Macular Degeneration Foundation

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Macular Degeneration
A Journey through the Eye
Dr Dianne Sharp Ophthalmologist Retina
Specialists, Auckland
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What is the Macula?
optic nerve
retina
macula
Normal Retina
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What is Macular Degeneration (AMD)?

• Progressive, chronic disease of central retina
• Loss of central vision
• Peripheral vision not affected
• Not black blind

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Macular Degeneration in New Zealand

• Leading cause of severe vision loss

Other
Macular Degeneration
Cataract
Glaucoma
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Macular DegenerationFacts and Figures

• Deloitte Access Economics 2011 and Macular
  Degeneration Foundation Australia
• www.mdfoundation.com.au

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Macular Degeneration in NZAustralian pop 22
million NZ pop 4.4million approx. 1/5th

• Macular Degeneration (MD) is a chronic disease
  with no cure1
• Cause of up to 50 of all blindness
• Affects 1 in 7 people over 50 in some way1
• 170,000 have early MD in NZ
• 33,400 have late MD in NZ. 7,000 are legally
  blind.
• 1 in 4 people over 80 have vision loss from MD1
• The number of people with MD will increase by 70
  by 20301 

¹ Deloitte Access Economics
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Prevalence of chronic diseasesAustralia 2010
ref Deloitte
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The Impact of Macular Degeneration
The impact of MD on quality of life is equivalent
to cancer or coronary heart disease.

• Access Economics AMDAI 2010.

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Cost of vision loss from Macular Degeneration

• AU2.55 billion in 2010 in Australia
• NZ 0.64 billion in NZ
• (Adjusted for population and currency)

Deloitte Access Economics Macular Degeneration
Foundation 2011,
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Optimal integrated model of care for Macular
Degeneration (AMD)

1. Primary prevention
2. Early detection timely diagnosis
3. Early regular treatment with on-going
   monitoring for wet AMD
4. Rehabilitation emotional support

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Macular Degeneration symptoms
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How does MD Develop?
Normal Retina
Macula Retina RPE Choroid
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Healthy retina
RETINA
RPE
Bruchs membrane
CHOROID
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Early AMD -Drusen
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Early AMD
Drusen
Normal Retina
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Early AMD
Drusen
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Early Stages of MD

• Normally no symptoms but at risk of progression
• Lipid deposits (drusen)
• No treatment but progression slowed by diet and
  lifestyle modifications

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Dry AMDDrusen Atrophy
7rs later
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Dry AMD
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Late Stages of AMD

• Dry AMD
• Atrophy of retinal tissue.
• Gradual loss of central vision over years
• end stage has significant vision loss
• Wet AMD
• Formation leaky blood vessels under retina
• Rapid loss central vision

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Wet AMD
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Advanced Wet AMD
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Wet AMD
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Late Stages of MD

• Dry MD
• Atrophy of retinal tissue.
• Gradual loss of central vision over years
• end stage has significant vision loss
• Wet MD
• Formation leaky blood vessels under retina
• Rapid loss central vision over weeks or
  months

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Visual impairment by severity of vision loss
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Optimal integrated model of care for Macular
Degeneration (AMD)

1. Primary prevention
2. Early detection timely diagnosis
3. Early regular treatment with on-going
   monitoring for wet AMD
4. Rehabilitation emotional support

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Risk Factors for MD
Age
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Prevalence AMD () Blue Mountains Eye Study
Age group Early AMD Dry Late AMD Wet Late AMD All Late AMD
50-59 yr 6 lt0.5 lt0.5 lt0.5
60-69 yr 11 lt0.5 0.5 0.5
70-79 yr 20 1 2 3
80-89 yr 25 3 7 10
90 yr 35 18 13 31
All 50 yr 13 0.7 1.5
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Prevalence AMD by age
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Risk Factors for MD
Genetics

• 50 -70 cases have a genetic link
• 50 risk of MD if a direct family history

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AMD Principal genes CFH ARMS2Rotterdam Eye
Study

• Early AMD 75 had one risk allele
• Late AMD 93 had one risk allele
• Risk of developing AMD by 85yrs increases with
  number of alleles

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Genetics Risk Alleles

• CFH
• Mainly dry AMD
• Inhibitory effect on complement pathway
• ? Less effective inhibition of inflammatory
  pathway

• ARMS2
• Mainly wet MD
• Gene located in mitochondria
• ? Interferes with normal oxidation

