Transcript The Artificial Retina

The Artificial Sight
http://www.nbcnews.com/video/night
ly-news/50816422#50816422
Light enters the
eye through the
transparent
cornea, passing
through the pupil
at the center of
the iris.
The lens adjusts
to focus the light
on the retina,
where it appears
upside down and
backward.
Receptor cells on
the retina send
information via the
optic nerve to the
visual cortex.
The left and right eyes each send
information to both the left and the right
brain hemisphere
Photosensitive cells called rods
and cones in the retina convert
incident light energy into signals
that are carried to the brain by
the optic nerve.
In the middle of the retina is a
small dimple called the fovea or
fovea centralis. It is the center of
the eye's sharpest vision and the
location of most color perception.
When light falls on the retina, it creates a photochemical reaction in the rods and
cones at the back of the retina. The reactions then continue to the bipolar cells,
the ganglion cells, and eventually to the optic nerve.
Retina
A thin layer (about 0.5 to
0.1mm thick) of light
receptor cells covers the
inner surface of the
choroid.
The focused beam of light
is absorbed and initiates
electrochemical reaction in
this pinkish multilayered
structure..
Rods process low level light
but do not process color
Cones process color
120 million rods and 5 million cones
Fovea Centralis/Macula
The eye receives data from a field of about
200 degrees but the acuity over most of
that range is poor.
To form high resolution images, the light
must fall on the fovea, and that limits the
acute vision angle to about 15 degrees.
In low light, this fovea constitutes a second
blind spot since it is exclusively cones
which have low light sensitivity.
At night, to get most acute vision one must
shift the vision slightly to one side, say 4 to
12 degrees so that the light falls on some
rods.
Gsu.edu
Since the fovea provides the sharpest and most detailed
information, the eyeball is continuously moving, so that light from
the object of primary interest falls on this region. ...the rods are
multiply connected to nerve fibers, and a single such fiber can be
activated by any one of about a hundred rods.
By contrast, cones in the fovea are individually connected to nerve
fibers. The actual perception of a scene is constructed by the eyebrain system in a continuous analysis of the time-varying retinal
image."(Hecht)
Pathology of the Eye

Two most common pathologies are age-related macula
degeneration (ARMD) and retinitis pigmentosa (RP)
ARMD
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•
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Slow degeneration of the photoreceptor cells culminating in death of these
cells
Distorted central vision
700,000 new cases in US per year
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RP
Associated with over 100 genetic defects
Strikes rods first resulting in poor night and peripheral visions
Eventually effects cones
1/4000 people in US have RP
ARMD is more prevalent and RP is generally more severe at a
younger age
ARMD
There are two forms of ARMD, atrophic
(commonly known as dry) and neovascular
(commonly known as wet).
All ARMD begins as the atrophic form, in
which the nourishing outer layer of the
retina withers, or atrophies.
Approximately 90 percent of ARMD
remains in this form and progresses slowly.
In the remaining 10 percent, new blood
vessels begin to grow erratically within the
choroid, the blood-rich membrane that
nourishes the retina.
These blood vessels are thin and fragile,
and bleed easily.
The resulting hemorrhages cause the
retina to swell, distorting the macula and
accelerating the loss of cells.
Nih.gov
RP
Retinitis pigmentosa can run in families.
The disorder can be caused by a number
of genetic defects.
The cells controlling night vision (rods) are
most likely to be affected. However, in
some cases, retinal cone cells are
damaged the most.
The main sign of the disease is the
presence of dark deposits in the retina.
The main risk factor is a family history of
retinitis pigmentosa.
It is an uncommon condition affecting
about 1 in 4,000 people in the United
States.
Artificial Sight
Creating a sense of
vision by electrically
activating neural cells
in the visual system
Other visual pathways
can be stimulated as well
such as the optic nerve
and visual cortex
Passive devices rely on incident light for power whereas
Active devices have an external power source
Which Site is Best for Sight

