DOE Artificial Retina Program

Mark S. Humayun, M.D. Ph.D.Professor of Ophthalmology, Biomedical Engineering, and Cell & Neurobiology

Doheny Eye InstituteKeck School of Medicine

University of Southern California

Overview

Artificial Retina Research Update Doheny Retina-DOE Research

Implants Electrophysiology

Bioelectronic Research Lab Surgical/Imaging/Histology Resource ftp host site for DOE Artificial Vision

Project

Human Visual System and Retinal Blindness•

• Retina is a light sensitive neural network

• Diseases such as Retinitis Pigmentosa (RP) and Age-related Macular Degeneration (AMD) primarily affect the photoreceptors, are both presently incurable, and render 100,000s blind each year

Webvision, Kolb, Fernandez, and Nelson, 2003.

Retinal Prosthesis – Epiretinal vs. Subretinal

Epiretinal Less disruptive to the

retina. More flexibility in

component placement More complex stimulus

algorithms required Subretinal

In natural position of photoreceptors

Disruptive to retina Devices relying on

incident light for power cannot generate effective stimulus

State of the Art – Retinal Prostheses

• Epiretinal and Subretinal at Investigational Device Exemption Stage

• Epiretinal - encouraging results, but better technology required

• Subretinal – No direct evidence demonstrating functional electrical stimulation, but patients report subjective improvements in vision

Optobionics ASRTM

Second Sight Retinal StimulatorTM

20 months

16 months

8 months

Rows and Columns

Computer Controlled Testing

  Test type HEC01 YSL02 CS03

Sequential activation

4AFC (25%)

6/8, 6/8, 4/8 (67%)

9/10, 9/10, 10/10 (93%)

2/10, 6/10, 6/10, 6/10 (50%)

Form vision (Row vs. column)

2AFC (50%)

1/4, 2/4, 5/8, 7/8, 4/8 (55%)

10/10, 9/10, 10/10 (97%)

4/10, 9/10, 10/10 (77%)

Spatial Location (Right vs. left)

2AFC (50%)

4/10, 6/10, 10/12, 4/5, 8/10 (69%)

10/10, 10/10, 10/10 (100%)

4/10, 7/10, 6/10 (57%)

Spatial Location (Up vs. down)

2AFC (50%)

12/12, 8/8, 5/8, 3/8, 8/8, 8/8, 5/10 (79%)

10/10, 10/10, 10/10 (100%)

4/10, 10/10, 9/10 (77%)

Camera Tests  

Camera still

Test type HEC01 YSL02 CS03

Lights on/off

2AFC (50%)

10/10 (100%)

10/10, 10/10 (100%)

9/10 (90%)

Moving directions

4AFC (25%)

4/8 (50%) 7/10, 9/10, 10/10 (87%)

5/10, 5/10, 2/10 (40%)

Camera TestsScanning Test Type HEC01 YSL02 CS03

Finding objects (Ø, R, L)

3AFC (33%)

9/10 (90%) 10/10, 10/10, 10/10 (100%)

9/10, 7/10, 7/10 (77%)

Counting/finding objects (Ø, R, L, R+L)

4AFC (25%)

8/10, 7/10, 8/10 (77%)

10/10, 8/10, 7/10, 9/10 (90%)

8/10, 8/10, 7/10, 8/10 (77%)

Objects recognition (plate, knife and cup)

3AFC (33%)

8/10, 7/10, 4/10, 5/10, 8/10, 8/10 (67%)

8/10, 7/10, 7/10 (73%)

7/10, 8/10, 4/10 (63%)

L position 4AFC (25%)

5/10 (50%) 7/10, 6/10, 9/10 (73%)

4/10, 6/10, 9/10 (63%)

Considering only results with multiple pixels setting.

Camera Tests: Multiple vs. Single pixel

Scanning Test Type Multipixel Single pixel

Finding objects (Ø, R, L)

3AFC (33%)

62/70 (89%) 54/70 (77%)

Counting/finding objects (Ø, R, L, R+L)

4AFC (25%)

88/111 (79%)

77/110 (70%)

Objects recognition (plate, knife and cup)

3AFC (33%)

81/120 (68%)

45/80 (56%)

L position 4AFC (25%)

46/70 (66%) 61/104 (59%)

Design Requirements for Higher Resolution Artificial Retina

Unaided Mobility 256-600 pixels

Reading Large Print/Recognizing faces 1024 pixels

Reading regular print at regular reading speed 10,000 pixels

Design Implications for Future Implants

Stimulus Threshold Electrode Size

Best Case: 6 uA -> 15 micron diameter (irOx, 1 mC/cm2) Conservative: 100 uA - > 200 micron diameter (Pt, 0.1

mC/cm2) Device Power

Smaller electrode size will lead to higher impedance, but P=I2R, so lowering threshold stimulus has large effect on decreasing power

