Phytochemicals and Ocular Phytochemicals and Ocular DiseaseDisease

Paul S. Bernstein, MD, PhDPaul S. Bernstein, MD, PhDMoran Eye CenterMoran Eye CenterUniversity of UtahUniversity of Utah

Eye Tissues in which Eye Tissues in which Phytochemicals May Play a RolePhytochemicals May Play a Role

• Cornea and ocular surfaceCornea and ocular surface

• Ciliary body and trabecular meshworkCiliary body and trabecular meshwork

• IrisIris

• LensLens

• Optic nerveOptic nerve

• RetinaRetina

Phytochemicals and Phytochemicals and the Ocular Surface Ithe Ocular Surface I

• XerophthalmiaXerophthalmia– A leading cause of A leading cause of

blindness in developing blindness in developing countriescountries

– Caused by vitamin A Caused by vitamin A deficiencydeficiency

– Leads to keratinization of Leads to keratinization of the conjunctiva, severe dry the conjunctiva, severe dry eye, ulceration, and eye, ulceration, and scarringscarring

– Bitot’s Spots Bitot’s Spots – Easily treated in early Easily treated in early

stages with vitamin A or stages with vitamin A or ββ--carotene supplementscarotene supplements

Phytochemicals and the Ocular Phytochemicals and the Ocular Surface IISurface II

• Chronic dry eyeChronic dry eye– One of the more One of the more common complaints common complaints

encountered in encountered in clinical ophthalmologyclinical ophthalmology– Often is related to a tear film Often is related to a tear film

deficiencydeficiency– ωω-3 fatty acids may help -3 fatty acids may help

enhance the wetting properties enhance the wetting properties of the tear filmof the tear film

– Flax seed oil is the primary Flax seed oil is the primary consumer source of consumer source of

αα-linolenic acid (ALA)-linolenic acid (ALA)

Cyclosporine for Dry EyeCyclosporine for Dry Eye

• Cyclosporine (Restasis) Cyclosporine (Restasis) was recently approved for was recently approved for severe dry eye severe dry eye

• Immunosuppressive Immunosuppressive molecule isolated from a molecule isolated from a fungus fungus Tolypocladium Tolypocladium inflatum Gamsinflatum Gams

• Decreases inflammation Decreases inflammation by inhibiting activation of by inhibiting activation of T-cells permitting more T-cells permitting more normal tear productionnormal tear production

Phytochemicals and GlaucomaPhytochemicals and Glaucoma

• Glaucoma is an optic Glaucoma is an optic neuropathy often associated neuropathy often associated with high intraocular pressurewith high intraocular pressure

• Minimal evidence that Minimal evidence that nutrient deficiencies nutrient deficiencies contribute to riskcontribute to risk

• Interest in Interest in ωω-3 and -3 and ωω-6 -6 PUFAs because synthetic PUFAs because synthetic prostaglandins are prostaglandins are

commonly used commonly used to lower intraocular to lower intraocular pressurepressure

Pilocarpine and GlaucomaPilocarpine and Glaucoma

• One of the earliest One of the earliest approved medications for approved medications for glaucoma is pilocarpineglaucoma is pilocarpine

• Extracted from a South Extracted from a South American shrub: American shrub: Jaborandi --“slobber Jaborandi --“slobber mouth plant”mouth plant”

• Muscarinic agonist that Muscarinic agonist that causes pupil constriction causes pupil constriction and lowers intraocular and lowers intraocular pressurepressure

Marijuana and GlaucomaMarijuana and Glaucoma

• Cannabinoids can lower Cannabinoids can lower intraocular pressure, but intraocular pressure, but the effect is modest and the effect is modest and side effect profile is poor side effect profile is poor compared to currently compared to currently available drugs.available drugs.

