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Age related macula degen
1.
2.
3.
4.
5. Trouble with vision as
we get older...
• Is not always due to Age-
related macular
degeneration !
• Your doctor needs to
perform a complete eye
exam before reaching a
diagnosis
14. Colour photography is
routinely undertaken with
angiography. It helps to
determine the nature of
changes seen on the
angiogram… particularly
the cause of blocked
fluorescence due to
haemorrhage, pigment or
other cause.
15. Side by side
comparison
of the color photo
and
the fluorescein
picture
often complement
each
other !
21. • Diagnostic imaging technique that examines
living tissue non-invasively. It is based on a
complex analysis of the reflection of low
coherence radiation from the tissue under
examination.
• Real time cross sectional analysis
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37. • Macular Degeneration
Leading cause of
blindness in people
over 55
• 1:10 people over
55
• Increases by a
factor of 6 in
people over 80
• 1.75 million
Americans over
age 40 have severe
AMD
• Estimated that 2.95
million people
affected by 2020
39. • What is Macular
Idiopathic
• Central vision
Degeneration?
loss
• Peripheral vision
preserved
• Two forms
• Dry
(Nonexudative)
• 90% of people
• Wet (Exudative)
• Affects 10% of
people
40. What does my Doctor
•
•
Drusen
see?
Metabolic waste
products
accumulating under
the retina
• Pigment clumping
and atrophy
• Death of support
cells under retina
• Geographic atrophy
• Large areas of cell
death
• Hemorrhage
(blood)
• Hallmark of wet
AMD
41. My Doctor told me I have Macular
Degeneration. Will I go blind?
• Not necessarily
• Only 10% develop
the wet form which
is responsible for
90% of blindness
from AMD
• Newer treatments
may reduce risk of
blindness
• Only 10% of the dry
patients will develop
severe vision loss
42. Risk factors for Vision
• Non-modifiable:
things we cannot loss
change
• Age
• (If you figure out how
to stop aging, please let
me know)
• Caucasian race
• Female gender
• Family history
• 2.5x increased risk of
first degree family
relative
43. Risk factors for Vision
• Modifiable
• Smoking Loss
• Hypertension
• High
Cholesterol
• Obesity
• Sedentary
Lifestyle
• Heart Health= Eye
44. What about those
AREDS study
• Vitamins? II
Followed 3640 patients
for average 6.3 years
• AREDS
• High doses of
antioxidant vitamins • Started in 2006 –
ongoing
• Hope they will reduce
oxidative stress in • Added
macula
• Lutein: forms macular
• Vitamin A pigment
• Vitamin C • Zeaxanthin
• Vitamin E • Subtracted
• Zinc: antioxidant in • Vitamin A: Potential
conjunction with C and increased risk of lung
E cancer in smokers
• Copper
45. • Vitamins
Not found helpful for
everyone
• No benefit
• No AMD • Benefit:
• Mild AMD • If everyone took AREDS,
• Beneficial
300,000 people could be
prevented from developing
• Moderate AMD
advanced AMD over 5 year
• Severe AMD
• Persons with wet AMD • Unfortunately will not stop
progression of AMD in all
• Benefit patients
• Reduced risk of
progression of AMD by
25%
• Reduced risk of vision
46. Which is the best
Multivitamin?
• They are all basically the
same as long as they have
the AREDS formula
• Differences in brands
• AREDS I vs AREDS II formula
• Dosing
• Price
• Packaging
• Advertising
47. • Stop Smoking Summary
• Exercise
• Heart Healthy Diet
• Eat leafy green
vegetables
• Control blood
pressure and
cholesterol
• AREDS
Multivitamin if
indicated by your
eye doctor
• Monitor vision and
regular eye checks
48.
49.
50.
51.
52.
53.
54.
55.
