1. Brittney J. Pfeifer
University of Missouri – Saint Louis
11 March 2013

2. Outline of Today’s Presentation:
• Anatomy of the Eye
• Hereditary Retinal Diseases
• Macular Degeneration (AMD)
• Retinitis Pigmentosa (RP)
• History of Visual Prosthesis
• Introduction
• Types of Visual Prostheses
• Research behind Alpha-IMS
• Introduction and Hypothesis
• Methods
• Results
• Conclusions of Study
• Conclusions and Future Outlook

3. Anatomy of the Eye
 Sclera – white of eye
 Optic nerve – transmits
visual information from
retina to brain
 Retina – photoreceptor
cells arranged in several
layers
 Fovea – provides
sharpest images

4. Macular Degeneration (AMD)
 Results in gradual destruction of
the macula among people age 50+
 Causes:
 Loss of vision, but not complete
blindness
 Can still see using peripheral
vision
 Image is there, but detail is lost
 Two types:
 Dry
 Wet
 Detected by:
 Visual acuity test
 Dilated eye exam

5. Retinitis Pigmentosa (RP)
 Results in loss of photoreceptors
during childhood or late 40s to
early 50s
 Causes:
 Difficulty seeing at night or in
dim lighting
 Gradual loss of peripheral
vision
 Loss of central vision (in
advanced cases)
 Incurable blindness
 Detected by:
 Dilated eye exam
 Electroretinography (ERG) test

6. History of Visual Prosthesis
 1929: German neurologist, Otfrid Foerster, discovered
electrically stimulating occipital lobe caused patients to see
phosphenes
 1931: Fedor Krause and Heinrich Schum performed same
experiment on a patient who had been blind for 8 years
 1956: Australian, Graham Tassicker, described how a
photosensitive cell placed behind retina of a blind patient
resulted in phosphenes
 1960s and 1970s: Giles Brindley and William Dobelle
established Field of Visual Prosthesis by implanting electrodes
into visual cortex and demonstrating their ability to induce
consistent phosphenes
 1990s to Present: Advances in biomaterials, electronics, and
retinal surgery have led to a cascade of developments in the field

7. Introduction
 Blindness affects over 40 million people around the world with 15
million suffering from blindness due to a hereditary retinal disease
 Looking to restore visual function, Field of Visual Prosthesis began
 All visual prostheses must perform these steps:
1. Detect and capture ‘light-based’ images
2. Transduce images into electrical stimuli
3. Deliver stimuli to axons of ganglion cells within optic nerve
4. Evoke a response in visual cortex to induce phosphenes
 There are a variety of prostheses:
 Cortical prosthesis
 Optic nerve prosthesis
 Retinal prosthesis
 With advancement in surgical techniques and bioengineering,
retinal prosthesis is the most advanced visual prosthesis

8. Cortical Prosthesis
 First device to artificially induce phosphenes
 However, because electrode arrays were situated on
the cortex it caused:
 Poor spatial resolution
 Discomfort from stimulation
 Focal epileptic activity
 The Utah Electrode Array (UEA) was developed to
counteract these side effects
 Main advantage is that they are the only therapeutic
treatment for individuals with non-functioning
retina or optic nerves

9. Optic Nerve Prosthesis
 Used for blind patients with functional
retinal ganglion cells
 Multiple electrodes are inserted onto optic
nerve
 Stimulation of electrodes in acute settings have
produced phosphenes
 Achieving focal stimulation and retinotopic
distribution are challenging

10. Retinal Prosthesis
 Replace photoreceptors by producing small, localized currents that alter
membrane potential of adjacent retinal neurons
 Energy required by device is derived from:
 External power source
 Incident light acting through a photoelectric cell
 Subjects utilizing this device have been subjected to tests demonstrating:
 Improvements in mobility
 Motion detection
 Object localization and recognition
 Grating identification
 Retinal ganglion cells and visual pathways need to be viable for device to
function
 Two types categorized according to site of implantation:
 Epiretinal prosthesis
 Subretinal prosthesis