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Retinal implants have advantages
It’s best to place the implant as
peripherally to the CNS as
possible
• Reduces chance of serious
infection
• Takes advantage of existing
signal processing ability to
reduce mechanical processing
• May make learning easier by
involving more potentially
plastic systems
• More accessible
• The retina has a physical
mapping system that is easier
to understand and decipher
Retinal Prostheses Basics
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Retinal prosthesis replaces function of the
photoreceptors and detects light
There must be viable cells in the inner retina
Signal from prosthetic detected by inner retinal cells–
generally via electrical impulses
• Chemical signals that replicate neurotransmitter function are also
being proposed
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Safe, biocompatible, effective and able to withstand the
watery, salty eye environment
600-1000 electrodes would be needed to allow blind
patients to read and recognize faces – not yet achieved
Retinal Implant Location:
Subretinal vs. Epiretinal
Subretinal

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A microphotodiode array is placed between the inner
and outer layers of the retina, between the bipolar cell
layer and the retinal pigment epithelium
Concept is to directly replace native photoreceptors with
artificial silicon-based photodiodes
Subretinal

Advantages
• Utilizes the surviving bipolar cells – the next step in the pathway
–Retinal processing can take place
• Placing the microphotodiodes between layers on the retina will
allow for it to be held in position next to functioning cells
• Proximity with existing neurons requires less current and leads
to better resolution

Disadvantages:
• Limited space
• Heat damage due to proximity of device to retinal cells
• Ambient light may not be adequate to generate current in this
array

Outside power source may be needed
Subretinal Artificial Devices

Artificial Silicon Retina (ASR) by Optiobionics
• 2mm by 25 microns (thinner than a human hair)
• 3,500 solar cells that convert light into electrical
pulses
• Implanted in the subretinal space
• Powered by ambient light
The ASR Device
Relative size of the ASR Device
Placement of the ASR Device in the
subretinal space
The ASR Device
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The ASR device works by producing visual signals
similar to those produced by the photoreceptor layer
These artificial “photoelectric” signals from the ASR
microchip induce biological visual signals in the
remaining functional retinal cells which may be
processed and sent via the optic nerve to the brain
The microchip is designed to interface and function with
a retina that has partial outer retinal degeneration
Epiretinal
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Implanted on the surface of the retina
The implant converts externally captured data to a
sequence of electrical stimuli
Stimulates ganglia leading to optic nerve activation
Epiretinal

Advantages
• Minimizes the amount of microelectronics implanted
and upgrades are easy to do on the wearable portion
thus avoiding future surgery
• Heat can be dissipated into the vitreous humor
• External control over image processing allowing for
customizability, possible better clarity

Disadvantages
• Difficulty attaching the implant to the fragile inner
retina
• Complicated processing due to the stimulation at the
ganglion which is output of the retina
Epiretinal Artificial Devices

Artificial Retina Component Chip (ARCC)
• 2 mm by 20 microns
• Placed on retinal surface
• Secondary device attached to a pair of common
eyeglasses directs a laser at the chip's solar cells to
provide power
• Requires small battery pack
The ARCC Device

ARCC is powered by an external
laser aimed at a photovoltaic cell
implanted on the back of the eye
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The laser is mounted on glasses
that must be worn for the chip to
function

The photosensors on the chip
convert the light and images into
nerve impulses, much like the
normal human retina
The ARCC Device

This system is, in essence, a video camera which views an
image, sends the information of the pattern of light in the
image by laser to the photovoltaic cell, which then stimulates
the ganglia of the optical nerve to recreate a partial image
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Image is a rough pattern of light and dark areas that provides
clues on the shape and size of objects being viewed

The electrodes do not pass current to stimulate the ganglia
directly. Instead, the electrodes charge a plate that then
stimulates the ganglia. This step is intended to reduce the risk
of damage to the retinal tissue from the electrical current
The ARCC Device
Device Complications and
Limitations
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Biocompatability
• Device materials silicon and silicon oxide (for chip itself), titanium and
iridium oxide (for wiring and electrodes)
• Device pre-clinical trials and preliminary clinical studies show good
biocompatability

Surgical Complications
• Incision into eye, draining of vitreous gel creates opportunities for infection
• Silicon disc difficult to handle in surgery due to flexibility