• Effect is central—topical Effect is central—topical THC does not workTHC does not work

Iris Dilation and PhytochemicalsIris Dilation and Phytochemicals

• Atropine has long Atropine has long been known to dilate been known to dilate the pupil the pupil

• Muscarinic antagonist Muscarinic antagonist extracted from the extracted from the deadly nightshade deadly nightshade Atropa belladonnaAtropa belladonna

• Counteracted by Counteracted by muscarinic agonists muscarinic agonists such as pilocarpinesuch as pilocarpine

Phytochemicals and CataractPhytochemicals and Cataract

• Leading cause of preventable Leading cause of preventable blindness in developing worldblindness in developing world

• Cataract surgery is one of the Cataract surgery is one of the most common surgeries most common surgeries performed in the USperformed in the US

• Reducing the rate of cataract Reducing the rate of cataract formation would have dramatic formation would have dramatic impact on Medicare spending impact on Medicare spending and world blindnessand world blindness

• Moderate epidemiological Moderate epidemiological evidence that antioxidant evidence that antioxidant

rich foods are associated rich foods are associated with decreased risk of cataractwith decreased risk of cataract

– Ascorbic acidAscorbic acid– Vitamin EVitamin E– CarotenoidsCarotenoids

• Prospective studies equivocalProspective studies equivocal

Phytochemicals and Optic Phytochemicals and Optic NeuropathyNeuropathy

• Minimal evidence that Minimal evidence that phytochemicals play a phytochemicals play a positive or negative rolepositive or negative role

• Tobacco/alcohol amblyopia Tobacco/alcohol amblyopia is the best example of a is the best example of a nutritional optic neuropathynutritional optic neuropathy– Cumulative oxidative stress Cumulative oxidative stress

in nutritionally compromised in nutritionally compromised smokers and drinkers can smokers and drinkers can lead to irreversible optic lead to irreversible optic nerve damagenerve damage

– May be related to thiamine May be related to thiamine or vitamin B12 deficiency or vitamin B12 deficiency

Phytochemicals and Retinal Phytochemicals and Retinal DiseaseDisease

• Multiple conditions in which Multiple conditions in which phytochemicals play a rolephytochemicals play a role– Night blindnessNight blindness– Retinal degenerationsRetinal degenerations– Macular dystrophiesMacular dystrophies– Nutritional maculopathiesNutritional maculopathies– Age-related macular degenerationAge-related macular degeneration

Phytochemicals and Night Phytochemicals and Night BlindnessBlindness

• The first described association The first described association between diet and ocular disease between diet and ocular disease (ancient Egypt)(ancient Egypt)

• Caused by vitamin A deficiencyCaused by vitamin A deficiency– Common in the developing worldCommon in the developing world– Rare in the developed worldRare in the developed world– May be associated with May be associated with

malabsorption syndromesmalabsorption syndromes

• Night blindness (nyctalopia) Night blindness (nyctalopia) generally precedes ocular surface generally precedes ocular surface diseasedisease

• Lack of retinoids inhibits function of Lack of retinoids inhibits function of the visual cyclethe visual cycle

• Multiple white spots on the retinaMultiple white spots on the retina• Reversible with prompt Reversible with prompt

supplementationsupplementation

Phytochemicals and Retinal Phytochemicals and Retinal DegenerationsDegenerations

• Retinitis pigmentosa refers to Retinitis pigmentosa refers to a wide variety of inherited a wide variety of inherited retinal degenerations retinal degenerations affecting over 100,000 people affecting over 100,000 people in the USin the US

• Multiple genetic defects Multiple genetic defects responsibleresponsible

• Night blindness and visual Night blindness and visual field constriction are field constriction are prominent clinical symptomsprominent clinical symptoms

• Bone spicules and Bone spicules and photoreceptor degeneration photoreceptor degeneration are prominent clinical signsare prominent clinical signs

Phytochemical Treatment of Phytochemical Treatment of Retinitis Pigmentosa (RP)Retinitis Pigmentosa (RP)

• Vitamin A supplementation (15,000 units per Vitamin A supplementation (15,000 units per day of retinyl palmitate) can slow the day of retinyl palmitate) can slow the progression of RP, but the effect is modestprogression of RP, but the effect is modest

• ωω-3 fatty supplementation may also help, but -3 fatty supplementation may also help, but the effect is even weakerthe effect is even weaker

• Lutein supplementation has been proposed, Lutein supplementation has been proposed, but there is little evidence there is a but there is little evidence there is a deficiency in the first place deficiency in the first place

Phytochemicals May Make Some Phytochemicals May Make Some Forms of RP WorseForms of RP Worse

