SIGHT AND LIFE - University of Georgiataurine support ocular structures. Multiple antioxidants, such as vitamin E and the carotenoids lutein and zeaxanthin, provide protec-tion against

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Nutrition as a Mediator of Visual Health Acrossthe Lifespan

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Lisa M Renzi, Billy R Hammond, Jr

Human Biofactors Laboratory, the University of Georgia, Athens, GA, USAVision Sciences Laboratory, the University of Georgia, Athens, GA, USA

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Introduction

For the approximately 314 millionpeople with visual impairment, 12million of whom are children,2 the

presence of visual dysfunctionoften leads to reduced quality oflife, financial burdens, and evenincreased mortality. Many formsof visual loss are irreversible and

lack efficacious treatment options(e.g., age-related macular degener-ation, or “AMD”), and those thatare treatable are costly to treat andoften require surgical intervention(e.g. age-related cataract, or“ARC”). The World HealthOrganization has prioritized ten ofthe most commonly occurringand/or damaging eye diseases intoa list of Priority Eye Diseases3 (seeTable 1) that should receive specialattention from the medical,research, and non-governmental(NGO) communities. Conditionson this list differ in terms of theseverity of visual dysfunction pro-duced, the number of peopleimpacted worldwide, and the costand difficulty of treatment. Someconditions, such as Trachoma andOnchocerciasis, are present largelyin the developing world and occursecondarily to a different primaryinfection, such as Chlamydia or aparasitic infection. Other condi-tions on the list, such as AMD andARC, are responsible for a highproportion of blindness world-wide

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Key messages• The World Health Organization has prioritized ten of the most com-

monly occurring and/or damaging eye diseases into a list of PriorityEye Diseases. These diseases are known for their high incidence andtreatment difficulty.

• Lifestyle changes can be implemented as a preventive strategy, withthe exception of diseases that are caused by gene defects or infec-tion. Nutrition is an extremely promising potential lifestyle interven-tion, as it plays a major role in all of these diseases.

• Nutrition influences both development and progression, and caneven help manage the symptoms of visual disease.

• Vitamin A (in the form of retinal), for instance, is involved in thephysiology of visual transduction. Polyunsaturated fatty acids andtaurine support ocular structures. Multiple antioxidants, such as vitamin E and the carotenoids lutein and zeaxanthin, provide protec-tion against oxidative stress and can slow the development of oculardegenerations.

• Nutrition can also reduce the symptoms of visual disease. Lutein andzeaxanthin, for instance, improve the optical quality of the eye orbitand have been shown to decrease glare disability and discomfort,speed photostress recovery, and improve chromatic contrast andvisual processing speeds.

Nutrition as a Mediator of VisualHealth Across the Lifespan

Lisa M Renzi, Billy R Hammond, JrHuman Biofactors Laboratory, the University of Georgia, Athens, GA,USAVision Sciences Laboratory, the University of Georgia, Athens, GA, USA

Correspondence: Billy R Hammond, Jr, PhD, Neuroscience and BehaviorProgram, 520 Psychology Building, Department of Psychology, TheUniversity of Georgia, Athens, GA 30602-3013, USAE-mail: [email protected]

“Of the traditional five senses man is more consciously dependent onsight to make his way in the world than on the other senses. He is predom-inantly a visual animal. … Most people probably regard sight as theirmost valued faculty, and would rather lose a limb or become deaf or dumbthan to sacrifice vision.”1

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Condition Prevalence/Impact Cause Treatment Cataract Responsible for 48% Opacification of the Emulsification of catarac-

of worldwide blindness crystalline lens due to tous region, implantationenvironmental insult, with an intraocular lensoxidation, advancing age implant

Trachoma 84 million people Chlamydia Antibiotics, surgicalworldwide affected, interventionand responsible for at least 3% of world blindness