Rotterdam Eye Study
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Modifying Genetic Risk Factors

• Smoking
• With 1 CFH allele
• Risk of AMD
• Non smokers risk 12x
• Smokers risk 34x

• Diet
• 1 CFH /or ARMS2 allele
• High dose Zn, omega 3, lutein rate close to no
  genetic risk

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Risk Factors for MD
Smoking

• Smoking increases risk 3 to 4 times
• Smokers get MD 10 years earlier, on average
• BUT 20 years after quitting, a smokers risk is
  the same as a non-smoker

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Reduce Your Risk of MD

• Eye test every 2 years or earlier if any new
  symptoms
• Recommend family members have eye test.
• Protect eyes from sun
• Healthy lifestyle
• Control weight
• Exercise
• Eat eye health foods
• Consider a supplement

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Eating for Eye Health Lutein
Dark green and naturally yellow vegetables and
fruit every day
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Eating for Eye Health Omega 3

• Fish 2-3 times per week
• (salmon, sardines, mackerel, anchovies, tuna)

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Eating for Eye Health

• Handful of nuts per week
• (brazil nuts, almonds, walnuts, pine nuts)
• Limit fat intake

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Low Glycaemic Index foods
Low GI Foods

• Break down more slowly
• Prolong energy release
• Leave less waste products in the eye

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What supplements?

• 3 key supplements to consider
• AREDS formulation
• Lutein
• Omega 3 (fish oil)

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AREDS Formula Age Related Eye Disease Study

• Per day
• Zinc 80mg
• Vitamin C 500mg
• Vitamin E 400IU
• Copper 2mg
• ß-carotene 15mg

Macu-Vision
Daily dose 2 tablets
People who smoke, suffer from lung cancer or
asbestosis should not take a supplement with
beta-carotene. This is the reason it is removed
from most AREDS supplement products.
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Diet supplements

• AREDS Formulation for intermediate or late AMD
  in one eye, reduces risk of progression by 20-25
• AREDS 2 trial in progress. Reducing Zn, removing
  beta-carotene, addition Lutein

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Optimal integrated model of care for Macular
Degeneration (AMD)

1. Primary prevention
2. Early detection timely diagnosis
3. Early regular treatment with on-going
   monitoring for wet AMD
4. Rehabilitation emotional support

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Symptoms of Macular Degeneration

• Early stages
• Early MD may be asymptomatic. Eye tests are the
  key.
• Late stages
• Difficulty distinguishing faces
• Difficulty reading fine vision
• Distortion (straight lines appear wavy or bent)
• Dark / blank patches in central vision

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Use an Amsler grid (one eye at a time)
Lines distorted
Dark patches or empty spaces
Normal
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Treatments for AMD

• Chronic disease
• Dry AMD diet and lifestyle important
• Wet AMD treatment available
• diet and lifestyle also important

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Treatment for Wet MD

• Injection Lucentis or Avastin into the eye
• Average every 46 weeks
• Early treatment saves sight! Aim to stabilise
  vision and prevent further vision loss.

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AMD Treatment Trials (Anchor Marina)Lucentis
treatment Mean gain in vision over 2yr
0
ANCHOR 2
2
MARINA 1.5
1
0
2
4
6
8
10
12
14
16
18
20
22
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Lines on vision chart
-1
PDT -2
-2
sham -3
-3
Month
plt0.0001 vs. sham
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Current drug treatments

• Lucentis or Avastin
• Normally given as monthly injections
• Highly effective.
• CATT study Comparing Lucentis and Avastin
• Similar effect at 24 months
• Still some unanswered questions re adverse events
  with Avastin

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Optimal integrated model of care for Macular
Degeneration (AMD)

1. Primary prevention
2. Early detection timely diagnosis
3. Early regular treatment with on-going
   monitoring for wet AMD
4. Rehabilitation emotional support

51
AMD treatment trials (PIER) Subset analysis
highlights need for individualised dosing
Maintained initial gain (gt0 at month 3)(n16,
26 total 40 initial gainers)
Initial gain not maintained (n24, 40 total
60 initial gainers)
No initial gain (no gain at month 3) (n21, 34
total)
BCVA, best corrected visual acuity
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New Therapies on horizon

• Treatments that allow decreased Rx frequency
• Improved drug delivery methods (drops, oral)
• Therapies allowing self monitoring rather than
  doctor visits
• Combined drug therapies ?improve efficacy
  decreasing Rx burden
• Drugs that reverse disease process

