support of the New Freedom Initiative:
Promoting Opportunities for People with Disabilities October 13-14, 2004

"Age-related macular degeneration is the leading cause of blindness among veterans and the general population."—Joseph F. Rizzo III, MD

Joseph D. Rizzo III, MD, is an Associate Professor of Ophthalmology at Harvard Medical School and the Massachusetts Eye and Ear Infirmary. He is also the codirector of the Boston Retina Implant Project at the Boston VA Medical Center (VAMC) and the director of the Center for Innovative Visual Rehabilitation at the Boston VA. He earned his medical degree from Louisiana State University in 1978, and completed his residency at Tufts New England Medical Center (1982) and Boston University Hospital (1985). Dr. Rizzo then completed a fellowship at the Massachusetts Eye and Ear Infirmary, in neuro-opthalmology in 1986. Dr. Rizzo initiated the Boston Retinal Implant Project in the late 1980s.

Thank you very much for the opportunity to speak here today.

This meeting is devoted to the discussion of disabilities, and we should be mindful of the fact that we rarely see those individuals with the most severe disabilities. A giant spectrum of disability exists in the general population.

The field that means the most to me in my professional work is vision. I´ll tell you a little about myself and how I got into my research and how it might be relevant to our long-term goal.

Originally, I was a neurologist, and within neurology I found the visual system to be the most interesting. Then I became an ophthalmologist and, subsequently, a neuro-ophthalmologist, and I still see patients two days a week.

It has been that opportunity to work with patients individually as their doctor—to come to know them and understand their problems—that has motivated me to try to help people more by doing research. If I´m lucky, my research will make it possible for me to help a large number of people, people whom I would never meet in my capacity as a physician.

The balance between helping individuals in the role as a physician and hoping to help a large number of people in my research led me to begin our program at Harvard Medical School/Massachusetts Eye and Ear Infirmary.

I want to tell a personal story, if you can indulge me for just a moment. The Department of Veterans Affairs (VA) has played a large role in my work. There are two reasons I wound up joining the VA team. One of those was my father, who served in World War II in both Europe and the Pacific, and received a Purple Heart and a Bronze Star, and who just passed away very recently. Today, in fact, would have been his 82nd birthday.

Now, to return to my research, let´s think for a moment about the kinds of patients we´re trying to help, for example, veterans at our VA hospital in Boston. The patients we´re most likely to help early on are those who are severely blind, primarily from retinitis pigmentosa. They can get around reasonably well with a cane, but just think what it would be like if I were that person right now and I wanted to leave this room without asking someone for assistance. It would be essentially impossible.

You can understand what a hazard it would be, and how likely it would be I would run into someone or something and possibly hurt myself. I consider our primary goal to be improving quality of life for severely disabled patients so they can ambulate independently and safely in an unfamiliar environment.

If we are ever fortunate enough to achieve our primary goal, we can move onto advanced objectives, such as getting severely visually disabled patients to perform more sophisticated tasks.

We should also remember that patients do reasonably well with a cane, so whatever we build has to be substantially better than a cane. Of course, anything we develop would also have to take into account whatever risks and costs are associated with the new therapies.

This goal to improve vision is a very special VA initiative, first and foremost because of the veterans. Age-related macular degeneration is the leading cause of blindness among veterans and in the general population. Here´s a beautiful win/win opportunity not just for veterans, but for our population at large.

No available therapy can restore lost function in neural forms of blindness. To be able to do this requires advanced technology, and we´ve established a VA/academic partnership that has been, for me at least, a remarkable opportunity.

Our project will be successful only if a long-term and comprehensive approach is maintained. These technologies are hard, and they will only be developed if the institutions that work together understand it will take a long time.

Let´s think for a moment about the various forms of blindness. The retina lines the back wall of the eye. The retina is nerve tissue, actually a part of the brain that grows forward out of the skull so it can capture light. It is connected to the visual part of the brain, which is in the back of the skull, by way of the optic nerve.

Light enters the front of the eye and strikes the retina. Light goes through the retina tissue. By the way, each retina holds about 150 million nerve cells. It´s quite a complicated neural structure.