Onchocerciasis More than 17.7 million Parasite transmission Pharmaceutical treatment(river blindness) affected worldwide,

and 90% occurring in Africa

Childhood blindness 1.4 million children Nutritional deficiencies, Nutritional supplementa-worldwide heredity, retinopathy of tion (vitamin A), pharma-

prematurity ceuticals, proper medical care throughout the lifespan

Refractive errors and Refractive errors Various affecting axial Optical correction andlow vision responsible for blindness length, degenerative vision devices

in 5 million people, and disease124 million people affected by low vision worldwide

Diabetic retinopathy Cause of 5% of world Diabetes; result of Glycemic sontrol,blindness thickening in retina due photocoagulation of

to growth of new blood retinal vasculaturevessels

Glaucoma 65 million reported Risk factors include age Early medical diagnosis,cases world wide and genetics; however, surgical intervention,

exact causes are still medicationunknown

Age related macular Responsible for 8.7% Degenerative lesions No reported efficacious degeneration of world blindness and circulatory treatment

dysfunctions Corneal opacities Responsible for 5.1% Corneal scarring due to Surgical grafting of cornea

of world blindness xerophthalmia, nutritional deficiencies, injury

Genetic eye diseases No available statistics Genetic Surgery, gene therapy,on extent of genetic grafting of retinal cellsdiseases worldwide; however, they are a significant cause of blindness in industrialized countries

Table 1: Priority Eye Diseases, listed by condition prevalence, cause and treatment strategy. World Health Organization, 2010.

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and are difficult or particularly expensive to treat.Consequently, it is not surprising that research hasalready begun to address the prevention of these latterdiseases.

Disease prevention should undoubtedly be a highpriority, but often requires substantial lifestyle modifi-cation over many years of life. Consequently, onemajor challenge has been to identify those specificlifestyle choices that have the highest probability ofleading to reductions in disease incidence. This task ismade even more difficult by the fact that the etiologyof high-impact diseases such as AMD is clearly notuniform across populations. Thus, the importance of agiven lifestyle modification probably depends uponthe characteristics of the group being studied. Forexample, a central event in AMD development is theoxidation of polyunsaturated fatty acids in photorecep-tor membranes, which probably results from stressorssuch as high-energy light being focused on the retinaover decades of life. The products of this oxidationform adducts that elicit an immune response.4

Individuals with a certain genotype, such as the CFHY402H mutation, however, also have altered immuneresponses. Such alterations make this group even moresusceptible to damage due to oxygen when comparedto individuals without this specific mutation.5

Ultimately, determining what changes are significantmust be done on an individual level with due consider-ation of age, genotype, risk exposure, lifestyle habits,etc.

If, however, a single factor could be chosen thatlinked all of the various risk factors for degenerativedisease, a strong argument could be made for choosingoxidative stress. Oxidative stress is central to manytheories of both aging and degenerative diseases suchas AMD and ARC. Oxidative stressors such as freeradicals and reactive oxygen species are produced as anatural byproduct of cellular respiration and immunefunction, but most humans incur a higher free radicalload than would be predicted by endogenous sourcesalone. Consequently, exogenous sources must beresponsible for much of the free radical load.Fortunately, many of the lifestyle changes that can leadto increased or decreased oxidative damage can beidentified and implemented. For example, one of themost consistent behavioral risk factors for AMD issmoking tobacco. Smoke contains numerous pro-oxi-dants, increases lipid oxidation in vivo and in vitro, and

lowers serum concentrations of antioxidant nutrients,such as vitamin C and carotenoids. According to thisoxidative stress model of AMD and ARC develop-ment, by making the correct lifestyle choices (notsmoking, increasing dietary intake of antioxidants,etc), oxidative stress to the retina and crystalline lens islowered, and the probability that an individual will suf-fer age-related diseases such as AMD or ARC isreduced.