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Wet AMD New treatments

• VEGF Trap-Eye
• Similar effect to Lucentis / Avastin
• lasts two months
• Available later this year in NZ
• Pazopanib (Eye drop)
• Used with anti-VEGF injections to help
  spread number of injections
• In phase 3 trials

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Dry AMD New treatments

• Fenretinide
• A tablet, derived from Vitamin A
• Slows development of drusen
• Reduces risk of wet AMD by 2 fold
• In phase 3 trials
• Brimonidine
• An implant inside eye
• May protect against late dry AMD
• In phase 2 trials

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Laser for early (dry) AMD

• Ellex 2RT (Laser)
• Ultra-short duration, non-thermal laser
• Appears to reduce formation of drusen
• May improve waste transport in retina
• Trials ongoing

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Gene therapy for wet AMD

• Gene therapy inserts a normal gene into cells
  to replace disease-causing genes.
• RetinoStat gene-therapy to stop new blood
  vessel formation.
• Early clinical trials.

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When retinal cells die

• Treatments that could directly replace lost
  retinal cells
• RPE cell transplantation from donor
• Stem Cell treatment
• Artificial (bionic) vision
• Only useful if total vision loss

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Retinal cell transplantation

• Many animal studies, some human studies
• Only limited efficacy reported
• Very difficult surgery

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Stem cells

• Stem cells have the ability to develop into
  different types of adult cells such as
  photoreceptor cells or RPE cells
• Possible sources Embryonic stem cells (Most
  adaptable), Adult stem cells (more restricted)

Please note MDNZ recognises and respects
different points of view concerning stem cell
research. Our role is to simply report on all
research occurring for your information.
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Stem cell treatment
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Artificial vision Bionic eyes

• An electronic prosthesis to replace the function
  of dead retinal cells.
• NOTE
• Current bionic eyes provide MUCH LESS vision
  than most people with end stage AMD already
  possess.

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Pathogenesis of AMD for future treatments
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Early AMD Drusen
OCT
Auto fluorescence
Infra red
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Normal
Anti-inflammatory
AMD
Pro-inflammatory
Drusen
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Complement inflammation pathways
Membrane Attack Complex
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Complement mediated inflammation in AMD
Drusen contain almost all alternative complement
pathway proteins
C5 cleavage products beneath RPE.
Anti-C5b-9 Membrane Attack Complex
Rattner and Nathans 7, 860872 (November 2006)
doi10.1038/ nrn2007
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Complement inflammation pathways
Exercise
CFB
CFH
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Complement inflammation pathways
Exercise
Tobacco
CFB
CFH
CFH
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Complement inflammation pathways
Exercise
Tobacco
CFB
CFH
CFH
High fat intake
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Complement inflammation pathways
Exercise
Tobacco
CFB
CFH
CFH
High fat intake
HDL
Membrane Attack Complex
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INTERACTION OF ENVIRONMENTAL AND GENETIC RISK
FACTORS IN AMD

• Risk of AMD
• Genetic and environmental risk factors are not
  merely additive
• Resultant risk in some cases is greater than that
  conferred by each risk factor individually.

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Potential Targets for AMD Therapy
Membrane Attack Complex
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AMD is a complex disease

• Medical research takes time and vast amounts of
  money.
• New drug 12 years and 500m - 1.2 billion
• Other research
• New mechanisms
• Identify risk and protective factors
• More research is needed!

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Optimal integrated model of care for Macular
Degeneration (AMD)

1. Primary prevention
2. Early detection timely diagnosis
3. Early regular treatment with on-going
   monitoring for wet AMD
4. Rehabilitation emotional support

75
Optimal integrated model of care for Macular
Degeneration (AMD)

1. Primary prevention
2. Early detection timely diagnosis
3. Early regular treatment with on-going
   monitoring for wet AMD
4. Rehabilitation emotional support

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• Our Vision
• To reduce the incidence and impact of
• Macular Degeneration in New Zealand

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Our Objectives

• Education
• Awareness
• Representation
• Research
• Support Services

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For more information

• 0800 MACULA
• Free call, NZ-wide
• Web www.mdnz.co.nz

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The Ageing Eye Integrated Care
GP
Optometrist
Ophthalmologist
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The Ageing Eye Integrated Care
GP
Optometrist
Ophthalmologist