Maurits Ortmanns: visual prosthesis research benefits from microelectronics research in Ulm
“Around one third of all visual prosthesis research in Germany is done by the Institute of Microelectronics at Ulm University,” said Maurits Ortmanns, a young electrical engineer who has been head of the Institute of Microelectronics since 2008. He is responsible for half of this figure and his colleague Albrecht Rothermel for the other half. The two engineers work for two German manufacturers who are developing competing versions of retinal implants. The two approaches have already been tested in clinical trials.
While Ortmanns' research has led to a system built around the epiretinal approach, his colleague Albrecht Rothermel focuses on the subretinal approach.
Ortmanns brought the epiretinal approach to Ulm when he moved here in 2008. He received his PhD from the University of Freiburg in 2004 and worked for a Hanover-based subsidiary of Infineon for two years before returning to Freiburg where he was appointed junior professor at the Institute of Microsystems Engineering (IMTEK) at the University of Freiburg in 2006. In Freiburg, he worked with Thomas Stieglitz, a professor of biomedical microtechnology who "encapsulates" microelectronics to make it biocompatible with human tissue.
Major focus on the eye
Maurits Ortmanns is a specialist in integrated circuits, a subfield of microelectronics that, after 40 years of development, now makes it possible to accurately position around one billion switches on silicium. Ortmanns’ institute uses miniaturised electronics for biomedical applications. At the moment, Ortmanns and Rothermel and their eight doctoral students are concentrating mainly on the eye. The researchers are developing and optimising a prototype platform that will considerably expand the biomedical application spectrum of microelectronics.
For Ortmanns, combining the two completely different worlds of electronics and biology is a highly challenging task. The organism does not tolerate voltage or electricity, and it is crucial that integrated circuits do not come into contact with the aqueous environment of human organisms.
While researchers from Freiburg or Reutlingen focus on encapsulating the electronics and on connecting the device to the body tissue, the researchers from Ulm are developing circuits that require as little electrical power as possible so that the heat generated does not destroy the surrounding body tissue. Ortmanns’ team is developing wireless systems that transfer energy into the body.
Two competing systems at one and the same institute
Several years ago, Ortmanns developed an integrated circuit for a visual prosthesis that had been developed by the Bonn-based start-up company IMI Intelligent Medical Implants GmbH. This visual prosthesis had already been successfully tested and Ortmanns continued the project when he returned to Freiburg. Since being appointed head of the Institute of Microelectronics in 2008, Ortmanns has been producing and developing the next generation of the implant in cooperation with Stieglitz in a BMBF-funded project.
Ortmanns' colleague Albrecht Rothermel has been involved in the further development of Reutlingen-based Retina Implant AG's microelectronic retinal implant since 2007. IMI Intelligent Medical Implants GmbH and Retina Implant AG are the only two companies in Germany focusing on the development of retinal implants. Ortmanns estimates that there are only six teams in the world working on retinal implants. The company Second Sight, which is based in Southern California, follows the same approach as the Bonn-based start-up company and has covered the same ground as the two German companies in the development of retinal implants.
Reading, recognising faces and moving around without a guide dog
Retinal implants replace defective photoreceptors in the eye and bridge the interrupted connection from the retina to the brain by electrically stimulating the sensory nerves, thereby evoking neural responses in order to activate artificial vision. Retinal implants have the potential to enable blind patients to recognise letters, to read and move around without help, to recognise faces and to differentiate people from each other.
Biomedical implants such as cardiac pacemakers or hearing aids like the cochlear implant have been on the market for many years. However, the human eye is a major challenge for developers of implantable circuits because, in contrast to the heart and ears, there is minimal space available in the eye to place visual prostheses, which is why they are positioned either on or inside the eye. Visual prostheses that are placed inside the eye need to be immobilised effectively in order to prevent damage caused by eye movements.
The challenge of 70 million photoreceptors
An even greater problem faced by biomedical implant researchers is the large number of photoreceptors: 70 million. This raises the question as to how many photoreceptors are actually required for visual perception. Some researchers believe that around a hundred to a thousand pixels would provide sufficient sight to be able to differentiate people. The implant developed by Retina Implant AG uses 1,600 pixels, and IMI Intelligent Medical Implants GmbH's implant uses 250.
The two competing approaches focus on different retinal stimulations. In subretinal implants (Retina Implant AG), the chip is implanted under a layer of nerve cells in the retina where it receives light impulses, converts them into electrical signals and transmits them to the nerve cells of the retina. In epiretinal implants (IMI Intelligent Medical Implants GmbH), the chip is fixed to the uppermost layer of nerve cells where it receives data from a small camera installed in the patient's glasses and the data is then converted into impulses directed at the nerve cells. Teams from other countries are developing other systems, including a system in which the chip is implanted outside the eye on the dermis that protects the eyeball in the socket. However, these systems are still at the experimental stage.