56. • Macular Degeneration
Leading cause of
blindness in people
over 55
• 1:10 people over
55
• Increases by a
factor of 6 in
people over 80
• 1.75 million
Americans over
age 40 have severe
AMD
• Estimated that 2.95
million people
affected by 2020
58. • What is Macular
Idiopathic
• Central vision
Degeneration?
loss
• Peripheral vision
preserved
• Two forms
• Dry
(Nonexudative)
• 90% of people
• Wet (Exudative)
• Affects 10% of
people
59. What does my Doctor
•
•
Drusen
see?
Metabolic waste
products
accumulating under
the retina
• Pigment clumping
and atrophy
• Death of support
cells under retina
• Geographic atrophy
• Large areas of cell
death
• Hemorrhage
(blood)
• Hallmark of wet
AMD
60. My Doctor told me I have Macular
Degeneration. Will I go blind?
• Not necessarily
• Only 10% develop
the wet form which
is responsible for
90% of blindness
from AMD
• Newer treatments
may reduce risk of
blindness
• Only 10% of the dry
patients will develop
severe vision loss
61. Risk factors for Vision
• Non-modifiable:
things we cannot loss
change
• Age
• (If you figure out how
to stop aging, please let
me know)
• Caucasian race
• Female gender
• Family history
• 2.5x increased risk of
first degree family
relative
62. Risk factors for Vision
• Modifiable
• Smoking Loss
• Hypertension
• High
Cholesterol
• Obesity
• Sedentary
Lifestyle
• Heart Health= Eye
63. What about those
AREDS study
• Vitamins? II
Followed 3640 patients
for average 6.3 years
• AREDS
• High doses of
antioxidant vitamins • Started in 2006 –
ongoing
• Hope they will reduce
oxidative stress in • Added
macula
• Lutein: forms macular
• Vitamin A pigment
• Vitamin C • Zeaxanthin
• Vitamin E • Subtracted
• Zinc: antioxidant in • Vitamin A: Potential
conjunction with C and increased risk of lung
E cancer in smokers
• Copper
64. • Vitamins
Not found helpful for
everyone
• No benefit
• No AMD • Benefit:
• Mild AMD • If everyone took AREDS,
• Beneficial
300,000 people could be
prevented from developing
• Moderate AMD
advanced AMD over 5 year
• Severe AMD
• Persons with wet AMD • Unfortunately will not stop
progression of AMD in all
• Benefit patients
• Reduced risk of
progression of AMD by
25%
• Reduced risk of vision
65. Which is the best
Multivitamin?
• They are all basically the
same as long as they have
the AREDS formula
• Differences in brands
• AREDS I vs AREDS II formula
• Dosing
• Price
• Packaging
• Advertising
66. • Stop Smoking Summary
• Exercise
• Heart Healthy Diet
• Eat leafy green
vegetables
• Control blood
pressure and
cholesterol
• AREDS
Multivitamin if
indicated by your
eye doctor
• Monitor vision and
regular eye checks
68. What is Age-Related Macular
Degeneration?
• Age-related macular degeneration (AMD) is a
deterioration or breakdown of the eye's macula.
• The macula is a small area in the retina — the
light-sensitive tissue lining the back of the eye.
• The macula is the part of the retina that is
responsible for your central vision, allowing you
to see fine details clearly.
• American Academy of Ophthalmology
72. Genetics
• DNA
• All information of life encoded in DNA and
expressed by proteins.
• James Dewey Watson (US) & Francis Crick
(UK) – Co-discoverers Structure of DNA
1953
• Awarded Nobel Prize in Physiology or
Medicine 1962
75. Genetic Basics…get
small…
• The human body is made up of trillions of Cells,
• and with a few exceptions, each cell contains a
Nucleus
• and with a few exceptions, each nucleus contains
a COMPLETE set of Chromosomes
• And the chromosomes are made of DNA
77. …and smaller…From Cells to
Nucleus to Chromosomes
• Every human cell contains 23 pairs of
chromosomes, for a total of 46 chromosomes.
• Each Chromosome is made up of
• a double- stranded,
• Tightly-coiled,
• helix of DNA
79. …and smaller…
• A CHROMOSOME contains hundreds to
thousands of genes.
