Nutrition and eye health:Eating for healthy eyes

Associate Professor Laura DownieBOptom, PhD(Melb), PGCertOcTher, FACO, FAAO, DipMus(Prac), AMusA

Dame Kate Campbell FellowLaboratory Head - Anterior Eye, Clinical Trials and Research Translation Unit

Department of Optometry and Vision Sciences, University of Melbourne

Disclosures

My research laboratory has received funding from Allergan, Alcon,

CooperVision and Azura Ophthalmics for anterior eye disease research, and

research laboratory infrastructure support from Medmont.

Learning objective

• To understand how diet and nutritional supplementation can

affect eye health.

Diet and general health

• A balanced diet is essential to staying healthy

• Australian Dietary Guidelines provide up-to-date advice on the amount and kind of foods to eat for general health and well-being, and to reduce risk of chronic disease

• Adherence is poor

• Inadequate intake of vegetables, fruit, wholegrain cereals, milk

• ~35% of daily energy intake derived from energy-dense, nutrition poor foods

https://www.eatforhealth.gov.au/guidelines

Nutrition and eye health

• “You are what you eat”… are “our eyes what we eat”?

• Diet and nutrition strongly influence eye health

Nutrition and eye health

• Evidence for an association between specific dietary patterns and a reduced risk of certain eye diseases

• Age-related macular degeneration

• Dry eye disease

• Cataract

• Glaucoma

Age-related macular degeneration

• Leading cause of irreversible vision impairment in developed countries

• 1.25 million Australians with AMD• 1 in 7 people >50 years

• Prevalence predicted to double over the next 20 years

• Non-modifiable

1. Age

2. Genetics: risk of developing AMD 3x higher with first-degree relative having AMD

• Modifiable1. Cigarette smoking: 2-4x risk of developing AMD; association between number of cigarettes smoked over time and risk of developing late-stage AMD.

2. Diet and Nutrition

• Foods rich in anti-oxidants proposed to limit photoreceptor damage at the macula

• Xanthophyll carotenoids: zeaxanthin and lutein

• Omega-3 fatty acids

AMD risk factors

• Lutein and zeaxanthin• Xanthophyll carotenoids present in human

macular pigment

• Plant pigments that must be ingested

• Roles: anti-oxidant protection, filtration of short-wavelength light, maintenance of structural integrity of cell membranes

• Omega-3 fatty acids• EPA + DHA

• DHA = component of lipid membranes in retinal photoreceptor outer segments

• EPA = anti-inflammatory

• Retinoprotective effects -> alter gene expression, cellular differentiation and cell survival

Key players: nutrition and AMD

• Eye disease case control study group (Seddon et al., JAMA, 1994)• People in highest quintile of dietary consumption of retinal carotenoids had a

43% lower risk of developing late AMD (n = 356 AMD vs 520 controls)

• AREDS report no. 2, Arch Ophthalmol, 2007

• Case-control study of AREDS participants (n = 4519) at baseline

• Dietary intake of lutein + zeaxanthin inversely correlated with the odds of developing nAMD

• Augood et al., Am J Nutr, 2008

• Eating oily fish ≥1 x per week (c/w <1 per week) associated with a halving of the odds of developing nAMD (n = 105 CNV vs 2170 controls)

Epidemiological evidence

• Routinely counsel patients about diet: 62%

• Routinely ask about nutritional supplement intake: 55%

• Routinely advise about nutritional supplement intake: 80%

11

• 2015 survey• Responses from

283 Australian optometrists

Do optometrists ask/advise about diet?

Do our patients expect us to ask/advise about diet?

• 2017 survey• Responses from

225 patients presenting for optometric care

What to recommend to patients?

• Eat dark green leafy vegetables and fresh fruit daily

• Eat a serving of oily fish 2-3x per week

• Choose low GI carbohydrates whenever possible

• Eat a handful of nuts a week

• Limit consumption of fats and oils.

What about supplements for AMD?

• High-dose anti-oxidant vitamin and mineral supplements

• Age-Related Eye Disease Studies

• Key findings

• AREDS (AREDS Study Group, Arch Ophthalmol, 2001)

• Potential benefit only in people with intermediate AMD

• risk progression to late AMD from 28% to 20% at 5

yrs

• AREDS2 (AREDS2 Study Group, JAMA Ophthalmol, 2013)

• Adding lutein + zeaxanthin, DHA + EPA or both, to the

AREDS formula did not further reduce the risk of

progression from intermediate to late AMD

AMD Classification

Definition(lesions assessed within two disc diameters

of the fovea in either eye)

Evidence?