Image Processing Eye tracking system, digital zooming, digital

saccading, automated optimization System layout and packaging

Extraocular component placement is feasible

DOE’s Unique Role in Artificial Retina Development

DOE LABS have sophisticated design and fabrication capabilites (ORNL, LLNL, SNL, ANL, LANL)

DOE labs have the ability to work cooperatively with Universities (USC, UCSC, NCSU) and Industry (Second Sight)-- CRADA

DOE has the ability to provide sustained support for high risk, high payoff projects

DOE is used to managing large projects (Genome)

DOE Implants

PDMS conformable electrode array from LLNL

MEMs spring electrode array from SNL

UNCD hermetic coating from ANL

OCT measurementsFront of eye

Retina

ExcitationReflection

Pt

DOE Implants – PDMS electrode

Goal: To develop a PDMS substrate stimulating electrode

Progress: Four normal sighted dogs were

implanted. Three of them have been followed for 3 months, 2 months and 1 month.

Multilayer cable PDMS test devices were received and evaluated.

 

Implantation of LLNL device #4

Postoperative 1st month OCT imaging (horizontal scan)

Postoperative 1st month OCT imaging (vertical scan)

DOE Implants – PDMS Electrode

#2 LLNL dog, postoperative 2nd month, OCT imaging

#2 LLNL dog, postoperative 3rd month, OCT imaging

#3 LLNL dog, postoperative 1st month, OCT imaging

#3 LLNL dog, postoperative 2nd month, OCT imaging

DOE Implants – PDMS Electrode

Retinal Implant – MEMS Component

microelectronics

electroplated or assembled electrodes

bulk micromachinedelectrode seats

surface micromachinedsprings(polymer) frame

flexible frame for attachment

micromachined electrode array (silicon substrate)

retina

posts for assembly and electrical interconnect

electrodes

flexibleinterconnect

tack

antenna

inner-eyeelectronics

Bulk Micromachined Components

Bosch etched single crystal silicon electrodes

Polymer frame / test parts

9x9 electrode array(test part/ no posts)

array placed in the polymer frame

3D modeland fabricatedpolymer mold

INITIAL WORK ON COATING OF SNL MEMS ELECTRODE STRUCTURES WITH UNCD LAYERS

SEM picture of SNL MEMS SEM picture of SNL MEMS Si electrode test structuresSi electrode test structures

SEM pictures of ANL Si tips and posts SEM pictures of ANL Si tips and posts coated with UNCD filmcoated with UNCD film

SEM pictures of SNL MEMS Si electrode SEM pictures of SNL MEMS Si electrode test structure coated with UNCD filmtest structure coated with UNCD film

SCALING OF UNCD GROWTH PROCESS

Next Generation 11” Microwave Next Generation 11” Microwave Plasma System Suitable for Plasma System Suitable for Scaling to 6” and 8” Substrates Scaling to 6” and 8” Substrates (On order-Available January 2004)(On order-Available January 2004)

New Substrate holder with New Substrate holder with heating and cooling capabilities heating and cooling capabilities under design to achieve better under design to achieve better control of low temperature control of low temperature growthgrowth

Next Generation 11” Microwave Next Generation 11” Microwave Plasma System Suitable for Plasma System Suitable for Scaling to 6” and 8” Substrates Scaling to 6” and 8” Substrates (On order-Available January 2004)(On order-Available January 2004)

New Substrate holder with New Substrate holder with heating and cooling capabilities heating and cooling capabilities under design to achieve better under design to achieve better control of low temperature control of low temperature growthgrowth

(FURTHER FUTURE ALREADY HERE: 16” SYSTEM DEMONSTRATED - 2003!(FURTHER FUTURE ALREADY HERE: 16” SYSTEM DEMONSTRATED - 2003!

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8 - 9 ” ” CH4 / Ar Plasma

Bioelectronics Lab at Doheny

Implant Testing - Digital Ophthalmic Photography and Microscopy.

Accelerated testing of devices (in conjunction with Second Sight under CRADA).

Bioelectronics Lab Use established methods of retinal

neurobiology to investigate electrically elicited vision Multichannel extracellular recording Intracellular recording

Retinal and ocular tissue properties ftp://doheny.ws/doeretina

Conference call minutes/action items Data repository to facilitate conference calls