• A GENE is a segment of DNA containing
the code used to synthesize a protein.
• A TRAIT is any gene-determined
characteristic and is usually determined by
more than one gene.
• Some traits are caused by abnormal genes
that are inherited or that are the result of
a mutation.
81. WhatStudies we know?…
• Genetic do
• 1988-2010 so far
• DNA and Gene-Environment Data
Collection
• Twin Study – WWII Registry
• 1997 Familial Aggregation Study – Relatives of
Cases with Wet AMD. Relatives of controls.
• 1997 Phenotypic Heterogeneity in Families
with AMD
• Johanna M. Seddon, M.D., Sc.M.
82. What do we know?…
so far
• From the US Twin Study, we’ve learned
• Substantial Genetic Component –
• 46 to 71% of the variation in
phenotype
• Important Environmental Influence:
19 to 37%
83. OK…what “Genetic
Factors”?...
• It’s not so much as a “bad” gene, but rather
• Variations of “normal genes” that influence
the risk of developing AMD.
• Specific DNA chromosomes associated
with the defective genes are located on
chromosomes
• 1q and 10q
90. Epidemiology
• Epidemiology is the study of
• the distribution and patterns of health-events,
• health-characteristics and
• their causes or influences in well-defined
populations.
91. Epidemiology
• It is our principal method of public health
research, and
• helps us make policy decisions as well as
evidence-based medicine
• by identifying risk factors for disease and
helps us with recommendations for
appropriate preventive medicine.
92. Epidemiologic studies looking at
• Meta-analysis of 15 genome-wide
the genetics of AMD
association studies
• Began in 2009
• 8,000 cases and 50,000 controls
• 19 groups from 13 countries
• 19 genomic loci associated with AMD
• Six novel loci not previously associated
with disease
• Pathways similar to other known genes.
• ASHG Oct 2011
93. Epidemiology and
Causation
Risk factors for cardiovascular disease (CVD)
are associated with age-related AMD;
• Smoking
• Dietary antioxidants, fats, omega-3 fatty
acids
• Physical activity
• Obesity, abdominal adiposity
• Hypertension
• Cholesterol
• CRP (C-reactive protein)
94. Epidemiology and
Causation
• For the homozygous (pure trait) risk
genotype
• Risk of AMD was
• Increased for BMI (Body Mass
Index) and
• Increased with smoking
95. So what can we say?
• Genetic mutations make us susceptible to
the development of AMD
• Multiple genetic factors are at work
• Risk profiles help us to change life style to
decrease the chance of AMD development
• Which leads us to…
96. The big question (at least for the
retina specialists)
• What information from
• TV,
• Radio,
• Internet,
• YouTube,
• Email,
• Fax, Photocopy, Text, Blog,
Wikipedia….etc
• Should You believe?
111. Getting the Right
Device(s)devices
• Because there is such a variety of
available, it can be somewhat overwhelming to
locate the correct device.
• Individuals should receive an evaluation from an
Optometrist who specializes in treating
individuals with low vision.
• This assures that the individual receives the
correct device with consideration of all goals
and needs.
113. Handheld Magnifying Cameras
• Miracle Mouse
Electronic TV
Magnifier
• MonoMouse-RM B&W
Electronic Magnifier
• Max Digital Color
Magnifier
• Primer 2 Color
Electronic Magnifier
114. Traditional CCTV Video
Magnifiers reading
• Increased
speed
• Increased duration
• Reduced visual effort
• Comfortable
• Desktop systems working position
• Variable
Magnification
• Color, W/B, B/W
• Large Field of View
115. Magnifiers
Integrated LCD
• Available from all major vendors
Displays
• Sizes: 17” to 24” + with WS
• Adjustable height screens
• High contrast
• Flicker free
• Improved response rates
• Well received by consumers
117. Video
Magnification
• Variable Systems
Magnification
• Adjustable brightness
• Selectable contrast
setting
• Wide field of view
for better viewing
abilities
122. Portable Video
• More Compact, 7-inch screens
Magnifiers
• Extensive reading tasks
• Two handed use
• Optelec Traveler
• FS Sapphire
• EV Amigo
• Fusion 7” LCD Portable Video Magnifier
123. Compact Video
Magnifiers:
• Variable Magnification
• Replaceable Batteries
• Longer battery life
• Image Freeze
• Color Select
• Light off mode: for reading cell phones, other
displays
• Writing Cameras
• Distance Viewing
• Smaller Designs
124. Compact/Pocket
Video Magnifiers
• Advantages
• Wide field of view
• Image at display level
• Use at arms-length
• Reverse contrast available
• Cell phone, PDA displays!
