Download Macular Carotenoids Conference

DOI: 10.5301/EJO.2013.11169
Eur J Ophthalmol 2013; 23 ( 4 ): 604-613
ABSTRACTS - Macular Carotenoids Conference - Cambridge, United Kingdom, July 10-12, 2013
Macular Carotenoids Conference
Downing College, University of Cambridge
Cambridge, United Kingdom
July 10-12, 2013
Lectures
LUTEIN AND ZEAXANTHIN: THE AUTOBIOGRAPHY
Britton G.
University of Liverpool, School of Biological Sciences, Crown Street, Liverpool,
United Kingdom
Nature makes a great diversity of carotenoids; more than 700 different ones
have been identified. In an ordinary diet, containing a good variety of fruit and
vegetables, we probably ingest about 100, and 20-30 can usually be detected
in the blood. And yet the macula specifically accumulates just two carotenoids,
the dihydroxy xanthophylls lutein and zeaxanthin. Why and how are these two
carotenoids so special? Every carotenoid has a unique structure and this determines its chemical and physical properties. Any biological function or action depends on these properties and on interactions of the carotenoid with
its environment. This talk will introduce lutein and zeaxanthin (including mesozeaxanthin) and explore what their structures tell us about factors such as their
shape, solubility, reactivity and stability, and interactions with light. The biological behaviour and functioning of lutein, zeaxanthin and meso-zeaxanthin must
be compatible with these properties, which may be modified by the physical or
molecular environment. Knowledge of these properties is therefore an essential
foundation for understanding the biological significance of these particular xanthophylls, including their presence and role in the macula.
We obtain lutein and zeaxanthin from natural or manufactured food, or from
health supplements. The form or physical state in which the carotenoids are
present in these sources is an important factor in determining bioavailability and
how efficiently they may be taken up into the body and tissues.
LUTEIN AND INFLAMMATION
Berendschot T.
University Eye Clinic Maastricht, The Netherlands
Lutein selectively accumulates in the primate retina and as a major component
of the macular pigment it plays an important role as a filter to prevent harmful
effects of blue light (Landrum, 1997). It also protects the retina from oxidative
damage by quenching free oxygen radicals (Khachik, 1997). Lutein also has
anti-inflammatory properties that may be important in the prevention of Agerelated Macular Degeneration (Kijlstra, 2012). They will be discussed as well as
recent studies on the role of lutein in the inflammatory pathway of the innate
immune system.
EFFECTS OF THE MACULAR CAROTENOIDS FROM EYE TO BRAIN, FROM
INFANCY TO OLD AGE
Hammond Billy R.
Behavioral and Brain Sciences Program, University of Georgia, Athens, GA, USA
The macular carotenoids influence many aspects of central nervous system
function. These effects extend from optical filtering within the eye to physiological activity of neurons within the brain. With respect to the latter, the macular carotenoids appear to enhance chromatic contrast, increase visual range, decrease
photostress recovery times, glare disability, and discomfort. Post-receptorally,
they have been linked to faster visual processing speeds as assessed by numerous tasks: e.g., macular pigment optical density (MPOD) is significantly (p<0.05)
related to fixed and variable reaction time, coincidence anticipation errors (estimating the arrival of a stimulus at a target location moving at varying velocity),
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and balance ability. Reduced processing speed is a central feature of cognitive decline and current data suggest that higher MPOD (likely a biomarker for
more central levels of lutein and zeaxanthin) is related to preservation of cognitive
function: e.g., our current data link (p<0.05) MPOD to executive cognitive functions in the healthy elderly and subjects with mild cognitive impairment. Taken together, the multiple effects of the xanthophylls on nervous system function seem
to manifest throughout life and address vulnerabilities that also seem to change
with age: e.g., increased actinic stress to the retina in infants and the elderly.
REFINING THE MEASUREMENT OF MPOD BY HETEROCHROMATIC
FLICKER PHOTOMETRY
Bone Richard A.
Department of Physics, Florida International University, Miami, USA
Purpose: To design a heterochromatic flicker photometer (HFP) for MPOD measurement which minimizes the difficulties that subjects often experience with a
traditional HFP, and which removes the effect of age-dependent lens yellowing
upon results.
Methods: MapcatSF™ is a blue/green LED-based HFP providing centrally
fixated 1.5 and 15° stimuli. With the 1.5° stimulus, subjects adjust the blue
intensity in the usual way to produce a flicker null. With the 15° stimulus, they
adjust for elimination of flicker around the periphery. Blue and green intensities are recorded by a photo-detector. A microprocessor computes the subject's lens-corrected MPOD as well as lens optical density, LOD, at 425 nm,
and lens equivalent age, LEA. Test-retest repeatability was assessed for 55
subjects.
Results: Subjects found the test easy, particularly the peripheral measurement. A Bland-Altman plot of the test-retest MPOD data provided an average
difference between two consecutive measurements of 0.00194, and limits of
agreement (±1.96 SD) of ± 0.079. Corresponding results for LOD and LEA were
-0.012±0.090 and -0.5±6.7 yr respectively.
Conclusions: We have developed an HFP with novel features, notably a centrally fixated, large stimulus for the peripheral part of the test. The test-retest
MPOD results for the MapcatSF™ were superior to those reported for other
instruments, including those employing physical techniques.
Disclosures: Science Advisory Board member, Guardion Health Sciences.
LUTEIN AND ZEAXANTHIN: FROM THE RETINA TO THE BRAIN
Johnson EJ.
Carotenoids & Health Laboratory, Jean Mayer USDA Human Nutrition Research
Center on Aging, Tufts University, Boston, MA, USA
Lutein and zeaxanthin (L/Z) may play a role in the prevention or delay the progression of cognitive decline. Among the carotenoids, L/Z are the only ones that
cross the blood-retina barrier to form macular pigment (MP) in the eye. Lutein
also preferentially accumulates in the human brain. To evaluate the relationship
between L/Z as MP and their levels in the human brain, matched macula and
brain tissue were analyzed for L/Z and significant relationships for both carotenoids were found. Therefore, MP may be a biomarker of L/Z in brain tissue.
This is of interest given our work in the Health Aging and Body Composition
Study in which MP levels were significantly associated with a variety of measures of cognition. Therefore, MP may be a potential biomarker of cognition.
Furthermore, we found a significant relationship between serum levels of L/Z
© 2013 Wichtig Editore - ISSN 1120-6721
ABSTRACTS - Macular Carotenoids Conference - Cambridge, United Kingdom, July 10-12, 2013
and cognition in the Georgia Centenarian Study. We also examined the relationship between cognition and L/Z levels in brain tissue of descendants from this
study. Among the carotenoids, lutein was most consistently associated with
a range of cognitive measures. Lutein concentrations in the brain were also
significantly lower in individuals with mild cognitive impairment compared to
those with normal cognition. Lastly, in a double-blinded, placebo controlled trial
in older adults involving lutein supplementation, alone or in combination with
docosahexaenoic acid (DHA) it was reported that following supplementation,
verbal fluency scores improved significantly in the DHA, lutein and combined
treatment groups. Memory scores and rate of learning improved significantly
in the combined treatment group, who also displayed a trend toward more efficient learning. These findings suggest that lutein supplementation may have
cognitive benefit for older adults. These observations suggest that lutein can
influence cognitive function in older adults. As with the adult brain, lutein is the
major carotenoid in pediatric brain tissue. However, the lutein’s contribution to
total carotenoids is 60%, twice that found in adult brain, suggesting that lutein
may also have a role in early neural development.
RETINAL CAPTURE OF THE MACULAR CAROTENOIDS
Bernstein PS.
Moran Eye Center, University of Utah, Salt Lake City, Utah, USA
Over 600 carotenoids are found in nature, and 30-50 are part of the normal human diet, yet only 10-15 are routinely detectable in the human serum, and just
two carotenoids, lutein and zeaxanthin and their various metabolites including
meso-zeaxanthin, 3’-epilutein, and 3’-oxolutein, are present in the retina. The
biochemical mechanisms underlying this remarkable selectivity of uptake into
the eye have been a focus of my laboratory for the past two decades. In the
first part of this talk, I will review the work from my laboratory and others to
characterize the pathways these dietary xanthophylls must take from the gut
to the macula with special attention to cellular transporters, nonspecific carrier proteins, specific binding proteins, and metabolic enzymes. Next, I will report recent clinical studies from my group on the development of the macular
pigment in infants and children including the influence of maternal carotenoid
status on newborn infant macular pigment optical density (MPOD). Finally, I will
conclude with an update on the quest to identify the biochemical mechanisms
underlying the last frontier of macular carotenoid metabolism, the conversion of
lutein to meso-zeaxanthin in the human retina.
EFFECTS OF LUTEIN SUPPLEMENTATION ON MACULAR PIGMENT OPTICAL DENSITY AND VISUAL ACUITY IN PATIENTS WITH AGE-RELATED
MACULAR DEGENERATION
Schmetterer L.1,2, Weigert G.3, Kaya S.1, Werkmeister R.2, Gahöfer G.1
1
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria; 2Center of Medical Physics and Biomedical Engineering, Medical University
of Vienna, Vienna, Austria; 3Department of Ophthalmology, Medical University of
Vienna, Vienna, Austria
In the present study (LISA = Lutein Intervention Study Austria) we hypothesized that lutein supplementation increases macular pigment optical density
(MPOD) as measured using optical reflectometry. In addition, we investigated whether lutein supplementation improves visual acuity (VA) and macular
function (mean differential light threshold, MDLT) as assessed with microperimetry. One hundred twenty six patients with AMD were included in this
randomized (2:1), placebo-controlled, double masked parallel group study.
Lutein or placebo was administered for 6 months. MPOD was measured using a custom-built reflectometer. An illumination field of approx. 2 degrees
centered at the fovea was used. VA was determined with ETDRS charts and
MDLT was measured using a commercially available microperimeter (Microperimeter MP-1; Nidek Technologies, Padova, Italy). Lutein significantly increased MPOD by 27.9±2.9% (p<0.001 versus placebo). No significant effect
of lutein supplementation on MDLT (p=0.096 versus placebo) or VA (p=0.070
versus placebo) was seen although a tendency towards an increase was
seen. A significant correlation was found between the increase in MPOD after
6 months and the increase in MDLT after 6 months (r=0.25, P=0.027) and
between the increase in MPOD after 6 months and the increase in VA after 6
months (r=0.27, P=0.013). The present study shows that lutein supplementation increases MPOD as assessed with an objective method. The correlation
between the change in MPOD and the change in VA and MDLT indicates that
patients who show a pronounced increase in MPOD also benefit in terms of
visual function.