Physical Complications related to device and eye
• Distance between electrodes and targeted cells can result in crossed
signals between electrodes and increase in current required, which can be
damaging to tissue
• Limit of size and density of implantable chip limits resolutions
• Fragility and curvature of retina
Device Complications and
Limitations
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Long term Complications
• Replacement of vitreous fluid with saline may cause irritation or damage to
retinal surface
• Irritation or damage due to long term electrical stimulus, and residual heat
• Ionic interactions between retinal cells and metallic electrodes may cause
long term degradation to tissue
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Limitations
• Devices are not expected to produce full, clear vision.
• Allows patient to perceive basic shapes, direction of movements,
boundaries between contrasting objects
Device Complications and
Limitations: Subretinal
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Surgical Complications
• Injection of fluid to create space for device in retina, injection of air to
close space create further chance of infection
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Physical Complications related to device and eye
• Coarse edges may damage retina with eye movement
• Risk of device damage also due to movement

Long term Complications
• Irritation or damage due to long term electrical stimulus, and residual
heat
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Limitations
• Not yet clear whether solar power is sufficient to create threshold
stimulus to retinal cells
Device Complications and
Limitations: Epiretinal
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Surgical Complications
• Implant trauma

Physical Complications related to device and eye
• Movement may cause detachment of device from retinal surface
• Fragility and curvature of retina

Long term Complications
• Replacement of vitreous fluid with saline may cause irritation or
damage to device

Limitations
• Head-mounted cameras do not respond to natural eye
movement
• Small eye movements may be necessary for image to persist
Gene Therapy to Treat Blindness
http://www.cbsnews.com/sections/i_video/
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Anatomy of the Eye
•
Cornea
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Continuous with sclera
•
Aqueous humor
•
Pupil
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•
Surrounded by iris
Lens

Suspended by zonule fibers and ciliary muscles
•
Vitreous body
•
Retina
Structures and Functions

Detection, localization, and analysis of light
•
Cornea

Outermost layer/domed-shaped surface that covers front of
eye

Provides refractive power and protection

Obtains nutrition and oxygen from tears (lacrimal duct in
the front) and fluid (aqueous humor in the back)
•
Sclera

White of the eye

Serves protective functions
•
Aqueous humor

Fluid that nourishes the cornea
•
Pupil

Allows the light to reach the lens
Structures and Functions
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Iris
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Pigmented and responsible for eye color
Lens

Allows the eyes to adjust its focus in order to view things
 Contraction of ciliary muscles releases tension of zonule fibers and
the lens becomes thicker
 Relaxation of ciliary muscles increases tension of zonule fibers and
the lens becomes thinner
Retina
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Rods
 Black and white aspects of vision
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Cones
 Color and shape aspects of vision
Functions of the Cornea
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Protection
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Transparency
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Allows light to pass through
No blood vessels to interfere with vision
Filtering
•
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Physical barrier that shields the inside of the eye from germs, dust, and other
harmful materials
Shares protective task with sclera
Protects lens and retina against harmful Ultraviolet (UV) light by filtering out the most
damaging wavelengths
Refraction
Functions of the Cornea