• Short-term writing tasks
• Kids reading comic books
under the blanket
125. Compact Systems with
Distance Capabilities
• Near and distance capabilities
• Read mail, products on a shelf and get a
better view of distance object.
• Allows users to see an object that is at
distance close up on the screen
• Limited clarity and magnification at a
distance
126. GW Micro
Sense View Duo
• Two cameras
• Stores up to 20 images
• 3X to 13X magnification
• Lights off mode
• Image panning
• 7 Viewing modes, 4
Brightness levels
• 4.5 hour battery life,
integrated, rechargeable
• Cost: $1299.00
128. Desktop Video Magnifiers
• Full Size screen
Features
• Full Features
• Remote Controllable
• Near and Distance Viewing
• For Classroom, Conference or In- Service
Training Activities
• Transportable “Luggable”
• AC or optional battery
132. Laptop Compatible Video
Magnifiers
• Most students
use laptop
computers
• Video
magnification
could be helpful
• Portable camera
using notebook
display
133. Clarity PCMate
• Powered by USB
• Requires 2 USB 2
ports
• Sequence, setup
• Remote control
camera
• Keyboard
controlled
software
134. Optelec
ClearNote
• Ease of camera
aiming
• Built in Light source
• Camera control
positioning
• Keyboard controlled
software
• Keyboard controlled
camera
• Dolphin, Zoom Text
compatible
135. Freedom Scientific Onyx
PC Edition arm and flex
• Swing
arm models
• Remote control
• MAGic with
EyeMerge software
included
• Camera can be
powered by USB port
• Distance, desktop, self
view modes
• Cost: $2895.00
155. Getting the Right
Device(s)devices
• Because there is such a variety of
available, it can be somewhat overwhelming to
locate the correct device.
• Individuals should receive an evaluation from an
Optometrist who specializes in treating
individuals with low vision.
• This assures that the individual receives the
correct device with consideration of all goals
and needs.
157. Handheld Magnifying Cameras
• Miracle Mouse
Electronic TV
Magnifier
• MonoMouse-RM B&W
Electronic Magnifier
• Max Digital Color
Magnifier
• Primer 2 Color
Electronic Magnifier
158. Traditional CCTV Video
Magnifiers reading
• Increased
speed
• Increased duration
• Reduced visual effort
• Comfortable
• Desktop systems working position
• Variable
Magnification
• Color, W/B, B/W
• Large Field of View
159. Magnifiers
Integrated LCD
• Available from all major vendors
Displays
• Sizes: 17” to 24” + with WS
• Adjustable height screens
• High contrast
• Flicker free
• Improved response rates
• Well received by consumers
161. Video
Magnification
• Variable Systems
Magnification
• Adjustable brightness
• Selectable contrast
setting
• Wide field of view
for better viewing
abilities
166. Portable Video
• More Compact, 7-inch screens
Magnifiers
• Extensive reading tasks
• Two handed use
• Optelec Traveler
• FS Sapphire
• EV Amigo
• Fusion 7” LCD Portable Video Magnifier
167. Compact Video
Magnifiers:
• Variable Magnification
• Replaceable Batteries
• Longer battery life
• Image Freeze
• Color Select
• Light off mode: for reading cell phones, other
displays
• Writing Cameras
• Distance Viewing
• Smaller Designs
168. Compact/Pocket
Video Magnifiers
• Advantages
• Wide field of view
• Image at display level
• Use at arms-length
• Reverse contrast available
• Cell phone, PDA displays!