CLINICAL DETERMINANTS OF MACULAR PIGMENT: THE ALIENOR STUDY
Rougier M.1, Delcourt C.2,3, Delyfer M.1,2,3, LeGoff M.2,3, Malet F.1, Dartigues JF.2,3,
Korobelnik JF.1,2,3
1
Service d'Ophtalmologie, CHU de Bordeaux, Bordeaux, France; 2INSERM,
ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France;
3
Université Bordeaux Segalen, Bordeaux, France
Purpose: To determine whether individuals’ clinical parameters are associated with differences in macular pigment optical density measured with the two
wavelength autofluorescence method in a population-based study of elderly
subjects.
Methods: Subjects of the Alienor Study were recruited from an ongoing population-based study (Three City [C3] Study) on the vascular risk factors for
dementia. Subjects were initially recruited in 1999-2001, and were followed-up
every two years. In 2006-2008, an ocular examination was proposed, completed about 18 months later for those diagnosed with early ARM at baseline. An
equal number of subjects without early ARM was included. The eye examination
included: (1) a measurement of macular pigment optical density (MPOD) using
two wavelength autofluorescence method (Modified HRA I, Heidelberg Engineering, Heidelberg, Germany); (2) lens opacities gradation; (3) central retinal
thickness. General examination included: BMI, smoking and plasma fatty acids,
lutein and zeaxanthin. Among the 293 included subjects (534 eyes), associations of MPOD with the clinical data were estimated using multivariate mixed
linear regression models, taking into account data from both eyes and their
intra-individual correlations.
Results: MPOD within 0.5° increased with increasing plasma lutein and zeaxanthin (+0.064 for 1-standard deviation increase, p<0.0001) and decreased with
increasing BMI (-0.012 for 1 kg/m2, p<0.0001). No association was found between MPOD and plasma omega 3 fatty acids or smoking status. MPOD within
0.5° was higher in eyes having undergone lens extraction (+0.093 optical density units, p=0.03) and lower in eyes with nuclear cataract (-0.19 optical density
units, p=0.0001), but was not different according to cortical opacities. MPOD
within 0.5° tended to be lower in early AMD, but this association did not reach
statistical significance (-0.030, p=0.16). We also found no significant associations of MPOD with abnormalities of autofluorescence, epiretinal membranes or
retinal thickness at any eccentricity.
Conclusions: The present study, performed in elderly subjects, confirmed the
strong association of MPOD with plasma carotenoids and BMI. Lens status appears to affect macular pigment optical density measured using the two wavelength autofluorescence method.
Keywords: macular pigment, macular degeneration, epidemiology, risk factors
Financial support: Laboratoires Théa.
Conflict of interest: C Delcourt: consultant for Bausch + Lomb, Laboratoires
Théa, Novartis, MN Delyfer: consultant for Laboratoires Théa., JF Korobelnik:
consultant for Alcon, Allergan, Bayer Pharma, Carl Zeiss Meditec, Novartis,
Laboratoires Théa, MB Rougier: consultant for Allergan, Bausch + Lomb, Kemin, Laboratoires Théa.
METABOLISM OF LUTEIN AND ZEAXANTHIN IN THE OCULAR TISSUES
OF HUMANS, MONKEYS, AND NON-PRIMATE ANIMAL MODELS
Khachik F.
Department of Chemistry & Biochemistry, University of Maryland, USA
Purpose: To determine the stereochemistry of (3R,3'R,6'R)-lutein and (3R,3'R)zeaxanthin and their metabolites in human ocular tissues in comparison to plasma and liver. Similarly, characterize carotenoids in the eye tissues and plasma
of monkeys, quails, and frogs to determine an appropriate animal model for
metabolic studies.
Method: Stereoisomers of carotenoids and their metabolites from pooled human plasma, liver, RPE/choroid, ciliary body, iris, and lens were characterized
by HPLC on a chiral column. Carotenoids and their metabolites in extracts from
quail and frog plasma, liver, and ocular tissues were similarly characterized.
Results: (3R,3'R,6'R)-Lutein, (3R,3'R)-zeaxanthin, (3R,3'S; meso)-zeaxanthin,
3'-epilutein, 3'-ketolutein, and lycopene were detected in nearly all human ocular tissues. (meso)-Zeaxanthin was absent in human plasma and liver but was
present in human macula, retina, and RPE/choroid. The carotenoid profiles in
quail and frog ocular tissues were somewhat similar to humans. (3S,3’S)-Zeaxanthin was found in frog’s retina, plasma, and liver.
Conclusions: Transformations of carotenoids in the human eye involve a series of oxidation-reduction and double-bond isomerization reactions. Quail
and frog appear to possess the appropriate enzymes for conversion of dietary
© 2013 Wichtig Editore - ISSN 1120-6721
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ABSTRACTS - Macular Carotenoids Conference - Cambridge, United Kingdom, July 10-12, 2013
(3R,3'R,6'R)-lutein and (3R,3'R)-zeaxanthin to the same metabolites observed
in humans and thus are appropriate for metabolic studies.
THE ROLE OF THE MACULAR CAROTENOIDS, LUTEIN (L), ZEAXANTHIN
(Z), AND MESO-ZEAXANTHIN (MZ) IN THE EYE
Landrum JT.
Department of Chemistry and Biochemistry, Florida International University,
Miami, Florida, USA
This talk will review and summarize the nature and roles of the carotenoids lutein, zeaxanthin, and meso-zeaxanthin and their potential functions within the
retina. The distribution and levels of the macular carotenoids are consistent with
active transport and regulation of their accumulation within the macula. It is now
widely recognized that meso-zeaxanthin is a retinal metabolite of L. The maturation of the distributions of the macular pigments within the primate and human
retina offers insight into the existence ofpossible differential functions associated with these three macular xanthophylls. Their unique distributions within and
across the retina suggest that they function in distinctly different ways. Emerging evidence supports the argument that the xanthophylls fill a physiological role
in the retina as antioxidants and regulators of the inflammatory pathways. The
discussion will emphasize the ability of the macular xanthophylls to function as
a blue-light filter, directly interact with reactive oxygen species disrupting radical oxidation of membrane lipids as well as the probability that theyare involved
in regulation of cellular pathways associated with the inflammation response.
THE ROLE OF CAROTENOIDS IN THE EYE FOR VISUAL PERFORMANCE
Loughman J.1,2
1
Optometry Department, School of Physics, College of Sciences and Health,
Dublin Institute of Technology, Kevin Street, Dublin, Ireland; 2African Vision Research Institute, Faculty of Health Sciences, University of KwaZulu Natal, Durban, South Africa
The selective accumulation at the macula of only three dietary carotenoids,
suggests an exquisite biological selectivity for lutein, zeaxanthin and mesozeaxanthin at the site of maximum visual acuity in the human retina. Macular
pigment (MP) has ideal properties, in terms of location and spectral absorbance,
to be beneficial for visual performance and experience. Longer life expectancy,
increased exposure to short wavelength light, modern visual demands, and the
increasing incidence of ocular disease heightens the importance of optimising visual performance, and preserving such performance into old age. Recent
evidence suggests that, among normal subjects and those with age-related
macular degeneration (AMD), lutein supplementation over a one year period has
beneficial effects in terms of improvements in macular pigment optical density
and preservation of visual acuity. Furthermore, supplementation with combined
lutein and zeaxanthin has been observed to yield benefits in terms of the amelioration of functional deficits observed by multifocal electroretinography among
early AMD subjects, although the effects on measures of contrast sensitivity and
visual acuity proved less conclusive. Importantly, it has also recently been observed that the effect of supplementation on visual performance among normal
subjects is maximal for supplements containing all three macular carotenoids,
including meso-zeaxanthin. Improvements in contrast sensitivity and glare disability over the time course of supplementation were only significant for subjects
consuming all three macular carotenoids, and although high dose lutein and
meso-zeaxanthin retain the capacity to increase MP levels and affect vision, the
effects in isolation are delayed and reduced in comparison to the synergistic
effects observed for the combined supplement.
ENVIRONMENTAL AND GENETIC DETERMINANTS OF MACULAR PIGMENTS AND RISK FOR AGE-RELATED MACULAR DEGENERATION
Mares JA.1, Meyers KJ.1, Johnson EJ.2
1
University of Wisconsin School of Medicine and Public Health, Department of
Ophthalmology and Visual Sciences, Madison, WI, USA; 2Jean Mayer USDA
HNRCA at Tufts University, USA
Macular pigment density levels vary more than ten-fold across individuals.
Primary determinants of macular pigment optical density (MPOD) are levels of
macular carotenoids in the diet and blood. However, current evidence suggests
that a large number of other environmental and genetic exposures influence
MPOD. Some of the known genetic determinants are common variants in genes
related to carotenoid transport, uptake, and metabolism, many of which are also
related to age-related macular degeneration (AMD).
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Several other determinants of MPOD can be grouped into conditions and genotypes associated with processes thought to encourage AMD and other chronic
diseases of aging. These include metabolic syndrome (abdominal obesity, diabetes, and high blood triglycerides and genotypes associated with abnormal
blood lipids), oxidative stress (low dietary antioxidants, smoking and genotypes
associated with oxidative stress) and inflammation (low serum vitamin D or
omega-3 fatty acids and high C-reactive protein.) Low scores on composite
measures of healthy diet and/or lifestyles which influence all three of these processes are related to lower MPOD.
Macular pigment optical density is a multi-factorial phenotype which may be an
early biomarker for risk of age-related macular degeneration later in life. Some,
but not all, cross-sectional studies suggest that higher macular pigment density is related to lower risk for age-related macular degeneration. Data from
prospective studies are needed to determine whether macular pigment density
could predict risk for age-related macular degeneration and other chronic diseases of aging.
THE JOINT ROLES OF XANTHOPHYLLS AND OMEGA-3 FATTY ACIDS IN
MACULAR DISEASE: INSIGHTS FROM A NONHUMAN PRIMATE MODEL
Neuringer M.1,2, Renner L.1
1
Oregon National Primate Research Center, Oregon Health & Science University,
Portland, Oregon, USA; 2Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA
Purpose: Evidence for roles of xanthophylls and omega-3 fatty acids in macular
health comes from human epidemiological and supplementation studies. While
AREDS2 tests effectiveness of supplementation of these nutrients in AMD patients, nonhuman primate studies provide the opportunity to study the inverse
situation of lifelong dietary deprivation in an animal model with naturally-occurring maculopathy.