11. Epiretinal Prostheses
 Implanted on inner surface of retina
 Consists of three main components:
 External camera for capturing images
 Component that transforms images into electrical stimuli
 Component that stimulates remaining cells in inner retina
 Examples of devices in advanced stages of development:
 Argus II:
 Multielectrode array powered by externally worn battery pack
 Images are captured by camera mounted on glassestranslated into
pixilated images by visual processing unitdelivered via transscleral cables
to implant

12. Epiretinal Prostheses Continued
 EPI-RET3:
 Consists of an array of 25 electrodes apposed to ganglion cells
 Images are captured by mounted camera on glassestransferred
wirelessly to receiver unit placed in anterior chambersignal is
transmitted via micro cable to implant

13. Subretinal Prostheses
 Implanted between retina
 Alpha-IMS:
 Consists of microphotodiode array (MPDA) with 1500
microelectrodes and a direct stimulation (DS) test field
 Consists of three parts:
 Subretinal: MPDA implant
 Extraocular: foil strip carrying connection lanes to external
connection and reference electrode
 Subdermal: silicone cable that leads from implant to behind
the ear where it penetrates skin and ends in a plug

15. Epiretinal Prostheses
Advantages Disadvantages
 Easy surgical insertion
 Minimal disruption to retina
 Location of implant allows
for heat dissipation
 Easy upgrades can be made
without further surgery
 Camera is capable of zooming
 Long-term stability
 Decoded electrical signal is
sent directly to ganglion cells
 Only stimulates ganglion cells
 Eliminates use of natural eye
movements
 More sophisticated processing
is required

16. Subretinal Prosthesis
Advantages Disadvantages
 Stimulates bipolar and
amacrine cells
 Location helps keep
electrodes in close proximity
to viable retinal cells
 Uses natural eye movements
 Confined space limits size of
device
 Possible chance of thermal
injury
 Long surgery time (6-8 hours)

17. By Stingl, Katarina, et al.

18. Introduction and Hypothesis
 Hypothesis:
 If it is possible to replace photoreceptive function
using a technical device, then there may be a
treatment for hereditary retinal diseases.
 Purpose of Study:
 Restore visual function in patients by means of a
subretinaly implanted microelectronic device
 Uses light-sensitive detector arrays and amplifiers
 Converts light into signals that can stimulate bipolar
cell neurons via tiny metal electrodes

19. Methods:
The subretinal alpha-IMS visual implant
 Characteristics of implant:
 9 mm2 in size consisting of 1500 pixels
 Each pixel contains a:
 Photodiode
 Amplification circuit
 Electrode for charge transfer to adjacent retinal layers
 Records images at different frequencies
 Offers bipolar cells with a point-by-point electrical image
 Provides a diamond-shaped visual field of 10° × 10°
 Energy is provided by an external coil from a battery pack

20. Methods Continued:
The Patients
 Characteristics of participants:
 Four females
 Five males
 Between ages 35–62 years
 Eight patients had RP
 One patient had Cone-rod dystrophy
 Received subretinal implant in eye with worst vision
 Written informed consent was obtained prior to
inclusion in study

21. Methods Continued:
Efficacy Testing
 The following efficacy tests were performed:
 Standardized screen tasks
 Table tasks of activities of daily living
 Letter recognition
 Reports of daily life experiences
 Control:
 All tests (except reports of daily life experiences) were
administered with implant power source turned ‘ON’ or ‘OFF’
in a randomized order
 Other eye was always occluded during tests
 Tasks were performed over the course of 3 to 9 months

22. Test One:
Standardized screen tasks
 Light and motion tests
 Measures light perception in full
field illumination, light source
localization, and motion
detection with a moving random
dot pattern
 Basic grating acuity (BaGA) test
 Measures spatial frequency
resolution in cycles per degree
(cpd)
 Patient had to identify direction
of white stripes in a pattern on a
black background
 Visual acuity test
 Measures visual acuity using
Landolt C-rings