Refraction of light
 Occurs in the air-cornea interface
 Occurs when the speed of light
slows down upon entering the
cornea
 Curvature of lens produces focal
length of 2.4 cm
 After striking cornea, light is
focused on retina because distance
from cornea to retina is also about
2.4 cm
 Curvature of cornea converges
parallel light to the retina in the
back of the eye
A nearsighted person sees near objects clearly,
while objects in the distance are blurred.
Nearsightedness occurs when the
physical length of the eye is greater
than the optical length.
Farsightedness is difficulty seeing
objects that are nearby
Layers of the Cornea
Functions of the Layers
Epithelium
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Serves as a physical barrier
Absorbs oxygen and nutrients from tears
Thousands of tiny nerve endings (very
sensitive to pain)
Bowman’s Layer
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Below epithelium
Composed of collagen
Stroma:
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Comprises 90% of cornea’s thickness
78% water and 16% collagen
Function of the Layers
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Descemet’s Membrane
• Strong sheet of tissue composed of
collagen
Endothelium:
• Innermost layer and extremely thin
• Primary task is to pump excessive fluid
out of stroma
• If damaged, stroma becomes swollen and
opaque
•
(excessive damage
can lead to blindness)
* Cannot regenerate
Diseases of the Cornea
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Different layers of cornea can be affected
by different processes leading to blindness
Fuch’s Dystrophy
• Endothelial cells deteriorate without
any apparent reason
• Endothelial cells cannot pump water
out and the cornea swells and vision is
distorted
Lattice Dystrophy
• Accumulation of amyloid deposits in
stroma of cornea
• Amyloid: hard waxy deposit
composed of protein and
polysaccharide (resulting from
degeneration of tissue)
Diseases of the Cornea
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Corneal Dystrophy
• One or more parts of cornea loses clarity due to buildup of cloudy
material
• Inherited (not due to injury or infection)
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Keratitis
• Corneal scarring and opacity
• Caused by infection, chemical burns, mechanical trauma or allergy
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Keratoconus
• Progressive thinning of the cornea
Pathology - Keratitis
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Corneal inflammation due to infection, trauma, or allergic reaction leading to scarring and opacity
Infection
Causes
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Mycotic Keratitis
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Fungal infection, scar formation
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Herpetic Keratitis
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Herpes infection, scar formation
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Trauma
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Mechanical scratch, chemical burn, or thermal injury
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Allergic reaction:
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Steven-Johnson Syndrome, blisters on skin and cornea
Symptoms
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Pain
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Blurred vision
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Light sensitivity
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Discharge
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Redness
Leprosy-induced contact keratitis
Mycotic Keratitis
Herpetic Keratitis
Pathology - Keratoconus
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Progressive thinning of cornea
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Most common corneal dystrophy in the U.S.
• Affects 1/ 2000 Americans
• More prevalent in teenagers and adults in their 20s
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Middle of cornea thins and bulges outward
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Cornea becomes cone shaped
Abnormal curvature leads to severe visual distortion and
blurriness
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Pathology - Keratoconus
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Possible causes
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Inherited
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Injury
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7% of patients have family history of
keratoconus
Excessive eye rubbing or extensive
hard contact lens use for many years
Eye Disease

Retinitis Pigmentosa


Inherited disease that causes
gradual degeneration of
photoreceptors
Systemic Diseases:

Ehlers-Danlos Syndrome

Inherited disease causing faulty
collagen, weak connective tissue,
and inelasticity
Pathology - Keratoconus
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Solutions
• Specially fitted contact lenses
• Corneal transplant
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About 10-20% of people with keratoconus require corneal transplants
Necessary when the cornea becomes too scarred and contact lenses are
ineffective
An estimated 1 in 20,000 Americans may need corneal transplants due
to keratoconus alone
Corneal Transplants
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More than 40,000 per year in the U.S.
One of the most popular surgeries
$1800.00

Cons
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Viral infection from donor (AIDS)
Limited supplies
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Potential rejection in about 20% of cases
Growth of blood vessels and scar tissue throughout the donated cornea
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Cornea must be surgically removed within 12 hours of donor’s death
After 12 hours, cornea cannot be used for transplant
New cornea becomes just as opaque
Previous failures leads to reduction in chances of further transplants
Many cases considered too high risk to attempt transplant
Artificial Corneas
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Keratoprosthesis (KPro)
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High risk of complications
•
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Synthetic corneal replacement
Historically reserved for unilaterally blind patients
Design considerations
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Curvature, diameter and refractive power
Flexibility with sufficient tensile strength to accommodate minor surgery
Biocompatibility
Ability to monitor intraocular pressure
Re-epithelialization
Safety and/or reversibility
Artificial Corneas
AlphaCor™
AKA Chirilla Kpro
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1998
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$7000.00
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AlphaCor™
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In place of corneal transplant for highrisk patients
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Implant requirements
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Good eyelid health
Good tear film production
No inflammation
Functioning retina
Normal or controlled intraocular pressure
Counter-indications
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Inability to administer medications at
home
Smoking
Herpes Simplex Virus (HSV)
AlphaCor™
The Device
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Hydrogel core-and-skirt keratoprosthesis
One piece convex disc
•
Poly (2-hydroxyethyl methacrylate) (PHEMA)
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7mm diameter
0.5mm thick
Soft, flexible, biocompatible
3 components
• Outer skirt
• Central optic
• Interpenetrating polymer network (IPN)
AlphaCor™
Components
Central optic
• Transparent PHEMA gel
• Refractive powers ~ human cornea

