age related macula degen

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

Eye Examination - Diagnosis

Visual Acuity, Color Vision, Amsler Grid,Fundus Camera, Fluorescein Angiography,

Optical Coherence Tomography

O

Amsler Grid Testing

Drusen, the yellow spots so characteristicof Age-related Macular Degeneration

Drusen are sometimes more easily detectedOn Color Fundus photos than doctor’s exam

FluoresceinAngiography

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.

Side by side Side by side comparison comparison of the color of the color photo andphoto and

the fluorescein the fluorescein picture picture often often

complement complement eacheach

other !other !

-

Optical CoherenceTomography

•Diagnostic imaging technique that Diagnostic imaging technique that examines living tissue non-invasively. It examines living tissue non-invasively. It is based on a complex analysis of the is based on a complex analysis of the reflection of low coherence radiation reflection of low coherence radiation from the tissue under examination.from the tissue under examination.

•Real time cross sectional analysisReal time cross sectional analysis

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

How Does the Eye Work?

What is Macular Degeneration?•Idiopathic

•Central vision loss

• Peripheral vision preserved

•Two forms

•Dry (Nonexudative)

• 90% of people

•Wet (Exudative)

• Affects 10% of people

• Responsible for 90% of blindness

What does my Doctor see?• Drusen

• 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

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

Risk factors for Vision loss•Non-modifiable:

things we cannot 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

Risk factors for Vision Loss•Modifiable

•Smoking

•Hypertension

•High Cholesterol

•Obesity

•Sedentary Lifestyle

• Heart Health= Eye Health

What about those Vitamins?

AREDS study

• Followed 3640 patients for average 6.3 years

• High doses of antioxidant vitamins

• Hope they will reduce oxidative stress in macula

• Vitamin A

• Vitamin C

• Vitamin E

• Zinc: antioxidant in conjunction with C and E

• Copper

• AREDS II

• Started in 2006 – ongoing

• Added

• Lutein: forms macular pigment

• Zeaxanthin

• Subtracted

• Vitamin A: Potential increased risk of lung cancer in smokers

Vitamins• Not found helpful for

everyone

• No benefit

• No AMD

• Mild AMD

• Beneficial

• Moderate AMD

• Severe AMD

• Persons with wet AMD

• Benefit

• Reduced risk of progression of AMD by 25%

• Reduced risk of vision loss by 19%

• Benefit:

• If everyone took AREDS, 300,000 people could be prevented from developing advanced AMD over 5 year

• Unfortunately will not stop progression of AMD in all patients

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

Summary• Stop Smoking

• 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

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

How Does the Eye Work?

What is Macular Degeneration?•Idiopathic

•Central vision loss

• Peripheral vision preserved

•Two forms

•Dry (Nonexudative)

• 90% of people

•Wet (Exudative)

• Affects 10% of people

• Responsible for 90% of blindness

What does my Doctor see?• Drusen

• 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

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

Risk factors for Vision loss•Non-modifiable:

things we cannot 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

Risk factors for Vision Loss•Modifiable

•Smoking

•Hypertension

•High Cholesterol

•Obesity

•Sedentary Lifestyle

• Heart Health= Eye Health

What about those Vitamins?

AREDS study

• Followed 3640 patients for average 6.3 years

• High doses of antioxidant vitamins

• Hope they will reduce oxidative stress in macula

• Vitamin A

• Vitamin C

• Vitamin E

• Zinc: antioxidant in conjunction with C and E

• Copper

• AREDS II

• Started in 2006 – ongoing

• Added

• Lutein: forms macular pigment

• Zeaxanthin

• Subtracted

• Vitamin A: Potential increased risk of lung cancer in smokers

Vitamins• Not found helpful for

everyone

• No benefit

• No AMD

• Mild AMD

• Beneficial

• Moderate AMD

• Severe AMD

• Persons with wet AMD

• Benefit

• Reduced risk of progression of AMD by 25%

• Reduced risk of vision loss by 19%

• Benefit:

• If everyone took AREDS, 300,000 people could be prevented from developing advanced AMD over 5 year

• Unfortunately will not stop progression of AMD in all patients

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

Summary• Stop Smoking

• 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

Age-related Macular

Degeneration

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

What is going on in the eye?

Where exactly?

Where exactly?

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

Before…

…After…Age-related changes

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

From DNA…to You and Me…

…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

Human Chromosomes

…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.

From Chromosomes to

Genes

What do we know?…so far

•Genetic Studies

•1988-2010

•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.