An important implication of the oxidative stressmodel briefly presented above is the idea that dietarychoices are of primary importance. Dietary choices canbe classified into those choices that increase risk bypromoting oxidative damage, and those choices thatdecrease risk by reducing or preventing oxidative dam-age. The purpose of this review is, therefore, to exam-ine the dietary behaviors and dietary substances thatinfluence some of the most impactful diseases on thePriority Eye Disease list, such as ARC, childhood dis-eases (such as retinopathy of prematurity, ROP), dia-betic retinopathy, and AMD.

Age-related cataract

ARC is a condition that affects the crystalline lens(see Figure 1). Rarely, individuals are born with acongenital opacity that can be surgically removed atbirth or early in childhood. More commonly, thecrystalline lens undergoes a series of changes duringsenescence that results in ARC, the most commoncause of blindness worldwide.2 At birth, the crys-talline lens is composed of epithelial cells that thenelongate into clear fibers that lack organelles, co-localized with crystalline proteins (see Banh et al,2006).6 The cells of the lens do not undergo biologi-cal renewal; rather, old cells are compacted towardthe nucleus of the lens, and new growth occurs on thelens exterior.6 Older cells, located near the nucleus,tend to sustain damage over time, both from externalsources and from internal sources.7 As the proteinsnear the nucleus become oxidized, they tend to loseclarity (see Truscott, 2005).7 Over years of environ-mental stress and lens expansion, the nucleus of thelens becomes opaque and the lens loses flexibilityand the ability to accommodate, or to change its focallength depending on the size and distance of objectsin the environment. In this condition, the individualpresents with a nuclear cataract, which is the mostcommon type of ARC.

Disease prevention should be a high priority

Dietary choices are of primary importance

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ARC is one of the few age-relat-ed vision diseases that is treatablewith high efficacy. The most com-mon method for treating ARC isvia emulsification and removal ofthe cataractous nucleus, followedby replacement of the emulsifiedregion with an intraocular lensimplant. This procedure is obvious-ly surgical. In the United States andin many developed countries,cataract surgery is one of the mostcommon surgical procedures per-formed. On average, for example,the United States spends over $3.5billion in Medicare benefits onARC alone.8 As the world’s popu-lation continues to age, ARC willlikely increase in incidence, and thefinancial and quality-of-life burdenwill increase concomitantly.

Childhood blindness

Childhood blindness is a generalterm used to refer to a variety of

conditions that can cause visionimpairment in infants, young chil-dren and adolescents. Of all of thevaried conditions that can causechildhood blindness, the two condi-tions that seem to be most impact-ful on a global scale are ROP andvitamin A deficiency.

ROP, formerly known as retro-lental fibroplasia, is a conditionthat affects low birth weight (usual-ly less than about 1,250 grams),premature (less than 31 weeks)infants. The risk of ROP increasesproportionally to birth weight andgestational age: the smaller andmore premature the infant, thehigher the risk of ROP. Retinaldevelopment, especially the devel-opment of new retinal vasculature,is rapid during the last trimester ofpregnancy (see Hellström et al,2009).9 Premature infants are oftenborn before the new blood vesselsoriginating from the optic disk can

reach the edges of the retina.Premature birth can cause a lack ofmaternal oxygen and essentialnutrients, which can then cause acascade of pathological changeswithin the retina. When the normalprocess of neovascularizationstops, this can then cause vasocon-striction, scarring, and retinaldetachment. Once the retina is in ahypoxic state and suffering inade-quate nutrition, its response is thegrowth of abnormal blood vessels,which often break and leak. One ofthe most common treatments forROP is, consequently, laser andcryotherapy of the aberrant bloodvessels. The majority of infants(>90%) with ROP are in themildest category, which is associat-ed with abnormal vision (e.g.,restricted visual field), but notblindness. Premature birth is, how-ever, common enough that theprevalence of severe ROP, which isassociated with retinal detachment,severe neovascularization andblindness, is still significant world-wide. As medical technologyimproves and the survival rates ofextremely premature, extremelylow birth weight infants increase,severe ROP will also likelyincrease in incidence.

