S1W7: AMD-non LV considerations

What is the relationship between nutrition and AMD according to oxidative stress theory?

• Oxidative stress theory = most popular explanation

• Research focuses on antioxidant therapy to reduce circulation of ROS

• Antioxidants linked with risk reduction:

  • Vitamins C and E

  • Zinc

  • Omega-3 fatty acids

  • Carotenoids (xanthophylls and carotenes)

• Largest related clinical trials: AREDS I and II

What is the role of Vitamin C in AMD management?

• Water-sol antioxidant -protects against free radical damage

• Acts as an e- donor, interrupting oxidative proc’s

  • e.g citrus fruits, tomatoes, green peppers, broccoli, cauliflower

• Often administered alongside other vits + minerals

• AREDS I: showed reduced risk of progression to advanced AMD after 6.3 years in those w/ existing AMD

  • Results came from a well-nourished population; outcomes may differ in other groups

What is the role and evidence for Vitamin E in AMD?

• Group of 8 fat-soluble compounds w/ antioxidant ability

• Key function: stops ROS production when fats undergo oxidation

• e.g almonds, safflower oil, corn oil

• Women’s Health Study: no signif reduction in visually signif or advanced AMD vs placebo

What did the Cochrane review find?

Vitamin E

• Vitamin E + beta-carotene does not delay or prevent AMD onset

• Highlighted that vitamin supplements may also have harmful effects

What is the role of Zinc in ocular health and AMD?

• Mostly found in retina + choroid

• Acts as a cofactor for antioxidant enzymes

• Helps transport vitamin A to the retina, necessary for melanin production

• Not produced by the body → must be obtained through diet, supplements, or fortified foods

  • e.g red meat, seafood, poultry, eggs, wheat germ, mixed nuts, black-eyed peas, tofu, beans

Where is zinc found in the human body and how is it taken up?

• Human body contains ~2–3 g zinc

• Found in muscle + bone

• Oral uptake occurs via small intestine

• Distributed by serum, most zinc bound to proteins (albumin, transferrin, p-macroglobulin)

• Uptake can also occur by inhalation + through the skin

What factors affect zinc levels, and what issues can arise from supplementation or diet?

• High supplemental zinc dosage can lead to copper deficiency due to competitive absorption

• Diet surveys show low zinc intake in the elderly, irrespective of country

  • Causes incl:

    • reduced consumption of zinc-rich foods (e.g., red meat)

    • reduced absorption w/ older age

What are the key types and functions of PUFAs relevant to ocular health?

• 2 groups: Omega-3 + Omega-6 PUFAs

• DHA:

  • major dietary + structural omega-3 long-chain PUFA, predominantly present in disc mem’s of PR’s

• EPA :

  • thought to have anti-inflammatory properties

• Rich omega-3 sources

  • e.g flaxseeds, walnuts, sardines, and salmon

How are PUFAs linked to AMD risk, and what considerations affect serum lipid interpretation?

• High dietary intake of omega-3 FA’s =assoc’d w/ a reduction in risk of late AMD

• AREDS 2 reported no additional risk reduction in progression of advanced AMD

• Serum lipid levels must be interpreted w/ caution

  • comparisons depend on underlying medication + disease

What are carotenoids and how are they classified?

• Organic pigments

  • found in plants, algae, fungi, and some bacteria

• Cannot be synthesised by humans or animals → must be consumed

• 2 types:

  • Xanthophylls (oxygen-containing)

  • Carotenes (hydrocarbons only)

Which carotenoids have vitamin A activity and which form the macular pigments?

• 4 carotenoids w/ vit A activity:

  • β- + α-carotene, γ-carotene, and β-cryptoxanthin (can be converted to retinal)

• These+ other carotenoids can act as effective antioxidants

• Lutein, meso-zeaxanthin, + zeaxanthin = xanthophylls that form the macular pigments

  • Pigments give macula its characteristic yellow appearance

• Highest conc of lutein + zeaxanthin at fovea, dec’ing w/ eccentricity

What are the properties of xanthophylls?

• Absorb blue light

• Are antioxidants

What are macular pigments and where are they found in the diet?