• Refsum diseaseRefsum disease– Inability to metabolize phytanic Inability to metabolize phytanic

acid (a branched chain fatty acid)acid (a branched chain fatty acid)– Treated with a diet low in phytol Treated with a diet low in phytol

and phytanic acid (no green leafy and phytanic acid (no green leafy vegetables, animal fats, or milk vegetables, animal fats, or milk products)products)

• Gyrate atrophyGyrate atrophy– Defect in ornithine metabolismDefect in ornithine metabolism– Treated with a low protein, low Treated with a low protein, low

arginine dietarginine diet

Phytochemicals and Macular Phytochemicals and Macular DystrophiesDystrophies

• Stargardt disease is the Stargardt disease is the most common cause of most common cause of early onset inherited early onset inherited macular degeneration macular degeneration (~25,000 affected in US)(~25,000 affected in US)

• Recessive form (STGD1) Recessive form (STGD1) accounts for 95% of accounts for 95% of cases and is caused by a cases and is caused by a defect in the defect in the ABCA4ABCA4 gene gene

• Dominant form (STGD3) Dominant form (STGD3) accounts for <5% of accounts for <5% of cases and is caused by a cases and is caused by a defect in the defect in the ELOVL4ELOVL4 genegene

Nutritional Interventions Against Nutritional Interventions Against STGD1STGD1

• The ABCA4 protein transports The ABCA4 protein transports excess vitamin A aldehyde out excess vitamin A aldehyde out of the photoreceptor outer of the photoreceptor outer segmentssegments

• Excess vitamin A aldehyde Excess vitamin A aldehyde can react with can react with phospatidylethanolamine to phospatidylethanolamine to form toxic metabolites such as form toxic metabolites such as A2E, a component of A2E, a component of lipofuscinlipofuscin

• Vitamin A restriction might be Vitamin A restriction might be therapeutictherapeutic

ATP ADP

ABCR / RIMprotein

all-trans-Retinal

CYTOSOL

Disc Membrane

PEPhosphatidyl-ethanolamine

all-trans-Retinal

PE-bis-retinoid

Pyridinium salt Oxidation/CyclizationA2E

N-retinylidene-N-

retinylethanolamine

Hydrolysis

RPE

PE-RetinalSchiff base

IntradiscalSpace

Rhodopsin

ATP ADP

ABCR / RIMprotein

all-trans-Retinal

CYTOSOL

Disc Membrane

PEPhosphatidyl-ethanolamine

all-trans-Retinal

PE-bis-retinoid

Pyridinium salt Oxidation/CyclizationA2E

N-retinylidene-N-

retinylethanolamine

Hydrolysis

RPE

PE-RetinalSchiff base

IntradiscalSpace

Rhodopsin

N

CH2CH2OH

1

3

5

7

8

1910

12

18

16

17

15

14 20

14'

20'

12' 10'

19'

8'

7' 1'

5'3'

Nutritional Interventions Against Nutritional Interventions Against STGD3STGD3

• The ELOVL4 protein is The ELOVL4 protein is homologous to yeast homologous to yeast enzymes that elongate very enzymes that elongate very long chain fatty acidslong chain fatty acids

• A defect in ELOVL4 may A defect in ELOVL4 may inhibit production of EPA, inhibit production of EPA, DHA, and their metabolites DHA, and their metabolites in the human retinain the human retina

• The most affected family The most affected family members who consume the members who consume the least EPA and DHA (fish, least EPA and DHA (fish, algae, etc.) are the least algae, etc.) are the least affectedaffected

• A clinical trial of EPA and A clinical trial of EPA and DHA supplementation is in DHA supplementation is in progress at the Moran Eye progress at the Moran Eye CenterCenter

Some Phytochemicals Can Induce Some Phytochemicals Can Induce MaculopathiesMaculopathies

• Canthaxanthin is a xanthophyll Canthaxanthin is a xanthophyll carotenoid derived from carotenoid derived from microorganisms and fungi that has microorganisms and fungi that has been used as a skin tanning agentbeen used as a skin tanning agent

• At high cumulative doses, it can At high cumulative doses, it can crystallize in the macula, although crystallize in the macula, although visual loss is rarevisual loss is rare

• Oxalic acid found in many green Oxalic acid found in many green vegetables can form retinal vegetables can form retinal crystals, especially in susceptible crystals, especially in susceptible individualsindividuals

• Niacin (nicotinic acid, vitamin B6) Niacin (nicotinic acid, vitamin B6) can cause cystoid can cause cystoid

macular edema when taken macular edema when taken at high doses (>1.5 g/day) at high doses (>1.5 g/day) to lower cholesterolto lower cholesterol

AMD PrevalenceAMD Prevalence

• Leading cause of irreversible visual loss in Leading cause of irreversible visual loss in developed countries.developed countries.