The rods and cones receive light and create a nerve signal, sending that nerve signal to other cells that sit on the inside part of the retina. Those cells connect to the optic nerve. Light comes in and creates a complicated nerve signal that is eventually transported to the brain.

In macular degeneration and retinitis pigmentosa, these rods and cones are lost, but a substantial number of other nerve cells survive. The patients are blind because they no longer have the rods and cones that can convert light to a nerve signal. However, these cells had been formed properly at one point and are sitting there essentially unused. This creates the perfect situation for a prosthetic device to restore vision.

One can build that prosthetic device to put underneath the retina, as we´re doing, or one can build a prosthetic to put on the inner surface of the retina, as one of the Al Mann companies, Second Sight, is developing.

The VA has provided a home for our research group for the last three years. I told you there were two reasons I came to the VA. The second was, in fact, Dr. Mindy Aisen [Director, Rehabilitation Research and Development Service, Office of Research and Development, VA], whom I met about four years ago. I heard her give a talk, and she had a clear message of her desire for the VA to be at the forefront of rehabilitative technologies, and also her belief that multidisciplinary programs were important to the long-term success of VA rehabilitation research programs.

That attitude was exactly what we needed. Ultimately, it worked out very well, and we´ve now formed this collaboration between Harvard Medical School, the Massachusetts Eye Infirmary—where I see patients—MIT, and the Boston VA.

We have many other partners, and I have purposefully left one area blank in my presentation. That´s because what we really need, ultimately, is a partner to take our device into the commercial realm. We don´t have that now, and there are a lot of reasons why. I´ll talk more about that at the end.

In other words, developing the technological base is the beginning of the story, not the end of the story.

Our device includes an ultra-small camera mounted on a pair of glasses that takes pictures—in essence, replacing the lost photoreceptors. The visual information would be sent wirelessly from a transmission coil on the pair of glasses to a receiving coil around the back of the eye. The wireless transmission system resembles an old television set receiving an airwave. The details of the visual scene are sent into electronics that sit on the outside of the eye, and then from those electronics the information is translated to the retina to stimulate the nerve tissue.

Very briefly, the substrate, the material onto which we embed the electronics, is an ultra-thin material. It´s only 10 microns thick, several times thinner than a human hair. Yet it´s flexible and contains embedded electronics, which we do with standard microfabrication technologies. The receiving coil is roughly about the size of a dime.

One of the aspects of our design that we think is particularly favorable is the fact that 99 percent of this device—and remember, it´s about the width of a dime—sits outside of the eye.

We´re trying to develop a minimally invasive approach so that the only thing that goes into the eye is a very, very thin membrane that contains the stimulating electrodes. Our electrodes—and we can readily make hundreds of these on an array as easily as 10 with microfabrication technology—are only 50 microns in diameter, roughly about the size of a human hair. Each one of these electrodes has a wire, so you can communicate to it individually. Only that part, the very end of the structure, is put into the back of the eye. We can do this by raising a very small incision in the back of the eye and then inserting it all underneath the retina. Our hope is that we will be able to implant this type of device without going into the eye, just going through into the back of the eye to reach the retina.

How plausible is it that this kind of a strategy might work? The basic concept is that if you think about light falling on the retina where there are these thousands and thousands of nerve cells, and if you put an electrode array on those nerve cells and stimulate the cells in some particular pattern—let´s say a pattern that looks like the letter E—it is very reasonable to assume that, because of the anatomy that connects the eye to the brain, a person would in fact see a letter E. That´s a quite reasonable hope. What about being able to read a scoreboard? That´s a loftier hope.

To demonstrate how plausible our design is, I want to discuss our best results from the testing of six human patients.

In these patients, who are completely blind or nearly completely blind with retinitis pigmentosa, we put one of these ultra-thin arrays in the back of the eye. The electrode array includes eight large electrodes and a large number of smaller electrodes. In one instance, we drove those electrodes, and immediately a 72-year-old woman, who had been legally blind for 40 years, reported seeing four clouds. Under the surgical drape, we have them draw, and she drew an image that is a very close correlate to the pattern of stimulation.

