"The eyes have it"

In the Biotechnology in Medicine class that the four of us are taking, we are now reading the book Better by Atul Gawande. A fascinating read, it traces many developments in medicine and makes the ultimate observation that the focus of doctors and, in fact, the entire field of biotechnology, should be improvement. Noting this theme, I was struck by this article in the Economist which discusses rather recent developments in a type of surgery that has existed for more than half a century: replacing cataracts ("lenses darkened by cloudy imperfections") with artificial lenses. 

Cataracts affects many, many people each year. While the first cataract replacement surgeries were performed using perspex lenses, they have more recently been replaced with silicone lenses. Yet, as Gawande so astutely notes, medicine should always be prepared to change with the times. 

As such, it should not be surprising that this field of artificial vision has begun to change as well. For instance, we have recently seen the introduction of microsurgery, which allows the insertion of a lens through a 2 mm cut as opposed to an 11 mm cut. Unsurprisingly, this dramatic change allows for far shorter recovery times for patients. 

Aside from simply noting the obvious advantages of a smaller incision, it is significant to understand exactly how this change was made possible. For one, there was the innovative use of an ultrasound probe to remove the lens by breaking up the damaged lens into an emulsion. Soon thereafter, an injectable lens is implanted by rolling it up and allowing it to unfold within the narrow slit. 

What I found most interesting about these innovations is that, according to this article, these tools have actually been available for some time. In fact, the only real new innovation was combining them into "one snazzy little box" which can do all three steps. 

 I was also intrigued by the final paragraph of this article, which discusses what ophthamologists and lens-making companies would most like to achieve-- that is, a lens that can focus in both near and far distances, like a healthy eye. I think that it is important to note that in all fields of biotechnology, artificial vision not withstanding, innovation is critical. Innovation not simply in the sense of scientific research and discovery, but in terms of marketing and design so as to ensure to spread of new technologies as they are developed. 

link: http://www.economist.com/sciencetechnology/tm/displaystory.cfm?story_id=10012901

An Overview of the Visual Prosthesis Market

Visual Prosthesis Market May Follow Uncharted Path
by James Cavuoto, Neurotech Business Report, October 2002

A quick note on the relevance of the discussions presented in this article: This article might seem a bit outdated because it was published in 2002 and some of the "current" developments discussed within it are actually established technologies now. Nonetheless, this article still provides an interesting, yet general overview and outlook of the Visual Prosthesis Market that transcends the time stamp of its publication date.

The author begins by discussing several projects and their developments back in 2002, which gives an insight into the principle actors involved in this market. The author makes specific references to these commercial developers and research teams: Optobionics Corp., Second Sight LLC, Intelligent Implants, Naval Research Laboratories, London’s University College, the University of Houston, and NASA’s Space Vacuum Epitaxy Center. This wide range of projects and their progress in the field indicate that the market is appropriately populated with healthy, innovative and well-funded firms, which speaks to the commercial viability of this market segment. This is not a market segment that is stuck or floundering. It is a healthy--albeit underdeveloped--- segment that has potential to be quite successful.

Besides outlining the principle actors in the visual prosthesis market, this article also comments on the similarities and differences between the retinal implant market and the cochlear implant segment of the neural prosthesis market. This article indicates that many believe that the retinal implant market will follow the trajectory of the cochlear implant segment, but the author suggests otherwise. He points to two major factors that differentiate the segments: complexity and density. Retinal implants are far more technologically complex (with much more data processing) than cochlear implants and involve a nerve system whose organization is still not entirely understood. Furthermore, these implants are also facing manufacturing obstacles
in regards to inflated electrode density. As more electrode arrays are demanded in order to increase the quality of the processed data, issues of tissue damage and component failure are becoming more prevalent. These major differences between the retinal and cochlear implant market segments, the author argues, are so pronounced that the retinal implant market segment should not be modeled on the cochlear implant segment. He provides his own assessment of how the retinal implant market should be developed later on in his article.