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%

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

From Chromosomes to

Genes

Genes associated…so far

• CFH – Y402H

• CFH – rs1410996

• CFB

• C2

• Complement Component 3 (C3)

• Complement Factor I CFI

• ARMS2/HTRA1 gene region

• Hepatic Lipase C (LIPC)

• CETP

• ABCA1

• TIMP 3 / SYN3

• VEGFA

• COL10A1

• COL8A1

• TNFRSF10A

Gene location… leads to therapy

•For example, the VEGFA locus and the development of

•Avastin

•Lucentis and recently

•Eylea

Antigen/Antibody cell membrane

Bayer Healthcare – Bayer Schering Pharma

Surface antigens/antibodie

sEylea.com

Relative risk of Genetic loci

Nature Genetics 38: 1057, 2006

Epidemiology

•Epidemiology is the study of

•the distribution and patterns of health-events,

•health-characteristics and

•their causes or influences in well-defined populations.

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.

Epidemiologic studies looking at the genetics of

AMD•Meta-analysis of 15 genome-wide 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

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)

Epidemiology and Causation

•For the homozygous (pure trait) risk genotype

•Risk of AMD was

•Increased for BMI (Body Mass Index) and

•Increased with smoking

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…

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?

Types of Optical Devices

Near Devices

Stand Magnifier

Dome Magnifier

Illuminated Stand Magnifier

Hand Held Pocket Magnifier

Hand Held Illuminated

Microscopes or Reading Glasses

Types of Optical Devices

Distance Devices

Binoculars

Monocular

Full-Field Telescopic Systems

Bioptic Systems

Sunfilters

Night Vision Scopes

Getting the Right Device(s)•Because there is such a variety of

devices 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.

What’s New in Low Vision Technology

Handheld Magnifying Cameras

•Miracle Mouse Electronic TV Magnifier

•MonoMouse-RM B&W Electronic Magnifier

•Max Digital Color Magnifier

•Primer 2 Color Electronic Magnifier

Traditional CCTV Video Magnifiers

•Desktop systems

•Variable Magnification

•Color, W/B, B/W

•Large Field of View

•Options

• Increased reading speed

• Increased duration

•Reduced visual effort

•Comfortable working position

Desktop Video Magnifiers

Integrated LCD Displays•Available from all major vendors

•Sizes: 17” to 24” + with WS

•Adjustable height screens

•High contrast

•Flicker free

• Improved response rates

•Well received by consumers

Integrated LCD Systems

Video Magnification

Systems•Variable Magnification

•Adjustable brightness

•Selectable contrast setting

•Wide field of view for better viewing abilities

Magnification

Brightness

Contrast

Windowing and Underlining

Portable Video Magnifiers

•More Compact, 7-inch screens

•Extensive reading tasks

•Two handed use

•Optelec Traveler

•FS Sapphire

•EV Amigo

•Fusion 7” LCD Portable Video Magnifier

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

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

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

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

Ash Technology Quicklook Focus

Desktop Video MagnifiersFeatures

•Full Size screen

•Full Features

•Remote Controllable

•Near and Distance Viewing

•For Classroom, Conference or In- Service Training Activities

•Transportable “Luggable”

•AC or optional battery

Vision Technology: VIEW

Enhanced Vision Acrobat

LCD

Onyx Deskset

Laptop Compatible Video Magnifiers

•Most students use laptop computers

•Video magnification could be helpful

•Portable camera using notebook display

Clarity PCMate

•Powered by USB

•Requires 2 USB 2 ports

• Sequence, setup

•Remote control camera

•Keyboard controlled software

Optelec ClearNote

• Ease of camera aiming

• Built in Light source

• Camera control positioning

• Keyboard controlled software

• Keyboard controlled camera

• Dolphin, Zoom Text compatible

Freedom Scientific Onyx PC Edition

•Swing arm and flex arm models

•Remote control

•MAGic with EyeMerge software included

•Camera can be powered by USB port

•Distance, desktop, self view modes

•Cost: $2895.00

Specialty Video Magnifiers

•Flipper

•Shoppa

Headborne Low Vision System

• Eyetonomy SightMate LV920

• www.vuzix.com/medical/lv920.html

• 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

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)

Assessment Factors

•Evaluation of visual functioning

•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

Types of Optical Devices

Near Devices

Stand Magnifier

Dome Magnifier

Illuminated Stand Magnifier

Hand Held Pocket Magnifier

Hand Held Illuminated

Microscopes or Reading Glasses

Types of Optical Devices

Distance Devices

Binoculars

Monocular

Full-Field Telescopic Systems

Bioptic Systems

Sunfilters

Night Vision Scopes

Getting the Right Device(s)•Because there is such a variety of

devices 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.