• Short-term writing tasks
• Kids reading comic books
under the blanket
169. Compact Systems with
Distance Capabilities
• Near and distance capabilities
• Read mail, products on a shelf and get a
better view of distance object.
• Allows users to see an object that is at
distance close up on the screen
• Limited clarity and magnification at a
distance
170. GW Micro
Sense View Duo
• Two cameras
• Stores up to 20 images
• 3X to 13X magnification
• Lights off mode
• Image panning
• 7 Viewing modes, 4
Brightness levels
• 4.5 hour battery life,
integrated, rechargeable
• Cost: $1299.00
172. Desktop Video Magnifiers
• Full Size screen
Features
• Full Features
• Remote Controllable
• Near and Distance Viewing
• For Classroom, Conference or In- Service
Training Activities
• Transportable “Luggable”
• AC or optional battery
176. Laptop Compatible Video
Magnifiers
• Most students
use laptop
computers
• Video
magnification
could be helpful
• Portable camera
using notebook
display
177. Clarity PCMate
• Powered by USB
• Requires 2 USB 2
ports
• Sequence, setup
• Remote control
camera
• Keyboard
controlled
software
178. Optelec
ClearNote
• Ease of camera
aiming
• Built in Light source
• Camera control
positioning
• Keyboard controlled
software
• Keyboard controlled
camera
• Dolphin, Zoom Text
compatible
179. Freedom Scientific Onyx
PC Edition arm and flex
• Swing
arm models
• Remote control
• MAGic with
EyeMerge software
included
• Camera can be
powered by USB port
• Distance, desktop, self
view modes
• Cost: $2895.00
181. Headborne Low Vision
System
• Eyetonomy SightMate LV920
• www.vuzix.com/medical/lv920.h
tml
• Zoom at near: 3X optical, 4X
digital
• Zoom at distance: 0.5X to 6X
• Edge contrasting, Inverse mode
• Sleek design, 8 ounces
• $3499.00
• Not yet available for purchase
or review
182.
183. Scan and Read Devices
• Kurzweil 1000 (software)
• ABiSee Zoom-Ex, EyePal Vision (portable,
Solo)
• FS Pearl (laptop compatible)
• KNFB Reader (smartphone)
• AI Squared ZoomReader (app)
184. Assessment functioning
• Evaluation of visual Factors
• Response to low vision approaches
• Analysis of tasks, task specific
• Required performance level
• Integration of systems
• Training
• Trial of system; speed, duration,
productivity
• Modifications
• Provision
185. Pharmacogenomics
• Treatment based on
genetic profile
• “Personalized
medicine”
• AREDS – 70% with
certain gene did not
progress (vs. 11%
without)
• Relationship between
certain genes and
outcomes with
Lucentis and Avastin
187. • Trials
Phase I Dose Escalation Safety Study
of RetinoStat in Advanced Age-
Related Macular Degeneration
(AMD) Oxford BioMedica
• Subretinal injection of virus vector that produces
anti-VEGF proteins
• Safety and Efficacy Study of
rAAV.sFlt-1 in Patients With
Exudative Age-Related Macular
Degeneration
• Intravitreal injection of a non-pathogenic virus to
express a therapeutic protein within the eye
191. What tests are used?
Why are they necessary in the
diagnosis and management?
Not everything that looks like
macular degeneration
is macular degeneration
Importance of continued
monitoring and care
50% chance of developing wet AMD
in fellow eye over 5 years
195. • AREDS vitamins shown to be beneficial in
patients with high risk AMD
• Vitamins slow the progression; they do not
stop it
• Benefits of AREDS II not proven yet
196. Will the high dose of vitamins in the
AREDS formula have side effects?
