Slide 1: Development of a Visual Prosthesis: The Orion Visual Prosthesis System
Development of a Visual Prosthesis: The Orion Visual Prosthesis System Nader Pouratian, M.D., Ph.D. Daniel Yoshor, M.D., Ph.D. Study partly funded by NIH BRAIN Initiative grant: UH3NS103442 Ex 99.2
Slide 2: Disclosures
Disclosures Second Sight – Grant Support for this project Consultant BrainLab – Grant Support Medtronic – Fellowship Support Boston Scientific – Consultant, DSMB
Slide 3: 39 million people worldwide are legally blind
39 million people worldwide are legally blind 8 million patients globally are legally blind due to unpreventable causes Retinitis Pigmentosa (RP) [fj 375,000 > Waal Age Related Macular Degeneration (AMD) Fe 2,000,000 Other Untratable Causes (i.e. Glaucoma, Infection, etc.) 5,800,000
Slide 4: Overall Goal: Cortical Prosthesis for Previously Sighted Patients
Overall Goal: Cortical Prosthesis for Previously Sighted Patients with No or Bare Light Perception Safe – Implant-related concerns (infection) Seizures Practical –Surgically Practical and Adoptable (microarray “tiles” vs ECoG) Clinically Useful –Perceptions Shadows Edges
Slide 5: Visual Cortical Prosthesis: Orion I Implant
Visual Cortical Prosthesis: Orion I Implant Leverages existing Argus II technology Bypasses the eyes and optic nerve and directly stimulates the visual cortex Early Feasibility Study underway in U.S. Designated a Breakthrough Device by FDA In planning stages for next phase (pivotal or feasibility st
Slide 6: Orion I Implant
Orion I Implant Medial View Lateral View Electrode array (60 channels) Cable Implant coil (receiving antenna) Cover Video Processing Unit Glasses & Antenna
Slide 7: Early Testing in a Blind Subject with Off the shelf Device
Early Testing in a Blind Subject with “Off the shelf” Device 30 year old with an 8 year history of bare light perception blindness due to Voght-Koaynagi-Harada Syndrome Implantation of a Neuropace responsive neurostimulation device with 2 parallel 4-contact leads implanted over the right medial occi
Slide 8: Results: Retinotopic Localization and Reproducibility Over Time
Results: Retinotopic Localization and Reproducibility Over Time Frequency Modulation of thresholds Different shapes and sizes Consistent Localization
Slide 9: Current Thresholds: Relationship to Stimulus Parameters
Current Thresholds: Relationship to Stimulus Parameters
Slide 10: Differential phosphene modulation with modulation of distinct stimulation parameters
Differential phosphene modulation with modulation of distinct simulation parameters
Slide 11: Stimulation thresholds are stable over months
Stimulation thresholds are stable over 19 months
Slide 12: Orion Early Feasibility Study: subjects
Orion Early Feasibility Study: 6 subjects Eligibility: Subjects are completely bilaterally blind due to any cause other than damage to the visual cortex May include trauma to eyes or optic nerve, diabetic retinopathy, glaucoma, or other etiology Primary outcome: safety (adverse events) Secondary out
Slide 13: Orion Early Feasibility Study – Enrollment
Site Subject Implant Date Age at time of implant Gender Reason for Vision Loss Implant Duration as of 6/28/19 (months) UCLA S1 01/30/2018 56 Male Optic neuropathy secondary to burn/trauma 17 UCLA S2 03/29/2018 29 Male Head Trauma – motor vehicle accident 15 UCLA S3 04/26/2018 64 Female Endophthalmit
Slide 14: Primary Endpoint - Safety
6 adverse device or procedure-related adverse events (ADEs) in 2 (out of 6) subjects 1 serious ADE 5 non-serious ADEs Four out of 6 subjects have not experienced any device- or procedure-related Aes Data as of last independent medical safety monitor meeting of May 3, 2019 Primary Endpoint - Safety E
Slide 15: Orion System Programming and Home Use
Orion System Programming and Home Use After implantation, subjects undergo “programming” process to customize settings for use of the system in video mode (with stimulation driven by the camera image) No earlier than 3 months, subjects are cleared to use the system outside the clinic Visual rehabili