• Macular pigments: lutein + zeaxanthin

• Food sources incl green leafy vegetables (spinach, kale) + fresh fruit

What is the evidence linking macular pigment levels and dietary intake with AMD risk?

• Dec’d serum, dietary, + retinal levels have been assoc’d w/ inc’d AMD risk in some but not all observational studies

• In AREDS I, higher dietary intake (measured via FFQ) was linked to a lower risk of developing advanced AMD

What is known about lutein supplementation, macular pigment optical density, and AMD progression?

• Lutein supplementation + inc’d macular pigment optical density have been assoc’d,

  • but their relevance + relationship to AMD is NOT fully established

• AREDS 2 reported

  • NO extra reduction in risk of progression to advanced AMD from adding lutein + zeaxanthin

What key factors should be considered when evaluating a study on AMD risk or progression?

• Study outcomes:

  • reducing risk of AMD incidence or reducing risk of AMD progression

• Study sample:

  • age, ethnicity, location, sample size, effect size/change

• Study type:

  • observational, cross-sectional, intervention, placebo-controlled, cross-over, longitudinal

• Outcome measures:

  • VA, serum, CS, OCT parameters, lesion size

• Measurement of study parameters:

  • How was diet assessed?

  • How was supplement intake controlled?

What is the current evidence regarding diet, supplements, and AMD incidence versus progression?

• Most studies have evaluated risk of AMD progression

• To date, there is NO evidence that diet or dietary supplements can prevent AMD development

Why is it difficult to measure whether diet or supplements can prevent AMD from developing?

• Measuring prevention would req using the same pt twice:

  • Once w/o intervention, hoping they develop AMD

  • Then again w/ intervention, hoping they do not develop AMD

• Imposs due to absence of reincarnation + cloning

What factors related to age, ethnicity, and location should be considered when evaluating a study sample?

• Age:

  • consider age range in relation to study methods, incl compliance + cognitive abilities

• Ethnicity:

  • results useful for your clinical setting? applicable to your pt population

• Location:

  • May influence diet, population characteristics + environ factors

What sample size and effect size considerations are important when interpreting study findings?

Sample size:

• how large (sample) + how much power study had?

• Can you draw concl’s from this study to suit a larger population/ your pt population?

  • i.e. if all cases of a given disease were assessed -any "stronger" conclusions from it compared to a situation where you might have only a proportion of a population

Effect size

• how much did the parameter change/ what is the spread?

What should be considered when evaluating study type and outcome measures

• Was study ST/LT + how were concl’s drawn?

• Were all measurements repeated at each time point?

• Are the outcome measures perceivable by the pt?

• What “improvement” means (e.g., better vision/overall health?).

• Check whether control subjects or placebo treatments were used.

How is dietary nutrient intake measured in study parameters?

• Sampling info from indiv

• Non-contact methods (no practitioner required):

  • Food frequency questionnaires

  • Food diaries

Compare frequency questionnaires and food diaries

Frequency questionnaires

• Pt ticks off foods on a list that they have eaten each day.

• Foods often left out of the lists.

Food diary

• Pt journalises their intake.

What are the limitations of frequency questionnaires and food diaries?

• Self-report method tends to underestimate food intake.

• Portion sizes = diffic to det unless everything is weighed + measured.

What discussion points highlight limitations of FFQs and food diaries?

• Are all food groups listed?

• Seasonality.

• Weight measures.

• Difficulty remembering food from 1 week ago.

• Difficulty remembering food from 50 years ago (e.g., age 70).

• Tendency to tick “what you should eat” vs “what you really ate”.

What problems occur with Food Frequency Questionnaires and Food Diaries?

• FFQs issues:

  • Often no record of portion intake

  • Summary over several days

  • No info on meal prep

  • Predefined lists lead to omitted or wrongly grouped foods

• Food diary issues:

  • Very focused on calorie counting

  • Diffic to judge portion size unless defined

  • Does not accommodate changes in calorific intake from cooking methods

  • Difficulty collating “food groups”

What are the contact methods used to measure or estimate nutrient intake?

