Dr. Mark S. Humayun, former director of the Intraocular Prosthetic laboratory at the Wilmer Ophthalmological Institute at Johns Hopkins Hospital, has taken a different approach to retinal prosthesis than the subretinal implants being designed by Optobionics. He believes that the intensity of light entering the eye is not great enough to effectively stimulate artificial photoreceptors. Instead, he and his colleagues have developed a system using a small external camera that transmits a signal to an epiretinal implant positioned on the outer surface of the retina. This implant then stimulates the ganglion cell layer which transmits the signal to the optic nerve and then to the brain. Humayun began his research at Johns Hopkins and then teamed up with Eugene de Juan to form the Intraocular Retinal Prosthesis Group at the Doheny Retina Institute at the University of Southern California. Several organizations are currently collaborating in research and clinical trials to develop and improve upon these devices.

Dr. Humayun and Dr. de Juan

Development:

Humayun and de Juan conceived the idea and then outsourced various aspects of the project to other organizations. Oak Ridge, Sandia, Argonne, and Los Alamos national laboratories each took on a different aspect of the electrode array and retina interface. The University of Southern California provided the facilities for implantation of the devices and a company called Second Sight in Sylmar, CA will be the commercial producers of the finished product. These organizations make up the $9 million collaborative effort to produce a successful implantable device to replace vision. In 2002, Sandia Labs announced their completion of the Multiple-unit Artificial Retinal Chipset (MARC). The device includes an externally mounted camera on a pair of glasses that takes video images and converts them to digital signals in a belt-mounted visual processing unit (VPU). These signals are then transmitted via radio waves from a small antenna behind the ear to the implant on the retina.

The implant itself has two main components, one extraocular and one intraocular. The extraocular electronic case component is surgically attached to the temporal area of the skull and a small subcutaneous wire connects it through the eye wall to the intraocular electrode array. This 4mm x 5mm array is composed of 16 separate micro-machined silicon electrodes in a 4 by 4 grid. The external antenna is magnetically attached to the extraocular implant behind the ear and wirelessly transmits the radio signals from the VPU to the electronic case, which feeds to the intraocular array. The radio waves provide the energy needed to power all of the internal components, much like a crystal radio set. This eliminates the need for percutaneous wires or and internal power source.

All pieces combined, this device takes light input and converts it to electrical signals that stimulate the still-working cells in the retina to send impulses to the brain.

The complete implanted portion of the device: The electronic case shown on the left connected to the electrode array by a cable through the eye wall.

The 4x4 electrode array shown after implantation with the cord from the electronic case on the left.

Clinical Trials:

In 2002, the Intraocular Retinal Prosthesis Group received FDA approval for clinical trials to test the feasibility of the retinal prosthesis device. A team of researchers from the Keck School of Medicine and the Doheny Retina Institute, both at USC, and from Second Sight performed the implantation in three patients that had complete loss of vision due to retinitis pigmentosa. A team of four surgeons, including Humayun and de Juan as well as Michael Burnstine and Dennis Maceri performed the first operation in February of 2002, the second in July, and the third in March of 2003, all with great success.

Implantation:

Under general anesthesia, the electronic case component was implanted into a recessed well in the temporal skull as done in cochlear implants. The cable was passed through a groove created in the skull, into the periocular space, and into the eye through a 5mm scleral incision. The 16 electrode array was positioned on the retina near the ganglion cells that it is intended to stimulate with a single retinal tack. After the operation, the electrodes were tested for conductivity to ensure that all wires and connections are intact.

A representation of the retinal prosthesis: (A) Camera in the glass frame; (B) wireless transmitter; (C) extraocular electronic case (receiver) and (D) intraocular implant (electrode array)

Results:

Each patient accepted the implants well with little sign of rejection. “And we have found that the devices are indeed electrically conducting, and can be used by the patients to detect light or even to distinguish between objects such as a cup or plate in forced choice tests conducted with one patient so far,” says Humayun [39]. The first tests of the implants simply involved sending computer generated signals of light points directly to each of the electrodes and patients reported perception of light on all sixteen. Next they “graduated” to images generated by the eyeglass mounted digital video camera. Although the device only allows for a 16 pixel image, patients reported being able to tell when a light was turned on and off, follow the movement of objects, and even count discrete objects. When individual photoreceptors were stimulated by the computer, patients could successfully identify which area of their visual field was being stimulated. During the camera trials, patients could locate light sources follow them around the room and even make out certain images and shapes. They described the phenomenon as seeing spots of light (generally yellow or white but sometimes red/orange or blue) about the size of a quarter at arms length. Humayun says that testing in the three patients is ongoing and “We plan in the near future to look at how useful the prosthesis can be in activities of daily living.” [39]

Another look at the implanted electrode array on the surface of the retina.

Click on the picture to see a video explaining what the patient actually sees with the implant.

Funding:

The Department of Energy has provided the majority of the funding for this retinal prosthesis project. They have given over $9 million to the organizations involved, (mainly Second Sight) and plan to invest around $20 million more in the few years to come. The NIH gave a grant in 2000 during the initial research stages as well. Other sources of funding include the Office of Naval Research, the Whitaker Foundation, The Foundation Fighting Blindness, the Defense Advanced Research Projects Agency, and the National Eye Institute. Second Sight has also invested much of its own funds into all aspects of this project

Challenges:

One of the first issues to be tackled was how to determine the strength of the impulse that would be needed to stimulate ganglion cells and send signals down the optic nerve to the brain. Humayun performed extensive research in mice and rabbit retinas to determine a level at which stimulation would be maximized but no burning or scarring was caused. Another potential problem was that the eye is constantly moving and the electrode array would be prone to damage or separation from the retina. So far, the single retinal tack has proved effective. The electrode array also must be protected from the fluids inside the eye. The original design utilized a titanium and ceramic casing to enclose the device, and while effective, it was a bit bulky and would hinder future miniaturization and increased pixilation. To improve upon this, Second Sight has developed a diamond coating for the device. This thin film provides an extremely tough, electrically insulating, hermetic seal for the device. Unwanted interactions of the electrodes with non-local ganglion axons passing nearby also caused Humayun to worry.

D&E- Targeted Ganglion Cells

These interactions were thought to produce light in the wrong places, however clinical trials have proved this effect to be minimal. This suggests that the deeper retinal cells can be successfully targeted rather than only the superficial ones. It is not possible to know exactly what a patient is seeing; their own introspection and threshold tests are the only methods of obtaining data and determining the success of the implant. Thus “flash of light” may be perceived differently between subjects. Pure objective results are imposible to obtain.