Is it possible to restore some vision to patients who have been blind? The answer is yes. If you can accomplish what we did in a relatively brief experiment, there is a hope that we will be able to produce better vision, perhaps creating a letter with a device like the one we are developing.

Although this is highly debatable within our field, I would just like to say we haven´t been able to get patients to integrate images more complex than very simple geometric shapes.

I´ve been fond of saying that even if the scientists at MIT provided me with the perfectly engineered device, blind patients aren´t going to see any better because I don´t know how to use it, nor will they know how to interpret these artificial stimuli. That will take a while to learn. We have to learn how to stimulate. They have to learn how to interpret.

The point is, when you think about making a device like this, or any prosthetic device, you have to remember that for a complex behavior you have to learn how to interface with the nervous system.

Our field of retinal prosthetics is moving into what I think of as a Phase II. Many very interesting devices have been built. Now our job is to learn how to use them. This goes back to my neurology background, because ultimately we´re moving from an engineered device to working with the nervous system. This is the part of the domain I really love.

I was asked to make a comment how close we are. Well, numerous things are standing in the way. I have to say, as much success as I think we´ve had, and although I hope we have a lot more in the future, we have faced some significant impediments.

I was happy in some ways to hear Al Mann´s talk earlier, because I agreed with almost every word he said. No path had been forged for a project like ours at the time we had begun our work. No precedent existed for this type of endeavor.

No governmental funding program was available for a long-term, high-risk project. In addition, no commercial opportunities were accessible, given that a prosthetic device had to be built. We also did not fit into the drug or pharmacy markets. The device companies, some of which are very successful, typically become interested once the developmental work has been completed.

As a country, we need funding programs for biomedicine to support long-term development projects akin to those at NASA. The individuals who are here today have the opportunity to solve this problem. New ideas emerge typically from academic centers, but academic centers do not have the infrastructure, nor do they have the culture, to know how to transfer these technologies into the marketplace.

From our standpoint, institutional and administrative issues have impeded our effort. I will offer my services and time to anyone interested to hear our side of the story. I am eager to help work to try to solve our problem, which I suggest is a collective problem faced by many researchers.

Venture capitalists are often suggested as a solution to our problem to help sustain a large developmental program. But venture capitalists come in quickly and want to get out quickly.

Our goals are completely different. It´s already taken nearly two decades to get where we are. It´s going to take longer to create higher quality vision. There´s a very, very long-term horizon. The question is, how does one sustain high levels of funding for a period of decades without having a return? It´s a real problem.

From a technical standpoint, I see three potential problems with the retinal prosthesis. One is their biocompatability. As we´ve learned just recently here in this country, we often find that biocompatibility problems develop long after devices have been implanted. The FDA has a difficult job, but an important one. Biocompatibility has gone well with these retinal prosthetics, but it´s still not a completely solved problem.

Power safety is another potentially significant problem. If we want to give higher quality vision, we have to use more electrodes. The more electrodes we use, the more power we need. The more power we use, the more potential damage there could be from the radiation exposure. These are mutually antagonistic forces, and we don´t know yet how to resolve the issue.

The last potential problem is hermetic encapsulation. Just within the last month, in fact, a significant recall of cochlear prostheses occurred because of problems of this type. Some very experienced companies have trouble solving this problem, and it´s because it´s a really tough technical problem.

Assuming all of these issues are successfully resolved, I believe that once retinal prosthetics are properly built, we will still need to learn how best to use them. Learning how to use these sophisticated devices will be the core of our research effort for the foreseeable future.

I´d like to thank the VA, the National Science Foundation, and NIH for their support. My program represents just one within the VA´s system. You´ll hear today from Hunter Peckham [Director, Cleveland Functional Electrical Stimulation Center]. You heard from John Donoghue [Professor of Neuroscience, Boston University] earlier. The VA has a number of programs with technologies that bear a lot of similarity. A culture flourishes within the VA for developing advanced engineering developmental work for the purpose of rehabilitation.

Lastly, I´d like to thank our patients. They almost get overlooked in the partnership with researchers. Of course, they´re the people who are heroic and who make themselves available for the experimentation that gives us the information to be successful. Thank you very, very much.