• Vitamin A in smokers - lung cancer
• Vitamins A and E stored in the liver - potential
liver toxicity
• Zinc - anemia if not taken with copper
• Vitamin E - cardiovascular issues not typical in
dose prescribed, prostate cancer?
• AREDS II - High dose Vitamin A removed; Lutein
and Zeaxanthin added
198. • Genetics of AMD is complex with many
associated genes
• Hereditary forms exist and can express
themselves at different ages and in different
degrees of severity
• Environmental factors may trigger the disease in
susceptible people
199. Known risk factors:
• Smoking, diet, exercise, obesity (BMI)
• Hypertension, Hypercholesterolemia
• Does this sound familiar??
200. Will I go totally blind?
• AMD causes central vision loss with
preservation of peripheral vision
• 90% of severe vision loss occurs in the wet
(neovascular) type. 10% of patients have wet
AMD
• 90% of patients have dry (atrophic) AMD. 10%
of these with develop severe vision loss
202. • Millions of dollars have been appropriated to
AMD research
• Medications based on a person’s individual
genetic profile (pharmacogenomics)
• Gene therapy to enhance a person’s own
production of beneficial compounds
• Retina implant / retinal prosthesis
• Stem cells
• Antioxidant eye drops for dry / atrophic AMD
203. Which treatment is best for me
and why?
• Thermal “Hot” Laser (1970’s)
• PDT “Cold” Laser (Visudyne)
• Macugen - First anti-VEGF intraocular treatment
• Lucentis - First to show improved vision
95% stabilized 40% improved
• Avastin - Cost
• Eylea - Less frequent treatment
206. How many injections will I need? Is there a limit to the
number of treatments I can get? What is the side
effect of long-term treatment?
Lucentis Study - injection every 4 weeks. May still give best
outcome
Treat and Extend protocol
Double-dosing
Combined PDT with anti-VEGF therapy
Risks: Infection, Retinal detachment, Cataract, Inflammation,
Glaucoma
Therapy for a chronic condition requires long term treatment.
Underlying degenerative changes will continue with potential
gradual vision loss even with treatment.
207. What will happen if I do nothing?
• Natural history of AMD is to cause significant
and permanent loss of central vision leading to
legal blindness
208. Will changing my glasses help?
Multiple aids to help people with decreased vision with AMD:
• Spectacle-mounted magnifiers
• Hand-held and spectacle-mounted telescopes
• Hand-held and stand magnifiers
• Video magnification / Computer devices
• Importance of illumination, brightness and increased contrast
• Writings devices, voice command, “gadgets”
• Importance of early evaluation when moderate vision loss by a
low vision specialist
• Devices require training; use of eccentric vision
212. What tests are used?
Why are they necessary in the
diagnosis and management?
Not everything that looks like
macular degeneration
is macular degeneration
Importance of continued
monitoring and care
50% chance of developing wet AMD
in fellow eye over 5 years
216. • AREDS vitamins shown to be beneficial in
patients with high risk AMD
• Vitamins slow the progression; they do not
stop it
• Benefits of AREDS II not proven yet
217. Will the high dose of vitamins in the
AREDS formula have side effects?
• Vitamin A in smokers - lung cancer
• Vitamins A and E stored in the liver - potential
liver toxicity
• Zinc - anemia if not taken with copper
• Vitamin E - cardiovascular issues not typical in
dose prescribed, prostate cancer?
• AREDS II - High dose Vitamin A removed; Lutein
and Zeaxanthin added
219. • Genetics of AMD is complex with many
associated genes
• Hereditary forms exist and can express
themselves at different ages and in different
degrees of severity
• Environmental factors may trigger the disease in
susceptible people
220. Known risk factors:
• Smoking, diet, exercise, obesity (BMI)
• Hypertension, Hypercholesterolemia
• Does this sound familiar??