No aging changes No drusen and no AMD pigmentaryabnormalities

Evidence for NO benefit

Normal aging changes

Only drupelets (small drusen ≤63µm) and no AMD pigmentary abnormalities

Evidence for NO benefit

Early AMD Medium drusen (>63µm and ≤125µm) and no AMD pigmentary abnormalities

Evidence for NO benefit

Intermediate AMD Large drusen (>125µm) and/or any AMD pigmentary abnormalities

Yes* (AREDS, AREDS2)* Risk vs benefit (former/current smoker)

Late AMD Neovascular AMD and/or any geographic atrophy

N/A

What about supplements for AMD?

Key points: AMD and nutrition

• Diet is a key modifiable risk factor for AMD development and progression

• Opportunity for optometrists to provide general advice (and evidence-based

information) about dietary patterns that can reduce AMD risks

• High-dose anti-oxidant nutritional supplementation may be of benefit in

specific high-risk populations

• Sub-types

• Evaporative

• Aqueous deficient

• Features

• Reduced tear stability

• Elevated tear tonicity

(hyperosmolarity)

• Ocular surface injury (damage)

• Treatments

• Supportive (non-curative)

• Therapeutic

High evaporation

Low aqueous production

↑ Tear osmolarity

Inflammatory cascades

Inflammatory cytokines

Apoptosis of ocular surface

cells

↓ Epithelial and goblet

cells

↓ Tear film stability

Dry eye disease

Adapted from: International Dry Eye Workshop (DEWS II) Report 2017; Ocular Surface.

Loss of tearhomeostasis

Dry eye management

Key management recommendations

• Primary goal of DED management is to restore homeostasis to

the ocular surface

• Chronic sequelae, rather than short-term treatments

• Management is complicated, due to multifactorial aetiology

• Requires multifaceted approach

Step 1 Step 2 Step 3 Step 4

• Education• Environmental / dietary modifications, including omega-3 supplementation• Eliminate offending systemic medications• Artificial tear substitutes, gels / ointments• Eyelid therapy

If Stage 1 options are inadequate, consider:• Non-preserved ocular lubricants to minimise preservative-induced toxicity• Tea tree oil treatment for Demodex (if present)• Tear conservation• Overnight treatments (such as ointment or moisture chamber devices)• In-office, physical heating and expression of the meibomian glands• Prescription drugs

If Stage 2 treatments are inadequate, add:• Oral secretagogues• Autologous/allogeneic serum eye drops• Therapeutic contact lenses (soft bandage; rigid scleral lenses)

If Stage 3 treatments are inadequate, consider• Topical corticosteroid for longer duration• Amniotic membrane grafts• Surgical punctal occlusion• Other surgical approaches

Staged management algorithm

Step 1 Step 2 Step 3 Step 4

• Education

• Environmental / dietary modifications, including omega-3 supplementation• Eliminate offending systemic medications• Artificial tear substitutes, gels / ointments• Eyelid therapy

If Stage 1 options are inadequate, consider:• Non-preserved ocular lubricants to minimize preservative-induced toxicity• Tea tree oil treatment for Demodex (if present)• Tear conservation• Overnight treatments (such as ointment or moisture chamber devices)• In-office, physical heating and expression of the meibomian glands• Prescription drugs

If Stage 2 treatments are inadequate, add:• Oral secretagogues• Autologous/allogeneic serum eye drops• Therapeutic contact lenses (soft bandage; rigid scleral lenses)

If Stage 3 treatments are inadequate, consider• Topical corticosteroid for longer duration• Amniotic membrane grafts• Surgical punctal occlusion• Other surgical approaches

Staged management algorithm

Essential fatty acids

Type Name of fatty acid Common food sources

Omega-3 SHORT CHAIN:Alpha-linolenic acid (ALA)

LONG CHAIN:Eicosapentaenoic acid (EPA) Docosahexaenoic acid (DHA)

Flaxseed, Canola oil,Soybean oil, Chia seeds, Walnuts

Oily fish (salmon, trout, sardines, mackerel, swordfish, tuna), Shellfish

Omega-6 Linoleic acid (LA)

Arachidonic acid (AA)

Soybean oil, Safflower oil, Corn oil

Meat, Poultry, Eggs

Can only be obtained from diet and/or supplementation

Omega-3 fatty acids: biological effects

Eicosanoids

Resolvins

Protectins

Anti-inflammatory

Neuroprotective

Anti-inflammatory

5 – 20%

Omega-3s and health

• Ratio of consumed ω-6:ω-3 influences systemic

inflammatory status

• Western diets: > 15:1 vs Ideal: ≤ 4:1

• Diets rich in ω-3s:

• Risk coronary heart disease, mortality, stroke

• Risk late-stage AMD

• Dry eye disease

• Diets low in ω-3s or high ω-6:ω-3 ratio = risk

• 30% risk with each additional gram/day of

consumed ω-3 fatty acids

Omega-3s: how much do we need?