Methods: Rhesus monkeys were fed strictly-controlled diets lacking xanthophylls from infancy to old age and therefore had retinas lacking macular pigment. Subgroups received 1) very low or 2) adequate levels of omega-3 fatty
acids as 18:3w-3, or 3) the long-chain forms EPA and DHA.
Results: Half of the monkeys lacking xanthophylls developed drusen by
15 years of age (equivalent to 45 human years), compared to 20% in monkeys
fed normal diets. Some of those also deficient in omega-3 fatty acids proceeded
to undergo atrophic changes resembling dry AMD. In all cases, the area of atrophy appeared in a crescent 1 mm superior to the fovea. In addition, MRI studies
demonstrated differences in functional connectivity within the visual pathway
in the omega-3 fatty acid deficient group.
Conclusions: It has been proposed that sparing of the central fovea in AMD
may be due to its high xanthophyll concentration; however, in our model this
sparing occurs in the absence of macular pigment. Advanced atrophic maculopathy is not observed in macaque monkeys fed normal diets, so its presence
in animals deprived of both xanthophylls and omega-3 fatty acids strongly supports the importance of these nutrients for AMD protection
OCCURRENCE OF THE MACULAR CAROTENOIDS IN EDIBLE FOODS
Nolan JM., Mendes Pinto MM., Meagher K., Kashani S., Beatty S.
Macular Pigment Research Group, Waterford Institute of Technology, Waterford,
Ireland
The carotenoids lutein (L), zeaxanthin (Z), and meso-zeaxanthin (MZ) accumulate in the central retina, where they are collectively known as macular pigment
(MP). MZ, Z and L are the dominant carotenoids at the epicenter, mid-periphery
and periphery of the macula, respectively. There is a growing and evidencebased consensus that MP is important for optimal visual performance, because
of its short wavelength light-filtering properties and consequential attenuation of
chromatic aberration, veiling luminance and blue haze. It has also been hypothesized that MP may protect against age-related macular degeneration because
of the same optical properties and also because of their antioxidant properties.
An understanding of the origins of these carotenoids is therefore required.
Studies have shown that L and Z are plentiful in many foodstuffs typical of a
western diet (e.g. spinach, kale, corn and egg). It has been shown that MZ is
generated from L in the primate retina, but challenges inherent in the separation and quantification of MZ have resulted in a paucity of data on the content
of this carotenoid in foodstuffs. As a consequence, the few studies that have
investigated MZ have, perhaps, been disproportionately influential in the ongoing debate about the origins of this macular carotenoid. Certainly, the narrative
that retinal MZ is derived wholly and solely from retinal L is not conclusive and
needs to be revisited. The PI is supported by The European Research Council
grant 281096 and The Howard Foundation.
© 2013 Wichtig Editore - ISSN 1120-6721
ABSTRACTS - Macular Carotenoids Conference - Cambridge, United Kingdom, July 10-12, 2013
SUPPLEMENTATION WITH THREE DIFFERENT MACULAR CAROTENOID
FORMULATIONS IN PATIENTS WITH EARLY AMD: MOST REPORT 2
Beatty S.1, Akuffo KO.1, Stack J.1, Howard AN.2, Nolan JM.1
1
Macular Pigment Research Group, Waterford Institute of Technology, Waterford, Ireland; 2Howard Foundation, Cambridge, United Kingdom
Purpose: To investigate the impact of three different macular carotenoid formulations on macular pigment optical density (MPOD) and visual performance, in
subjects with early age-related macular degeneration (AMD).
Methods: Fifty subjects were assigned to one of three intervention Groups:
18 in Group 1 (20 mg/day lutein [L], 2 mg/day zeaxanthin [Z]), 17 in Group 2
(10 mg/day meso-zeaxanthin [MZ], 10 mg/day L, 2 mg/day Z), and 15 in Group 3
(17 mg/day MZ, 3 mg/day L, 2 mg/day Z). Study visits were at baseline, six, 12
and 24 months. MPOD was measured using customised heterochromatic flicker
photometry. Visual function was assessed using corrected distance visual acuity (CDVA), letter contrast sensitivity (CS) and CS (in presence and absence
of glare) using the Functional Vision Analyser (FVA).
Results: A statistically significant increase in MPOD was observed in all Groups
at all measured eccentricities (P<0.05), with the exception of a non-significant
increase in MP at 0.25° in Group 1 (P=0.102), and a non-significant increase in
MP at 1.0° in Group 3 (P=0.078). Enhancements in visual function parameters
were more common in Group 2 and Group 3 (i.e. the formulations containing high
amounts of MZ); for example, statistically significant improvements in letter CS
were seen at low spatial frequencies (1.2cpd, P=0.018) in Group 2 and at high
spatial frequencies (6.0 cpd, P=0.042, 9.6 cpd P=0.042 and 15.15 cpd, P=0.008)
in Group 3, with no significant change found in Group 1 (P>0.05, for all).
Conclusion: In subjects with early AMD, augmentation of MP across its spatial
profile and enhancements in CS can be best achieved following supplementation with a formulation that includes high doses of MZ in combination with
L and Z.
NEW APPROACHES TO PREVENTION OF AMD
Humphries P.
The Ocular Genetics Unit, Institute of Genetics, Trinity College Dublin, Ireland
We recently reported a procedure for modulating the inner blood retina barrier
(iBRB), by reversible down-regulation of transcripts encoding the tight-junction
protein, claudin-5 in endothelial cells of the retinal microvasculature, allowing
efficient systemic access of low molecular weight compounds into the retina
and used this system to preserve vision in a number of murine models (1). The
technique was further developed for ocular use by incorporating a claudin-5
shRNA gene into AAV2/9 vector. The virus is injected once-off into the retina
where it transduces vascular endothelial cells. Treatment of animals with doxycycline induces claudin-5 suppression, allowing peripherally administered
low molecular weight drugs to access the retina with high efficiency. Using
this system we demonstrated suppression of choroidal neovascularization
(CNV) in murine retinas by systemic delivery of VEGF receptor antagonists,
sunitnib and 17-AAG (2). This procedure can be used to non-invasively deliver any drug to the retina up to a MW of approx 1 kD. Following a second
line of investigation, we have recently shown that the NLRP3 inflammasome
has a protective role in age-related macular degeneration through the induction of IL-18 by drusen components (3). Incubation of ARP19 and vascular
endothelial cells with IL-18 inhibits VEGF. Moreover, laser-induced choroidal
neovascular lesions (CNV) are much greater in IL-18-/- mice and inoculation
of IL-18 antibody into the eyes of wild-type mice exacerbates laser-induced
CNV. The current implications of these observations in terms of prevention of
AMD will be outlined.
References
1. Campbell M, Nguyen AT, Kiang AS, Tam LC, Gobbo OL, Kerskens C, Ni
Dhubhghaill S, Humphries MM, Farrar GJ, Kenna PF, Humphries P. An experimental platform for systemic drug delivery to the retina. Proc Natl Acad
Sci U S A. 106(42), 17817-22, 2009.
2. Campbell M, Humphries MM, Nguyen ATH, Gobbo OL, Tam LCS, Suzuki M,
Hanrahan F, Ozaki E, Farrar G-J, Kiang A-S, Kenna PF, Humphries P. Systemic low molecular weight drug delivery to pre-selected neuronal regions.
EMBO Mol Med, 3, 235-245, 2011.
3. Doyle SL, Campbell M, Ozaki E, Salomon RG, Mori A, Kenna PF, Kiang
A-S, M. Humphries M, Lavelle E, O¹Neill L, Hollyfield JG and Humphries P.
NLRP3 plays a protective role during the development of age related macular degeneration through the induction of IL-18 by drusen components. Nature Medicine 18(5) 791-798, 2012.
© 2013 Wichtig Editore - ISSN 1120-6721
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ABSTRACTS - Macular Carotenoids Conference - Cambridge, United Kingdom, July 10-12, 2013
Posters
DIETARY AND LIFESTYLE RISK FACTORS ASSOCIATED WITH AGERELATED MACULAR DEGENERATION: A HOSPITAL BASED STUDY FROM
SOUTHERN INDIA
Nidhi Bhatiwada1, Mamatha Bangera Sheshappa1, Padmaprabhu Chamrajnagar
Anantharajiah2, Pallavi Prabhu2, Baskaran Vallikannan1
1
Department of Biochemistry and Nutrition CSIR-Central Food Technological
Research Institute, Mysore, Karnataka, India; 2Sushrutha Eye Hospital, Mysore,
Karnataka, India
Purpose: To assess the association of dietary carotenoids and life style variables with the risk of age-related macular degeneration (AMD).
Method: It is a cross-sectional hospital based study of 3549 subjects (2090
men & 1459 women), aged ≥45 years, who attended Sushrutha Eye Hospital in
Mysore, India. Participants underwent ocular evaluation and were interviewed
for lifestyle variables and dietary intake of carotenoids by structured food frequency questionnaire.
Results: Either form of AMD was detected in 77 (2.2%) participants. Early and
late AMD was present in 63 (1.8%) and 14 (0.4%) subjects, respectively. Binary
logistic analysis showed that the incidence of AMD was significantly higher with
increasing age (Odds ratio [OR] 1.17; 95% CI 1.13-1.22), family history of AMD
(OR 7.12; 95% CI 2.34-13.81) and diabetes (OR 3.97; 95% CI 2.11-7.46). However, AMD was significant among cigarette smokers (OR 5.58; 95% CI 0.887.51) and alcoholics (OR 4.85; 95% CI 2.45-12.22). Dietary lutein/zeaxanthin
(L/Z) and b-carotene intake were associated (p<0.001) with the reduction in risk
for AMD, with an OR of 0.38 (95% CI 0.33-0.69) and 0.65 (95% CI 0.42-0.86),
respectively.
Conclusions: Higher dietary intake of carotenoids, especially L/Z was associated with lower risk for AMD. Risk of AMD was found to be higher among patients with diabetes or family history of AMD. Cessation of smoking and alcohol
may reduce the risk of AMD.
Disclosure: None.
