Overview of the development of Age related Macular...
Transcript of Overview of the development of Age related Macular...
Micronutrients and their effect on Age
Related Eye Diseases such as Age Related Macular Degeneration and Cataract
Ian Grierson, Angela Reidy, Simon Harding, Luminita Paraoan,
Carl Sheridan, Rachel Williams
Epivision, London;Department of Eye and Vision Science, Liverpool University and
St Paul’s Eye Unit
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The Eye
An extension of the brain
See with the brain
Each eye contains 1/3rd of
the bodies sensory neurons
Retina has huge oxygen
demand
Factory for converting light
to electric impulses
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Looking into the eye to see the retina – 140m rods and cones
Retinal nerve fibres track from the inner retina, via the LGN to the visual cortex.
Eye Diseases of Ageing
Glaucoma – neuro-degeneration of the retinal
ganglion cells (exacerbated by high eye pressure)
Cataract – opacity of the lens
Diabetic Eye Disease – complication of diabetes
associated with retinal vessel leakage and new
vessel formation.
Age Related Macular Degeneration (AMD) –
atrophic and neovascular forms of macular vision
loss.
ALL 4 ARE ASSOCIATED with a lack of crucial
ANTIOXIDANTS and OXIDATIVE DAMAGE
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Nutritional Association makes sense – is intervention proven for age-related chronic
eye diseases?
Age Related Macular Degeneration (AMD) – yes.
Cataract – not hopeful.
Glaucoma – the jury is still out.
Age-Related Macular Degeneration (AMD) – 3.3% of population over 65yrs
Two forms wet and Dry
Dry is more common
Wet is rapid and
blinding
Treatments for Wet but
not for Dry
Augood et al (2006) Arch Ophth 125; 529-535
Wet AMD Treatment St Paul’s Liverpool AntiVEGFs
1996 PDT introduced --- 120 episodes per year
1999 PDT part of clinical service --- 440 episodes per year
2003 Nice approved referral system --- 2,110 episodes per year
2006 Introduction Macugen, Avastin and Lucentis --- 5,440 episodes
per year
2015 Current activity --- 12,000 estimated episodes per year
Clear social and
financial need to better
understand disease
processes and
intervene effectively and
early for all AMD.
The AMD Effect – UK (RNIB Report 2010; Minassian, Reidy et
al (2010) BJO; Owen et al (2012) BJO)
2010
Numbers with early AMD
– 1,493,963
Numbers with
Geographic Atrophy –
132,970
Major Sight Loss AMD –
223,220
2020
Numbers with early AMD
– 1,821,434
Numbers with
Geographic Atrophy –
240,358
Major Sight Loss AMD –
291,982 (Model assumes 75% of NV-AMD will be treated)
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AMD Risk Factors
Age
Family history (genetics)
Gender – women
Race – caucasians
Hyperopia – long sightedness
Phototoxicity
Oxidative stress
High blood pressure
Body weight
Smoking
Alcohol - ?
Diet – key antioxidants
Inflammatory response
RNIB and
The Eye Book
(Grierson 2000)
Retinal Antioxidant defense provided by
Antioxidant vitamins – vitamins E, A and C
Xanthophylls - Lutein and Zeaxanthin
Omega 3 fatty acids - EPA, DHA
many others
Handelman and Dratz (1986) Adv Free Rad Biol Med 2; 1-89.
Antioxidant Vitamins in the Retina
Vitamin E – potent free radical scavenger throughout
retina and antioxidant protecting cell membranes
particularly in outer segment of photoreceptors.
Vitamin A – retinol converts to retinal in visual process.
Local antioxidant rich in RPE cells keeping them viable.
Vitamin C – very high concentrations in the normal retina
serving partly as antioxidant
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Berman (1987) Proc Doc Ophth 50; 163-167; Kagan et al (2012) Clin
Zanthophylls - Lutein and Zeaxanthin
Fat soluble yellow
plant pigments
Abundant in the
macula
Provided by diet
rich in fruit and
vegetables
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Lutein and Zeaxanthin
Protects macula against light-induced damage:
– Act as optic filters through which light passes before reaching
the photoreceptor cells. Lutein and zeaxanthin absorb blue light
(400-550 nm, peak at 460 nm) which is the most damaging
wavelength in the visible light spectrum.
Protects retina from free radicals:
– Act as antioxidant
• Quench singlet oxygen
• Interacts with free radicals
• Prevents lipid peroxidation
Beatty et al. The role of oxidative stress in the pathogenesis of age related macular degeneration. (2000) Surv Ophthalmol. 45: 115-134
Key Omega-3 Fatty Acids supplied by diet
Alpha linolenic acid (ALA) – found mainly in vegetable products such as rapeseed, canola and nut oils
Eicosapentaenoic acid (EPA) - found in oily fish
Docosahexanoic acid (DHA) – found in oily fish
DHA makes up 50-60%
of the total fatty acid
content within the rod
outer segments
In AMD, oxidative
modification of DHA is
more common compared
to normal aging eyes
Nutrition Statistics on 5 portions of fruit and veg per day.