Main Page > Welcome Page > Dr. Rizzo's Address

	Joseph D. Rizzo III, MD, is an Associate Professor of Ophthalmology at Harvard Medical School and the Massachusetts Eye and Ear Infirmary. He is also the codirector of the Boston Retina Implant Project at the Boston VA Medical Center (VAMC) and the director of the Center for Innovative Visual Rehabilitation at the Boston VA. He earned his medical degree from Louisiana State University in 1978, and completed his residency at Tufts New England Medical Center (1982) and Boston University Hospital (1985). Dr. Rizzo then completed a fellowship at the Massachusetts Eye and Ear Infirmary, in neuro-opthalmology in 1986. Dr. Rizzo initiated the Boston Retinal Implant Project in the late 1980s.
Thank you very much for the opportunity to speak here today. This meeting is devoted to the discussion of disabilities, and we should be mindful of the fact that we rarely see those individuals with the most severe disabilities. A giant spectrum of disability exists in the general population. The field that means the most to me in my professional work is vision. I´ll tell you a little about myself and how I got into my research and how it might be relevant to our long-term goal.

Originally, I was a neurologist, and within neurology I found the visual system to be the most interesting. Then I became an ophthalmologist and, subsequently, a neuro-ophthalmologist, and I still see patients two days a week. It has been that opportunity to work with patients individually as their doctor—to come to know them and understand their problems—that has motivated me to try to help people more by doing research. If I´m lucky, my research will make it possible for me to help a large number of people, people whom I would never meet in my capacity as a physician. The balance between helping individuals in the role as a physician and hoping to help a large number of people in my research led me to begin our program at Harvard Medical School/Massachusetts Eye and Ear Infirmary. I want to tell a personal story, if you can indulge me for just a moment. The Department of Veterans Affairs (VA) has played a large role in my work. There are two reasons I wound up joining the VA team. One of those was my father, who served in World War II in both Europe and the Pacific, and received a Purple Heart and a Bronze Star, and who just passed away very recently. Today, in fact, would have been his 82nd birthday. Now, to return to my research, let´s think for a moment about the kinds of patients we´re trying to help, for example, veterans at our VA hospital in Boston. The patients we´re most likely to help early on are those who are severely blind, primarily from retinitis pigmentosa. They can get around reasonably well with a cane, but just think what it would be like if I were that person right now and I wanted to leave this room without asking someone for assistance. It would be essentially impossible.

You can understand what a hazard it would be, and how likely it would be I would run into someone or something and possibly hurt myself. I consider our primary goal to be improving quality of life for severely disabled patients so they can ambulate independently and safely in an unfamiliar environment. If we are ever fortunate enough to achieve our primary goal, we can move onto advanced objectives, such as getting severely visually disabled patients to perform more sophisticated tasks. We should also remember that patients do reasonably well with a cane, so whatever we build has to be substantially better than a cane. Of course, anything we develop would also have to take into account whatever risks and costs are associated with the new therapies. This goal to improve vision is a very special VA initiative, first and foremost because of the veterans. Age-related macular degeneration is the leading cause of blindness among veterans and in the general population. Here´s a beautiful win/win opportunity not just for veterans, but for our population at large. No available therapy can restore lost function in neural forms of blindness. To be able to do this requires advanced technology, and we´ve established a VA/academic partnership that has been, for me at least, a remarkable opportunity.

Our project will be successful only if a long-term and comprehensive approach is maintained. These technologies are hard, and they will only be developed if the institutions that work together understand it will take a long time. Let´s think for a moment about the various forms of blindness. The retina lines the back wall of the eye. The retina is nerve tissue, actually a part of the brain that grows forward out of the skull so it can capture light. It is connected to the visual part of the brain, which is in the back of the skull, by way of the optic nerve. Light enters the front of the eye and strikes the retina. Light goes through the retina tissue. By the way, each retina holds about 150 million nerve cells. It´s quite a complicated neural structure. The rods and cones receive light and create a nerve signal, sending that nerve signal to other cells that sit on the inside part of the retina. Those cells connect to the optic nerve. Light comes in and creates a complicated nerve signal that is eventually transported to the brain.