The author provides two factors that make the retinal implant segment attractive to commercial development: intense public interest and many funders. The heightened public interest in the success of these implants stems from the current lack of aides and therapies that improve the quality of daily life of the blind. Commerical developers have found that they must downplay some of the innovations made in their field because patients are so willing to test the newest technologies. Secondly, there seems to be a surplus of funding within this market segment. In addition to the government and VC funding for this device development, there are also private and quasi-governmental institution investors who are within the visual disabilities community and are very interested in these retinal implants. This could mean that even the first-generation of these devices will be profitable, which is rare in the medical device markets because typically a period of time to legitimize the technology is often required.

Lastly, the author provides his own suggestions for the development of the retinal implant market. In light of the intense public interest, he suggests that manufacturers are careful not to erode the sense of confidence placed in this segment by the public and investors. He suggests that manufacturers stay realistic about timetables and results. He also suggests preliminary steps into the market would include visual aids that could be developed first before the "next generation of more general purpose prostheses." Therefore, it is acknowledged that this market segment is still underdeveloped and has a long road ahead of it but has a great potential for profitability and commercial viability.

Creative Use of Materials for Retinal Implants

Artificial Retina Gets Diamond Coating

Second Sight, a company currently focusing on developing a bionic eye that will help people who have lost vision through diseases such as retinitis pigmentosa and macular degeneration. The silicon chip retinal implant is a device that bypasses diseased cells in the back of the eye by electrically stimulating the healthy cells that lie beneath them. The patient than acquires vision by using glasses with a small video camera that sends digitized images to the implant using radio waves. Although the theory was sound, scientists had a hard time figuring out how they could implant a piece of complex machinery into the eye without getting the circuitry damaged via reaction with the retinal fluid. The solution came in the form of an ultrananocrystalline diamond film.

When one hears the word diamond there is a tendency to envision a shiny stone set in a ring or displayed in a flashy showcase. However, current technology allows for the chemical formation of tiny diamond crystals (five millionths of a millimeter across) that can be grown directly onto a chip. This new film fulfills all of the necessary criteria for a coating as materials before hand had never succeeded in doing. It is safe, long-lasting, electrically insulating, and tough. The durability of materials used in bionic eyes is always an important point for vision is something that one will use as long and he or she is living.

In the article, there is no mention of the price of an artificial retinal implant, which must be considered for, realistically, a company will invest in research only if there is a possibility of profit. A diamond coating may be a great step forward in creating a device that has the potential of being used in human patients, but how this will affect the price tag on a retinal implant will be a vital factor for future users.

web link: http://www.nature.com/news/2005/050331/full/news050328-9.html

Innovation: Testing Visual Prostheses

Scientists Create Robot Surrogate For Blind Persons in Testing Visual Prostheses

ScienceDaily (Oct. 20, 2009)


(Credit: Caltech/Wolfgang Fink, Mark Tarbell)

Researchers have finally developed a way to objectively evaluate the performance of visual prostheses. It is a small mobile robotic platform (pictured above) named CYCLOPS. CYCLOPS allows scientists to better assess what the blind can see with a retinal implant. It also allows scientists to identify ways to improve upon the implants.

CYCLOPS will replace the two patient subpopulations that have been used traditionally to test these new prostheses: the blind who have an artifical retina and sighted patients who "downgrade" their vision in an attempt to replicate a blind person's experience. Both of these subpopulations present substantial obstacles in the pursuit of unbiased and scientifically sound data. Statistical issues as well as stamina problems limit the data that can be obtained from the blind population with artificial retinas. Not only are there relatively few patients who have undergone this operation, but these patients also tend to not be able to endure prolonged periods of testing. Therefore, this population is not ideal, because the artificial vision field demands exhaustive and extensive clinical testing. Sighted patients are also less-than-ideal. A sighted person's brain is very apt at processing poor-quality images and supplementing them with details; this is a skill that is very helpful when a sighted person encounters dim light, but it also makes them poor test subjects for visual prostheses.

The CYCLOPS is the much needed answer to the call for impartial testing subjects in the artificial vision field. Its camera, which can make left-to-right and up-and-down head movements, collects the visual input that an artificial retina would also collect. The camera can be adjusted to various arrays of pixels that would mimic those found in an artificial retina implant. These images are then processed on the onboard computing platform, which "does real-time processing." However, the CYCLOPS is still not entirely ready to make truly independent movements, but scientists are confident that they will reach that level soon.