• Contact methods require a practitioner.

• Blood serum levels (HPLC): reflects S-T nutrient intake.

• MPOD (macular pigment optical density): reflects L-T dietary exposure, only an indirect measure.

What are the limitations of blood serum testing for nutrient intake?

• Invasive for pt’s

• Must be used alongside food diaries/FFQs

• Absorption + excretion vary with age, disease, meds

• Usefulness = debatable due to indiv variability

How much antioxidant intake is enough for macular health and AMD?

• Healthy macula: varied, balanced diet provides sufficient antioxidants.

• Indiv’s w/ or at risk of AMD req higher antioxidant intake to slow oxidative effects.

• Research has investigated effects of diff antioxidant doses on AMD progression

  • results remain inconclusive.

What were the inclusion criteria for the AREDS study?

• Age 50–85 years

• Either:

  • Bilat large drusen, or

  • Large drusen in one eye + advanced AMD (neovascular AMD or central GA) in fellow eye

• At least 75% run-in medication consumed (verified by remaining tablet/capsule count)

• Smokers allowed to participate

What were the exclusion criteria for the AREDS study?

• Under 50 or over 85 years

• AMD affecting one eye only

• Non-compliance with supplementation adherence

• Taking any other supplementation

What were the key findings and formulation details of the AREDS study?

• Clinical trial on supplementation in AMD

• Taken for 6 years:
  • Vitamin C 500 mg
  • Vitamin E 400 IU
  • β-carotene 15 mg
  • Zinc oxide 80 mg
  • Cupric oxide 2 mg

• Showed 25% risk reduction in progression to advanced AMD over 5 years in pt’s w/ intermediate AMD or advanced AMD in one eye

• 19% reduction in risk of losing ≥3 lines of vision

What were the key design features and participant details of the AREDS study?

• 3640 pt’s w/ AMD

• Pt’s ranged from:
  • No evidence of AMD in either eye
  • To advanced AMD with vision loss in 1 eye but good vision in the other

• 90% of participants followed for ≥5 years

• Always look at pt no’s + FU numbers

What were the key findings of the Age-related Macular Disease Study (AREDS II)?

2013

• Study added lutein (L) and zeaxanthin (Z) to the original AREDS formulation

  • Overall: Did not further reduce risk of progression to advanced AMD

• Sub-analysis: substituting L and Z for beta-carotene reduced progression risk by an extra 18%

  • Beta-carotene may have masked benefits of L + Z in overall analysis

  • L + Z =useful substitutes for beta-carotene in the original formulation

What were the AREDS 2 study enrolment criteria and patient characteristics?

• Study added lutein + zeaxanthin to orig AREDS formula

• At enrolment pt’s had either:

  • bilateral large drusen

  • large drusen in 1 eye + advanced AMD (neovascular AMD or central geographic atrophy) in the fellow eye

What were the AREDS original and new supplement formulations?

• Original formula:

  • Vitamin C 500 mg, Vitamin E 400 IU, β-carotene 15 mg

  • Zinc: zinc oxide 80 mg + cupric oxide 2 mg

• Zinc reduced from 80 mg to 25 mg

• Lutein + zeaxanthin substituted for beta-carotene

What were the outcome findings of AREDS 2?

• Adding L + Z did not further reduce risk of progression to advanced AMD

• No adverse effects found w/ this formulation

What is the current gold-standard supplement formulation for AMD?

• AREDS 2 formulation is the current ‘gold standard’ (only large-scale clinical trial)

• Lutein = 10 mg

• Zinc = 25 mg

• Zeaxanthin = 2 mg

• Copper = 2 mg

• Vitamin C = 500 mg

• Vitamin E = 400 IU

How was compliance tested in AREDS 2?

Trial phase prior to study enrolment

Why is a balanced diet insufficient for lutein/zeaxanthin intake in those with or at risk of AMD?

• Simple balanced diet generally does not provide the req’d 10 mg of L+Z

• Standard portions of most veg + fruits do not contain enough lutein to meet this req

What is the current situation with UK dietary supplements for eye health?