In macular degeneration and retinitis pigmentosa, these rods and cones are lost, but a substantial number of other nerve cells survive. The patients are blind because they no longer have the rods and cones that can convert light to a nerve signal. However, these cells had been formed properly at one point and are sitting there essentially unused. This creates the perfect situation for a prosthetic device to restore vision. One can build that prosthetic device to put underneath the retina, as we´re doing, or one can build a prosthetic to put on the inner surface of the retina, as one of the Al Mann companies, Second Sight, is developing. The VA has provided a home for our research group for the last three years. I told you there were two reasons I came to the VA. The second was, in fact, Dr. Mindy Aisen [Director, Rehabilitation Research and Development Service, Office of Research and Development, VA], whom I met about four years ago. I heard her give a talk, and she had a clear message of her desire for the VA to be at the forefront of rehabilitative technologies, and also her belief that multidisciplinary programs were important to the long-term success of VA rehabilitation research programs. That attitude was exactly what we needed. Ultimately, it worked out very well, and we´ve now formed this collaboration between Harvard Medical School, the Massachusetts Eye Infirmary—where I see patients—MIT, and the Boston VA.

We have many other partners, and I have purposefully left one area blank in my presentation. That´s because what we really need, ultimately, is a partner to take our device into the commercial realm. We don´t have that now, and there are a lot of reasons why. I´ll talk more about that at the end. In other words, developing the technological base is the beginning of the story, not the end of the story. Our device includes an ultra-small camera mounted on a pair of glasses that takes pictures—in essence, replacing the lost photoreceptors. The visual information would be sent wirelessly from a transmission coil on the pair of glasses to a receiving coil around the back of the eye. The wireless transmission system resembles an old television set receiving an airwave. The details of the visual scene are sent into electronics that sit on the outside of the eye, and then from those electronics the information is translated to the retina to stimulate the nerve tissue.

Very briefly, the substrate, the material onto which we embed the electronics, is an ultra-thin material. It´s only 10 microns thick, several times thinner than a human hair. Yet it´s flexible and contains embedded electronics, which we do with standard microfabrication technologies. The receiving coil is roughly about the size of a dime. One of the aspects of our design that we think is particularly favorable is the fact that 99 percent of this device—and remember, it´s about the width of a dime—sits outside of the eye.

We´re trying to develop a minimally invasive approach so that the only thing that goes into the eye is a very, very thin membrane that contains the stimulating electrodes. Our electrodes—and we can readily make hundreds of these on an array as easily as 10 with microfabrication technology—are only 50 microns in diameter, roughly about the size of a human hair. Each one of these electrodes has a wire, so you can communicate to it individually. Only that part, the very end of the structure, is put into the back of the eye. We can do this by raising a very small incision in the back of the eye and then inserting it all underneath the retina. Our hope is that we will be able to implant this type of device without going into the eye, just going through into the back of the eye to reach the retina.

How plausible is it that this kind of a strategy might work? The basic concept is that if you think about light falling on the retina where there are these thousands and thousands of nerve cells, and if you put an electrode array on those nerve cells and stimulate the cells in some particular pattern—let´s say a pattern that looks like the letter E—it is very reasonable to assume that, because of the anatomy that connects the eye to the brain, a person would in fact see a letter E. That´s a quite reasonable hope. What about being able to read a scoreboard? That´s a loftier hope.

To demonstrate how plausible our design is, I want to discuss our best results from the testing of six human patients. In these patients, who are completely blind or nearly completely blind with retinitis pigmentosa, we put one of these ultra-thin arrays in the back of the eye. The electrode array includes eight large electrodes and a large number of smaller electrodes. In one instance, we drove those electrodes, and immediately a 72-year-old woman, who had been legally blind for 40 years, reported seeing four clouds. Under the surgical drape, we have them draw, and she drew an image that is a very close correlate to the pattern of stimulation.

Is it possible to restore some vision to patients who have been blind? The answer is yes. If you can accomplish what we did in a relatively brief experiment, there is a hope that we will be able to produce better vision, perhaps creating a letter with a device like the one we are developing. Although this is highly debatable within our field, I would just like to say we haven´t been able to get patients to integrate images more complex than very simple geometric shapes. I´ve been fond of saying that even if the scientists at MIT provided me with the perfectly engineered device, blind patients aren´t going to see any better because I don´t know how to use it, nor will they know how to interpret these artificial stimuli. That will take a while to learn. We have to learn how to stimulate. They have to learn how to interpret. The point is, when you think about making a device like this, or any prosthetic device, you have to remember that for a complex behavior you have to learn how to interface with the nervous system.