In the meantime, the benefits of the CYCLOPS are still rather incredible. Researchers can perform countless tests without the worries of exhausting a patient or obtaining unreliable data. Other applications of the CYCLOPS would include enhancing workplace or living environments to be more "blind-friendly" and pre-screening particular versions of prostheses and their on-board image-processing software. The CYCLOPS means that the artificial vision field can finally undertake even more extensive prostheses trials, which could translate to huge leap forwards in this field in the very near future.

Innovation: Silicon Optoelectronic Devices on a Curved Surface

"Optics: Electronic Eyeballs"
By Takao Someya
Nature 454, 703-704 (7 August 2008) | Published online 6 August 2008

A recent innovation in the artificial vision field deals with the shape of artificial imagers. Specifically, engineers are now developing curved imagers that can more accurately mimic those seen in nature as compared to the already established artificial-vision systems that rely on flat-image recording surfaces. These curved imagers overcome shortcomings of the conventional systems, which use multiple lens combinations to reduce distortions at the edges of lenses. These arrangements, however, make artificial-vision less viable as a therapeutic option because they are "heavy, expensive, and produce darker results than they would with a single layer of lenses". Therefore, this innovation could open up the option of artificial vision to many new patients who had been deterred in the past by the operation's price tag, its lack of comfort, and its limited functionality.

The advent of this new technology depends on two main advances:

1) A network of semiconductor photodetectors (on a silicon wafer) that can withstand elastic compressiblity is required. Thin metallic wires would be used to interconnect the photodetectors in order to create the compressibility. It is also required that this network hold up even when "subjected to high levels of strain (typically exceeding 50%)".

2) The photodetector network must use elastomeric elements that would allow for it to be created in a planar configuration and then stretched into a hemispherical shape. This would lead to imagers with "wide-angle fields of view, low distortion and compact size."

This new technology could truly revolutionize the optics design field and generate other beneficial uses for industrial applications. It would bring more clarity and precision to the world of medical optics as distortions are minimized and optical transperancy are increased, which would help us to see our world in a new light.

"Opening a New Channel"

Karin Kloosterman of the Jerusalem Post

Published only a few weeks ago, on October 16, 2009, this article from the Jerusalem Post highlights a new and exciting discovery in the field of artificial vision. Israeli researcher Dr. Amir Amedi sought to discover a way to harness the well-known capability of bats to “see” vis-à-vis sounds and in doing so, develop a way for blind humans to “see” by hearing. This fascinating article describes the process of teaching the blind to use their brain in a unique manner. The idea is that visual information is transformed into audio signals by creating an auditory soundscape, which acts like a new language for the blind. To create this soundscape, the individual essentially creates a new alphabet by playing a sound and handing the blind individual an object. The shape of that object is therefore correlated to that sound. Later, a webcam is used to transform what is seen into a sound, which the blind person can understand. Interestingly, Amedi discovered that when these individuals began to learn this new language, their auditory cortexes were activated. Soon after they began learning, however, their visual cortex actually began to be activated (or re-activated)!

I discovered this article from LexisNexis. I think that it adds a new element to the conventional perception of “artificial vision.” Amedi approached the problem of blindness from a new angle, and in doing so, discovered a new way to give blind individuals the chance to “see.” I think that Amedi’s research is fascinating and reminds readers of the importance of innovative and creative thinking, especially in the field of scientific research.

Weblink: http://www.jpost.com/servlet/Satellite?cid=1255547726163&pagename=JPArticle%2FShowFull

"Blinded by the war: Eye injuries hit troops hard; Mortars, roadside bombs send lives into darkness"

 by Gregg Zoroya , USA Today, November 14, 2009

In our biotechnology class this semester, we learned that the Department of Veterans Affairs is a key player in many stages of research in biotechnology, from bionic arms to artificial vision. As Zoroya notes in this article, the Pentagon provides no rehabilitation centers for veterans blinded in combat, and it is therefore left to the VA to prepare veterans for civilian life without sight. The first half of this article focuses on individual cases that are exemplary of the large-scale picture of army veterans who have been unfortunate enough to have lost their vision—these are people who were once capable of sight and have lost this sense while fighting for their country. Many people argue that because these people have already sacrificed much in fighting overseas, they deserve every care possible (including expensive research into things like artificial vision) to ensure that they can reawaken their lost senses.