221. Will I go totally blind?
• AMD causes central vision loss with
preservation of peripheral vision
• 90% of severe vision loss occurs in the wet
(neovascular) type. 10% of patients have wet
AMD
• 90% of patients have dry (atrophic) AMD. 10%
of these with develop severe vision loss
223. • Millions of dollars have been appropriated to
AMD research
• Medications based on a person’s individual
genetic profile (pharmacogenomics)
• Gene therapy to enhance a person’s own
production of beneficial compounds
• Retina implant / retinal prosthesis
• Stem cells
• Antioxidant eye drops for dry / atrophic AMD
224. Which treatment is best for me
and why?
• Thermal “Hot” Laser (1970’s)
• PDT “Cold” Laser (Visudyne)
• Macugen - First anti-VEGF intraocular treatment
• Lucentis - First to show improved vision
95% stabilized 40% improved
• Avastin - Cost
• Eylea - Less frequent treatment
227. How many injections will I need? Is there a limit to the
number of treatments I can get? What is the side
effect of long-term treatment?
Lucentis Study - injection every 4 weeks. May still give best
outcome
Treat and Extend protocol
Double-dosing
Combined PDT with anti-VEGF therapy
Risks: Infection, Retinal detachment, Cataract, Inflammation,
Glaucoma
Therapy for a chronic condition requires long term treatment.
Underlying degenerative changes will continue with potential
gradual vision loss even with treatment.
228. What will happen if I do nothing?
• Natural history of AMD is to cause significant
and permanent loss of central vision leading to
legal blindness
229. Will changing my glasses help?
Multiple aids to help people with decreased vision with AMD:
• Spectacle-mounted magnifiers
• Hand-held and spectacle-mounted telescopes
• Hand-held and stand magnifiers
• Video magnification / Computer devices
• Importance of illumination, brightness and increased contrast
• Writings devices, voice command, “gadgets”
• Importance of early evaluation when moderate vision loss by a
low vision specialist
• Devices require training; use of eccentric vision
231. • Can only be used in patients with functioning inner
retinal cells – for example AMD and RP
• Uses an artificial means to detect light (video
camera)
• Converts light energy into an electrical signal
• Deliver the electrical signal to the retinal neurons
other than photoreceptors to elicit activity that is
interpreted as vision
• Vision equivalent to 20/1260
237. Emerging treatments for
Dry AMD
Atrophic AMD AL-8309B (Alcon Laboratories)
• 2 year study evaluating an Eye drop
for dry AMD
• Primary endpoint is size of the
atrophic area
• Randomized, double blind
• 772 patients
• Study completed July 2011
238. ACU-4429 - Acucela
Phase II granted fast track status
Fenretinide
Phase III began 2011
239. Emerging treatments for dry
AMD
• Encapsulated human cells genetically modified
to secrete ciliary neurotrophic factor (CNTF)
• CNTF is a growth factor capable of rescuing
dying photoreceptors and protecting them from
degeneration
240. Emerging treatments
• OT- 551 Antioxidant Eye drops
for Dry AMD
• Othera Pharmaceuticals/ National Eye Institute
• A Multicenter, Proof-Of-Concept Study
Of Intravitreal AL-78898A In Patients
With Geographic Atrophy
• Alcon
241. Human embryonic
stem • Can differentiate into any of
cells
the 220 cell type in the
human body
• Cells acquired from
unwanted or discarded
embryo
• Can propagate indefinitely
• Proposed for regenerative
medicine and tissue
replacement after injury or
disease
243. • hES Cells modified to become RPE cells which
nourish damaged photorecptors
•First study of human transplantation reported in
January 2012
• Study of safety and tolerability of subretinal
transplantation
• 2 patients studied, one with AMD and one with
Stargardt’s disease, vision did not worsen in either one
• No tumor formation or signs of rejection
244. Stem Cells – Current
• Rejection Problems
• Tumor formation
• Expense – producing and cultivating cell
lines is costly
• Intellectual property rights
• Ethics
• No good animal models of macular
degeneration
Notas do Editor
Amsler grids are everywhere. Check the vision in each eye daily.