THE EFFECTS OF LUTEIN ON INFANT BRAIN DEVELOPMENT: ASSESSMENT USING A NOVEL TEMPORAL DEVICE
Janet E. Frick, Sarah E. Saint, Kevin O’Brien, B. Randy Hammond
Infant Attention Lab, Department of Psychology, University of Georgia, Athens,
GA, USA
Purpose: The capabilities of the visual system develop at dramatically different
rates. Hyper-acuity, for instance, is not mature until the teen years. Temporal processing (TP), however, matures between 3-6 months. This is interesting since TP
is known to be determined cortically and is related to lutein status in adults. Individual differences in its early development, however, are unknown. Hypothesis:
Babies who are breastfed, or given formula containing lutein, will have improved
thresholds and faster TP compared to infants fed a formula without lutein.
Method: We designed a novel apparatus for measuring TP in 3-6 month old
infants. This device is based on electronically driven super-bright white LEDs
that are optically delivered to two diffusing screens (8 deg), each 22 deg L/R
of midpoint (presenting infant-friendly shapes and patterns). One screen has a
flickering stimulus while the other screen, luminance-matched, is solid. A preferential looking task determines the babies’ ability to detect the flickering target.
Absolute thresholds for detecting flicker are determined using classic behavioral
methodology (video analysis and blind observer determination).
Results: Testing of infant subjects is on-going. Although past data suggest little
age-related change in the overall temporal function, our preliminary data indicate
an increase in the high-frequency cut-off value. Current averages are 40 Hz in
infants (<12 months), 64 Hz in children (age 8-11), and 72 Hz in our adult subjects
(age 19-43), with a correlation of r=0.44 between age and CFF threshold (p<.05).
Additional developmental data will be presented at the conference.
Conclusions: Expected differences in TP for infants who do and do not receive
dietary lutein in early infancy will provide highly novel information about the
cognitive and neural impacts of lutein status early in the lifespan.
Disclosure: None.
REPEATABILITY OF A NEW HETEROCHROMATIC FLICKER PHOTOMETER
(HFP) FOR MEASURING MACULAR PIGMENT OPTICAL DENSITY
Anirbaan Mukherjee, Richard A Bone
Florida International University, Miami, Florida, USA
Purpose: To evaluate an LED-based (HFP) for measuring macular pigment optical density (MPOD) that incorporates changes in luminous efficiency with age.
This can otherwise lead to an apparent decline in the MPOD with age.
608
Methods: Mapcat SF, a central fixation HFP, uses LEDs for the flickering stimuli
and bright background. Subjects adjusted the blue intensity to obtain a flicker
null for a 1.5° stimulus. For a 14° stimulus, a flicker null was obtained in the
periphery. MPOD was computed based on an age-related luminosity function
[J. Opt. Soc. Am. A18, 2659 (2001)]. The apparent effect of age on MPOD was
investigated by simulating subjects with a range of ages and MPOD. We then
calculated their apparent MPOD by not including an age correction for luminous
efficiency.
Results: 53 subjects were recruited. Test-retest results were analyzed using
a Bland-Altman plot. The average difference in MPOD was 3.52e-3. Limits of
agreement (±1.96 SD) were ±0.083. Comparison with other instruments indicated superior repeatability of the Mapcat. From the simulation study, an apparent age-related decline in MPOD of (1.44±0.51) e-2 per decade was observed,
comparable to other studies on MPOD and age.
Conclusion: We successfully demonstrated high degree of repeatability of the
Mapcat and the importance of the changing luminous efficiency with age on the
measurement of MPOD.
Disclosure: Mukherjee: NONE. Bone: Scientific Advisory Board, Guardion Health
Sciences.
TOXICITY STUDY OF MESO-ZEAXANTHIN IN RODENTS
Xinde Xu, Lihua Zhang, Bin Shao, Xiaoxia Sun
Zhejiang Medicine Co., Ltd. Xinchang Pharmaceutical Factory, Xinchang,
Zhejiang Province, P. R. China
Purpose: To assess the potential toxicity of meso-zeaxanthin which was obtained from double bond isomerization of lutein, by investigating its acute oral
toxicity, subchronic toxicity and genotoxicity.
Method: In the acute oral toxicity study, SD rats and ICR mice were administered with meso-zeaxanthin at 10000 mg/kg body weight (bw) for two weeks by
intragastric gavage. In the subchronic study, SD rats (10/sex/group) were administered at dose levels of 0, 300, 600 and 1200 mg/kg bw/day for 90-days by
oral gavage. Ames test was administered at 5000, 1000, 200 and 40 μg/plate,
mice bone marrow erythrocyte micronucleus test and sperm abnormality assay
were performed at three different groups with 5000, 2500, 1250 mg/kg bw/day,
a negative and a positive group as control.
Results: No compound-related mortality and clinical toxicity as well as genotoxicity was observed, except that the number of liver cells with vacuolar
degeneration increased in 1200 and 600 mg/kg bw/day dose groups. Mesozeaxanthin at dose of 300 mg/kg bw/day was well tolerated in rats.
Conclusion: No acute toxicity and genotoxicity were found in rodents, subchronic toxicity study indicated that safety dose of meso-zeaxanthin is 300 mg/kg bw/
day in rats. The no-observed-adverse-effect-level (NOAEL) of meso-zeaxanthin in
rats is 300 mg/kg bw/day when administered orally for 90-day. Application of a
100-fold safety factor to the rat study, the ADI level is 3 mg/kg bw/day.
Disclosure: None.
A PROSPECTIVE STUDY OF DIETARY OMEGA-3 FATTY ACIDS AND THE
RISK OF AGE-RELATED MACULAR DEGENERATION IN US WOMEN
Juan Wu1, Eunyoung Cho3, Debra A. Schaumberg2,4,5, Srinivas M. Sastry6, Walter
C. Willett1,2,3
1
Department of Nutrition, Harvard University School of Public Health, Boston,
MA, USA; 2Department of Epidemiology, Harvard University School of Public
Health, Boston, MA, USA; 3Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School,
Boston, MA, USA; 4Division of Preventive Medicine, Department of Medicine,
Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA;
5
Department of Ophthalmology & Visual Sciences, University of Utah, Salt Lake
City, UT, USA; 6Suburban Hospital, Bethesda, MD, USA
Purpose: To examine whether dietary omega-3 fatty acids affect the incidence
of age-related macular degeneration (AMD).
Method: From 1984 to 2008, we prospectively followed 67,206 women aged
≥50 y in the Nurses’ Health Study who had omega-3 fatty acid intake assessed
by a validated food frequency questionnaire and were free of AMD, cancer, cardiovascular disease and diabetes at baseline.
Results: We confirmed 1,258 AMD cases with 672 early and 586 late AMD. Comparing the highest quintile to the lowest of docosahexaenoic acid (DHA) intake,
the multivariate-adjusted hazard ratios (HR) for total, early and late AMD were
0.81 (95% CI, 0.66, 1.00), 0.63 (0.48, 0.84; p trend, 0.003), and 1.07 (0.80, 1.43).
© 2013 Wichtig Editore - ISSN 1120-6721
ABSTRACTS - Macular Carotenoids Conference - Cambridge, United Kingdom, July 10-12, 2013
The results were similar for eicosapentaenoic acid (EPA). For alpha-linolenic acid
(ALA), the corresponding HRs were 1.26 (1.00, 1.58), 1.43 (1.05, 1.96; p trend,
0.02) and 1.08 (0.77, 1.51). Compared with women who consumed <1 serving/
mo of fish, women who consumed ≥5 servings/wk had a HR of 0.49 (0.27, 0.90;
p trend, 0.002) for early AMD. The inverse associations between DHA and total
and early AMD were more evident in women aged <70 y (p for interaction, 0.03)
and those who took ≥1 tablet of aspirin/wk (p=0.06).
Conclusion: Both DHA and EPA were associated with decreased risk of early
AMD but not late AMD. ALA was associated with increased risk of early AMD
and warrants further investigation. Higher intake of fish may benefit primary prevention of AMD.
Disclosure: None.
LUTEIN AS A NEUROPROTECTANT IN RETINAL ISCHEMIA/REPERFUSION
INJURY
Amy C.Y. Lo1,2, Suk-Yee Li1, Frederic KC Fung1, David Wong1,2
1
Department of Ophthalmology, The University of Hong Kong, Hong Kong;
2
Research Centre of Heart, Brain, Hormone and Healthy Aging, Li Ka Shing
Faculty of Medicine, The University of Hong Kong, Hong Kong
Purpose: Retinal ischemia/reperfusion (I/R) occurs in many ocular diseases and
causes neuronal death. The effects of lutein on retinal neurons and Muller cells
after I/R injury were studied.
Method: Unilateral retinal I/R was induced in mice with/without lutein treatment.
Retinal function was assessed by flash ERG. In retinal sections, viable RGC
count, apoptosis, oxidative stress marker expression, and GFAP activation were
studied. Lutein’s effects were further evaluated in cultured RGC-5 and rat Müller
cells (rMC-1) challenged with either cobalt chloride or hydrogen peroxide. Levels of IL-1β, Cox-2 and NF-κB were examined by Western analysis.
Results: Lutein treatment minimized deterioration of b-wave/a-wave ratio in
retinal I/R injury. Less cell loss, decreased apoptotic cells, decreased NT and
nuclear PAR immunoreactivity, and less GFAP up-regulation were observed in
lutein-treated I/R retina. Lutein treatment increased RGC-5 and rMC-1 cell viability while reducing level of NF-κB, IL-1β and Cox-2.
Conclusion: Lutein treatment resulted in preserved retinal function, reduced
neuronal loss, reduced oxidative stress, reduced gliosis and less pro-inflammatory factors in retinal I/R injury, confirming its neuroprotective effects. Lutein has
been used for protection of outer retinal elements in AMD. Our study suggests
that it may also be relevant for protection of inner retina from I/R injury by its
anti-oxidative, anti-apoptotic and anti-inflammatory properties.
Disclosure: None.
EFFECT OF AGE AND OTHER FACTORS ON MACULAR PIGMENT OPTICAL DENSITY MEASURED WITH RESONANCE RAMAN SPECTROSCOPY
Akira Obana1, Yuko Gohto1, Masaki Tanito3, Shigetoshi Okazaki2, Werner Gellermann4, Paul S Bernstein5, Akihiro Ohira3
1
Department of Ophthalmology, Seirei Hamamatsu General Hospital Hamamatsu, Japan; 2Department of Medical Spectroscopy, Applied Medical Photonics
Laboratory HAMAMATSU University School of Medicine, Japan; 3Department of
Ophthalmology, Shimane University Faculty of Medicine, Japan; 4Department of
Physics and Astronomy, University of Utah, USA; 5Moran Eye Center, University
of Utah School of Medicine, USA
Purpose: We investigated the effects of age and other factors on macular pigment optical density (MPOD) measured with resonance Raman spectroscopy
(RRS) in pseudophakic eyes.