500 mg/day of long-chain omega-3s

~2 servings (100 g/serving) oily fish per week

• 80% of Australians do not meet this recommendation

• Upper safety limit: 3000mg / day (food + supplements)

• Important to:• Quantify dietary (baseline) intake

• Consider GH before recommending supplements• Medical contraindications• Bleeding risks

Zhang et al. (2019) Nutrients

Omega-3s: what are optometrists doing in practice?

Ceecee Zhang

Optometrists’ general clinical approach to omega-3 fatty acids for

improving eye health

I recommend for my patients to consume omega-3s 79%

I do not make recommendations relating to omega-3s 21%

I recommend my patients not to consume omega-3s 0%

Omega-3s: what are optometrists doing in practice?

Supplement dose: Median: 2000 mg; range: 250 mg to 6000 mg per day

53% of optometrists aware that omega-3 supplements have potential side effects

Omega-3s: what are optometrists doing in practice?

How can we measure omega-3 levels in clinical practice?

• Blood spot tests

• Dietary questionnaires (dietary records, food-frequency questionnaires)

• Almost no respondents used a quantitative tool to survey patients’ baseline dietary intake of omega-3s

Omega-3s: what are optometrists doing in practice?

Omega-3 dietary intake

!

!

OMEGA PROFILE

DBS-Omega-3 Index = 6.9%

An Omega-3 Index of 8% and above is desirable and should be the target for everyone. An Omega-3 Index

level >8% means that you have low risk for developing heart disease in future.

Your omega 3 index is below the target. This can be improved by increasing your omega 3 intake

through an increase in fish consumption or an increased intake of fish oil supplements.

DBS-Omega6/3 Ratio = 5.2

The desirable target Omega 6/3 ratio of less than 4. This is also a good indicator of predicting cardiovascular

health. Higher the ratio, greater is the risk.

Your omega 6/3 ratio is above the threshold; you should increase your intake of foods rich in omega-3 fats

such as oily fish and/or dietary fish oil and reduce intake of vegetable oil, margarine and Omega-6 rich

foods.

DBS-AA/EPA Ratio = 6.5

An AA/EPA Ratio between 1.5 and 3 is desirable and should be the target for everyone. The AA/EPA ratio is

an indicator of chronic inflammation which may play a role in causing several conditions such as

hypertension, high cholesterol and diabetes. Your AA/EPA ratio is above the threshold. You need to increase intake of omega 3 rich foods, reduce your

intake of vegetable oil, margarine and Omega-6 rich foods

Name: Laura Downie

I.D Number: XXXX

Collection Date: 13 January 2017

Result Date: 9 February 2017

6.9%

6.5

5.2

CODS: Clinical Omega-3 Diet Survey

Compared CODS with omega-3 estimations from (n=40):

• Systemic fatty acid marker (Dried Blood Spot test)

Food nutritional information from the AUSNUT (2011–2013) database

CODS: Clinical Omega-3 Diet Survey

33

(%)

8%

550 mg/day

CODS: Clinical Omega-3 Diet Survey

CODS is a useful tool for estimating the sufficiency of a persons’ dietary omega-3 intake

Omega-3 index vs CODS

What about omega-3 supplements?

What about omega-3 supplements?

• Multiple small, short-term (1-12m) trials• Dose: 600 – 1800mg/day (combined EPA and DHA)

• Mostly positive findings with respect to symptoms and signs

• High dose

• ‘Real world’ trial

• Unrestricted use of

anti-inflammatories

• Changed therapies

during study

• Moderate-to-severe

dry eye, based upon

symptoms

Omega3-s: the (current) verdict

Review included:

• Data from 34 randomisedcontrolled trials

• 4,314 dry eye participants• Spectrum of doses and

formulations (135mg to 3000mg EPA+DHA/day)

Considerations

• Optimal dose and formulation is unclear• Dry eye subtype recommendations are not known

Long chain versus short-chain? Long-chain form is preferable

Formulation? Ethyl ester versus re-esterified triglyceride forms

Dose? 1000mg EPA + 500mg DHA… how many capsules per day?

Duration? Ocular effects take ~3 months

Storage? Temperature <25°C, check expiration date, Vitamin E (anti-oxidant) should be incorporated.

Choosing an omega-3 supplement

Clinical considerations

Key points: Omega-3s and dry eye disease

• Patient dietary intake of omega-3 EFAs should be routinely captured

• Increasing omega-3 intake (if appropriate) is a first-line therapy for dry eye

disease:

• Restores tear film and ocular surface homeostasis

• Range of health benefits

• Dose and composition are important

• Time-course for dry eye symptomatic improvement is ~3 months