Slide 16: First Threshold Measurement
First Threshold Measurement Subject Average Threshold (µA) Standard Deviation (µA) No. of Thresholds S1 2893 1322 56/60 S2 1645 828 60/60 S3 2194 789 59/59 S4* 3765 1603 54/58 S5 2693 1248 59/59 S6 3730 1170 55/59 Thresholds amount of current required for subject to see phosphene 50% of the time on
Slide 17: Measuring Ultra-Low Vision Visual Function
Measuring Ultra-Low Vision Visual Function 20/20 20/200 Bare LP No LP Count Fingers Hand Motion LP with Projection LP = Light Perception Legally Blind Square Localization Direction of Motion Grating Visual Acuity (1.6 – 2.9 LogMAR) (20/800 – 20/16000)
Slide 18: Square Localization Performance
Square Localization Performance * Mean error significantly different ON vs. OFF, t-test, p<0.05 System OFF System ON Subject S2 at 6 months
Slide 19: UCLA
UCLA
Slide 20: Direction of Motion Performance
Direction of Motion Performance * Mean error significantly different ON vs. OFF, t-test, p<0.05 System OFF System ON Subject S2 at 6 months
Slide 21: Grating Visual Acuity - Performance
Grating Visual Acuity is measured between 2.9 – 1.6 logMAR. Gratings are presented for only 5 seconds No subjects (0 of 5) scored on the scale with the System ON or OFF at 6 months post-implant 1 subject (1 of 4) scored on the scale with the System ON or OFF at 12 months post-implant (2.8 logMAR) Tr
Slide 22: Functional Low-Vision Observer-Rated Assessment (FLORA)
Trained observers rate the impact of the Orion implant on patients’ well-being and functional vision periodically at specific time points Interview Observer-rated functional vision tasks (System ON and OFF) Final rating of benefit of Orion System on subject’s life Functional Low-Vision Observer-Rate
Slide 23: Real World Use: observations from rehabilitation sessions
“Real World Use”: observations from rehabilitation sessions Subjects are finding success with Orion for everyday visual tasks “…He was able to find the cue ball with no problems on the table. He was able to tell the cue ball from the blue ten, and also from balls with a stripe vs. the cue ball. He c
Slide 24: How does Orion compare to the Argus II Retinal Prosthesis System?
How does the Orion Visual Cortical Prosthesis System compare to the Argus II Retinal Prosthesis System? Argus II System: retinal implant for end-stage Retinitis Pigmentosa Orion System: potentially treats any cause of profound bilateral blindness other than cortical damage Eye injury, optic nerve di
Slide 25: Argus II System Indications for Use (U.S.)
Argus II System Indications for Use (U.S.): Bilaterally blind due to retinitis pigmentosa with bare light or no light perception Implanted in the worse-seeing eye Commercial Approval in European Economic Area (CE Mark) in 2011 Commercial Approval in U.S. (HDE) in 2013 Over 350 implanted worldwide (E
Slide 26: Safety Comparison
Safety Comparison Rates of Adverse Events due to the Device or Procedure # Subjects # Events Serious Adverse Events 1 1 Non-serious Adverse Event 2 5 Grand Total 2 6 # Subjects # Events Serious Adverse Events 2 2 Non-serious Adverse Event 4 23 Grand Total 4 25 5 Orion Early Feasibility Study Subject
Slide 27: Performance Comparison
Performance Comparison Argus II at 12 months Orion at 12 months* Square Localization 94% (N = 16) 80% (4 of 5) Direction of Motion 63% (N = 16) 80% (4 of 5) Grating Visual Acuity 48% (N = 29) 20% (1 of 5) FLORA 80% (N = 15) 100% (5 of 5) Improvement = significantly better ON than OFF (SL & DOM), on
Slide 28: Conclusions
Conclusions Visual Cortical Prostheses are promising. Visual cortical prostheses are generally safe. Visual cortical stimulation in previously sighted blind subjects results in consistent and reliable thresholds and phosphenes Surgery is only the first step. The implant will evolve – Need for penetr