New wide-field, dual-array, suprachoroidal-transretinal stimulation prosthesis demonstrates surgical feasibility

Take-home message: Prof. Fujikado presents his research, which demonstrated the surgical feasibility and safety of a newly developed, dual-array, suprachoroidal-transretinal stimulation prosthesis in animals. The dual-array design was able to activate retinal neurons and optic nerve axons. Findings indicate the future possibility of activating of a larger visual field with the prosthesis.

By Prof. Takashi Fujikado, MD, PhD and Dr Tibor Lohmann, MD

The focus of my research is the application of visual science in the field of ophthalmology, especially visual rehabilitation using artificial vision. Recently, we conducted an animal study into a new retinal prosthesis designed to restore sight in patients who are blind as a consequence of advanced retinitis pigmentosa (RP). This is the first step towards elucidating its feasibilty in humans.

Acheiving artificial vision

Generally speaking, a retinal prosthesis creates an artificial vision named phophene by electrically stimulating the residual retinal neurons in blind patients. There are three key approaches to achieving this: one is via the use of an epiretinal prosthesis in which electrodes are placed directly on the retina, the second one is the subretinal prosthesis in which electrodes are placed beneath the retina, and the third one is the suprachoroidal-transretinal prosthesis (STS) in which electrodes are placed in the suprachoroidal space or in the scleral pocket.

Retinitis pigmentosa (RP) is an inherited degenerative retinopathy that initially causes a loss of the rod photoreceptors and eventually affects the neural structures involved in the transmission of visual signals to the brain. Several clinical trials using epi- or sub-retinal electrode array have reported efficacy in recovering some kind of vision in patients with advanced RP, however, in these epi- or sub-retinal prostheses, the phosphenes are only able to cover a small visual field (up to 15 degrees) as they are limited by the size of stimulating array (3 to 5 mm square). Compared with epi- or sub- retinal prostheses, the STS retinal prosthesis has the advantage of an enlarged visual field. This is because with the STS retinal prosthesis, multiple electrode arrays or large electrode array can be implanted in the scleral pocket or suprachoroidal space without penetrating the choroid.

Developing the prosthesis

Figure 1: A photo of the dual-array system with 32 electrodes. Electrodes are 0.5 mm in diameter and 0.3 mm in height on both the main (left) and the secondary (right) array. The distance between the centers of the electrode is 0.75 mm on the main array and 1 mm on the secondary array. E1- 4 indicate the active electrode for functional testing. *Denotes a multiplexer system to deliver currents to each electrode. Black line indicates 5mm.Previously, our laboratory developed a 9 channel STS prosthesis (now termed the 1st generation)¹ and a 49 channel STS prosthesis (the 2nd generation)² with a visual field of around 10 degrees, the second of which has also undergone clinical trial. Both types of prosthesis had 1 electrode array that was 5x5mm square in size. Patients were able to identify a white bar and to grasp it. However, they did need to do head scanning to catch the image as a consequence of the small visual field. It is important to remember that in daily life, although a high-resolution central visual field is necessary for tasks such as reading, a wide peripheral visual field is also needed for tasks such as walking. It was this fact that prompted us to develop the dual-array stimulation prosthesis, which covers a larger visual field and has more flexibility in the area of stimulation. This newer prosthesis consisted of two arrays with a total of 32 electrodes (Figure 1).

Testing the prosthesis

In our initial feasibility study, the prosthesis was implanted for 14 days into four middle-sized animals (two rabbits in the first experiment and two cats in the second). All procedures were approved by the Animal Care and Use Committee of Osaka University and followed the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research.

Optical coherence tomography (OCT) and ophthalmoscopy were performed 7 and 14 days after implantation in the first experment. In the second experiment, the ability of the implanted rays to elicit neural responses was determined by electrically evoked potentials (EEPs) at the chiasm and by optical imaging of the retina.

All arrays were successfully implanted, and no major complications occurred during the surgery or during the two-week postoperative period. Both OCT and ophthalmoscopy results showed no major complications or instability of the arrays (Figure 2). Histological evaluations showed only mild cellular infiltration and overall good retinal preservation.

Stimulation of the retina by the arrays evoked EEPs that were recorded from the chiasm. In addition, retinal imaging showed that the electrical pulses from the arrays altered the retinal images, indicating activation of retinal neurons.

Conclusions

Figure 2: Infrared fundus image (A, C, E) and OCT images (B, D, F) two weeks after the chronic implantation in rabbits. The white arrow shows the direction of the OCT scan. Photographs show the implanted electrode array and the OCT images. Electrodes are stably fixed in the scleral pocket.The results highlighted above represent only a brief summary of our research findings. However, these key discoveries did illustrate that the two-week implantation of the dual-array STS prosthesis in this experiment was both surgically feasible and safe. The results of the retinal imaging and EEPs successfully demonstrated the ability of the dual array system to activate retinal neurons. We therefore concluded that the dual-array design can be implanted without complication and is able to activate retinal neurons and optic nerve axons.

When the dual-array system is implanted in patients with a small residual visual filed, their residual vision can be used for the central target, while additional information can be gathered from the peripheral visual field using the prosthetic vision. Under these conditions, the eye tracking system is necessary to partner the residual and prosthetic vision (see below).

Future work will be required to fully investigate the difference in visual perception provided by devices implanted in the various locations in the eye, but the initial signs are promising that suprachoroidal stimulation is a safe and viable clinical option for patients with certain degenerative retinal diseases.

Future directions

We are now in the process of conducting a simulation experiment for a wide-field retinal prosthesis. Currently, the charge-coupled device camera is attached directly on the glasses, meaning the line of patient sight and the viewing line of the camera are not always the same. Therefore an eye-movement detection system is necessary to match the line of sight and the line of camera. Using the eye-movement detection system, the time taken to detect objects and the accuracy of this detection is greatly improved. In the next generation STS system, we plan on combining the dual-array system with eye-movement detection system in an attept to recover walking vision for blind patients.

References

• T. Fujikado et al., Invest. Ophthalmol. Vis. Sci. 2011; 52: 4726-4733.

• T. Fujikado et al., Conf. Proc. IEEE Eng. Med. Biol. Soc. 2013; 2013: 3119-3121

Prof. Takashi Fujikado, MD, PhD and Dr Tibor Lohmann, MD

E: fujikado@ophthal.med.osaka-u.ac.jp

Prof. Fujikado is a Professor at the Department of Applied Visual Science, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Dr. Lohmann is a student at the Department of Ophthalmology, RWTH Aachen University, Aachen, Germany.

The author has financial interests in Nidek Inc. USA>.