The World Health Organizationhas estimated that about 190 mil-lion children under the age of fiveare deficient in vitamin A. 250 to500,000 of these children willbecome legally blind from the defi-ciency and most of those will bedead within a year. Vitamin A isessential for vision because, in theform of retinal, it binds with a pro-tein opsin (in its 11-cis configura-tion) to form photopigment.Retinal straightens (changes to itsall-trans-form) when exposed to

Figure 1: A schematic showing the crystalline lens and the neuralretina lining the back of the eye. The expanded retinaon the right shows the yellow macular pigments in theinner retinal layers.

Crystalline lens

Macularpigment Photoreceptors

Retina

(expanded)

190 million children aredeficient in vitamin A

light and it is this process that initiates the activation ofthe photorector. When a child is deficient, the morenumerous rods are initially affected and night blind-ness (nyctalopia) results. The idea that carrots are“good for your eyes” is based on the fact that carrotsare rich in �-carotene which is a pro-vitamin Acarotenoid that can be coverted to vitamin A.Glycoprotein synthesis and endothelial cell functionalso require vitamin A (now in the form of retinol).Hence, deficiency can lead to corneal dryness andulcerations, and eventually blinding, conditions thatare common in children from developing countries.

Diabetic retinopathy

Diabetes is pandemic and worsen-ing. The prevalence of diabetes isprojected to rise to 366 millionpeople by 2030, an increase ofalmost 40 percent since the year2000.10 The most common form ofdiabetes (Type II or adult-onsetdiabetes) is a disease characterizedby membrane insensitivity toinsulin. This insensitivity is due tomultiple factors, including geneticsusceptibility and overexposure toinsulin caused by excessive sugarintake. In the absence of sufficientglucose, insulin-resistant cells sendout angiogenic cytokines that pro-mote neovascularization. Tissueswith high metabolic needs, like theretina, are particularly affected.The retinopathy resulting from diabetic complicationsfollows a similar pattern to the retinopathy seen afterbirth in ROP: new, weak blood vessel growth occurs inorder increase sugar delivery to retinal tissues withhigh, unmet metabolic demand. Treatment proceduresare also similar to those for ROP: new blood vesselsare cauterized with lasers, often with the aid of photo-sensitizers (photodynamic therapy).

Age-related macular degeneration

AMD is a progressive neural degenerative conditionaffecting the macular region of the retina and the reti-nal pigment epithelium (or “RPE”). AMD is the lead-ing cause of blindness in developed countries and isthe third leading cause of blindness worldwide.2

AMD’s etiology is complex; the damage that ultimate-ly leads to AMD accrues over a lifetime, and that dam-age, once incurred, is thought to be irreversible.Traditionally, physicians have classified AMD into

two forms, “dry” and “wet”. The “dry” or nonexuda-tive form involves both atrophic and hypertrophicchanges in the retinal pigment epithelium (RPE)underlying the central retina (i.e. macula), as well asdeposits, called drusen, on the RPE. Patients withnonexudative AMD can and often do progress to the“wet” or exudative form of AMD, in which abnormalblood vessels develop under the retina, leak fluid andblood, and ultimately cause a blinding “disciform”scar in and under the retina in a relatively short amountof time. The exudative form is thought to be responsi-ble for the majority of blindness in patients with AMD.

Once AMD becomes exudative, laser photocoagula-tion and photodynamic therapy are the standard treat-ments to control the growth of new blood vessels.Treatment efficacy, however, remains low; thus, greatinterest exists in delaying the progression of AMD andmore effectively treating the factors leading to visionloss once AMD is diagnosed.