Method: MPOD levels were measured using RRS in 144 of 144 patients who
received cataract surgery under approval from the institutional review board.
All subjects were aged 50 years and over. Factors potentially associated with
MPOD levels such as age, gender, smoking habits, body mass index, diabetes, glaucoma, axial length, pupil diameter, spherical equivalent refractive
error, and retinal thickness were examined by multiple regression analysis. Results: MPOD levels ranged from 776 to 11,815 Raman counts (average;
4,375±1,917 (SD). Multiple regression analysis revealed that age and axial length
were factors that induced significant deterioration of MPOD levels. An age increase of 1 year resulted in a mean decrease in the MPOD level by 59 Raman
counts (p=0.0076). No significant relationship was exhibited with other factors.
Conclusions: After removing the potential confounding effect of age-related
lens yellowing on RRS, age was still a significant, but fairly small factor for
MPOD decline. Axial length was a negative predictor of MPOD. The present
study included patients aged 50-years and older, and this relatively small age
range might affect the small effect of age.
Disclosure: Financial disclosure: WG and PSB hold patents for the ocular RRS
device. No other authors have commercial associations.
ZEAXANTHIN-BIOFORTIFIED SWEET-CORN AS AN ENHANCED DIETARY
SOURCE OF MACULAR PIGMENT
Tim J O’Hare1, Kent Fanning2, Ian Martin3, Sharon Pun3, Aldo Zeppa4, Solomon
Fekybelu5
1
The University of Queensland, QAAFI, CNAFS, Gatton Research Facility,
Queensland, Australia; 2Department of Agriculture, Fisheries and Forestry,
Queensland, Australia; 3Innovative Food Technologies, Primary Industries
and Fisheries, Department of Employment, Economic Development and Innovation, 19 Hercules Street, Hamilton, Queensland, Australia; 4DEEDI, Kingaroy Research Station, Kingaroy QLD 4610, Australia; 5DEEDI, Hermitage Research Station, Yangan Road, Warwick, Qld 4370, Australia
Purpose: To create a sweet-corn variety with sufficiently high concentration
of zeaxanthin to provide a 2 mg supplemental dose of zeaxanthin as part of a
normal meal.
Method: Sweet-corn kernels at eating-stage (21 days after pollination) were
screened from a breeding population of supersweet tropical yellow sweetcorn. Carotenoid profiles of cobs were determined by high performance liquid
chromatography. Lines with high total carotenoids and/or a high ratio of the
zeaxanthin-arm of the carotenoid synthesis pathway relative to lutein-arm were
identified. Identified lines were continually inbred to maximize these parameters,
re-profiled, and subsequently crossed to produce high-zeaxanthin sweet-corn
lines.
Results: Kernel zeaxanthin concentration was increased approximately seven-fold from 0.3-0.4 mg/100 g FW (control) to 2.4-2.5 mg/100 g FW through
screening and interbreeding. Total carotenoid synthesis was increased from 1.7
to 3.7 mg/100 g FW, and the percentage of zeaxanthin increased from 21% to
75% in zeaxanthin-enriched corn.
Conclusions: Zeaxanthin-biofortified sweet-corn provides an enriched source
of dietary zeaxanthin, potentially minimizing the need for artificial supplements.
Half-cobs (100 g kernels) possessed greater than 2 mg zeaxanthin, similar to the
zeaxanthin supplemental dose-rate used in the ARED2 clinical study. Bioavailability of sweet-corn zeaxanthin relative to artificial zeaxanthin supplements
remains to be assessed.
Disclosure: None.
LUTEIN IS THE PREDOMINANT CAROTENOID IN INFANT BRAIN
Rohini Vishwanathan1, Matthew J. Kuchan3, Elizabeth J. Johnson2
1
Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University,
Boston, MA, USA; 2Carotenoids & Health Laboratory, Jean Mayer USDA Human
Nutrition Research Center on Aging, Tufts University, Boston, MA,USA; 3Abbott
Nutrition, 3300 Stelzer Rd, Columbus, OH, USA
Purpose: Lutein has been associated with cognitive health in the elderly but its
impact on cognitive development in infants is unknown. Our objective was to
determine distribution of carotenoids in the infant brain.
Method: Voluntarily donated brain tissues (hippocampus and prefrontal, frontal,
auditory and occipital cortices) of infants who died during the 1st year of life
from SIDS or other conditions were obtained from the NICHD Brain and Tissue
Bank.
Results: Concentration of lutein in the brain was significantly higher than the
other carotenoids (p<0.05) irrespective of the brain region. Lutein accounted for
nearly 60% of the total brain carotenoids. Lutein in the brain of infants with no
cryptoxanthin was significantly lower than lutein in the brain of infants with measurable amounts of cryptoxanthin. Since cryptoxanthin is not present in infant formula this difference indicates that infants with higher lutein levels in the brain were
most likely breast milk fed. Lutein concentration is higher in breast milk compared
to other carotenoids. Lutein bioavailability from breast milk is higher compared to
infant formula. We found that infants <4 months of age had more lutein and zeaxanthin in the brain, while infants >4 months had more β-carotene suggestive of a
greater percentage of breast milk fed infants in the first 4 months of life.
Conclusions: Lutein is the predominant carotenoid in the infant brain. Investigation on lutein’s role in neural development is warranted.
Disclosure: None.
THE EFFECTS OF MACULAR PIGMENT ON VISIBILITY IN HAZE CONDITIONS
Laura M. Fletcher, Billy R. Hammond
University of Georgia Psychology Department, Georgia, USA
Purpose: Macular pigment (MP) may increase visual range by attenuating
the effects of atmospheric haze. Atmospheric scatter is shortwave dominant,
peaking at approximately 460 nm (i.e., Rayleigh scatter), which is also the peak
absorbance of MP. Thus, higher MP could improve vision outdoors. This hypothesis was tested under simulated outdoor conditions.
© 2013 Wichtig Editore - ISSN 1120-6721
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ABSTRACTS - Macular Carotenoids Conference - Cambridge, United Kingdom, July 10-12, 2013
Method: MP was assessed psychophysically in 14 young (mean=20.2 years)
healthy individuals. Thresholds for a 7.5 cpd sine wave grating superposed on
a background were assessed in a 2-channel, free-view optical system using
the method of limits followed by an abbreviated three-alternative forced choice
procedure (in which subjects determined the orientation of the grating). Thresholds were obtained for three conditions: blue-haze, which closely approximates
atmospheric haze; broadband xenon, which closely approximates sunlight; and
a 558 nm background which is outside the absorption spectrum of MP.
Results: MP ranged from 0.26–0.72 and was positively related to energy required to veil the target in both the haze and xenon conditions. MP was unrelated to energy required to veil the target in the 558 nm background condition.
Conclusions: Our earlier modelling data and results using a simulated macular
pigment filter indicated that higher MP had the potential for significantly increasing
visual range. These cross-sectional data are also consistent with this possibility.
Disclosure: None.
CRITICAL FLICKER FUSION THRESHOLDS: RELATIONS TO NEUROCOGNITIVE FUNCTION
Emily R. Bovier1, Laura M. Fletcher1, S. Anna Thorne1, Billy R. Hammond Jr.1,
Lisa M. Renzi2
1
The University of Georgia Department of Psychology, Georgia, USA; 2Abbott
Nutrition, Columbus, Ohio, USA
Purpose: Macular pigment has been related to measures of temporal vision
and cognitive function, but the independence of these relations is unclear. The
purpose of this project was to investigate the relationship between CFF and
neurocognitive assessments in young subjects.
Method: CFF was assessed with a customized light-emitting diode device with
a 660nm one-degree target and a 5.5 degree surround. Neurocognitive function
was assessed with the CNS Vital Signs VSX Brief-Core assessment. 15 subjects
(age 22 yrs) with the highest CFF (mean=29.7hz) and 15 subjects (age 21 yrs) with
the lowest CFF (mean=22.5hz) were selected for comparisons of neurocognitive
function.
Results: The high-CFF group scored in higher percentiles within the following
clinical domains: Executive Function (t=2.226, p=0.034), Psychomotor Speed
(t=1.969, p=0.059), and Cognitive Flexibility (t=2.273, p=0.031). Low-CFF subjects were in the 55th percentile for these domains and high-CFF subjects were
in the 75th percentile.
Conclusions: Higher CFF is associated with better performance on tasks related to motor and information processing speed. Past relations between macular
pigment and temporal vision and cognition may reflect the same underlying
phenomena: speed of neural processing. Cellular studies suggest lutein effects
processing speed via direct physiological mechanisms, such as enhancing gap
junction communication.
Disclosure: Dr. Renzi is employed by Abbott Nutrition, Columbus, OH.
GRADING OF FOODS ACCORDING TO THEIR LUTEIN AND ZEAXANTHIN
LEVELS
Antonio J. Meléndez-Martínez1, Paula Mapelli Brahm1, Ana Benitez1 González1,
Carla M. Stinco1, Enrique Murillo2
1
Department Nutrition & Food Science, Universidad de Sevilla, Facultad de
Farmacia, Sevilla, Spain; 2California State University, San Bernardino, CA, USA
Purpose: Following our recent screening of foods for good sources of lutein
(LUT) and zeaxanthin (ZX), we have revised the bibliography to grade sources
of such carotenoids from diverse regions. This information is important to assess the macular carotenoid (MC) intake of different populations, the update
of carotenoid databases with new items, the domestication of species and the
food industry, among others.
Method: Reported HPLC data were evaluated. Due to the diverse factors affecting the carotenoid levels in foods, the reported minimal and maximal contents
were considered to grade them as low, moderate, high and very high, according
to Britton and Khachik (2009).
Results: The revision revealed the existence of “non-traditional sources” of MC
(including wild species) that are important in the diet of some populations. The
identification of fruits with very high content on ZX was noteworthy as very few
good sources of ZX had been reported until recently.
Conclusions: The screening of the biodiversity in search of “new sources”
of carotenoids remains an important research field that can help improve the
diet of the population. It can also contribute to the development of less favored regions through the trade of quality products for the food industry.
Disclosure: There are no commercial relationships relevant to the content of
the abstract.
610
EXTRACTION AND MICROENCAPSULATION OF CAROTENOIDS FROM
RED PEPPER
Bi Bi Marzieh Razavizadeh, Rasoul Kadkhodaeei
Research Institute for Food Science and Technology (RIFST), Mashhad, Iran
Purpose: The present work aimed at imparting long term stability to red pepper
oleoresin by entrapping it into a polymeric matrix.