• 1.7-20 million Americans have AMD, ~200,000 1.7-20 million Americans have AMD, ~200,000 have advanced forms.have advanced forms.

• ~2% of 50-60 year olds have AMD~2% of 50-60 year olds have AMD• ~30% of individuals over age 75 have some ~30% of individuals over age 75 have some

form of AMD.form of AMD.• Wet AMD accounts for 10-15% of AMD, but Wet AMD accounts for 10-15% of AMD, but

90% of blindness.90% of blindness.

AMD Clinical FeaturesAMD Clinical Features

More AMD Pictures

Choroidal Neovascularization

AMD Diagnostic StudiesAMD Diagnostic Studies

• Visual acuityVisual acuity

• Amsler gridAmsler grid

• Dilated eye Dilated eye examinationexamination

• Fluorescein Fluorescein angiographyangiography

• ICG angiographyICG angiography

• Optical coherence Optical coherence tomographytomography

Laser AMD TreatmentsLaser AMD Treatments

• Laser Laser photocoagulationphotocoagulation

• Transpupillary Transpupillary thermotherapythermotherapy

• External beam External beam irradiationirradiation

• Visudyne Visudyne Photodynamic Photodynamic therapy +/- Kenalogtherapy +/- Kenalog

Surgical AMD TreatmentsSurgical AMD Treatments

• CNVM removalCNVM removal

• Macular translocationMacular translocation

• RPE or retinal RPE or retinal transplantationtransplantation

• Gene therapyGene therapy

• Prosthetic visionProsthetic vision

• Focal radiation deliveryFocal radiation delivery

• Encapsulated cell Encapsulated cell technology (CNTF)technology (CNTF)

Nonsurgical AMD TreatmentsNonsurgical AMD Treatments

• Low vision services Low vision services • PlasmapheresisPlasmapheresis• ““Alternative” medicine Alternative” medicine • Angiogenesis inhibitorsAngiogenesis inhibitors

– MacugenMacugen– LucentisLucentis– AvastinAvastin– Bevasiranib Bevasiranib – VEGF TrapVEGF Trap– Anecortave acetateAnecortave acetate– SqualamineSqualamine

AMD Risk factorsAMD Risk factors

• NonmodifiableNonmodifiable– AgeAge– HeredityHeredity– GenderGender – PigmentationPigmentation– RaceRace– Iris colorIris color

• ModifiableModifiable– Smoking Smoking – Cardiovascular Cardiovascular

disease, blood lipid disease, blood lipid status, and status, and hypertensionhypertension

– Alcohol consumptionAlcohol consumption– Light exposureLight exposure– NutritionNutrition

Nutrition and AMDNutrition and AMD

• Retina/RPE have highly unsaturated lipids Retina/RPE have highly unsaturated lipids susceptible to oxidative damage in a region of susceptible to oxidative damage in a region of high oxygen and light.high oxygen and light.

• AMD is in part a disease of oxidative stress, AMD is in part a disease of oxidative stress, so antioxidant nutrients may play a role in so antioxidant nutrients may play a role in protection against AMD.protection against AMD.

• Difficult studies to perform since many Difficult studies to perform since many interacting factors are involved.interacting factors are involved.

Approaches to Identifying Approaches to Identifying Nutritional Factors for AMDNutritional Factors for AMD

• Epidemiology Epidemiology

• Animal StudiesAnimal Studies

• PhysiologyPhysiology– Nutrient should be found in appropriate Nutrient should be found in appropriate

quantities in the retina.quantities in the retina.– Physiological mechanisms should be plausible.Physiological mechanisms should be plausible.– Deficiency states should be associated with Deficiency states should be associated with

higher risk of AMD. higher risk of AMD.