Although damage within the RPE (the supportivetissue behind the retina) is one of the primary develop-mental features of AMD, it is the loss of the overlyingphotoreceptors that ultimately leads to loss of visualfunction. Losses within the RPE and retina occurthroughout life. It is typically only later in life, howev-er, that the declination of visual function is observed.Indeed, older subjects and patients often classifiedwith “early or atrophic AMD” often present with min-imal losses in every day visual performance. The factthat visual function loss does not seem to parallel thedamage leading to the disease may be due to the fact

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Structure of a rod cell. Rod cells in the retina can function in lessintense light than can cone cells.

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that central nervous tissue (including the neural retina)is capable of compensating for this loss. Certainly, itwould be advantageous for the brain to compensate forage-related losses in order to maintain optimal visualfunction as long as possible.

Although damage to the retina accumulates asa monotonic function of age, this effect is probably notlinear. Children, for instance, tend to have very clearlenses, which transmit a higher percentage of energeticshorter-wave light. Photochemical damage to the reti-na and RPE is probably higher at this time (evidencedby increased accumulation of lipofuscin during adoles-cence) than later in life, when the lens yellows andtransmits less actinic light. Such observations have ledmany scientists to conclude that, although AMD ismanifest later in life, it reflects the accumulation ofdamage that occurs throughout life (e.g., Hammond etal, 2008) .11 AMD, ultimately, is a disease of aging,where loss accrues over time and at some point issevere enough that the disease process begins.

Disease prevention strategies

The conditions listed on the Priority Eye Diseases listare varied in their etiologies and treatment strategies,which makes drawing a single conclusion about howto handle the problem of increasing incidence of manyof these diseases difficult. Nevertheless, one point isclear: these conditions are often difficult to treat, andtheir treatment often requires expensive surgical inter-vention, which is impractical on a global scale.Furthermore, no efficacious treatment exists for someof these conditions (e.g., AMD), practical or other-wise. Consequently, as stated previously, emergingresearch should be focused on prevention of these con-ditions, rather than treatment alone.

In 2005, the World Health Organization preparedthe Vision 2020 Report, which made the striking claimthat approximately 80 percent of the world’s blindnessis preventable. There are many possible strategies forprevention, including renewed focus on controllingvectors that can cause eye disease, such as the black-fly, which carries the Onchocerca volvulus parasiteresponsible for Onchocerciasis. Programs aimed atimproving public health, sanitation, and reduction ofsexually transmitted infections such as Chlamydia mayalso reduce sight loss. In the developed world andincreasingly in developing countries too, strategies

aimed at combating diabetes and obesity may reducerisk for conditions such as Diabetic Retinopathy, andadequate sun protection may help reduce risk for ARC.

Many of the prevention strategies discussed aboveare promising. The bulk of the above strategies, how-ever, are single strategies focused on a single condi-tion, despite the fact that many of these conditionshave common etiological features. As shown above,oxidative stress is part of the etiology for ARC, AMD,diabetic retinopathy and ROP. It should be noted thatoxidative stress is also part of the etiologies of diseasessuch as cardiovascular disease and Alzheimer’s dis-ease and is the major component of aging itself.Inflammation and neovascularization are also commonto the bulk of these diseases. Perhaps the best preven-tive approach is, then, one that targets all of these com-mon issues. Diet is a likely candidate.

Nutrition as a preventive strategy

The Age-Related Eye Disease Study (AREDS, 2001)12

was the first large intervention trial to be sponsored bythe National Institutes of Health that examined thequestion of whether intervention with dietary nutrientscould influence the progression of eye disease in eld-erly, highly susceptible, individuals. The four treat-ments were placebo, antioxidants, zinc, or antioxidants+ zinc. The supplements contained (amount/day): 500mg vitamin C, 400 IU all-rac-�-tocopherol acetate, 15mg �-carotene, 80 mg zinc as zinc oxid with 2 mg cop-per as cupric oxide. This is now a common formulationthat is used by ophthalmologists to promote eye healthand retard disease progression. There were, however,several concerns about the formulation of these sup-plements. For example, �-carotene (not found in theeye, but the only carotenoid available at the time) wasused in lieu of the xanthophylls which are concentrat-ed in the vulnerable macula and are known to protectocular tissues. Notwithstanding these limitations, thestudy yielded strong results. The largest result was thatthe combination of the antioxidant cocktail and zincreduced the risk of disease progression by 25 percentfor subjects with intermediate drusen or advancedAMD in one eye (from 16 percent risk over five yrs to12 percent risk). Risk of vision loss was also reduced(around 19 percent) for these subjects. Since thatoriginal study, follow-up studies have focused onnutrients that are thought to be even more important tovisual health. For example, AREDS II (2007)13