Methods: To this end, carotenoids were first solvent extracted and the effect
of solvent type, temperature, solid matter to solvent ratio and mixing ratio
of binary solvents on the extraction efficiency were evaluated. The extracted
carotenoids were encapsulated by ultrasonic emulsification and spray drying with using gum Arabic and whey protein concentrated as wall materials.
The effect of mixing ratio of wall materials and pH on the size and specific
surface area of resulting powder particles and encapsulation efficiency were
evaluated.
Results and Conclusions: The results showed that the type of solvent significantly influenced the extraction efficiency. On the other hand, temperature in the
range of 25-55ºC and solid matter to solvent ratio were found to have no effect
on this character. It was observed that the type and concentration of wall material as well as the pH of aqueous phase affected mean droplets diameter, their
size distribution curves and viscosity of emulsion.
Disclosure: None.
DEVELOPMENT OF EXTRACTION PROCESS OF THE XANTHOPHYLLS
LUTEIN AND ZEAXANTHIN FROM BRAZILLIAN MAIZE (ZEA MAYS L.)
LANDRACES
Simone Kobe de Oliveira1, Carina Malinowsky1, Maira Tomazzoli1, Virgílio Uarrota1,
Rosendo Augusto Yunes2, Marcelo Maraschin1
1
Plant Science Department, CCA, UFSC, Florianópolis, Brazil; 2Chemistry Department, CFM, UFSC, Florianópolis, Brazil
Purpose: The most abundant carotenoids found in corn kernels and leaves
are lutein/zeaxanthin and there is a positive correlation between their intake and prevention of AMD and cataract. Population has ingested smaller
amounts of carotenoids, thus, xanthophylls intake should occur through the
food enrichement or by ingesting capsules. Therefore, identification of raw
materials that can be used as source of such compounds and the development of economically profitable and non toxic method for extraction are of
great importance.
Method: Seeds and leaves flours from 5 maize landraces (LP, MPA1, MG, PR,
R8C) were incubated with edible oils (sunflower, corn, canola, soybean and rice
oils) and irradiated for 30’ with a ultrasound (40 kHz, 100 W) or with a microwave
(2.45 GHz, 70 W). The carotenoid-rich oleoresin content was determined by
UV–vis at 450nm and identified by HPLC.
Results: The HPLC showed predominance of Lutein. In leaf maize extracts,
canola oil was the best extractor. R8C variety has the highest carotenoid content (423 µg/mL) followed by MPA1. In both varieties, the extraction was best
using ultrasound method. For seeds the best extractor oil was also canola
using microwaves method. PR, MG and LP showed higher carotenoid levels
(~80 µg/mL).
Conclusions: The leaves of the landraces R8C and MPA1 incubated with
canola oil and ultrasound irradiated was the best carotenoids extractor system. By the point of view of waste treatment, the usage of corn leaves is quite
interesting.
Disclosure: None.
THE MACULAR PIGMENT OPTICAL DENSITY SPATIAL PROFILE AND
INCREASING AGE
Raymond Beirne
University of Ulster, Northern Ireland
Purpose: To investigate the relationship between the central spatial profile
of macular pigment optical density (MPOD) and increasing age in normal
eyes.
Method: 98 individuals (aged 19-71 yrs) with good visual acuity, free from ocular disease and with clear ocular media participated. Macular pigment optical
density was measured at 0.25, 0.50, 1.00 and 1.75 degrees eccentricity from the
foveal centre using a heterochromatic flicker photometry based densitometer
instrument.
Results: Linear regression analysis revealed that there was no statistically
significant association between MPOD and increasing age for the group as a
whole at 0.25, 0.50 and 1.00 degrees eccentricity (p>0.05 for all eccentricities). However, there was a small but statistically significant positive associa-
© 2013 Wichtig Editore - ISSN 1120-6721
ABSTRACTS - Macular Carotenoids Conference - Cambridge, United Kingdom, July 10-12, 2013
tion between increasing age and MPOD at 1.75 degrees eccentricity (F=5.44,
p=0.02), but age only accounted for 5% of the variation in MPOD values.
11% of all participants had a non-exponential macular pigment spatial
profile.
Conclusions: There was no statistically significant relationship between MPOD
and increasing age for three of the four locations measured. A proportion of
individuals show an atypical macular pigment spatial profile which should be
considered when interpreting results from studies which report macular pigment
optical density estimates from only one retinal location.
Disclosure: None.
COD LIVER OIL AND FATTY FISH CONSUMPTION IN RELATION TO
AGE-RELATED MACULAR DEGENERATION. THE TROMSØ STUDY
Maja Gran Erke1, Geir Bertelsen1, Tunde Peto2, Inger Njølstad3
1
Department of Ophthalmology and Neurosurgery, University Hospital of North
Norway, Tromsø, Norway and Research Group of Epidemiology of Chronic
Diseases, Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway; 2NIHR Biomedical Research Centre for Ophthalmology, at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute
of Ophthalmology, Head of Reading Centre, London, United Kingdom; 3Research
Group of Epidemiology of Chronic Diseases, Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway
HERITABILITY OF THE RING-LIKE DISTRIBUTION OF MACULAR PIGMENT
ASSESSED IN A TWIN STUDY
Omar, A Mahroo1, Ambreen Tariq1, Fredericus J Van Kuijk2, Shiao Hui Melissa
Liew3, Stephen Beatty4, Clare E. Gilbert5, Christopher J. Hammond1,3
1
Department of Ophthalmology, King’s College London, St Thomas’ Hospital
Campus, London, United Kingdom; 2Department of Ophthalmology, University
of Minnesota, Minneapolis MN, USA; 3Department of Twin Research and Genetic Epidemiology, King’s College London, St. Thomas’ Hospital Campus, London, United Kingdom; 4Macular Pigment Research Group, Waterford Institute
of Technology, Waterford, Ireland; 5International Centre for Eye Health, London
School of Hygiene and Tropical Medicine, United Kingdom
Purpose: Omega 3 fatty acids and fatty fish consumption have been shown to
have protective effect on progression/incidence of age-related macular degeneration (AMD). The present study aims to investigate associations between cod
liver oil supplement and fatty fish consumption and AMD.
Method: The Tromsø study is a longitudinal, population-based study in Norway
initiated in 1974. Retinal photography was included in the 6th survey and was
completed in 2008. Photographs were graded for AMD. Participants with gradable photos and data on cod liver oil and/or fatty fish consumption from any of
the 3rd through 6th Tromsø study were included in analysis. Logistic regression
calculated adjusted odds ratios (OR) with 95% confidence intervals (CI) for late
AMD and drusen >125 µm. We analysed the association between AMD and the
data from the different surveys singly. Further we combined the data from all
studies to a combined variable by taking the mean of the consumption from the
3rd through 6th survey.
Results: The sample included 2611 participants with both photos and data
on cod liver oil and fatty fish consumption, of whom 92 (3.5%) had late
AMD. We observed no significant association between AMD and cod liver
oil (OR 1.09, 95% CI 0.78-1.52) use or with consumption of fatty fish (OR
0.91, 95% CI 0.55-1.51) in age- and sex-adjusted analyses for the combined
variables.
Conclusions: Neither cod liver oil nor fatty fish consumption was significantly
associated with AMD controlled for confounders. This may be due to the fact
that supplement use is associated with other health related factors and therefore confounded by many factors.
Disclosure: None.
Purpose: A ring-like distribution of macular pigment (identified by a second
peak in the profile at ~0.5 degrees eccentricity) may be associated with reduced AMD risk. We explored how much of the variation in pigment profiles is
explained by genetic factors using a classic twin study.
Method: Macular pigment (MP) optical density was measured by two-wavelength
fundus autofluorescence in 314 healthy Caucasian female twins (88 monozygotic
(MZ) and 69 dizygotic (DZ) pairs), aged 16-50 (mean 40) years. The right eye MP
profile was assessed for the presence of a ring-like pattern by two graders independently, using common criteria. Concordance was calculated as 2C/(2C + D),
where C is the number of twin pairs concordant, and D the number discordant,
for the ring-like pattern.
Results: Respective concordances for MZ and DZ twins were 0.73 and 0.27 for
the first grader, and 0.75 and 0.30 for the second grader. The graders found an
overall prevalence of the ring pattern of 0.21 and 0.26 respectively.
Conclusions: Inter-grader agreement was reasonable, and concordance in
MZ twins was over two times the DZ concordance in both cases, suggesting
that genetic factors are important in determining the presence of the ring-like
pattern.
Disclosure: The authors have no financial relationships to disclose.
A CROSS-SECTIONAL STUDY OF NUTRITIONAL ADVICE GIVEN BY UK
EYE CARE PROFESSIONALS TO PEOPLE WITH OR WITHOUT AMD
John Lawrenson1, Jennifer Evans2
1
Division of Optometry, City University London, London United Kingdom; 2International Centre for Eye Health, London School of Hygiene and Tropical Medicine,
London United Kingdom
Purpose: The aim of this study was to conduct a cross-sectional survey of the
current practice of UK eye care professionals in relation to nutritional advice
given for people with or at risk of AMD.
Method: Optometrists and ophthalmologists on the membership databases of
professional organisations for the two professions were invited to participate in
an online survey.
Results: A total of 1,468 responses were received (96.3% from optometrists
and 3.7% from ophthalmologists). A majority of respondents reported that they
frequently provide dietary advice to patients with established AMD (67.9%) and
those at risk of AMD (53.6%). Typical advice consisted of a recommendation
to eat plenty of leafy green vegetables and eat more oily fish. The decision
to recommend nutritional supplements was based on the risk of progression
to advanced AMD, with approximately 93% of respondents recommending
supplementation in a patient with advanced AMD in one eye. However, there
were significant differences in the recommendations of optometrists and ophthalmologists with optometrists most likely to recommend a supplement containing macular carotenoids only or a product containing lutein and zeaxanthin
in combination with antioxidant vitamins.
Conclusions: Within a large sample of UK eye care professionals responding to
this cross-sectional survey, there was active engagement in providing nutritional
advice to patients with or at risk of AMD.
Disclosure: None.