• Prospective TrialsProspective Trials

Nutrients Epidemiologically Linked Nutrients Epidemiologically Linked to Decreased AMD Riskto Decreased AMD Risk

• Antioxidant mineralsAntioxidant minerals– ZincZinc– SeleniumSelenium

• Antioxidant vitaminsAntioxidant vitamins– Vitamin CVitamin C– Vitamin EVitamin E– Vitamin AVitamin A

• Polyunsaturated fatsPolyunsaturated fats– DHA and its DHA and its

precursorsprecursors

• CarotenoidsCarotenoids– LuteinLutein– ZeaxanthinZeaxanthin – -Carotene-Carotene– LycopeneLycopene

• HerbalsHerbals– BilberryBilberry– PolyphenolsPolyphenols– Other “herbals”Other “herbals”

Age-Related Eye Disease Study Age-Related Eye Disease Study (AREDS)(AREDS)

• National Eye InstituteNational Eye Institute• 4757 subjects, 55-80 years old4757 subjects, 55-80 years old• Followed for at least 5 yearsFollowed for at least 5 years• Randomized antioxidant Randomized antioxidant

supplementation—neither lutein nor supplementation—neither lutein nor zeaxanthin in supplementzeaxanthin in supplement

• Incidence of cataracts, severe vision Incidence of cataracts, severe vision loss, and AMD progression monitoredloss, and AMD progression monitored

AREDS Grading ScaleAREDS Grading Scale

• 1) No drusen or a few small drusen. Good acuity 1) No drusen or a few small drusen. Good acuity (better than or equal to 20/32).(better than or equal to 20/32).

• 2)2) Pigment abnormalities or non-extensive small Pigment abnormalities or non-extensive small or intermediate drusen. Good acuity.or intermediate drusen. Good acuity.

• 3)3) Extensive intermediate drusen or any large Extensive intermediate drusen or any large drusen or non-central atrophy. Good acuity.drusen or non-central atrophy. Good acuity.

• 4)4) Good acuity and no advanced AMD in the Good acuity and no advanced AMD in the study eye. Advanced AMD in the fellow eye study eye. Advanced AMD in the fellow eye (choroidal neovacularization or geographic atrophy) (choroidal neovacularization or geographic atrophy) or acuity worse than 20/32 due to AMD in the fellow or acuity worse than 20/32 due to AMD in the fellow eye.eye.

The AREDS FormulationThe AREDS Formulation

• 80 milligrams of zinc 80 milligrams of zinc oxide oxide

• 2 milligrams of cupric 2 milligrams of cupric oxide oxide

• 500 milligrams of 500 milligrams of vitamin Cvitamin C

• 400 international units 400 international units (IU) of vitamin E(IU) of vitamin E

• 15 milligrams (25,000 15 milligrams (25,000 IU) of beta-carotene IU) of beta-carotene

AREDS ResultsAREDS Results

• Significant reduction in progression for Significant reduction in progression for AMD patients supplemented with high-AMD patients supplemented with high-dose zinc, vitamin C, vitamin E, and dose zinc, vitamin C, vitamin E, and beta-carotene for categories 3 and 4.beta-carotene for categories 3 and 4.

• No significant reduction in cataract No significant reduction in cataract progression.progression.

• Role of Role of lutein and zeaxanthinlutein and zeaxanthin and other and other antioxidants remain to be determined.antioxidants remain to be determined.

• Formulation not optimized.Formulation not optimized.

Arch Ophthalmol. 2001;119:1417-1436.

AREDS IIAREDS II

• New generation formulationNew generation formulation– Add fish oil (EPA/DHA) 1000 mgAdd fish oil (EPA/DHA) 1000 mg– Add lutein 10 mg and zeaxanthin 2 mgAdd lutein 10 mg and zeaxanthin 2 mg– Decrease zinc and Decrease zinc and ββ-carotene-carotene

• 4000 patients for 5 years at 100 sites4000 patients for 5 years at 100 sites• Age 50-80 with high risk dry AMDAge 50-80 with high risk dry AMD• Moran Eye Center participatesMoran Eye Center participates• Recruitment is in progressRecruitment is in progress

Why Fish Oil?Why Fish Oil?