Outer skirt
• Opaque, high water content PHEMA sponge
• Macroporous: encourages biointegration of stromal
fibroblasts

Interpenetrating polymer network (IPN)
• Fuses the skirt and the optic together at the
molecular level
• Prevent splitting, leakage, down-growth

AlphaCor™
The Surgery
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Stage I:
• Create lamellar corneal pocket
 Remove scarred cornea and any
remaining attachment tissue
• Insert the device into the lamellar
pocket
• Cover with conjunctival flap
• Mattress suture to keep the device
from migrating while biointegration
occurs
• Suture the pocket closed
AlphaCor™
The Surgery
AlphaCor™
The Surgery
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Stage II: 12 weeks post-surgery
• Removal of the flap and anterior
corneal layer which includes the
conjunctiva and anterior corneal lamella
• Reveal the optical surface and allow
light through
AlphaCor™
The Surgery
AlphaCor™
Post-Op
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Incidence of severe complications low
Topical 1% medoxyprogesterone (MPG)
•
•
Routine prescription for the first
postoperative year
Benefits
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Freedom from complications,
especially stromal melt
Visual acuity outcomes
significantly better
24 months post-op
AlphaCor™
Pros
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Probability of retention to one year: 80%
• With MPG use, increases probability to 100%

Best-corrected visual acuity
• Range: Light Perception - 20/30
• 93% of cases: preoperative vision retained or improved

Patients report that eyes are comfortable
• appreciate the relatively ‘low-maintenance’ regimen
• absence of requirement for systemic steroids and other cytotoxic drugs

No patient to date has lost an eye or developed endophthalmitis
AlphaCor™
Cons
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Insufficient attachment of the prosthesis to the corneal tissue
• Poor primary bio-integration
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Stromal melts and optic deposition
AlphaCor™
Cons
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Stromal melt
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Inflammation of the cornea associated with a loss of the epithelium and stroma
Trigger: Collagenolytic activty
Leads to the extrusion of the skirt
Solutions
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Implant removal and replacement
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Mucous membrane grafts
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Re-epithelialization of the optic is important for prevention
•
In clinical trials, found that there was a strong correlation between melts and HSV

MPG as a effective preventative measure

HSV is now considered a counter-indication for AlphaCor™
AlphaCor™
Cons
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Optic deposition
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Brown, white
Explantation and replacement with new prosthetic or donor graft
AlphaCor™

Secondary glaucoma
• Caused by build up of pressure inside
the eye.
• Increased intraocular pressure results
in impaired drainage of aqueous humor
out of the eye
• Damage to the optic nerve and vision
loss
• Can result in blindness, especially in
peripheral vision
• Visual field damage permanent even if
pressure corrected
Other complications traditionally associated with
KPros

Infection
 Endophthalmitis

Intraocular infection often results in
catastrophic loss of vision or loss of an eye

Often attributed to Strep and Staph
bacterial species

Correlation with dry, actively inflamed
eyes

Sterile endopthalmitisis seen in more
commonly in KPro surgeries than any other
intraocular surgical procedures
 Spoiling of the optic
Other complications traditionally associated with
KPros

Extrusion
•
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Intraocular pressure and poor bio-integration
Retroprosthetic Membrane Development
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Ingrowth of epithelium between the corneal stroma and the prosthesis material into
the anterior chamber

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Development of a dense, relatively avascular fibrotic tissue and consequent
extrusion
Epithelium opens a canal for infections.
Membrane formation may also cause secondary glaucoma by growing into
the chamber angle

Laser treatment or surgical excision