INFLUENCE OF UNDESIRABLE FUNDUS REFLECTION ON THE MEASUREMENT OF SPATIAL DISTRIBUTION OF MACULAR PIGMENT BY VISUCAM®
Takahiko Seto1, Yuko Gohto1, Akira Obana1,2, Norihito Etoh3, Shigetoshi Okazaki2,
Yuji Nishiwaki4
1
Department of Ophthalmology, Seirei Hamamatsu General Hospital, Hamamatsu, Japan; 2Department of Medical Spectroscopy, Applied Medical Photonics
Laboratory, Medical Photonics Research Center, Hamamatsu University School
of Medicine, Hamamatsu, Japan; 3Department of Biomedical Enginnering, Tokai
University School of Engineering, Kanagawa, Japan; 4Department of Environmental and Occupational Health, Toho University Faculty of Medicine, Otaku,
Tokyo, Japan
Purpose: Fundus reflectometry (FR) and autofluorescence spectrometry (AF)
are objective methods to measure macular pigment (MP). Both methods demonstrate not only optical pigment density but also the spatial distribution of MP.
We investigated spatial profile of MP by FR and AF, and evaluated the influence
of reflection from the fovea in FR.
Method: The spatial profile of MP was measured using FR (Visucam 200®,
Zeiss) and AF in 32 eyes of 32 healthy volunteers under approval from
the institutional review board. The three-dimensional images were obtained by Image J software, and the profile was analyzed by MATLABR
software.
Results: High quality image was obtained in 32 eyes by FR and 28 eyes by AF.
The spatial profile of MP by FR represented mountain shape with a single peak
of various heights in 32 eyes, but a small depression was demonstrated at the
central area in 28 eyes. No such depression was noted in AF images. From
the analysis on fundus photographs, we concluded that the depression on FR
caused by reflection of emission light from the fovea. The loss by such depression was calculated to be 0.01-0.58% (mean; 0.17%) of the total amount of MP
optical density.
Conclusions: FR and AF demonstrated mountain shaped profile of MP with a
single peak. The depression in FR was supposed to be an artifact by undesirable reflection. Although the influence of artifact was limited, we should pay
attention to it in the analysis of the results by FR.
Disclosure: All authors have no commercial associations.
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ABSTRACTS - Macular Carotenoids Conference - Cambridge, United Kingdom, July 10-12, 2013
AN INVESTIGATION INTO THE USE OF A NOVEL PSYCHOPHYSICAL
TECHNIQUE FOR MACULAR PIGMENT MEASUREMENT IN OPTOMETRIC
PRACTICE
Graham O’Regan1, Sarah O’Regan2
1
Cotswold Eyecall, Avening, Gloucestershire, United Kingdom; 2Macular Pigment Research Group, Department of Chemical and Life Sciences, Waterford
Institute of Technology, Waterford, Ireland
Purpose: Evidence shows a role for macular pigment (MP) for vision in diseased and normal retinae, thus there is an increasing need to quantify MP optical density (MPOD) in optometric practice. Currently, all validated instruments
are based upon heterochromatic flicker photometry, however this is difficult for
many patients, especially the peripheral observation. We have developed a novel technique using perceived rotation photometry (PRP) on a laptop to measure
MPOD in optometric practice.
Method: The PRP test has been calibrated against the validated Macular Metrics II Densitometer. The patient fixates on a “spinner”, and using the keyboard,
makes adjustments in the luminosity until the rotation appears to reverse, at
which point their foveal MPOD is determined. For the 7° peripheral measurement the patient fixates on a centre of a ring of spinners. We have piloted the
PRP test in high-street, hospital and domiciliary settings, and on subjects in
whom a range of measurements is anticipated, e.g. heavy smokers and young
healthy black subjects.
Results: The PRP test generates MPOD measurements within an anticipated
range (0.2 to 1.0). Limitations have been observed, namely sensitivity to angle
of observation and inconsistency between different computers.
Conclusions: The PRP test is promising, and further research investigating the
potential of a standardised and high-resolution display in the form of the Apple
iPad is underway to optimise the potential of this technology.
Disclosure: None.
CELL CULTURE MODELS OF RETINAL DIFFERENTIATION: XANTHOPHYLL
METABOLISM IN HUMAN RETINAL PIGMENT EPITHELIUM
Lewis P. Rubin1, Xiaoming Gong2
1
Texas Tech University HSC at El Paso, USA; 2Human Genetics Centre, The
University of Texas Health Science Center, Houston, Texas, USA
Purpose: Xanthophylls (lutein [LUT]/zeaxanthin/[ZEA]) preferentially accumulate
in the human macula and play a critical role in retinal protection from oxidant
and light stress. Retinal/macular LUT/ZEA accumulation is inversely related to
severity of retinopathy of prematurity (ROP) and age-related macular degeneration (AMD). This study investigates xanthophyll accumulation, transfer and
metabolism in two RPE cell models.
Method: Human ARPE-19 and transformed human RPE cells were cultured and
differentiated in defined medium. Targeted gene expression was determined
by qRT-PCR and western blot. LUT uptake and transport were assessed using
polarized cells and quantified by HPLC.
Results: ARPE cells express scavenger receptors (SR-BI, CD36, LDLR, but not
SR-A), carotenoid cleavage enzymes (CMO1, CMO2), and transporter (ABCA1).
CMO2 is highly expressed in ARPE-19 cells, regardless of differentiation state.
LUT supplementation yielded dose- and time-dependent cellular LUT accumulation as well as basal-to-apical transfer. RPE exposure to specific carotenoids
(β-carotene, lycopene, LUT, astaxanthin) differently affected RPE gene expression patterns. Pathway analysis showed LUT is cytoprotective following hypoxic
and ischemic damage.
Conclusions: This data supports the hypothesis that xanthophyll uptake,
metabolism and transport in RPE cells are critical for retinal pigment homeostasis. LUT metabolism is regulated principally by CMO2. We speculate that
altering RPE gene expression profiles by protective (xanthophyll) or deleterious (oxidative stress) factors is a molecular mechanism in the pathogenesis
of ROP and AMD.
Disclosure: The authors have no financial conflict of interest.
AN LC-MS/MS METHOD FOR STABLE ISOTOPE DILUTION STUDIES OF
b-CAROTENE BIOAVAILABILITY, BIOCONVERSION AND VITAMIN A STATUS IN HUMANS
Anthony Oxley1, Philip Berry2, Michael John Hall3, Joseph Cowell3, John
Hesketh4, Georg Lietz1, Alan V. Boddy2
1
Human Nutrition Research Centre, School of Agriculture, Food and Rural Development, Newcastle University, United Kingdom; 2Northern Institute for Cancer Research, Newcastle University, United Kingdom; 3School of Chemistry,
Newcastle University, United Kingdom; 4Institute for Cell and Molecular Biosciences; Newcastle University, United Kingdom
612
Purpose: Isotope dilution is currently the most accurate technique in humans
to determine vitamin A status and bioavailability/bioconversion of provitamin A
carotenoids. However, limits of MS detection, coupled with extensive isolation
procedures, have hindered investigations of physiologically-relevant doses of
stable isotopes.
Methods: We developed a sensitive liquid chromatography-tandem-mass
spectrometry (LC-MS/MS) analytical method to study the plasma response
from co-administered oral doses of 2 mg [13C10]-β-carotene and 1 mg [13C10]retinyl acetate in human subjects.
Results: A single one-phase solvent extraction, with no saponification or purification steps, left retinyl esters intact for determination of intestinally-derived
retinol in chylomicrons versus retinol from the liver bound to retinol-binding protein (RBP). Co-administration of [13C10]-retinyl acetate with [13C10]-β-carotene not
only acts as a reference dose for inter-individual variations in absorption and
chylomicron clearance rates, but also allows for simultaneous determination of
an individual’s vitamin A status.
Conclusions: This new analytical method enables the detection of physiological concentrations of provitamin A carotenoids, their cleavage products as well
as preformed vitamin A for a period of at least 2 weeks post dose administration
and allows high throughput analysis due to its simplicity and short run times.
Disclosure: This study was funded by the BBSRC.
MACULAR RESPONSE TO SUPPLEMENTATION WITH DIFFERING CAROTENOID FORMULATIONS IN SUBJECTS WITH AND WITHOUT AGE-RELATED MACULAR DEGENERATION
Katherine Meagher1, John M. Nolan1, David I. Thurnham2, Alan N. Howard3,
Stephen Beatty1
1
Waterford Institute of Technology, Waterford, Ireland; 2University of Ulster, United
Kingdom; 3Downing College, Cambridge University, Cambridge, United Kingdom
Purpose: Macular pigment (MP), comprised of the carotenoids lutein (L),
zeaxanthin (Z) and meso-zeaxanthin (MZ), enhances visual performance and
may reduce risk of age-related macular degeneration (AMD). In this study, MP
response to three different macular carotenoid formulations were measured
in normal (n 36) and AMD subjects (n 28).
Method: Subjects were randomly assigned to: Group 1 (20 mg L, 2 mg Z),
Group 2 (10 mg L, 2 mg Z, 10 mg MZ) or Group 3 (3 mg L, 2 mg Z, 17 mg MZ).
MP was measured (at baseline, 2, 4, 6 and 8 weeks) at 0.25°, 0.5°, 1.0° and
1.75° of eccentricity using customised heterochromatic flicker photometry.
Results: MP increased significantly at 0.25°, 0.5°, 1° and 1.75° of eccentricity
in all Groups (P<0.05), with the exception of Group 3, where MP did not exhibit
a significant increase at 1.75° (P=0.242). MP response was statistically similar
for AMD versus normal subjects, with the exception of Group 2, where AMD
subjects exhibited a significantly greater response at a single eccentricity (1.75°;
P=0.024). Serum concentrations of MZ were positively and significantly related
to final MPOD at each eccentricity in AMD subjects (r=0.520, P=0.005), whereas
this was not the case for normal subjects (r=0.241, P=0.226).
Conclusions: Serum MZ response is strongly related to MPOD following supplementation in AMD subjects, and this finding suggests that circulating levels
of the centrally dominant carotenoid are important in any attempt to augment
MP in those with AMD.
Grant Support: The Howard Foundation.
Disclosure: None.
STUDY OF MACULAR PIGMENTS IN GLAUCOMA
We Fong Siah1, Estera Igras1, Colm O’Brien1,2, James Loughman3,4
1
Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland;
2
School of Medicine and Medical Science, University College Dublin, Belfield,
Dublin, Ireland; 3Optometry Department, School of Physics, College of Sciences and Health, Dublin Institute of Technology, Dublin 8, Ireland; 4African Vision
Research Institute, Faculty of Health Sciences, University of KwaZulu Nalal,
Durban, South Africa
Purpose: Oxidative stress plays a major role in the pathogenesis of retinal neurodegenerative disorders such as glaucoma and age-related macular degeneration
(AMD). MP has antioxidant properties and is believed to play an important role in
visual performance such as glare sensitivity. Individuals with glaucoma suffer from
glare and the cause remained poorly understood. To our knowledge, the role of
MP has not been explored in glaucoma. This study was designed to investigate
the relationship, if any, between the optical density of MP (MPOD) and glaucoma.