• Multiple epidemiological Multiple epidemiological studies have shown studies have shown protection against AMDprotection against AMD

• Major constituent of Major constituent of photoreceptor photoreceptor membranesmembranes

• Shown to be protective Shown to be protective against an inherited against an inherited macular dystrophy macular dystrophy (STGD3)(STGD3)

• Safe and well toleratedSafe and well tolerated

Dietary Carotenoid GroupsDietary Carotenoid Groups

Group 3Group 3Corn, mandarin oranges, Corn, mandarin oranges,

orange peppers orange peppers (0.4 mg zeaxanthin)(0.4 mg zeaxanthin)

Group 4Group 4Carrots, winter squash, Carrots, winter squash,

cantaloupe, apricotscantaloupe, apricots (8 mg beta carotene)(8 mg beta carotene)

Group 1Group 1Kale, spinach green Kale, spinach green

leafy vegetables leafy vegetables (6 mg lutein)(6 mg lutein)

Group 2Group 2Tomato productsTomato products(10 mg lycopene)(10 mg lycopene)

Xanthophylls and AMDXanthophylls and AMD

• Lutein and zeaxanthin Lutein and zeaxanthin form the macular form the macular pigmentpigment

• Dietary sources Dietary sources include green leafy include green leafy vegetables and vegetables and orange-yellow fruitsorange-yellow fruits

• Act as antioxidants or Act as antioxidants or light screening light screening compoundscompounds

OH

HO (3R,3'R,6'R)-Lutein

3'

3

6'

OH

HO (3R,3'R)-Zeaxanthin3

3'

HO(3R,3'S; meso)-Zeaxanthin*

3

HO

3'

3

3'

OH

(3S,3'S)-Zeaxanthin*

OH

OH

HO(3R,3'S,6'R)-Lutein (3'-Epilutein)*

3'

3

6'

HO

(3R,6'R)-3-Hydroxy--carotene-3'-one*

3'

3

6'

O

all-E-Lycopene

1 2 56

1'2'

5'6'

5Z-Lycopene

12

56

1'2'

5'6'

OH

HO (3R,3'R,6'R)-Lutein

3'

3

6'

OH

HO (3R,3'R)-Zeaxanthin3

3'

HO(3R,3'S; meso)-Zeaxanthin*

3

HO

3'

3

3'

OH

(3S,3'S)-Zeaxanthin*

OH

OH

HO(3R,3'S,6'R)-Lutein (3'-Epilutein)*

3'

3

6'

HO

(3R,6'R)-3-Hydroxy--carotene-3'-one*

3'

3

6'

O

all-E-Lycopene

1 2 56

1'2'

5'6'

5Z-Lycopene

12

56

1'2'

5'6'

(3’-oxolutein)

Figure 1: Xanthophyll carotenoids found in the human retina and macula.Asterisks denote metabolites of dietary lutein and zeaxanthin.

Eye Disease Case-Control Eye Disease Case-Control Study (1993-1994)Study (1993-1994)

• Inverse correlation between Inverse correlation between serumserum carotenoid carotenoid levels and risk of exudative AMD.levels and risk of exudative AMD.

• Dietary consumptionDietary consumption of green leafy vegetables of green leafy vegetables high in lutein and zeaxanthin (spinach and high in lutein and zeaxanthin (spinach and collard greens) associated with lower risk of collard greens) associated with lower risk of AMD compared to diets high in AMD compared to diets high in -carotene such -carotene such as carrots.as carrots.

• BUT…It is probably more important to know BUT…It is probably more important to know ocularocular carotenoid levels. carotenoid levels.

Carotenoids as Light Screening Carotenoids as Light Screening CompoundsCompounds

• The macular carotenoids absorb phototoxic The macular carotenoids absorb phototoxic blue light strongly.blue light strongly.

• The anatomical localization of macular The anatomical localization of macular carotenoids is ideal for them to act as an carotenoids is ideal for them to act as an optical filter.optical filter.

• Animals raised on carotenoid-free diets Animals raised on carotenoid-free diets appear to be more susceptible to light appear to be more susceptible to light damage.damage.