Ortmanns explains that the integration of these implants into the body is at different stages of development: Retina Implant AG, which is the only developer of subretinal implants, will conduct a second clinical trial to test the latest version of the implant. The new version no longer has external parts; its power supply is positioned under the skin behind the ear, connected with a thin cable that leads to the eyeball. IMI Intelligent Medical Implants GmbH uses a completely encapsulated system that is shorter than a fingernail, weighs only 1.5 g and can remain in the eye. The American company Second Sight follows the same approach as IMI Intelligent Medical Implants GmbH.
Reutlingen-based Retina AG is the clear leader in terms of the number of pixels (i.e. light-sensitive photodiodes). The Baden-Württemberg researchers connect the electronic chips directly to the retina's macular region. The chip absorbs the light entering the eye and converts it into electricity to stimulate functional retinal nerves. The stimulation is then relayed to the brain through the optic nerve. IMI Intelligent Medical Implants and Second Sight establish a biocompatible (encapsulated) connection between the chip and the tissue. Since their implants are 10 to 100 micrometres from the site where the signals are produced, much stronger stimulation is required. Ortmanns believes that the epiretinal approach is simpler and the implant can be easily inserted during surgery. On the other hand, the chip requires more amperes to stimulate the retinal nerves.
It is still not known which of the two systems will finally make it to the market
Ortmanns is currently unable to say which of the two systems will make it to the market. All three companies have already carried out clinical trials on patients. Retina Implant AG only tested the feasibility of its implant on a few patients due to ethical concerns that arose (the initial model had wires that stuck out from behind the ear; a new version, where the power supply is positioned under the skin behind the ear, is soon to be tested in a larger pool of patients). IMI Intelligent Medical Implants GmbH and Second Sight have already carried out international clinical trials. Ortmanns believes that the fastest company will make it to the market as he feels that additional clinical trials to test the slower concept might fail to convince for ethical reasons.
Seeing aids for millions of blind people
Epi- and subretinal prostheses can be used to treat patients suffering from retinitis pigmentosa, a genetic disease affecting around three million people worldwide and around 30,000 people in Germany. The systems should also be used for the restoration of vision in people suffering from age-related macular degeneration (AMD). Many people in industrialised countries over the age of 50 lose their eyesight due to this disease. Worldwide, around 25 to 30 million people suffer from AMD and every year 500,000 more people are diagnosed with the disease. It is believed that around two million people in Germany suffer from AMD.
Both types of implants rely on an intact connection between the retina and the brain. Both implants are indicated when damage is restricted to the retina, and the nerves that lead to the brain and the optic nerve remain intact. Neither implant is able to restore vision in people with a defective optic nerve. Other research approaches target the visual cortex, which is responsible for processing visual images and is situated at the rear of the brain above the cerebellum.
Open question: how long can the implant remain in the eye?
Whilst all potential technical problems now seem to be solved or can at least be controlled, it is still not clear how long the implants can remain in the eye. According to Ortmanns, the different research groups are all working hard to prolong this time and current knowledge suggests that the implants can remain in the eye for five to ten years.
Ortmanns and Rothermel’s doctoral students deal with biomedical implants. Ortmanns would like to focus on broadening his field of activity, as 90 per cent of his research is currently used for eye-related developments. He is planning to establish a kind of prototype platform with greater functionality. He also envisages non-implantable applications, and free selection of the number of channels (between 1 and several thousand channels).
Ortmanns explains why he is striving to move away from eye implants. The development of implants of the kind that Ortmanns and Rothermel are working on takes around 12 to 15 man years. The implants have close to one million individual structures and are based on a great deal of individual knowledge, which is why the cost of development can rapidly reach between one and two million euros. A more variable prototype platform would enable Ortmanns to react flexibly to both industrial and academic client requirements. Ortmanns believes that another major advantage of his prototype is that it enables development time to be reduced from three years to six months. And last but not least, single modifications would only cost around 20,000 euros, making them considerably cheaper than they are now. Taking all this into account, “we will be able to react relatively quickly to many diverse requirements.”
Can the bladder muscle be stimulated?
Ortmanns is planning to work with neurobiologists to investigate the transfer patterns on freshly isolated neural tissue using a microchip. The researchers from Ulm are already in negotiations with a Danish bladder prosthesis manufacturer. The prerequisites are already known: the microchip will use only one or two channels but require quite high amounts of electrical power to stimulate the muscle. If the negotiations lead to a cooperation agreement, it would be the first ever project on muscular stimulation.