included L and Z and found that these carotenoidswere independently related to risk: those individualsthat were in the highest quintile of dietary intake of Land Z had a 27 percent, 35 percent, and 55 percentlower probability of developing large or extensive

Emerging research should focus on disease prevention

intermediate drusen, neovascularAMD, or geographic atrophy,respectively. Another large follow-up (12-year longitudinal design,2009)14 focused on omega-fattyacids and found that individuals inthe highest quintile of omega-3intake (e.g., DHA) had 30 percentless change of developing centralgeographic atrophy and neovascu-lar AMD when compared to thosein the lowest quintile. If aggressivenutritional intervention can be soeffective at late stages, one caninfer that optimal diet, starting ininfancy and maintained over alifespan, could have even more dra-matic results.

A full description of all of thenutrients involved in the visual sys-tem would, of course, require a setof texts. What follows is simply ashort description of the two recentnutrients that were the focus of thelatests AREDs trials, polyunsatu-rated fatty acids such as docosa-hexaneoic acid (DHA) and the xan-thophylls L and Z.

Xanthophylls

L, its isomer Z and a novelcarotenoid, meso-zeaxanthin (MZ),formed in the retina itself, arefound ubiquitously in ocular tis-sues, such as cornea, crystallinelens and retina. In the retina, theyare the exclusive carotenoids locat-ed within the macula (here theyreach levels that are over 10,000times higher than those within cir-culating blood),5 where they aretermed macular pigment (MP). Alarge confluence of data (seeWhitehead, 2006)16 have consis-tently shown that L and Z protectthe lens, retina and retinal pigmentepithelium from the damage thataccrues from long-term exposure toactinic light and reactive oxygen.Data from Seddon et al.17 original-ly emphasized the importance ofthis prophylaxis on the prevention

of retinal disease. Seddon et al.found that individuals (n=356AMD cases, n=520 controls) in thehighest quintile of L+Z intake had a43 percent lower risk of AMDcompared with those in the lowestquintile. Direct measures of L andZ in retinal tissue supported thisstrong link to the disease. Forinstance, donor eyes with the high-est levels of macular pigment are82 percent less likely to have AMDwhen compared to donor eyes withthe lowest levels of MP.17,18 Manyrisk factors for AMD are correlatedwith low MP, including femalegender, smoking, iris color, andbody mass index (or “BMI”).19,20

A prospective study of 77,466female nurses and 36,344 malehealth workers showed that indi-viduals in the highest quintile ofcarotenoid intake (namely L and Z)had about a 20 percent less chanceof cataract extraction compared tothose in the lowest quintile ofintake.21,22

This protection by L and Z isbased on two complementarymechanisms: passive screening ofhighly energetic short-wave (blue)light and active quenching of reac-tive oxygen. Actinic blue light eas-ily reaches the retina, is focused onthe vulnerable macular area andcan convert inert oxygen into itsmore reactive forms. L and Zstrongly absorb this waveband oflight (400–500 nm) and can reducetransmission in the central maculaby as much as 98 percent. L and Zare found both in the inner retinallayers where they screen the vul-nerable outer retina, as well as thelipid membranes of receptoral outersegments. This latter placement isoptimal for protection against theperoxidation of membrane lipids. Land Z are known to quench thetriplet state of photosensitizers, sin-glet oxygen23 and oxygen radi-cals,24 react with free radicals,25,26

