DOE Artificial Retina Program Mark S Humayun M

DOE Artificial Retina Program Mark S. Humayun, M. D. Ph. D. Professor of Ophthalmology, Biomedical Engineering, and Cell & Neurobiology Doheny Eye Institute Keck School of Medicine University of Southern California

Overview n n Artificial Retina Research Update Doheny Retina-DOE Research n n n Implants Electrophysiology Bioelectronic Research Lab n n 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 Agerelated Macular Degeneration (AMD) primarily affect the photoreceptors, are both presently incurable, and render 100, 000 s blind each year Webvision, Kolb, Fernandez, and Nelson, 2003.

Retinal Prosthesis – Epiretinal vs. Subretinal n Epiretinal n n Less disruptive to the retina. More flexibility in component placement More complex stimulus algorithms required Subretinal n n n 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 Stimulator. TM

20 months 16 months 8 months

Rows and Columns

Computer Controlled Testing Test type HEC 01 YSL 02 CS 03 Sequential activation 4 AFC (25%) 6/8, 4/8 9/10, 10/10 (93%) 2/10, 6/10, 6/10 Form vision 2 AFC (50%) 1/4, 2/4, 5/8, 7/8, 4/8 10/10, 9/10, 10/10 (97%) 4/10, 9/10, 10/10 (77%) Spatial Location 2 AFC (50%) 4/10, 6/10, 10/12, 4/5, 8/10 (69%) 10/10, 10/10 4/10, 7/10, 6/10 (57%) Spatial Location (Up 2 AFC (50%) 12/12, 8/8, 5/8, 3/8, 8/8, 5/10 (79%) 10/10, 10/10 4/10, 10/10, 9/10 (77%) (Row vs. column) (Right vs. left) vs. down) (67%) (55%) (100%) (50%)

Camera Tests Camera still Test type HEC 01 YSL 02 CS 03 Lights on/off 2 AFC (50%) 10/10, 10/10 9/10 (90%) 4 AFC (25%) 4/8 (50%) 7/10, 9/10, 10/10 (87%) 5/10, 2/10 (40%) Moving directions (100%)

Camera Tests Scanning Test Type Finding objects 3 AFC (33%) 9/10 (90%) (Ø, R, L) HEC 01 YSL 02 CS 03 10/10, 9/10, 7/10, 10/10 (100%) 7/10 (77%) Counting/finding 4 AFC (25%) 8/10, 7/10, objects (Ø, R, L, 8/10 (77%) 10/10, 8/10, 7/10, 9/10 8/10, 7/10, 8/10 Objects 3 AFC (33%) 8/10, 7/10, recognition (plate, 4/10, 5/10, knife and cup) 8/10, 8/10, 7/10, 7/10 (73%) 7/10, 8/10, 4/10 (63%) L position 7/10, 6/10, 9/10 (73%) 4/10, 6/10, 9/10 (63%) R+L) (90%) (77%) (67%) 4 AFC (25%) 5/10 (50%) Considering only results with multiple pixels setting.

Camera Tests: Multiple vs. Single pixel Scanning Test Type Finding objects 3 AFC (33%) 62/70 (89%) (Ø, R, L) Multipixel Single pixel 54/70 (77%) Counting/finding 4 AFC (25%) 88/111 (79%) objects (Ø, R, L, 77/110 (70%) Objects 3 AFC (33%) 81/120 (68%) recognition (plate, 45/80 (56%) L position 61/104 (59%) R+L) knife and cup) 4 AFC (25%) 46/70 (66%)

Design Requirements for Higher Resolution Artificial Retina n Unaided Mobility n n Reading Large Print/Recognizing faces n n 256 -600 pixels 1024 pixels Reading regular print at regular reading speed n 10, 000 pixels

Design Implications for Future Implants n Stimulus Threshold n Electrode Size n n n Device Power n n Smaller electrode size will lead to higher impedance, but P=I 2 R, so lowering threshold stimulus has large effect on decreasing power Image Processing n n Best Case: 6 u. A -> 15 micron diameter (ir. Ox, 1 m. C/cm 2) Conservative: 100 u. A - > 200 micron diameter (Pt, 0. 1 m. C/cm 2) Eye tracking system, digital zooming, digital saccading, automated optimization System layout and packaging n Extraocular component placement is feasible

DOE’s Unique Role in Artificial Retina Development n n 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 n DOE has the ability to provide sustained support for high risk, high payoff projects n DOE is used to managing large projects (Genome)

DOE Implants n n n PDMS conformable electrode array from LLNL MEMs spring electrode array from SNL UNCD hermetic coating from ANL

OCT measurements Front of eye Excitation Retina Reflection Pt

DOE Implants – PDMS electrode n n Goal: To develop a PDMS substrate stimulating electrode Progress: n Four normal sighted dogs were implanted. Three of them have been followed for 3 months, 2 months and 1 month. n Multilayer cable PDMS test devices were received and evaluated.

DOE Implants – PDMS Electrode Postoperative 1 st month OCT imaging (horizontal scan) Implantation of LLNL device #4 Postoperative 1 st month OCT imaging (vertical scan)

DOE Implants – PDMS Electrode #2 LLNL dog, postoperative 2 nd month, OCT imaging #3 LLNL dog, postoperative 1 st month, OCT imaging #2 LLNL dog, postoperative 3 rd month, OCT imaging #3 LLNL dog, postoperative 2 nd month, OCT imaging

Retinal Implant – MEMS Component flexible frame for attachment (polymer) frame microelectronics surface micromachined springs posts for assembly and electrical interconnect antenna inner-eye electronics flexible interconnect micromachined electrode array (silicon substrate) bulk micromachined electrode seats tack electrodes retina electroplated or assembled electrodes

Bulk Micromachined Components Bosch etched single crystal silicon electrodes

Polymer frame / test parts 3 D model and fabricated polymer mold 9 x 9 electrode array (test part/ no posts) array placed in the polymer frame

INITIAL WORK ON COATING OF SNL MEMS ELECTRODE STRUCTURES WITH UNCD LAYERS SEM picture of SNL MEMS Si electrode test structures SEM pictures of SNL MEMS Si electrode test structure coated with UNCD film SEM pictures of ANL Si tips and posts coated with UNCD film

SCALING OF UNCD GROWTH PROCESS Next Generation 11” Microwave Plasma System Suitable for Scaling to 6” and 8” Substrates (On order-Available January 2004) 8 - 9 ” CH 4 / Ar Plasma New Substrate holder with heating and cooling capabilities under design to achieve better control of low temperature growth (FURTHER FUTURE ALREADY HERE: 16” SYSTEM DEMONSTRATED - 2003!

Bioelectronics Lab at Doheny n n Implant Testing - Digital Ophthalmic Photography and Microscopy. Accelerated testing of devices (in conjunction with Second Sight under CRADA).

Bioelectronics Lab n Use established methods of retinal neurobiology to investigate electrically elicited vision n n Multichannel extracellular recording Intracellular recording Retinal and ocular tissue properties ftp: //doheny. ws/doeretina n n Conference call minutes/action items Data repository to facilitate conference calls