a journey through the eye macular degeneration dr dianne sharp ophthalmologist retina specialists,...
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A Journey through the Eye
Macular Degeneration
Dr Dianne SharpOphthalmologistRetina Specialists, Auckland
What is the Macula?
Normal Retina
macula
retinaopticnerve
• Progressive, chronic disease of central retina
• Loss of central vision
• Peripheral vision not affected
• Not black blind
What is Macular Degeneration (AMD)?
Leading cause of severe vision loss
Macular Degeneration in New Zealand
MacularDegeneration
Glaucoma
Cataract
Other
Macular DegenerationFacts and Figures
• Deloitte Access Economics 2011 and Macular Degeneration Foundation Australia
www.mdfoundation.com.au
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 way:1
o 170,000 have early MD in NZ
o 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
Prevalence of chronic diseasesAustralia 2010 – ref Deloitte
2x
2x
4 to 8x
3x
Risk of falls
Risk of depression
Risk of hip fracture
Rate of social dependence
3yr Nursing home admission
Employment
The Impact of Macular Degeneration*
• Access Economics & AMDAI 2010.
The impact of MD on quality of life is equivalent to cancer or coronary heart disease.
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,
Optimal integrated model of care for Macular Degeneration (AMD)
1. Primary prevention2. Early detection & timely diagnosis3. Early & regular treatment with on-going
monitoring for wet AMD4. Rehabilitation & emotional support
Macular Degeneration symptoms
How does MD Develop?
MaculaRetinaRPEChoroid
Normal Retina
RETINA
CHOROID
RPE
Healthy retina
Bruch’s membrane
Early AMD -“Drusen”
Normal Retina
Drusen
Early AMD
Drusen
Early AMD
•Normally no symptoms but at risk of progression•Lipid deposits (drusen)•No treatment but progression slowed by diet and lifestyle modifications
Early Stages of MD
Dry AMDDrusen Atrophy 7rs later
Dry 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
Late Stages of AMD
Wet AMD
Advanced Wet AMD
Wet AMD
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
Late Stages of MD
Visual impairment by severity of vision loss
Optimal integrated model of care for Macular Degeneration (AMD)
1. Primary prevention2. Early detection & timely diagnosis3. Early & regular treatment with on-going
monitoring for wet AMD4. Rehabilitation & emotional support
Risk Factors for MD
AgeAge
Prevalence AMD (%) Blue Mountains Eye Study
Age group
Early AMD
Dry Late AMD
Wet Late AMD
All Late AMD
50-59 yr 6% <0.5% <0.5% <0.5%60-69 yr 11% <0.5% 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%
% Prevalence AMD by age
Risk Factors for MD
GeneticsGenetics
• 50 -70% cases have a genetic link
• 50% risk of MD if a direct family history
AMD Principal genes CFH & ARMS2
Rotterdam 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
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
Modifying Genetic Risk Factors
SmokingWith 1 CFH allele Risk of AMD:Non smokers risk 12x Smokers risk 34x
Diet1 CFH &/or ARMS2 allele
High dose Zn, omega 3, lutein rate close to no genetic risk
Risk Factors for MDSmokingSmoking
Smoking increases risk 3 to 4 times Smokers get MD 10 years earlier, on average BUT 20 years after quitting, a smoker’s risk is
the same as a non-smoker
• Eye test every 2 years or earlier if any new symptoms
• Recommend family members have eye test.
• Protect eyes from sun
• Healthy lifestyle:o Control weighto Exerciseo Eat eye health foodso Consider a supplement
Reduce Your Risk of MD
Eating for Eye HealthLutein
Dark green and naturally yellow vegetables and fruit
every day
Fish 2-3 times per week(salmon, sardines, mackerel, anchovies, tuna)
Eating for Eye HealthOmega 3
Handful of nuts per week(brazil nuts, almonds, walnuts, pine nuts)
Limit fat intake
Eating for Eye Health
Low Glycaemic Index foodsLow GI Foods
• Break down more slowly
• Prolong energy release
• Leave less waste products in the eye
3 key supplements to consider:
• AREDS formulation
• Lutein
• Omega 3 (fish oil)
What supplements?
Per day• Zinc 80mg • Vitamin C 500mg• Vitamin E 400IU• Copper 2mg• ß-carotene 15mg
AREDS Formula Age Related Eye Disease Study
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.
Macu-Vision
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
Optimal integrated model of care for Macular Degeneration (AMD)
1. Primary prevention2. Early detection & timely diagnosis3. Early & regular treatment with on-going
monitoring for wet AMD4. Rehabilitation & emotional support
Symptoms of Macular Degeneration
Early stageso Early MD may be asymptomatic.
Eye tests are the key.