and retard the peroxidation of phos-

pholipids.27 For example, a cellculture study in human lens epithe-lial cells (where L and Z are alsofound in the intact eye) showed thatL and Z inhibited UVB-inducedlipid peroxidation by 47–57 per-cent.28 L supplementation reducestotal hydroperoxide levels (a mark-er of oxidative stress) and increasesantioxidant activity when measuredin the blood of newborns.29 Sinceinfancy represents a time of specialvulnerability,11 such protection islikely vital.

Docosahexaenoic acid

The fatty acid composition of neu-ronal cells, including those of theretina, appears to be central to opti-mal neural function. For instance,DHA is exceptionally dense in thelipid membranes of photoreceptors.This high concentration confersgreat fluidity to the receptoralmembrane. In the absence of a dietsufficient in DHA (a commonoccurrence with the declining qual-ity of diets), DHA is replaced bydocosapentaeonoic acid (or“DPA”). This replacement resultsin a significant loss in membranefluidity.30

DHA, along with anotherpolyunsaturated fatty acid, eicos-apentaenoic acid (or “EPA”), haveother important protective effects.They modulate retinal cell geneexpression and promote cellulardifferentiation and survival. Theyare also effective anti-inflammato-ry agents.31 DHA, for instance, is aprecursor for neuroprotectin D1 (or“NPD1”). NPD1 promotes RPEcell survival by inhibiting theinduction of pro-inflammatorygenes and apoptosis in response tooxidative stress.32,33 Animal mod-eling34 has shown that NPD1,RVDI (another DHA derivative),and RVE1 (an EPA derivative) pro-tect against retinal vascular dis-

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ease.34 Consistent with these studies, a recent meta-analysis35 showed that high intake of polyunsaturatedfatty acids was related to a 38 percent reduction ofAMD. The Blue Mountain Eye study36 has shown thateating fish (rich in polyunsaturated fatty acids) is asso-ciated with a 40 percent reduction in the incidence ofearly AMD.

Nutrition as a treatment strategy

Eye disease is ultimately characterized by sight loss.Recently, it has become quite clear that many nutrientshave the potential for ameliorating such loss. Forexample, Richer et al.37 tested the effects of L supple-mentation in a double-masked placebo controlledstudy of veterans (average age = 65 years) with earlystage AMD. They found that the L-treated groupshowed improvements in visual function, such asSnellen acuity. These palliative improvements weredirectly related to increases in their MP density.Olmedilla et al.38 tested the visual effects of L supple-mentation on ARC patients also using a double-masked placebo controlled design. They also foundimprovements in visual acuity in only those patientssupplemented with L. Similar to Richer et al., the ARCsubjects in the Olmedilla et al. study also showedreductions in glare sensitivity after the two-year L sup-plementation period.

Glare disability and discomfort are common prob-lems for the elderly and individuals with cataracts and

AMD. As the eye ages, lenticularcells become increasingly disor-dered and scatter light towards theback of the eye (about 70 percentof the scatter comes from the lens,most of the rest comes from thecornea). Stringham andHammond,39 studying young,healthy subjects, found a directrelationship (r = 0.76) between reti-nal L and Z levels and the ability towithstand scattered light in the eyeand recover from a blinding lightexposure. In a follow-up study,Stringham and Hammond40 sup-plemented subjects for six monthswith 12 mg of L and Z. This inter-vention raised subjects’ MP levelsand improved their ability to see

under conditions of disabling glare by 58 percent andsignificantly shortened their photostress recovery.