Throughout the history of medicine, doctors have observed treatment variability among patients which we know now to be due to genetic differences. Why some people respond well to one drug and others don’t or why some people develop certain side effects and others don’t is due to small differences in genetic make up between us. Some preliminary pharmacogenetic relationships have been reported to exist between genetic risk factors associated with AMD and the response to treatment. These pharmacogenetic associations could be used in the future to create a personalized therapeutic plan whereby patients with different genotypes are offered different treatments.
So how can we use our knowledge of genetics to actually treat patients. Many diseases come about b/c of an abnormal protein produced by a faulty gene. Gene therapy aims to alter or stop the formation of proteins that lead to disease. This approach is still a long way off in treating AMD but is being used to treat other eye diseases. On the other hand creating a so called “biofactory” by injecting genes that produce proteins such as anti-VEGF compounds drugs would obviously be very helpful for patients with wet AMD. An injection every year or two rather than monthly is not an unrealistic possibility.
The wet form of AMD with bleeding and scarring (shown in the top picture) and the Atrophic form (bottom picture) with thinning and and loss of retinal tissue are the primary causes of severe loss of vision in pts with macular degeneration. The treatments I’ll discuss here pertain primarily to this subset of patients. Both of these forms of AMD will become less prevalent as we become better at indentifying those patients who are at greatest risk and as preventative treatments become available.
Three models are now in development or testing. Model 1, with 16 electrodes, has been implanted in six patients. As of mid-July 2009, a second model integrating a 60-electrode array has been implanted in 30 human subjects domestically and internationally. A third model, an array with a higher electrode count, is under development.
May 2012 – details released of a wireless, subretinal 256 channel implant being developed in Boston. Disadvantages: more complex surgical procedure. All the implant designs in development have advantages and disadvantages not the least of which is the complexity of the surgical procedure, the lack of long term follow-up and cost ($100K)
Moore’s law loosely defined says that the power of a computer chip doubles approximately every 2 years. Timeline for progress of the artificial retina. Progress started with the installation of the first 16-electrode device in 2002, which restored light perception and the ability to perform simple visual spatial and motion tasks (hand motion level). Theoretically, there is improvement with 60 and 200+ electrode implants (finger count level) with the possibility of face recognition and reading ability with a 1000+ electrode device. (Left scale) Progression in vision from bare hand motion to face recognition. At 20/200 visual acuity, large letters can be recognized. At 20/20, small letters can be seen with good reading ability. (Right scale) Number of patients potentially helped with the different generations of prosthetic devices.
Pixels (short for picture element) are the smallest controllable element of a digital image. It is a single point in a graphic image. The more pixels on the display the higher the resolution. Examples of pixilated vision. Lower resolution may allow crude shape recognition, but increasing resolution can lead to reading letters on an eye chart and face recognition.
AL-8309 protects the photoreceptors and RPE cells from photo-oxidative stress and may be a useful pharmacotherapy for AMD
Reducing the speed of the visual cycle has been shown to protect the retina from light damage, improve retinal vasculature (the arrangement of blood vessels) and reduce the accumulation of retinal-related toxic by-products, including A2E, which is implicated in AMD. RPE cells continually consume the tips of Photoreceptors as they grow (at a constant rate of speed), accumulating toxic by-products of the visual cycle. ACU 4429 slows Visual cycle modulation resulting in a decrease of toxic by-product accumulation, and a slowing of AMD.
Dry or atrophic AMD has become an orphan disease – we know a lot about it but we have no effective treatments. My point is not to overwhelm you with technical information but to highlight the exciting and extensive ongoing research in dry AMD.
This model consists of rats with a genetic disorder where they do not have one of the enzymes needed for the RPE cell layer to function. As a result, the rats become blind due to deterioration of their photoreceptors. Following transplantation of human ES cells, injected into the sub-retinal area of the eye, rats displayed recovery of their photoreceptors and improved visual ability compared to the control rats, which were injected with a mock treatment and showed no significant improvement.
RPE dysfunction is the most common cause of blindness in people over 60 in the United States, and it affects over 30 million people worldwide.