Late stages
o Difficulty distinguishing faces
o Difficulty reading & fine vision
o Distortion (straight lines appear wavy or bent)
o Dark / blank patches in central vision
Use an Amsler grid (one eye at a time)
Normal Lines distorted Dark patches or empty spaces
Chronic disease• Dry AMD: diet and lifestyle important
• Wet AMD: treatment available•diet and lifestyle also important
Treatments for AMD
Treatment for Wet MD• Injection Lucentis or
Avastin into the eye
• Average every 4–6 weeks
• Early treatment saves sight! Aim to stabilise vision and prevent further vision loss.
***p<0.0001 vs. sham
2 4 6 8 10 12 14 16 18 20 22 24
sham -3Month
-3
-2
-1
0
1
2ANCHOR +2
MARINA +1.5
PDT -2
Lin
es o
n v
isio
n c
har
t
AMD Treatment Trials (Anchor & Marina)Lucentis treatment: Mean gain in vision over 2yr
Current drug treatments
• Lucentis or Avastino Normally given as monthly injectionso Highly effective.
• CATT study: Comparing Lucentis and Avastino Similar effect at 24 monthso Still some unanswered questions re adverse
events with Avastin
Optimal integrated model of care for Macular Degeneration (AMD)
1. Primary prevention2. Early detection & timely diagnosis3. Early & regular treatment with on-going
monitoring for wet AMD4. Rehabilitation & emotional support
AMD treatment trials (PIER) Subset analysis highlights need for individualised
dosing
No initial gain (no gain at month 3) (n=21, 34% total)
Initial gain not maintained(n=24, 40% total & 60% initial gainers)
Maintained initial gain (>0 at month 3)(n=16, 26% total & 40% initial gainers)
Mean (SE) change in BCVA from baseline (letters)
Month0 1 2 3 4 5 6 7 8 9 10 11 12
-15
-10
-5
0
5
10
15
BCVA, best corrected visual acuity
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
Wet AMD: New treatments• VEGF Trap-Eye
o Similar effect to Lucentis / Avastino lasts two monthso Available later this year in NZ
• Pazopanib (Eye drop)o Used with anti-VEGF injections to help spread
number of injectionso In phase 3 trials
Dry AMD: New treatments
• FenretinideA tablet, derived from Vitamin A
• Slows development of drusen• Reduces risk of wet AMD by 2 fold• In phase 3 trials
• BrimonidineAn implant inside eye
• May protect against late dry AMD• In phase 2 trials
Laser for early (dry) AMD
• Ellex 2RT (Laser)oUltra-short duration, non-thermal laser o Appears to reduce formation of drusenoMay improve waste transport in retina
o Trials ongoing
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.
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
Retinal cell transplantation
• Many animal studies, some human studies
• Only limited efficacy reported
• Very difficult surgery
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.
Stem cell treatment
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.
Pathogenesis of AMD for future treatments
Early AMD: Drusen OCT
Infra redAuto fluorescence
Anti-inflammatory
Pro-inflammatory
Normal
AMD
Drusen
Complement inflammation pathways
Membrane Attack Complex
Rattner and Nathans 7, 860–872 (November 2006) | doi:10.1038/ nrn2007
Complement mediated inflammation in AMD
Anti-C5b-9 Membrane Attack Complex
C5 cleavage products beneath RPE.
Drusen contain almost all alternative complement pathway proteins
Complement inflammation pathways
CFH
CFB
Exercise
Complement inflammation pathways
CFH
Tobacco CFB
Exercise
CFH
Complement inflammation pathways
CFH
Tobacco CFB
Exercise
CFH
High fat intake
Complement inflammation pathways
CFH
Tobacco
HDL
CFB
Exercise
CFH
High fat intake
Membrane Attack Complex
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.
Potential Targets for AMD Therapy
Membrane Attack Complex
AMD is a complex disease
• Medical research takes time and vast amounts of money.oNew drug: 12 years and $500m - $1.2 billion oOther research:
New mechanisms Identify risk and protective factors
• More research is needed!
Optimal integrated model of care for Macular Degeneration (AMD)
1. Primary prevention2. Early detection & timely diagnosis3. Early & regular treatment with on-going
monitoring for wet AMD4. Rehabilitation & emotional support
Optimal integrated model of care for Macular Degeneration (AMD)
1. Primary prevention2. Early detection & timely diagnosis3. Early & regular treatment with on-going
monitoring for wet AMD4. Rehabilitation & emotional support
Our Vision:
To reduce the incidence and impact
of
Macular Degeneration in New Zealand
Our Objectives
• Education
• Awareness
• Representation
• Research
• Support Services
The Ageing Eye: Integrated Care
GP
Optometrist Ophthalmologist
The Ageing Eye: Integrated Care
GP
Optometrist Ophthalmologist