Effects on vision are not relegated to nutritionalinfluences on the eye itself. The brain is responsiblefor processing the signals that are initiated by the reti-na. Hence, effects on the brain might also be expectedto influence visual processing. This expectation is con-sistent with data showing that L and Z levels within theretina (a good proxy indicator for levels within thebrain) are related to faster visual processing speeds41,42

and even cognition.43 These central effects might beeven more pronounced when xanthophylls are com-bined with DHA.44 These effects may also be impor-tant for neural development. Meta-analyses (e.g.,SanGiovanni et al.45) of all available data suggest thatsufficient long-chain polyunsaturated fatty acid intakeis critical to early visual system development.Nutrients like L, Z and DHA might not only protect thevisual system but also promote its optimal functionand development.

Conclusion

Prior to the advent of effective antibiotics, infectiousdisease was the primary source of human morbidityand mortality. Infectious diseases are still quite com-mon in areas where medical facilities are still quitelimited. In developed countries, however, degenerativediseases such as acquired cancers, neurodegenerativedisease and cardiovascular disease are more prevalentand are expected to increase in incidence across theworld as the world’s population ages. These diseases,such as AMD and ARC, develop slowly over manyyears of life and have a disproportionately large impact

Many nutrients have the potential forameliorating sight loss

Lutein and zeaxanthin protect the retina by absorbing damaging‘blue’ light.

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upon the elderly. Because theydevelop slowly, however, lifestylethen becomes a much more seriouscontributor to their development.Optimal dietary behavior over thelifespan, for instance, is probablyof primary importance. Indeed,poor diet is a factor linking most ofthe acquired diseases emphasizedon the Priority Eye Disease list.

References

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3. World Health Organization. Priorityeye diseases. Geneva; 2010.

4. Hollyfield JG, Bonilha VL, RaybornME, et al. Oxidative damage-inducedinflammation initiates age-relatedmacular degeneration. Nat Med2008; 14: 194-198.

5. Despriet DDG, Klaver CCW,Witteman JCM, et al. ComplementFactor H polymorphism, comple-ment activators, and risk of age-relat-ed macular degeneration. J Am MedAssoc 2006; 296: 301-309.

6. Banh A, Bantseev V, Choh V, et al.The lens of the eye as a focusingdevice and its response to stress. ProgRetin Eye Res 2006; 25(2):189-206.

7. Truscott RJW. Age-related nuclearcataract – oxidation is the key. ExpEye Res 2005; 80: 709-25.

8. National Eye Institute. Report of thelens and cataract panel. Washington,DC; 2008.

9. Hellström A, Ley D, Hansen-Pupp I,et al. New insights into the develop-ment of retinopathy of prematurity –importance of early weight gain.Acta Pædiatrica 2009; 99(4): 502-8.

10. Wild S, et al. Global prevalence of

diabetes: estimates for the year 2000and projections for 2030. DiabetesCare 2004; 27(5):1047-53.

11. Hammond BR. A possible role fordietary lutein and zeaxanthin in visu-al development. Nutr Rev 2008;66(12): 695-702.

12. Age-Related Eye Disease StudyResearch Group. (2001). A random-ized, placebo-controlled, clinical trialof high-dose supplementation withvitamins C and E, beta carotene, andzinc for age-related macular degener-ation and vision loss. AREDS ReportNo. 8. Arch Ophthalmol., 2001;119:1417-1436.

13. SanGiovanni JP, Chew EY, ClemonsTE, et al (2007). The relationship ofdietary carotenoid and vitamin A, E,and C intake with age-related maculardegeneration in a case-control study:AREDS Report No. 22. ArchOphthalmol 125: 1225-1232.

14. Sangiovanni JP, Agrón E, ClemonsTE, et al. Omega-3 long-chainpolyunsaturated fatty acid intakeinversely associated with 12-year

progression to advanced age-relatedmacular degeneration. Arch.Ophthalmol. 2009; 127: 110–112.

15. Whitehead JA, et al. Macular pig-ment: A review of current knowl-edge. Arch Ophthalmol 2006;124:1038-45.

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Lisa M Renzi Billy R Hammond, Jr

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