Goal

The Optobionics Artificial Silicon Retina (ASR) aims to stimulate the outer retinal cells whose sensory mechanisms have been destroyed, which typically occurs due to macular degeneration or retinitis pigmentosa. This technology offers both a therapeutic element of cellular repair in addition to overall improvement in visual function.

A microphotodiode array (MPA), a microchip, is placed in the retina, and compensates for the damaged photoreceptors' inability to convert light into electrical signals by discharging its own current. These electrical signals stimulate the intact mechanisms of the visual system, depolarizing the next cells in the circuit, the inner retinal cells, and allowing the visual system to take on the higher order processing of visual perception.

Design Structure:

The MPA is an independent device, requiring no external power source or processing mechanisms; it is powered solely by solar incident light. The microchip contains two layers, an electrode layer and a silicon layer, that are bonded together by an adhesive material. The round device is 2 mm in diameter and 25 microns thick, and is composed of 5,000 “microphotodiodes,” as Optobionics terms it, a solar cell with its own electrode serving to register a pixel of space.

How It Works

The silicon layer is molded to best fit the light-sensing mechanisms of the eye. Patterns are etched into the silicon, and this “recipe,” as Chow, the engineer of the device, describes it, is monitored and modified for efficacy by microscope technology. As he says, “the implants are only 25 microns in thickness, and we have to sculpt different features into the surface to make it compatible with the eye.” [13] The MPA generates an electric charge from the electrodes, which “artificially alter the membrane potential of neurons in the remaining retinal layers in a manner to produce formed images.” [12]

Evolution of Design

In a previous design of the MPA, a gold electrode was attached to the silicon layer by a chromium adhesive layer. However, after six months, the gold layer dissolved, exposing the adhesive layer, leading to the proliferation of neuron-destroying chromium ions. Additionally, electrical function decreased over time due to the dissolution of the electrodes. A recent animal model study tracked the durability of an iridium oxide or platinum based electrode system coupled with a titanium adhesive layer. Researchers found increased durability of the product and recorded stable levels of electrical signals, indicating electrode preservation.

Six months, durable MPA in cats. Iridium oxide on left, platinum on right

One potential obstacle encountered from this study revealed damage to the photoreceptor layers directly above the implantation site (see the * in the figure below). However, since the MPA is replacing photoreceptor function, this damage may not be essential to overall visual function.

Surgical Procedure and Placement:

The typical implantation procedure takes about two hours and proceeds in three stages.

-During the vitrectomy, surgeons cut three incisions into the sclera, the white part of the eye's outer surface, and drain the vitreous humor from the inside of the eye, replacing it with a saline solution.

-During the second segment of the procedure, the retinotomy, a small incision is made in the inner retina and fluid is injected into the subretinal space, creating a pocket for the ASR.

-The final stage involves the implantation of the microchip. Surgeons “slide the implant into the subretinal space, just as one might slip a tiny coin into a pocket.” [10]. Surgeons apply a stream of air to close the pocket, and over the next several months the air pocket is taken up by the fluid of the eye.

Placement

Optobionics' semiconductor device is placed within the inner and outer layers of the retina in the subretinal space, relying on the existing mechanisms of the visual system (bipolar and ganglion cells) to continue the processing of visual input and send signals to the optic nerve. The device is placed 20° from the macula, the prime site of retinal processing. When placed behind the retina in a dry environment, the device is less likely to cause complications from biocompability. Other companies are developing an epiretinal device, which involves placement of the device outside the retinal membranes, directly stimulating nerve fibers.

Subretinal Placement:

Targeted Demographics:

Worldwide, thirty million people are directly affected by macular degeneration and retinitis pigmentosa. Those individuals who have damaged their photoreceptor layer by other means can benefit from this technology. A damaged lens, cornea, optic nerve or those who were born blind are also able to utilize this therapy.

Clinical History

Optobionics has devoted ten years to testing the ASR safety in animals and for the past six years, has been testing the product in human patients. In 2000, Optobionics implanted ASR devices the right eye of six patients with retinitis pigmentosa for a two-year study on device safety. Four more patients were added at a later time. Preliminary results reveal patients have not experienced any damage to the retina or any worsening of their symptoms. As exemplified by these pictures, after four and a half years, patients' implants were intact.

Furthermore, all patients cite improvements in vision. For example,

-An individual whose sight was limited to darkness now perceives blurry shapes.

-An individual who could perceive indistinct images now can watch a basketball game and distinguish between members of the opposing teams.

-An individual who could only see to his hand can now read twenty five letters off an eye chart. [15]

In 2004, Optobionics' clinical results were published in June 2004 in the peer-reviewed journal, the Archives of Ophthalmology. The media and medical community responded very favorably towards the published results. After two years, six patients experienced gains in reading letter charts and one remained the same in the eye with the ASR, while in the control eye, one patient experienced marginal improvement while two experienced significant loss of function. Researchers found acuity peaked one to six months after surgery, though after several years, gains in visual function slowed. In summary, Optobionics researchers found:

No patient showed signs of implant rejection, infection, inflammation, erosion, neovascularization, retinal detachment, or migration. Visual function improvements occurred in all patients and included unexpected improvements in retinal areas distant from the implant.

Subjective improvements included improved perception of brightness, contrast, color, movement, shape, resolution, and visual field size.

No significant safety-related adverse effects were observed. The observation of retinal visual improvement in areas far from the implant site suggests a possible generalized neurotrophic-type rescue effect on the damaged retina caused by the presence of the ASR. A larger clinical trial is indicated to further evaluate the safety and efficacy of a subretinally implanted ASR. [17]

As quoted in an article on the study, “time-to-onset of vision changes ranged from a few weeks to a few months after surgery, but the improvements have been maintained during the reported follow-up period of 9 to 21 months.” [14]

Additional, unanticipated benefits include the expanded function of retinal cells far from the site of microchip implantation. Dr. Chow, one of the designers of the chip and owner of the company, remarks, “ In addition, visual function improvements included unexpected improvements in retinal areas distant from the implant as well as adjacent to it, supporting the prospect that the mechanism of the ASR chip might involve some neurotrophic/neuroprotective effect on the damaged retina.” In effect, the electrical impulses could be acting as a therapeutic agent, reversing the effects of photoreceptor damage.

While the data is pointing to a biocompatible, effective device, critics point to the lack of a control group as a weakness in the study.

Currently, the device is still experimental. Individuals expressing interest about receiving an Optobionic ASR must fill out a questionnaire to be considered as a candidate. To see the questionnaire, follow this link.

Group History and Funding

In the 1980s, two brothers, Vincent and Alan Chow, began their research on developing artificial retinas. In 1990, they incorporated the name, but the business itself remained stagnant until 1997 when several venture capitalists invested millions of dollars. Investments exceed thirty million in 2003 with Arch Venture Partners, Polaris Venture Partners, Medtronic Inc, Ciba Vision all contributing. A Medtronic employee evaluates the cost-effectiveness of the privately owned company staffed by fifteen. In 2002, the company value was estimated to be over one hundred million dollars.