• No regulation (classed as complementary meds)

• Often contain antioxidants in varying doses plus extra ingredients (e.g., vit B, bilberry extracts, sunflower seed oil, marigold extract, beeswax)

• Aggressively marketed + often claim to be “backed by professionals”

Where are nutritional supplements sold in the UK?

• Pharmacies

• Supermarkets and other food shops

• High-street optical and contact lens practices

• Hospitals and university institutes

• Internet pharmaceutical companies

• Internet shopping companies (e.g., Amazon)

• No regulation on who can buy them

• Many have no age restriction (some packaging states “not for under 18s” but not enforced)

When and how much nutritional supplementation should be used for AMD?

• Only formulations supported by large-scale clinical trials are from AREDS + AREDS 2.

• Incl+ excl criteria guide decisions on who, which + when supplementation is appropriate.

• Problem: AREDS 2= complex study, practitioners may be confused about what to advise.

What are the problems with over-the-counter or remote-purchased medications?

• Diff combo’s + dosage rec’s for which no evidence exists

  • Dosage rec’s largely vary

• Remote purchasing or in outlets w/ no professional advice

• Risk of not considering interactions w/ current medication or health status

What did the Aston University survey reveal about AMD patients’ nutrition and supplement use?

• Many AMD patients confused over beneficial foods

• Pts taking variety of supplements, none AREDS 2, some doubling or tripling dose

• Food diary analysis: avg 1.3mg lutein/day, much lower than recommended 10mg/day for AMD or at-risk patients

What additional issues did the Aston University survey find regarding AMD patients’ information and knowledge?

• Pt’s felt they did not have enough info from optoms or ophthalmologists

• Concern over conflicting advice from ECP’s

• When quizzed on nutrition, none could name useful nutrients or describe why they were beneficial

When is supplement advice proven to affect AMD progression?

• Pts aged 50–85 years

• Pts with drusen >125 µm and/or geographic atrophy involving the centre of the macula

• Plus a fellow eye with drusen >125 µm and/or geographic atrophy not involving the centre of the macula

What dietary modification advice is given for AMD patients or at-risk patients outside supplement criteria?

• To get a good mix of antioxidants, L+Z, incorporate one of the following daily:

  • 2 eggs

  • 1 cup (150 g) cooked kale

  • 1 cup (150 g) cooked spinach

• Must be eaten every day to get the required L+Z

What is the optometrist’s role in nutrition advice for AMD patients?

• Give nutrition advice to all patients w/ or at risk of, AMD

• Ensure pt’s have access or can prepare + cook healthy food

• Pts with visual impairments may need extra help; may require referral for low vision support

What tools and considerations support optometrists in advising AMD patients?

• Clinical decision-making aid (Aston University) -help decide when and what to advise

• Knowledge of products + their indications

• Follow best practice + clinical guidelines on prescribing supplements

What should be considered when evaluating AMD patients for exercise-based case studies?

• Evaluate disease stage from images

• Assess evidence for benefit from supplementation or dietary modifications

• Consider:

  • evidence, age+ disease stage

  • reducing risk of developing AMD vs risk of AMD progression

Clinical scenario 1

Clinical scenario 2

Clinical scenario 3

Clinical scenario 4

Clinical scenario 5

What are the key conclusions about nutrition and AMD?

• Nutrition can slow AMD progression, poss via an overall healthier lifestyle, evidence = inconclusive

• Optoms responsibility to give nutrition advice to those with, or at risk of, AMD

• Advice can be based on AREDS 2 incl/excl criteria

What is the take-home message regarding nutrition and supplements for AMD?

• Nutritional substances can benefit AMD pts + those at risk

• Req’d amounts depend on indiv diet + lifestyle

• Consider diet, lifestyle + other factors

What considerations are needed when recommending nutritional supplements in AMD?

• Nutrient uptake depends on indiv absorption; some combos may be unsuitable due to competition

• Those recommending supplements must advise on adverse effects and overdosing, as supplements fall outside medicine regulation

What future developments are anticipated in eye health and AMD?

• Anti-ageing for the eye: synolitics

• Microbiome analyses: gut-ocular and gut-brain axes