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

1

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

2

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

5

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)

9

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

12

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)

20

Elaine W-T. Chong, et al Arch

Ophthalmol. 2008;126(6):826-833

Eric H Souled Touch Briefings, 2012 43-

47

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

21

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

22

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

23

The Age-Related Eye Disease Study 2 (AREDS2)

Study Design and Baseline Characteristics (AREDS2 Report Number 1)

24

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

25

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

26

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

27

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.