What’s New in Low Vision Technology

Handheld Magnifying Cameras

•Miracle Mouse Electronic TV Magnifier

•MonoMouse-RM B&W Electronic Magnifier

•Max Digital Color Magnifier

•Primer 2 Color Electronic Magnifier

Traditional CCTV Video Magnifiers

•Desktop systems

•Variable Magnification

•Color, W/B, B/W

•Large Field of View

•Options

• Increased reading speed

• Increased duration

•Reduced visual effort

•Comfortable working position

Desktop Video Magnifiers

Integrated LCD Displays•Available from all major vendors

•Sizes: 17” to 24” + with WS

•Adjustable height screens

•High contrast

•Flicker free

• Improved response rates

•Well received by consumers

Integrated LCD Systems

Video Magnification

Systems•Variable Magnification

•Adjustable brightness

•Selectable contrast setting

•Wide field of view for better viewing abilities

Magnification

Brightness

Contrast

Windowing and Underlining

Portable Video Magnifiers

•More Compact, 7-inch screens

•Extensive reading tasks

•Two handed use

•Optelec Traveler

•FS Sapphire

•EV Amigo

•Fusion 7” LCD Portable Video Magnifier

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

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

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

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

Ash Technology Quicklook Focus

Desktop Video MagnifiersFeatures

•Full Size screen

•Full Features

•Remote Controllable

•Near and Distance Viewing

•For Classroom, Conference or In- Service Training Activities

•Transportable “Luggable”

•AC or optional battery

Vision Technology: VIEW

Enhanced Vision Acrobat

LCD

Onyx Deskset

Laptop Compatible Video Magnifiers

•Most students use laptop computers

•Video magnification could be helpful

•Portable camera using notebook display

Clarity PCMate

•Powered by USB

•Requires 2 USB 2 ports

• Sequence, setup

•Remote control camera

•Keyboard controlled software

Optelec ClearNote

• Ease of camera aiming

• Built in Light source

• Camera control positioning

• Keyboard controlled software

• Keyboard controlled camera

• Dolphin, Zoom Text compatible

Freedom Scientific Onyx PC Edition

•Swing arm and flex arm models

•Remote control

•MAGic with EyeMerge software included

•Camera can be powered by USB port

•Distance, desktop, self view modes

•Cost: $2895.00

Specialty Video Magnifiers

•Flipper

•Shoppa

Headborne Low Vision System

• Eyetonomy SightMate LV920

• www.vuzix.com/medical/lv920.html

• 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

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)

Assessment Factors

•Evaluation of visual functioning

•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

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

Gene Therapy for retinal diseases

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

Dry AMD

Wet

Atrophic

So What Have We Learned?

Lory C. Snady-McCoy, MD

What defines macular degeneration?

Answers to Common Questions

What tests are used? Why are they necessary

in the diagnosis and management?

Not everything that looks like macular degeneration

is macular degenerationImportance of continued

monitoring and care50% chance of developing wet AMD

in fellow eye over 5 years

What Should I Eat?

•Foods rich in antioxidants may delay the progression of AMD

•Green leafy vegetables, berries, nuts, seaweed (?) Beta-carotene, omega 3 fatty acids, lutein

Which vitamins should I use?

•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

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

Is AMD hereditary? Are my children at risk?

•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

Known risk factors:

•Smoking, diet, exercise, obesity (BMI)

•Hypertension, Hypercholesterolemia

•Does this sound familiar??

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

Are there any new treatments in the making?

•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

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

PDT Laser/Visudyne

Argon/Krypton/Dye/Diode Laser

MacugenLucentis/AvastinEylea

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.

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

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

Congratulations!

You have now earned your

diploma!

So What Have We Learned?

Lory C. Snady-McCoy, MD

What defines macular degeneration?

Answers to Common Questions

What tests are used? Why are they necessary

in the diagnosis and management?

Not everything that looks like macular degeneration

is macular degenerationImportance of continued

monitoring and care50% chance of developing wet AMD

in fellow eye over 5 years

What Should I Eat?

•Foods rich in antioxidants may delay the progression of AMD

•Green leafy vegetables, berries, nuts, seaweed (?) Beta-carotene, omega 3 fatty acids, lutein

Which vitamins should I use?

•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

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

Is AMD hereditary? Are my children at risk?

•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

Known risk factors:

•Smoking, diet, exercise, obesity (BMI)

•Hypertension, Hypercholesterolemia

•Does this sound familiar??

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

Are there any new treatments in the making?

•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

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

PDT Laser/Visudyne

Argon/Krypton/Dye/Diode Laser

MacugenLucentis/AvastinEylea

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.

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

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

Congratulations!

You have now earned your

diploma!

• 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

Retinal Implant

ARGUS II Implant

60 electrodes (16 in ARGUS I)

250 electrode array in development

1000 electrode array on the drawing board

Subretinal implant

Microprocessor power

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

ACU-4429 - Acucela

Phase II granted fast track status

Fenretinide

Phase III began 2011

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

Emerging treatments for Dry

AMD•OT- 551 Antioxidant Eye drops

•Othera Pharmaceuticals/ National Eye Institute

•A Multicenter, Proof-Of-Concept Study Of Intravitreal AL-78898A In Patients With Geographic Atrophy

•Alcon

Human embryonic stem cells• Can differentiate into any

of 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

Stem Cell Research

• 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

Stem Cells – Current Problems

•Rejection

•Tumor formation

•Expense – producing and cultivating cell lines is costly

•Intellectual property rights

•Ethics

•No good animal models of macular degeneration