Method: A pilot study involving 40 subjects with open angle glaucoma and
54 age-matched normal controls were recruited for (i) visual field assessment,
using the 24-2 SITA-fast algorithm on the Humphrey visual field analyzer (II-i
Series), and (ii) measurement of MPOD at 0.50 of retinal eccentricity, using the
heterochromatic flicker photometry.
© 2013 Wichtig Editore - ISSN 1120-6721
ABSTRACTS - Macular Carotenoids Conference - Cambridge, United Kingdom, July 10-12, 2013
Results: Median (interquartile range) MPOD for subjects with glaucoma was
0.23 (0.42) compared to 0.36 (0.44) for controls. The difference in MPOD between the glaucoma cases and controls was statistically significant, (z=-2.158,
p=0.031).
Conclusion: The findings suggest that MPOD is lower in patients with glaucoma. Our future study will aim to (i) establish the MPOD response to dietary
MP supplementation in glaucoma patients, (ii) investigate the visual response to
dietary MP supplementation in glaucoma patients, and (iii) identify the relationship between MP and visual function in glaucoma patients compared to normal
controls. This will be a placebo-controlled, double-masked study whereby all
glaucoma patients are randomised into the treatment arm (dietary MP supplementation – MacuShield® ) and placebo arm.
Disclosure: None.
THE RELATIONSHIP BETWEEN SERUM CONCENTRATIONS OF LUTEIN
AND ZEAXANTHIN AND MACULAR PIGMENT MEASURED USING DUALWAVELENGTH FUNDUS AUTOFLUORESCENCE
Ekaterina Loskutova1,2, Jessica Dennison1, Stephen Beatty1,3, Alan Howard4,
John Nolan1,3
1
Macular Pigment Research Group, Department of Chemical and Life Sciences,
Waterford Institute of Technology, Waterford, Ireland; 2Moscow State University
of Medicine and Dentistry, Moscow, Russia; 3Institute of Vision Research, Whitfield Clinic, Waterford, Ireland; 4Howard Foundation, Downing College, Cambridge University, Cambridge, United Kingdom
Purpose: The new Heidelberg Spectralis® (HRA + OCT MuliColor)uses dualwavelength fundus autofluorescence to produce a full spatial profile image of
macular pigment optical density (MPOD). This study investigated the relationship between serum concentrations of lutein (L) and zeaxanthin (Z), and MPOD
in the normal population without signs of retinal disease.
Method: 51 subjects participated in this cross-sectional study. Serum concentrations of carotenoids L and Z were quantified using high-performance liquid
chromatography (HPLC), and MPOD was measured using the Spectralis. Demographic and lifestyle variables were also obtained by questionnaire.
Results: Mean (±SD) age was 63 (±16), 29 were male and 22 were female.
Mean (±SD) serum concentrations of L and Z were 0.209 (±0.139) and 0.011
(±0.007), respectively. Mean (±SD) max MPOD (i.e. at 0.23º) was 0.49 (±0.18).
The relationship between serum concentrations of L and Z, and MPOD was
positive and statistically significant (r=0.355, p=0.01 and r=0.3, p=0.025,
respectively).
Conclusions: MPOD measured using the Spectralis is positively correlated
with serum concentrations of L and Z. This is the first study to confirm the relationship between MPOD measured using this new technology with a known
biochemical predictor of MPOD (serum L and Z). This data is important as it
contributes to the validation of the Spectralis for measuring MPOD in vivo.
Grant support: The European Research Council grant 281096.
Disclosure: None.
A COMPARISON OF MACULAR PIGMENT SPATIAL PROFILES OBTAINED
USING DUAL-WAVELENGTH AUTOFLUORESCENCE AND CUSTOMIZED
HETEROCHROMATIC FLICKER PHOTOMETRY
Jessica Dennison1, Jim Stack1, Stephen Beatty1,2, John Nolan1
1
Macular Pigment Research Group, Department of Chemical and Life Sciences,
Waterford Institute of Technology, Waterford, Ireland; 2Institute of Vision Research, Whitfield Clinic, Waterford, Ireland
Purpose: The Heidelberg Spectralis® HRA + OCT uses dual-wavelength fundus autofluorescence to produce a spatial image of macular pigment (MP). The
Macular Densitometer™ uses customised heterochromatic flicker photometry
and provides measurements of MP at different eccentricities from which a MP
spatial profile is extrapolated.
Methods: MP was measured in one eye of 64 subjects on both devices. Profile
type (typical = peak at centre with exponential decline; atypical = secondary
peak or plateau) was determined by visualisation. Concordance between profile
types obtained from each device, and the relationship between profile type and
other variables (age, sex, smoking, MP), were investigated.
Results: On the Spectralis, MP spatial profiles were classed as typical in 61%
and atypical in 39% of subjects. On the Densitometer, MP spatial profiles were
classed as typical in 78% and atypical in 22% of subjects. Classification of
spatial profiles was concordant between devices in 51 subjects (80%). 12 spatial profiles (19%) were classed as atypical on the Spectralis, but typical on the
Densitometer. There was no significant relationship between spatial profile
type and age (p=0.995), sex (p=0.138), or smoking (p=0.115). Central MP (at
0.23°) was significantly lower in subjects with atypical versus typical MP profiles
(p=0.009).
Conclusions: Data from the Spectralis is more informative than data from the
Densitometer, reflected in the greater sensitivity for identification of atypical profiles using the former technique.
Grant support: The European Research Council grant 281096.
Disclosure: None.
PREVALENCE OF SIGHT-THREATENING OCULAR PATHOLOGY IN IRELAND:
THE IRISH LONGITUDINAL STUDY ON AGEING
Kwadwo Owusu Akuffo1, Rachel Moran1, Stephen Beatty1, Tunde Peto2,
John Nolan1 Rose Anne Kenny3, Hilary Cronin3
1
Macular Pigment Research Group, Department of Chemical and Life Sciences,
Waterford Institute of Technology, Waterford, Ireland; 2NIHR Biomedical Research Centre at Moorfields Eye Hospital and UCL Institute of Ophthalmology,
London, United Kingdom; 3The Irish Longitudinal Study on Ageing (TILDA), Trinity College Dublin, Dublin, Ireland
Purpose: Age-related eye diseases, such as age-related macular degeneration
(AMD), diabetic retinopathy (DR), and glaucoma, result in loss of vision. This
loss of vision inhibits patients’ ability to read, drive, and even recognise familiar
faces, with an overall loss of social independence and quality of life. The Irish
Longitudinal study on Ageing (TILDA) was designed to investigate factors that
influence ageing, including ocular disease status, in a large randomly selected
sample of the Irish population.
Method: Between 2009 and 2011, 8,175 participants aged 50 years and over
were enrolled into TILDA. Retinal photographs were taken at the TILDA clinical assessment centres in Dublin and Cork, Ireland. 5,143 participants had
retinal images taken using a NIDEK AFC-210 non-mydriatic fundus camera.
Photographs were graded for AMD, DR and glaucoma. AMD was graded using a modified version of the International Classification and Grading System
for AMD. DR was graded using the Early Treatment Diabetic Retinopathy classification. For glaucoma, optic discs were graded as normal or suspicious.
Grading was performed by trained graders at the Reading Centre, Moorfields
Eye Hospital, UK and the Macular Pigment Research Group, Waterford,
Ireland.
Results: 2,000 participants (3,951 eyes) were studied for this report. Of
these, 3,915 (99.1%) of eyes were suitable for grading. The overall prevalence AMD was 7.3% (CI: 6.11% to 8.39%), prevalence of DR was 1.4%
(CI: 0.84% to 1.86%), and suspicious discs were identified in 3.5% (CI:
2.65% to 4.25%).
Conclusions: AMD is the leading cause of sight-threatening ocular pathology
in Ireland, followed by glaucoma and DR. Public health measures, to include
lifestyle and nutritional optimisation, should now be considered in an attempt to
reduce the risk of blindness in Ireland.
Grant support: The European Research Council grant 281096 and Bayer.
Disclosure: None.
DIFFERENCES IN CAROTENOID CONTENT OF NORMAL ELDERLY AND
ALZHEIMER’S BRAINS
Neal E. Craft1, Dennis Gierhart2, C. Kathleen Dorey3
1
Craft Technologies, Inc., 4344 Frank Price Church Rd, Wilson, NC, USA;
2
ZeaVison, LLC. (PLEASE ADD City and State); 3Virginia Tech Carilion School of
Medicine, Virginia, USA
Alzheimer’s Disease (AD) is a severe neurodegenerative disease. AD and other
dementia afflicts >36 million elderly worldwide. Antioxidants, such as carotenoids, have been implicated in the prevention of degenerative diseases and
recent data correlates blood and macular carotenoid levels with cognition.
Purpose: To measure and compare the major carotenoids in normal elderly and
AD human brain.
Methods: Samples of normal and AD brain tissue from frontal lobe cortex and
occipital cortex were examined. Sections were dissected into gray and white
matter, extracted with organic solvents, and analyzed by HPLC.
Results: At least 16 carotenoids, 3 tocopherols, and retinol were present in
human brain. Xanthophylls accounted for >70% of carotenoids in brain. Mean
concentrations of carotenoids ranged from 3.5-15.3 pmol/g. Combining all
brains, lutein (LUT, P<0.001) and zeaxanthin (ZX, P<0.02) were higher in gray vs
white matter. ZX and LUT were lower in AD brain (P<0.002, P<0.04, respectively). Healthy brain had 2x more ZX and 30% more LUT than AD brain. Retinol and
a-tocopherol were lower in AD brain, (P<0.002, P<0.006). A carotenoid peak,
tentatively labeled peak 8, was positively correlated with AD.
Conclusions: AD status is negatively correlated with levels of ZX, LUT, vitamins
A and E in specific brain tissue.
Disclosure: Brain tissue donated by Mass. Alzheimer’s Disease Research Ctr.
Funded in part by Applied Food Biotechnology and ZeaVision.
NEC- Funding.
DG - ZeaVision, Patent.
CKD- None.
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