      

       In 2007, the VA took part in two clinical trials on artificial vision, which are discussed in the latter half of this article. These trials involved implanting silicon chips into the eyes of blind veterans. These chips apparently function as “receptors that can transform light into electrical signals that can be transmitted to the brain.” Although this article does not provide a very in-depth overview of the science behind artificial vision, it certainly raises many key points in many policy debates. For one, history shows us that it is often through the Departments of Defense and Veterans Affairs that many great steps in biotechnology are undertaken, from cutting-edge research to practical implementation. Moreover, the article highlights the philosophical question regarding what we as a nation owe our veterans. Is it the responsibility of the government and the American people to channel at least as much money into rehabilitating veterans as we do into developing new weapons technologies? This type of question resonates with the idea of artificial vision, because this sense is something that most of these wounded veterans would have most likely retained had it not been for their participation in war. Moreover, the research that goes into helping restore sight in veterans could one day easily help thousands of civilians. 

Weblink: http://www.usatoday.com/news/military/2007-11-13-eyeinjuries_N.htm

Building a bionic eye Peering into the future

When one uses google or any other search engine to look up "bionic eye" (another term for artificial vision or any form of neural prosthesis used to restore vision) numerous articles about how vision may be restored to the blind or extremely visually impaired comes up. Yet this article in the economist negates this fundamental definition by introducing research currently being performed to develop contact lenses that do not improve vision, but are "smart". They are trying to create a miniscule computer that can display information into the eye which can be perceived only by the wearer.
Clearly what constitutes artificial vision is not as narrow as one may at first perceive. It can be a means to enhance vision in numerous ways or manipulate vision as a source of information storage, not just restoring lost vision. Which concept will be more applicable to the general public in the future will depend on how quickly they will become something marketable and the needs of the future generations. Perhaps a bio-medical method for restoring vision will replace the technology/engineering method and obliterate all of the current developments. Although everything is still in the testing stage, it is highly intriguing to see in which direction artificial vision will go.

weblink: http://www.economist.com/sciencetechnology/tm/displaystory.cfm?story_id=14538587

Artificial Vision Moving from Science Fiction to Science Fact

In recent years artificial vision has become more than a fantasy and development has come to the point where there is extensive clinical trials going on with numerous patients getting implants to test the efficacy and potential marketability of the devices. Improvements in technology, increasingly safe and effective surgical procedures, and demonstration of tolerance by the human eye have corroborated to the optimistic view of attaining artificial vision. However, while clearly stating the advancements that have been made, this article also emphasizes how much more research and engineering abilities will be necessary before anything that is comparable with natural human vision can be recreated. The point is to have vision in order so that those who are legally blind can again become self reliant and live a normal life. Should people be investing a fortune in machines that may allow them to walk around their homes unguided but cannot allow them to cross the street? Also, whether implants can be used indefinitely is not clear at this point because most of the clinical trials have been going on for six months to a year, and no one knows the consequences of long term use.
Furthermore, the major companies dealing with artificial vision have been basing their research around restoration of vision for people with diseases of visual degeneration, especially retinitis pigmentosa, and not necessarily for the blind or for those who have lost eyesight through trauma, etc. The clinical trials mentioned in the article seems to have utilized retinitis pigmentosa patients exclusively to test the devices. Even within the field of visual problems, artificial vision is currently focusing on a very narrow realm, with a limited population that could use the developed technology. So although artificial vision is being increasingly recognized by the general public as a possible reality, they must keep in mind that it is still a very young field that has a long way to go.


weblink: http://www.eurotimes.org/09October/ArtificialVision.pdf

Retinal Implants: The Artificial Retina Project

" 'Bionic' eye restores vision after three decades of darkness"
 by Larry Greenmeier. Scientific American News Blog. Mar 4, 2009.