Only between 15 and 28%
reach the 5 a day target
Merseyside 5 a day
averages 14% but drops to
6% in Liverpool.
The sad fact is that around
50% of us don’t even reach
2 portions per day.
Expenditure and Food Survey 2004
National Diet and Nutrition Survey 2014
Heart of Mersey Survey 2004
BLUE MOUNTAIN EYE STUDY (2,454 examined at 5 and 10 years)
Poor intake of vegetables
and fruit leading to low
levels of ocular antioxidants
is associated with elevated
risk of developing AMD.
Risk Ratio 0.66 (0.48 – 0.92)
Tan et al (2008) Ophthalmology 115; 334-341
Netherlands Dietary Antioxidant Study
Population based cohort study of
4,170 people with an average
age of 68yrs.
Used dietary questionnaires to
estimate antioxidant intake.
560 developed AMD over 6 yr
follow up.
Those with a high intake of foods rich in beta carotene, vitamins C
and E and zinc had a 35% lower
risk of developing AMD.
Nurses Health Study plus Health Professionals follow up Study
Participants were at least 50yrs
118,000 filled out questionnaire over 12-18 yr period.
Eating fruit protective against wet AMD.
>3 servings of fruit compared to <1.5 lowered their AMD risk significantly.
Dietry Fish and Omega 3 consumption -Odds Ratios for selected studies
Fish and Early AMD
Delcort (2007) – 0.64
Chua (2006) – 0.62
Amasson (2006) – 0.61
Mares-Perlman (1995) – 0.90
Heuberger (2001) – 1.00
Cho (2001) – 0.65
All Studies – 0.76 (0.64-0.90)
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Elaine W-T. Chong, et al Arch
Ophthalmol. 2008;126(6):826-833
Eric H Souled Touch Briefings, 2012 43-
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AREDS (Age related Eye Disease Study which ran between 1992-1998)
Multicenter (27 hospitals) interventional trial sponsored
by the NEI – 4,757 volunteers
Tested the formula below
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AREDS - findings
Did show that people with early AMD who took the
AREDS formula had a 25% less risk of developing
more severe sight threatening AMD.
Was not powered to examine whether the risk of
developing AMD in the first place was in any way
diminished.
No effect on cataract
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AREDS - problems
Very high levels of
micronutrients (b
carotene and
smoking; zinc and
irritable bladder)
Formula did not
contain lutein or
omega-3
Genetic risk groups
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The Age-Related Eye Disease Study 2 (AREDS2)
Study Design and Baseline Characteristics (AREDS2 Report Number 1)
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The AREDS2 Research Group*
Writing Committee: Emily Y. Chew, MD (Chair),1 Traci Clemons, PhD,2 John Paul SanGiovanni,
ScD,1 Ronald Danis, MD,3 Amitha Domalpally, MD,3 Wendy McBee, MS,2 Robert Sperduto, MD,2
Frederick L. Ferris, MD1
Ophthalmology (2012)
1. Study the effect of addition of 10mg Lutein and 2mg Zeaxanthin to AREDS
formula
2. Study the effects of addition of omega-3 to AREDS formula ( 350mg DHA
and 650mg EPA)
3. Study the effects of eliminating beta carotene from AREDS formula
4. Study the effects of reducing zinc from 80 to 50mg in original AREDS
formula
5. Study the effects on cataract
6. Validate the AMD grading scale
THE TRIAL EXAMINS THE ADDITION OR SUBTRACTION FROM THE ORIGINAL
FORMULA NOT THE EFFECTS OF NEW COMPONENTS ON THEIR OWN
AREDS2 findings – altered AREDS formula (reported 2013 onwards)
Xanthophylls reduced risk of AMD progression by 10% over and above the
AREDS formula effect in those with low
dietary Lutein
B carotene interferes with the Lutein
effect – gain of a further 10% (20%plus) if it
is removed
Zinc levels can be reduced
No benefit shown for omega 3 fatty acids
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New recommended AREDs formulation based on AREDs 2
500mg Vitamin C
400IU Vitamin E
25 or 50 mg Zinc
2mg copper
10mg Lutein (non
esterified)
2mg Zeaxanthin
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IMPACT of AREDS and Nutritional Studies on Eye Professionals
Survey of European Ophthalmologists in 2014 –
90% aware of AREDS
Important micronutrients – Lutein, omega 3 , zinc and
antioxidant vitamins.
Micronutrient advice now part of routine AMD management
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Aslam et al (2014) Clinical Ophth (open access)
Final Comment
Nutrition research has a lot still to do with respect to AMD and other age–related eye diseases.
Supplements and good diet both have a role in combating AMD.
Preventive measures make social and financial sense for common diseases like AMD.