Our field of retinal prosthetics is moving into what I think of as a Phase II. Many very interesting devices have been built. Now our job is to learn how to use them. This goes back to my neurology background, because ultimately we´re moving from an engineered device to working with the nervous system. This is the part of the domain I really love. I was asked to make a comment how close we are. Well, numerous things are standing in the way. I have to say, as much success as I think we´ve had, and although I hope we have a lot more in the future, we have faced some significant impediments. I was happy in some ways to hear Al Mann´s talk earlier, because I agreed with almost every word he said. No path had been forged for a project like ours at the time we had begun our work. No precedent existed for this type of endeavor. No governmental funding program was available for a long-term, high-risk project. In addition, no commercial opportunities were accessible, given that a prosthetic device had to be built. We also did not fit into the drug or pharmacy markets. The device companies, some of which are very successful, typically become interested once the developmental work has been completed. As a country, we need funding programs for biomedicine to support long-term development projects akin to those at NASA. The individuals who are here today have the opportunity to solve this problem. New ideas emerge typically from academic centers, but academic centers do not have the infrastructure, nor do they have the culture, to know how to transfer these technologies into the marketplace. From our standpoint, institutional and administrative issues have impeded our effort. I will offer my services and time to anyone interested to hear our side of the story. I am eager to help work to try to solve our problem, which I suggest is a collective problem faced by many researchers. Venture capitalists are often suggested as a solution to our problem to help sustain a large developmental program. But venture capitalists come in quickly and want to get out quickly. Our goals are completely different. It´s already taken nearly two decades to get where we are. It´s going to take longer to create higher quality vision. There´s a very, very long-term horizon. The question is, how does one sustain high levels of funding for a period of decades without having a return? It´s a real problem.

From a technical standpoint, I see three potential problems with the retinal prosthesis. One is their biocompatability. As we´ve learned just recently here in this country, we often find that biocompatibility problems develop long after devices have been implanted. The FDA has a difficult job, but an important one. Biocompatibility has gone well with these retinal prosthetics, but it´s still not a completely solved problem. Power safety is another potentially significant problem. If we want to give higher quality vision, we have to use more electrodes. The more electrodes we use, the more power we need. The more power we use, the more potential damage there could be from the radiation exposure. These are mutually antagonistic forces, and we don´t know yet how to resolve the issue. The last potential problem is hermetic encapsulation. Just within the last month, in fact, a significant recall of cochlear prostheses occurred because of problems of this type. Some very experienced companies have trouble solving this problem, and it´s because it´s a really tough technical problem. Assuming all of these issues are successfully resolved, I believe that once retinal prosthetics are properly built, we will still need to learn how best to use them. Learning how to use these sophisticated devices will be the core of our research effort for the foreseeable future. I´d like to thank the VA, the National Science Foundation, and NIH for their support. My program represents just one within the VA´s system. You´ll hear today from Hunter Peckham [Director, Cleveland Functional Electrical Stimulation Center]. You heard from John Donoghue [Professor of Neuroscience, Boston University] earlier. The VA has a number of programs with technologies that bear a lot of similarity. A culture flourishes within the VA for developing advanced engineering developmental work for the purpose of rehabilitation.

Lastly, I´d like to thank our patients. They almost get overlooked in the partnership with researchers. Of course, they´re the people who are heroic and who make themselves available for the experimentation that gives us the information to be successful. Thank you very, very much.

White House/VA Conference Emerging Technologies in Support of the New Freedom Initiative: Promoting Opportunities for People with Disabilities October 13-14, 2004

"Age-related macular degeneration is the leading cause of blindness among veterans and the general population."—Joseph F. Rizzo III, MD

White House/VA Conference
Emerging Technologies in Support of the New Freedom Initiative:
Promoting Opportunities for People with Disabilities October 13-14, 2004