• Limited studies in humans indicate that long-Limited studies in humans indicate that long-term supplementation can change macular term supplementation can change macular pigment levels in humanspigment levels in humans

Carotenoids are AntioxidantsCarotenoids are Antioxidants

• The retina is exposed to high levels of light The retina is exposed to high levels of light and oxygen that can generate free radicals.and oxygen that can generate free radicals.

• Photoreceptor membranes are very Photoreceptor membranes are very unsaturated and are thus susceptible to free unsaturated and are thus susceptible to free radical damage.radical damage.

• Carotenoids are efficient quenchers of singlet Carotenoids are efficient quenchers of singlet oxygen and related free radicals.oxygen and related free radicals.

• It is debatable whether carotenoids are It is debatable whether carotenoids are located close enough to the photoreceptors to located close enough to the photoreceptors to allow for direct chemical quenching.allow for direct chemical quenching.

Dietary Carotenoid Intake and Dietary Carotenoid Intake and Macular Pigment DensityMacular Pigment Density

• Human autopsies and Raman studies have Human autopsies and Raman studies have shown ~30% less MP in those with AMD than shown ~30% less MP in those with AMD than without AMD.without AMD.

• Limited studies indicate that diet or Limited studies indicate that diet or supplementation can increase macular pigment supplementation can increase macular pigment levels. levels.

• Macaque monkeys deficient in carotenoids Macaque monkeys deficient in carotenoids exhibit drusen and pigment changes reminiscent exhibit drusen and pigment changes reminiscent of human ARM.of human ARM.

Herbals and AMDHerbals and AMD

• Traditional medicine has provided a wealth of Traditional medicine has provided a wealth of herbal medicines for eye disordersherbal medicines for eye disorders

• Objective evidence is generally lackingObjective evidence is generally lacking

• May provide leads for further interventionsMay provide leads for further interventions

• Popular AMD herbals:Popular AMD herbals:– BilberryBilberry– Red wineRed wine– EyebrightEyebright– Goji berries Goji berries

Bilberry and AMDBilberry and AMD

• Promoted to enhance Promoted to enhance dark adaptation and to dark adaptation and to treat AMDtreat AMD

• Rich in anthocyanidin Rich in anthocyanidin flavonoidsflavonoids

• High levels of High levels of antioxidant activityantioxidant activity

• Anecdotal reports Anecdotal reports (RAF pilots)(RAF pilots)

• No prospective studiesNo prospective studies

Red Wine and AMDRed Wine and AMD

• Some epidemiological Some epidemiological studies indicate lower studies indicate lower levels of AMD in red levels of AMD in red wine drinkerswine drinkers

• Similar findings for Similar findings for cardiovascular cardiovascular diseasedisease

• Rich in polyphenols Rich in polyphenols such as resveratrolsuch as resveratrol

Eyebright and AMDEyebright and AMD

• Herbal medicine Herbal medicine promoted for many eye promoted for many eye ailments including ailments including conjunctivitis, conjunctivitis, blepharitis, eyestrain, blepharitis, eyestrain, and AMDand AMD

• May be used topically, May be used topically, in compresses, as an in compresses, as an extract, or in teaextract, or in tea

• No objective No objective mechanism or datamechanism or data

Goji Berries and AMDGoji Berries and AMD

• Ancient Chinese Ancient Chinese herbal medicine for herbal medicine for eye disorderseye disorders

• Also known as Also known as wolfberrywolfberry

• Usually consumed as Usually consumed as dried fruit or in teadried fruit or in tea

• Extraordinarily rich in Extraordinarily rich in zeaxanthinzeaxanthin

General Recommendations for General Recommendations for AMD PatientsAMD Patients

• Eat a “healthy” diet with lots of fruits and vegetables Eat a “healthy” diet with lots of fruits and vegetables and fish, but no excessive fatand fish, but no excessive fat

• Consider AREDS supplement + ~6 mg lutein in high Consider AREDS supplement + ~6 mg lutein in high risk individualsrisk individuals

• Wait on other single nutrient supplements and Wait on other single nutrient supplements and herbals until more data is available. herbals until more data is available.

• Alcohol in moderationAlcohol in moderation• Don’t smokeDon’t smoke• Avoid excessive light exposureAvoid excessive light exposure• Support and participate in clinical studies (AREDS II)Support and participate in clinical studies (AREDS II)

John A. Moran Eye CenterUniversity of Utah