1. Eye or Brain Interface? surviving photoreceptor vs. higher neurons
retinal process vs. ‘computational eye chip’
higher neurons perform more complex and specialized tasks
biofeedback vs. ‘learned cells’
retina is a good candidate for stimulation
in case of artificial cochlea, 6 to 8 electrode stimulates 30,000 spiral ganglion cells
in RP, 30% of ganglion cells and 80% of inner nuclear layer cells are preserved
in AMD, 53% (exudative) - 100% (non-exudative) of ganglion cells are preserved

2. Mimicking visual stimuli
Photoreceptor rescue
Photoreceptor / RPE transplantation
Gene therapy for known carrier
Electrophysiological stimulation of remained neuron
electrical stimulation
stimulation with neurotransmitter
Other somatosensory modalities
‘braille’ stimulation by tactile stimuli
obstacle detector

3. Innovative progress Inspiration and Perspiration from late 1980’s
advances in semiconductor technology; VLSI
successful result in artificial cochlear implant
relatively well-preserved inner retinal neurons in RP & ARMD
from late 1980’s
retinal stimulation
U.S.A.: MEEI-MIT, Wilmer-NCSU, Utah
Deutschland: SUB-RET,EPI-RET
Austrailia: NSWU
Optic nerve stimulator
Belgium: Louvain

4. Please, keep in mind... Visual pathway Guiding principle
Photoreceptor - bipolar cell (BC) - ganglion cell (GC) - optic nerve (ON) - lateral geniculate nucleus (LGN) - primary visual cortex (VC)
in brief, BC - GC - ON - LGN - VC
Guiding principle
Minimizing the amount of implanted electronics
Minimizing disruption of the normal anatomy
What kinds of components are needed?
image acquisition
image processing
image transfer
neural stimulator
power supply

5. Retinal stimulation Stimulation of remained retinal neurons
Indication; RP, ARMD
Contraindication; diabetic retinopathy, glaucoma, retinopathy of prematurity
Electrical stimulation
subretinal
epiretinal
Chemical stimulation
neurotransmitter; glutamate

6. Structure of retinal stimulator
Silicon photodiode
Pt electrode imbedded silicone rubber
Gold electrode imbedded polyimide

7. Subretinal stimulator
Pros
Benefit from intraretinal neural processing
‘One-chip’ photosensor - stimulator: simple design
Cons
Not enough amount of light to stimulate ‘One-chip’
lack of image processing: difficult to personalize after transplantation
Reactions of retinal pigment epithelium (RPE)
Impair diffusion of nourishment
Stimulation level: BC  GC  ON  LGN  VC
SUB-RET; Tuebingen/Reutlingen
Univ. of Illinois / Optobionics
Artificial Silicon Retina (ASR™)
Human trial on July

8. Subretinal Optobionics

9. Optobionics
Experiments under FDA permission on ‘in vivo biocompatibility’
6 & 4 patients with RP, from 45 to 76, central island remained
No ERG response by daylight stimuli on ASR™, but active ERG by direct IR laser stimuli on it
Postoperative 1 to 6 months
ETDRS vision improvement: 1
up to 2 character reading: 4
no change: 5
HVF C30-2: improvement of central island in clover shape in 2 patients
All the patients showed decreased vision after 32 months
Cx.: Subretinal hemorrhage at PE
'RESCUE EFFECT(?)'
restoring cells located near the implant site - insisted by Chow
"What we think is happening is the implant is stimulating other cells around the retina. We're finding vision is improving not just where the implant is but also in areas near the implant,” Chow said (ABC News, May )

10. Subretinal SUB-RET

11. SUB-RET

12. Epiretinal Stimulator
Pros
Anatomical advantage: Easy accessibility by traditional method
Cons
Traumatic fixation
Protrusion
Inciting destructive cellular reactions
bypass intraretinal process: personalization is necessary
Retinal nerve fiber stimulation: noisy signal ?
Stimulation level: BC  GC  ON  LGN  VC
MEEI (Harvard) / MIT
Doheny / USC / SecondSight
‘Stevie Wonder’ happening
EPI-RET; Bonn / Koeln / IIP

13. Epiretinal Harvard-MIT

14. Epiretinal Doheny-SecondSight

17. MARC - Multiple Artificial Retina Chip Set
Image input can be taken from either PC or camera
FPGA performs any image processing on behalf of the implant
Class-E amplifier provides power and data wirelessly to the implant
Retina-3.55 provides 60 outputs

18. MARC - Multiple Artificial Retina Chip Set

21. Doheny / USC / Second Sight
4 x 4 active Pt electrode imbedded silicone rubber
powered by Clarion® cochlear implant system
Operation
stimulatory device was located in a pocket drilled in the temporal bone
cable was routed underneath the temporalis muscle to the orbit, encircled the eye once, and entered the intraocular cavity via a pars plana incision
electrode array was affixed to the retina with a single tack
preliminary study in 3 volunteers
detect room light: %
orientation of “L” : 75%
location of white object: 80%

22. Doheny / USC / Second Sight
FDA approved 2nd human trial in 6 patients
Electrodes are wirelessly activated using an external controller
Electrical stimulation was begun between 7 and15 days post-operative.
Thresholds varied both within and across subjects; S1: µA S2: µA S3: µA S4: µ A S5: µA S6: 6-41 µ A
5 patients demonstrated measurable pupil constriction in response to stimulation with their IRP
localize the position / count the number of high contrast objects with 74-99% accuracy by3 or 4 Alternative Forced Choice (AltFC)
discriminate simple shapes with 61-80% accuracy