1. 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

2. 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

3. 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.

4. 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

5. 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 ASR TM Second Sight Retinal Stimulator TM

6. 20 months 16 months 8 months

7. Rows and Columns

8. Computer Controlled Testing Test typeHEC01YSL02CS03 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%)

9. Camera Tests Camera stillTest typeHEC01YSL02CS03 Lights on/off2AFC (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%)

10. Camera Tests ScanningTest TypeHEC01YSL02CS03 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 position4AFC (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.

11. Camera Tests: Multiple vs. Single pixel ScanningTest TypeMultipixelSingle 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 position4AFC (25%)46/70 (66%)61/104 (59%)

12. 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

13. Design Implications for Future Implants Stimulus Threshold Electrode Size Best Case: 6 uA -> 15 micron diameter (irOx, 1 mC/cm 2 ) Conservative: 100 uA - > 200 micron diameter (Pt, 0.1 mC/cm 2 ) Device Power 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 Eye tracking system, digital zooming, digital saccading, automated optimization System layout and packaging Extraocular component placement is feasible

14. 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)

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

16. OCT measurements Front of eye Retina Excitation Reflection Pt

17. 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.

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

19. #2 LLNL dog, postoperative 2 nd month, OCT imaging #2 LLNL dog, postoperative 3 rd month, OCT imaging #3 LLNL dog, postoperative 1 st month, OCT imaging #3 LLNL dog, postoperative 2 nd month, OCT imaging DOE Implants – PDMS Electrode

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

21. Bulk Micromachined Components Bosch etched single crystal silicon electrodes

22. Polymer frame / test parts 9x9 electrode array (test part/ no posts) array placed in the polymer frame 3D model and fabricated polymer mold

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

24. SCALING OF UNCD GROWTH PROCESS Next Generation 11” Microwave Plasma System Suitable for Scaling to 6” and 8” Substrates (On order-Available January 2004) 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! ” 8 - 9 ” CH 4 / Ar Plasma

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

26. 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