23. Test Two:
Table tasks of activities of daily living (ADL)
 Part One:
 4 of 6 geometrical objects (square,
circle, triangle, rectangle, ring or
crescent) were placed on a table
 Part Two:
 4 of 6 tableware objects
(small/medium-sized plates, cup, fork,
spoon, and knife) were placed around
a large plate on a table
 Subjects were asked to:
 Report number of objects
(identification)
 Locate them (localization)
 Name them (discrimination)
 Performance scores ranged from 0 to 4
 Scores in ON and OFF power supply
states were compared

24. Test Three:
Letter recognition
 Correct reading of
alphabet letters was
recorded
 Patients were not given
any information
regarding letter choice
 All letters were visible
within visual field of
implant

25. Test Four:
Patient-reported experiences in daily life
 Subjects were permitted to use implant outdoors,
at home, or at work
 During first trial days, a mobility trainer
accompanied subjects during their visual
experiences in daily life
 Documentation of specific spontaneous
perception was performed by videotaping
experiences or by recording patients' oral reports

26. Results
 In all nine subjects, light-induced voltage changes
generated by implant showed reliable signal
generation
 In several patients, observation period was cut short
due to technical instability of implant:
 Subject (S8) developed post-operative subretinal bleeding
in area of implant and IOP increased significantly. Issue was
resolved with topical and general medication
 During implant surgery for Subject (S1), the tip of the
implant touched the optic nerve head, which resulted in
failure of light perception via the implant

27. Results for Standardized Screen Tasks
 Subjects (S2–S9) had light perception
 Subjects (S2 and S4-S9) were able to localize light
 Subjects (S4 and S6-S9) detected motion of dot patterns
 Grating acuity was successfully measured in Subjects (S4-S9)
 Visual acuity was assessed in Subjects (S5 and S8)

28. Results for Table Tasks of ADL
 For all of the following
tasks, significant
differences between
power ON and OFF
scores were found:
 Detection of objects and
localization were more
easily accomplished
than shape recognition

29. Results of Letter Recognition
 Subjects (S2, S6 and S8) were able to read
several letters (e.g. T, V, L, I, O) spontaneously
 Subject (S4) needed some training to correctly
discriminate among three letters in a three-
alternative-forced-choice test
 Patients saw letters as complete entities

30. Results of Patient-reported
Experiences in Daily Life
 Subjects (S2, S4-S6, and S8) reported visual perceptions in daily life
 In near-vision range, the most relevant reports included:
 Recognition of facial characteristics
 Differentiation between contours of people and clothing patterns
 Localization or discrimination of objects
 In far-vision range, the most relevant reports included:
 Finding the horizon and objects along the horizon
 A river was described as a bright, reflecting stripe
 Cars and glass windows were localized based on surface
reflections
 Recognition of stopped and moving cars at night due to their
headlights
 Recognition of letters on restaurant and store signs

31. Conclusions of Study
 Study showed alpha-IMS implant, positioned in
subretinal space, can restore useful visual function
in daily life for 2/3 of the blind patients
 Device may be an option for blind patients with no
alternative therapy treatments
 Long-term stability and safety, as well as
development of visual recognition abilities using
learning tasks, will be addressed in future patients
over a longer observation period

32. Conclusions and Future Outlook
 Visual prostheses are an innovative approach to restoring vision
 Field of Visual Prosthesis has grown to include a variety of designs
 The most advanced are retinal prostheses
 There are two in advanced stages of development:
 Argus II by Second Sight is close to commercial availability
 Alpha-IMS by Retina Implant AG is entering more test trials and may
produce an alternative concept with a subretinal implantation
 These devices have demonstrated improvements in motion
detection, object recognition, and letter recognition
 Prostheses that target optic nerve and visual cortex are also in
development
 Plans for more sophisticated designs and increasing number of
electrodes (to improve resolution and detail quality) are also in
current development