Winning the prestigious "2009 R&D 100" 100, the Argus Retinal Prosthesis is a collaborative effort among the academia, private institutions, and the government. The project is funded by  the US Department of Energy along with the National Institute of Health. It is similar to the Artificial Silicon Retina in that it requires surgery, but it is different in that it is placed epiretinally rather than subretinally. Patients need to wear a pair of eyeglasses which hold a camera that captures images and passes the information along to a video processor, which then converts the image into electronic signals. These signals are sent to a receiver attached to the surface of the eye, which are then passed on to the artificial retina, stimulating it to transmit electronic pulses to the brain through the optic nerve. The basis of this project is exactly the same as that of the Artificial Silicon Retina developed by Dr. Vincent Chow. However, the Argus Retinal Prosthesis seems to hold more promise in that the numerous electrodes on the epiretinal prosthesis (up to 200 electrodes in the current model) are capable of conjuring up images that are clearer and bigger than any other artificial retinal devices have done before. In fact, as the article mentioned, eleven of the study participants reported they could locate a door up to six meters away, which have previously not been shown. 

Photo Courtesy: The Artificial Retina Project

Creating a retinal prosthetic device is no easy task. Not only does the device have to be safe and effective, it also needs to be durable enough to last for a lifetime for the individual.
The device must be biocompatible with the delicate eye tissue, yet tough enough to withstand the corrosive, salty environment. It needs to be powered at a high enough level to generate a response, but it cannot generate enough heat that would damage the remaining functioning retinal cells. It also needs to stay put on the retinal macula. Another important aspect is that image processing needs to be instantaneous so that there is no delay in interpreting an object in view.

The article also mentions a few other artificial vision projects. It is obvious that this area is gaining speed; when reading about the numerous projects out there, I found myself getting confused by the subtle differences between each "innovation". I believe part of the reason why the Artificial Silicon Project is the leader in the field is that it is a collaborative, multi-institutional effort. By pooling talents and resources, it has been able to emerge with convincing clinical results. Although commercial profit provides a great incentive for innovation, I can't help but think that if research groups were to consolidate and focus on a few projects, artificial vision would become a reality much sooner. The flip-side of the argument, of course, is that this stifles creativity and does not give new ideas a chance to be developed. The outcome of this, most probably, is that we will end up with a plethora of artificial vision devices that ultimately achieve the same goal. The job of the FDA is therefore to set up clear guidelines to applying for new device approval. It is also crucial that in the future, when the field of artificial vision becomes even more advanced, that the FDA provide of set of standards that new artificial devices must achieve in order for them to be approved. 

Retinal Implants: The Artificial Silicon Microchip

Based on the knowledge that nerves behind the retina still functioned even when the retina had degenerated, as shown by Dr. Mark Humayun (Publication can be found here), researchers have been focusing on creating artificial retinas as a means of restoring vision. One such device that is capturing a lot of attention is Optobionic's Artificial Silicon Retina™ microchip.


"Ophthalmologists Implant Five Patients with Artificial Microchip". 

ScienceDaily, Apr 29, 2005.

The first retinal implant to move into clinical trials (currently Phase II), the ASR chip contains approximately 5,000 microscopic solar cells, called microphotodiodes, that convert light into electrical impulses. The chip is inserted into the subretinal space and basically takes on the role of photoreceptors: in response to light entering the eye, it sends the information along to the brain for interpretation. What is special about this microchip is that it requires no external battery source; the chip powered solely by incident light. This distinguishes the ASR from one of its competitors, ARCC (Artificial Retina Component Chip). The ARCC, like the ASR, is composed of light sensors and electrode arrays that send signals to the retinal neurons. However, the system requires additional power and is dependent upon an external camera to detect a picture and induce a laser pulse. Both the camera and the laser are built into a pair of sunglasses, which the patient will wear. Incoming laser light is then detected by the photo sensors in the implant to create a picture. The ASR is thus a much more elegant solution in terms of convenience and aestheticism.


The fact that the ASR does not require any external power also greatly reduces the size of the chip (2 mm in diameter, 25 microns in thickness and is less than the thickness of a human hair) and makes surgery less invasive. In addition, the microchip is strategically placed so as to directly stimulate the remaining healthy cells in the retina. Of the 10 patients who received the microchip implant surgery, all reported some degree of improvement in visual function.

Photo credit: Optobionics

The ASR™ is only one of the numerous artificial retinas that are currently undergoing FDA

approval. Although complete vision rescue has not be reported, being able to see hints of 

light has been a big step for most patients. Below are two patients describing what they were able to do after the implant surgeries: