Customized Heterochromatic Flicker Photometry Research Articles

Macular pigment is inversely related to circulating C-reactive protein concentrations in school-aged children

Xanthophyll carotenoids (i.e., lutein and zeaxanthin) are plant pigments that selectively deposit in the macula of the eye and provide retinal tissue with protection against photooxidative stress. Although having greater xanthophylls in various tissues is related to lower inflammation in adulthood and infancy, this relationship is underinvestigated in childhood. Thus, this study aimed to elucidate the relationships between macular xanthophyll status and inflammation in school-aged children. We hypothesized that greater macular pigment would be associated with lower systemic concentrations of C-reactive protein (CRP). Forty children (aged 7-12 years) from the East-Central Illinois area were recruited. Data were collected in a convenience sample over multiple visits to the laboratory that occurred over 1 month, including all individuals who provided adequate blood samples for analyses. Macular pigment optical density (MPOD) was assessed using customized heterochromatic flicker photometry. Dietary lutein and zeaxanthin were determined using 7-day diet records. Capillary dried blood spot samples were analyzed for CRP concentrations via enzyme-linked immunosorbent assay. Whole-body percentage fat (%Fat) was measured using dual-energy x-ray absorptiometry. Two-step hierarchical linear regression modelling was used to assess relationships between MPOD and CRP, following adjustment of pertinent covariates and the removal of outliers (N = 3). MPOD was negatively associated with CRP concentrations, after controlling for a priori covariates of age, sex, %Fat, and dietary lutein and zeaxanthin (β = –0.58, ΔR2 = 0.22, P = .004). Age, sex, dietary lutein and zeaxanthin, and %Fat did not significantly contribute to the model. This study provides novel evidence that macular pigment and peripheral inflammation are inversely related in childhood.

Single Nucleotide Polymorphisms in CD36 Are Associated with Macular Pigment among Children

BackgroundHigh macular pigment optical density (MPOD) has been associated with improved eye health and better cognitive functions. Genetic variations have been associated with MPOD in adults. However, these associations between genetic variations and MPOD have not been studied in children. ObjectivesThis was a secondary analysis of the FK2 (Fitness Improves Thinking in Kids 2) trial (n = 134, 41% male). The aim was to determine differences in MPOD among children (aged 7–9 y) based on genetic variants that either are biologically relevant to lutein (L) and zeaxanthin (Z) accumulation or have been associated with MPOD in adults. MethodsMPOD was measured using customized heterochromatic flicker photometry via a macular densitometer. DXA was used to assess whole-body and visceral adiposity. DNA was extracted from saliva samples and was genotyped for 26 hypothesis-driven single nucleotide polymorphisms and 75 ancestry-informative markers (AIMs). Habitual diet history was obtained via 3-d food logs completed by parents (n = 88). General linear models were used to compare MPOD between different genotypes. Principal component analysis was performed for the AIMs to account for ethnic heterogeneity. ResultsChildren carrying ≥1 minor allele on β-carotene-15,15′-monooxygenase (BCO1)-rs7501331 (T allele) (P = 0.045), cluster of differentiation 36(CD36)-rs1527483 (T allele) (P = 0.038), or CD36-rs3173798 (C allele) (P = 0.001) had significantly lower MPOD (range: 14.1%–26.4%) than those who were homozygotes for the major alleles. MPOD differences based on CD36-rs3173798 genotypes persisted after adjustment for dietary L and Z intake. ConclusionsThe findings indicate that genetic variations of CD36 and BCO1 contribute to MPOD in children. The influence of genetic variation in CD36-rs3173798 persisted after adjusting for variation in dietary intake.This trial was registered at clinicaltrials.gov as NCT01619826.

Investigation of Surrogate Biomarkers Associated with Macular Pigment Status in a Group of Older Irish Adults.

Macular pigment (MP) confers potent antioxidant and anti-inflammatory effects at the macula; however, its optical density in the eye is not routinely measured in clinical practice. This study explored a range of surrogate biomarkers including anthropometric, clinical, and plasma measures that may be associated with lower MP optical density (MPOD). Two thousand five hundred ninety-four subjects completed a full MP assessment as part of wave 1 of The Irish Longitudinal Study of Aging. Macular pigment optical density was measured using customized heterochromatic flicker photometry. Clinical (blood pressure), plasma (lipoproteins, inflammatory markers), and anthropometric (waist, hip, height, weight) biomarkers were measured for each participant. Mean (standard deviation) MPOD for the study group was 0.223 (0.161), with a range of 0 to 1.08. One-way ANOVA revealed that MPOD was significantly lower among participants with low plasma high-density lipoprotein (HDL; P = .04), raised plasma triglyceride-to-HDL ratio (P = .003), and raised total cholesterol-to-HDL ratio (P = .03). Subjects with an elevated waist circumference (WC) had a significantly lower MPOD (mean, 0.216 [0.159]) compared with those with an ideal WC (mean, 0.229 [0.162]; P = .03). Significant correlates of MPOD on mixed linear model analysis included education, smoking status, and WC. Higher abdominal fat is associated with lower MPOD in this representative sample of older Irish adults. Although altered lipoprotein profiles (low HDL, raised triglyceride-to-HDL ratio, raised total cholesterol-to-HDL ratio) may affect the transport, uptake, and stabilization of carotenoids in the retina, these plasma biomarkers were not predictive of low MPOD after adjustment for abdominal circumference. Although WC emerged as a viable anthropometric predictor of lower MPOD, its effect size seems to be small.

Auditory and Visual Working Memory Are Differentially Related to Carotenoid Status in Preadolescent Children

Abstract Objectives Carotenoids are plant pigments known to deposit in neural tissues including the hippocampus, a brain substrate that supports several memory forms. However, there is a dearth of knowledge regarding carotenoid status and working memory function in children. Accordingly, this study aimed to understand the relationship between macular and skin carotenoids to visual and auditory working memory (WM) function. Methods Seventy preadolescent children (7–12 years, 32 males) were recruited from the East-Central Illinois area. Auditory working memory was assessed using the story recall subtest of the Woodcock-Johnson IV Test of Cognitive Abilities. A subsample (N = 61, 27 males) completed a visual working memory task and reaction time was quantified to determine speed of memory processing at set sizes of 1 to 4 items. Macular pigment optical density (MPOD) was assessed using customized heterochromatic flicker photometry. Skin carotenoids were assessed using reflection spectroscopy (Veggie Meter). Hierarchical linear regressions were conducted to assess the relationship between carotenoid status and WM function, while controlling for age, sex, income, and whole-body % fat (DXA). Results Auditory WM was positively associated with skin carotenoids (b = 0.263, P = 0.039) but not MPOD (b = −0.044, P = 0.380). In contrast, MPOD was significantly associated with faster visual WM speed at set size 3 (b = −0.253, P = 0.039) and trending at set sizes of 1 (b = −0.225, P = 0.051), 2 (b = −0.171, P = 0.121), and 4 (b = −0.230, P = 0.055). Interestingly, skin carotenoids were not related to visual WM performance at either set size (all P’s > 0.300). Conclusions These results indicate that auditory and visual WM may be differentially related to carotenoids. While skin carotenoids encompass all carotenoids consumed in diet, lutein and zeaxanthin are the only carotenoids which deposit in the macula. Given that MPOD was only related to visual WM, this suggests lutein plays a larger role in these neural functions relative to auditory WM. Interestingly, MPOD's relationship with visual WM increased in strength with the more difficult trial type (i.e., increasing set size), indicating MPOD is related at higher levels of WM capacity. Funding Sources This study was funded by the Egg Nutrition Center.

Identification of Surrogate Biomarkers for the Prediction of Patients at Risk of Low Macular Pigment in Type 2 Diabetes

ABSTRACTPurpose: This cross-sectional study compared macular pigment (MP) levels among persons with Type 2 diabetes relative to healthy controls. Additionally, a range of behavioral, anthropometric, clinical and serum measures were explored as possible predictors of low MP optical density (MPOD) in diabetes.Methods: Two health status groups; Group 1: Type 2 diabetes (n = 188), and Group 2: Healthy controls (n = 2,594) completed a full MP assessment using customized heterochromatic flicker photometry, as part of The Irish Longitudinal Study on Aging (TILDA). Clinical [blood pressure; cataract status; MPOD] and anthropometric [waist (cm); weight (kg); hip (cm)] measurements were taken, and a blood sample drawn for analysis of serum biomarkers [lipoproteins; inflammatory markers (C reactive protein and vitamin-D)].Results: One-way ANOVA revealed lower MPOD in subjects with Type 2 diabetes relative to controls (p = .047). Amongst participants with diabetes, those with low serum vitamin D (≤50 nmol/L) had significantly lower mean MPOD compared to those with sufficient serum vitamin D levels >50 nmol/L (0.173(0.148) vs. 0.226(0.145); p = .006). Concomitantly, MP was significantly lower in diabetes participants with raised serum triglyceride (TG) to high density lipoprotein (HDL) ratio (TG/HDL); values >1.74 mmol/L (0.172 (0.140) vs 0.215 (0.152); p = .039). Body mass index, waist-to-height ratio and waist circumference, were all significantly negatively correlated with MPOD (Pearson’s correlation, p < .05 for all). Significant correlates of MPOD in the multivariate regression model included smoking, cataract, and vitamin D, which collectively contributed 18.5% of the overall variability in MPOD status amongst participants with Type 2 diabetes.Conclusions: This study provides additional evidence that low MP may indeed be a feature of Type 2 diabetes, and further identifies smoking, cataract and vitamin D status as plausible predictors of low MPOD amongst persons with Type 2 diabetes.

Effects of a Lutein and Zeaxanthin Intervention on Cognitive Function: A Randomized, Double-Masked, Placebo-Controlled Trial of Younger Healthy Adults.

Background: Past studies have suggested that higher lutein (L) and zeaxanthin (Z) levels in serum and in the central nervous system (as quantified by measuring macular pigment optical density, MPOD) are related to improved cognitive function in older adults. Very few studies have addressed the issue of xanthophylls and cognitive function in younger adults, and no controlled trials have been conducted to date to determine whether or not supplementation with L + Z can change cognitive function in this population. Objective: The purpose of this study was to determine whether or not supplementation with L + Z could improve cognitive function in young (age 18–30), healthy adults. Design: A randomized, double-masked, placebo-controlled trial design was used. Fifty-one young, healthy subjects were recruited as part of a larger study on xanthophylls and cognitive function. Subjects were randomized into active supplement (n = 37) and placebo groups (n = 14). MPOD was measured psychophysically using customized heterochromatic flicker photometry. Cognitive function was measured using the CNS Vital Signs testing platform. MPOD and cognitive function were measured every four months for a full year of supplementation. Results: Supplementation increased MPOD significantly over the course of the year, vs. placebo (p < 0.001). Daily supplementation with L + Z and increases in MPOD resulted in significant improvements in spatial memory (p < 0.04), reasoning ability (p < 0.05) and complex attention (p < 0.04), above and beyond improvements due to practice effects. Conclusions: Supplementation with L + Z improves CNS xanthophyll levels and cognitive function in young, healthy adults. Magnitudes of effects are similar to previous work reporting correlations between MPOD and cognition in other populations.

The Macular Carotenoids Lutein and Zeaxanthin Are Related to Increased Bone Density in Young Healthy Adults.

Lutein (L) and zeaxanthin (Z) status can be quantified by measuring their concentrations both in serum and, non-invasively, in retinal tissue. This has resulted in a unique ability to assess their role in a number of tissues ranging from cardiovascular to central nervous system tissue. Recent reports using animal models have suggested yet another role, a developmental increase in bone mass. To test this, we assessed L and Z status in 63 young healthy adults. LZ status was determined by measuring LZ in serum (using HPLC) and retina tissue (measuring macular pigment optical density, MPOD, using customized heterochromatic flicker photometry). Bone density was measured using dual-energy X-ray absorptiometry (DXA). Although serum LZ was generally not related to bone mass, MPOD was significantly related to bone density in the proximal femur and lumbar spine. In general, our results are consistent with carotenoids, specifically LZ, playing a role in optimal bone health.

Non-Dietary Correlates and Determinants of Plasma Lutein and Zeaxanthin Concentrations in the Irish Population.

To investigate non-dietary correlates and determinants of plasma lutein (L) and zeaxanthin (Z) concentrations in The Irish Longitudinal Study on Ageing (TILDA) sample. Cross-sectional study. Community dwelling adults in the Republic of Ireland (ROI). 3,681 participants aged 50 years and older. TILDA is a nationally representative prospective cohort study of community dwelling adults aged 50 years and over in the ROI. Demographic and health variables were collected during a face-to-face interview carried out in the home (n=8175), and a substantial proportion of these (n=5035; 62%) also attended a study visit in a health assessment centre. Blood samples collected at baseline (wave 1, the subject of the current study), were analysed for plasma concentrations of L and Z by reversed-phase high performance liquid chromatography, and macular pigment (MP) optical density was also measured (using customized heterochromatic flicker photometry). After excluding participants with eye disease, data from 3,681 participants were available for analysis. For this group of participants, plasma L and Z were inversely and significantly associated with body mass index (BMI), and were positively and significantly associated with MP, total cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) (p<0.001, for all). Plasma L and Z were significantly lower in males, current smokers, participants reporting less physical exercise, and participants reporting lower levels of education (p<0.05, for all). Plasma L was significantly higher in participants reporting a family history of age-related macular degeneration (AMD) (p=0.001), and in the group of ≥75 years old (p<0.05). For each of these variables, the significant associations remained after controlling for other potential confounding variables. The findings of this large study indicate that plasma concentrations of L and Z were lower in association with indicators of a poor lifestyle (high BMI, tobacco use, and less physical exercise) and in association with lower education, indicating that modifying lifestyle in a positive way is likely to be reflected in higher concentrations of plasma carotenoids, with consequential and putative health benefits.

Concordance of Macular Pigment Measurement Using Customized Heterochromatic Flicker Photometry and Fundus Autofluorescence in Age-Related Macular Degeneration.

We compared macular pigment (MP) measurements using customized heterochromatic flicker photometry (Macular Metrics Densitometer) and dual-wavelength fundus autofluorescence (Heidelberg Spectralis HRA + OCT MultiColor) in subjects with early age-related macular degeneration (AMD). Macular pigment was measured in 117 subjects with early AMD (age, 44-88 years) using the Densitometer and Spectralis, as part of the Central Retinal Enrichment Supplementation Trial (CREST; ISRCTN13894787). Baseline and 6-month study visits data were used for the analyses. Agreement was investigated at four different retinal eccentricities, graphically and using indices of agreement, including Pearson correlation coefficient (precision), accuracy coefficient, and concordance correlation coefficient (ccc). Agreement was poor between the Densitometer and Spectralis at all eccentricities, at baseline (e.g., at 0.25° eccentricity, accuracy = 0.63, precision = 0.35, ccc = 0.22) and at 6 months (e.g., at 0.25° eccentricity, accuracy = 0.52, precision = 0.43, ccc = 0.22). Agreement between the two devices was significantly greater for males at 0.5° and 1.0° of eccentricity. At all eccentricities, agreement was unaffected by cataract grade. In subjects with early AMD, MP measurements obtained using the Densitometer and Spectralis are not statistically comparable and should not be used interchangeably in either the clinical or research setting. Despite this lack of agreement, statistically significant increases in MP, following 6 months of supplementation with macular carotenoids, were detected with each device, confirming that these devices are capable of measuring change in MP within subjects over time. (http://www.controlled-trials.com number, ISRCTN13894787.).

Reliability of Heterochromatic Flicker Photometry in Measuring Macular Pigment Optical Density among Preadolescent Children.

Macular pigment optical density (MPOD)—assessed using customized heterochromatic flicker photometry (cHFP)—is related to better cognition and brain lutein among adults. However, the reliability of MPOD assessed by cHFP has not been investigated in children. We assessed inter-session reliability of MPOD using modified cHFP. 7–10-year-olds (n = 66) underwent cHFP over 2 visits using 11 examiners. Reliability was also assessed in a subsample (n = 46) with only 2 examiners. Among all participants, there was no significant difference between the two sessions (p = 0.59—session 1: 0.61 ± 0.28; session 2: 0.62 ± 0.27). There was no significant difference in the MPOD of boys vs. girls (p = 0.56). There was a significant correlation between sessions (Y = 0.52x + 0.31; R2 = 0.29, p ≤ 0.005), with a reliability of 0.70 (Cronbach’s α). Among the subsample with 2 examiners, there was a significant correlation between sessions (Y = 0.54x + 0.31; R2 = 0.32, p < 0.005), with a reliability of 0.72 (Cronbach’s α). In conclusion, there is moderate reliability for modified cHFP to measure MPOD in preadolescents. These findings provide support for future studies aiming to conduct noninvasive assessments of retinal xanthophylls and study their association with cognition during childhood.

Cognitive Function and Its Relationship with Macular Pigment Optical Density and Serum Concentrations of its Constituent Carotenoids.

Background: Macular pigment (MP) levels correlate with brain concentrations of lutein (L) and zeaxanthin (Z), and have also been shown to correlate with cognitive performance in the young and elderly.Objective: To investigate the relationship between MP, serum concentrations of L and Z, and cognitive function in subjects free of retinal disease with low MP (Group 1, n = 105) and in subjects with AMD (Group 2, n = 121).Methods: MP was measured using customized heterochromatic flicker photometry and dual-wavelength autofluorescence; cognitive function was assessed using a battery of validated cognition tests; serum L and Z concentrations were determined by HPLC.Results: Significant correlations were evident between MP and various measures of cognitive function in both groups (r = –0.273 to 0.261, p≤0.05, for all). Both serum L and Z concentrations correlated significantly (r = 0.187, p≤0.05 and r = 0.197, p≤0.05, respectively) with semantic (animal) fluency cognitive scores in Group 2 (the AMD study group), while serum L concentrations also correlated significantly with Verbal Recognition Memory learning slope scores in the AMD study group (r = 0.200, p = 0.031). Most of the correlations with MP, but not serum L or Z, remained significant after controlling for age, gender, diet, and education level.Conclusion: MP offers potential as a non-invasive clinical biomarker of cognitive health, and appears more successful in this role than serum concentrations of L or Z.

Reliability of Heterochromatic Flicker Photometry in Measuring Macular Pigment Optical Density among Preadolescent Children

Macular pigment optical density (MPOD)—assessed using customized heterochromatic flicker photometry (cHFP)—is related to better cognition and brain lutein among adults. However, the reliability of MPOD assessed by cHFP has not been investigated in children. We assessed inter-session reliability of MPOD using modified cHFP. 7-10-year-olds (n = 66) underwent cHFP over 2 visits using 11 examiners. Reliability was also assessed in a subsample (n = 46) with only 2 examiners. Among all participants, there was no significant difference between the two sessions (p = 0.59—session 1: 0.61 ± 0.28; session 2: 0.62 ± 0.27). There was no significant difference in the MPOD of boys vs. girls (p = 0.56). There was a significant correlation between sessions (Y = 0.52x + 0.31; R 2 = 0.29, p ≤ 0.005), with a reliability of 0.70 (Cronbach's α). Among the subsample with 2 examiners, there was a significant correlation between sessions (Y = 0.54x + 0.31; R 2 = 0.32, p < 0.005), with a reliability of 0.72 (Cronbach's α). In conclusion, there is moderate reliability for modified cHFP to measure MPOD in preadolescents. These findings provide support for future studies aiming to conduct noninvasive assessments of retinal

Macular pigment spatial distribution effects on glare disability

PurposeThis project explored the relationship of the macular pigment optical density (MPOD) spatial profile with measures of glare disability (GD) across the macula. MethodsA novel device was used to measure MPOD across the central 16° of retina along four radii using customized heterochromatic flicker photometry (cHFP)at eccentricities of 0°, 2°, 4°, 6° and 8°. MPOD was measured as discrete and integrated values at all measured retinal loci. GD was calculated as a difference in contrast sensitivity (CS) between no glare and glare conditions using identical stimuli presented at the same eccentricities. GD was defined as [(CSNo Glare−CSGlare)/CSNo Glare] in order to isolate the glare attenuation effects of MPOD by controlling for CS variability among the subject sample. Correlations of the discrete and integrated MPOD with GD were compared. ResultsThe cHFP identified reliable MPOD spatial distribution maps demonstrating a 1st-order exponential decay as a function of increasing eccentricity. There was a significant negative correlation between both measures of foveal MPOD and GD using 6cycles per degree (cpd) and 9cpd stimuli. Significant correlations were found between corresponding parafoveal MPOD measures and GD at 2 and 4° of eccentricity using 9cpd stimuli with greater MPOD associated with less glare disability. ConclusionsThese results are consistent with the glare attenuation effects of MP at higher spatial frequencies and support the hypothesis that discrete and integrated measures of MPOD have similar correlations with glare attenuation effects across the macula. Additionally, peak foveal MPOD appears to influence GD across the macula.

A double-blind, placebo-controlled study on the effects of lutein and zeaxanthin on photostress recovery, glare disability, and chromatic contrast.

Past studies have shown that higher macular pigment optical density (MPOD) and lutein (L) and zeaxanthin (Z) supplementation are related to improvements in glare disability, photostress recovery, and chromatic contrast. This study assessed those links using a randomized, double-blind, placebo-controlled design. The visual effects of 1 year of supplementing L (10 mg/d) and Z (2 mg/d) were investigated. One hundred fifteen young, healthy subjects were recruited and randomized into the study (58 received placebo, 57 L+Z). Several dependent measures were collected at baseline and then once every 3 months: serum L and Z measured by HPLC chromatography; MPOD measured using customized heterochromatic flicker photometry; photostress recovery assessed by measuring the time needed to recover visual acquisition of a grating target after 30 seconds of an intense xenon white flash exposure; glare disability evaluated as the energy in a surrounding annulus necessary to veil a central grating target; and chromatic contrast assessed by measuring thresholds for a yellow grating target superposed on a 460-nm background. Macular pigment optical density increased significantly versus placebo at all eccentricities (10, 30, 60, and 105 minutes from the center of the macula). Serum L and Z also increased significantly by the first follow-up visit (at 3 months), and remained elevated throughout the intervention period of 1 year. Chromatic contrast and photostress recovery time improved significantly versus placebo. Glare disability was correlated with macular pigment density throughout the study period but did not increase significantly in the treated group. Daily supplementation with L+Z resulted in significant increase in serum levels and MPOD and improvements in chromatic contrast and recovery from photostress. These results are consistent with past studies showing that increasing MPOD leads to improved visual performance. (ClinicalTrials.gov number, NCT00909090.).

Concordance of macular pigment measurements obtained using customized heterochromatic flicker photometry, dual-wavelength autofluorescence, and single-wavelength reflectance

This study compares in vivo measurements of macular pigment (MP) obtained using customized heterochromatic flicker photometry (cHFP; Macular Metrics Densitometer™), dual-wavelength fundus autofluorescence (Heidelberg Spectralis® HRA + OCT MultiColor) and single-wavelength fundus reflectance (Zeiss Visucam® 200). MP was measured in one eye of 62 subjects on each device. Data from 49 subjects (79%) was suitable for analysis. Agreement between the Densitometer and Spectralis was investigated at various eccentricities using a variety of quantitative and graphical methods, including: Pearson correlation coefficient to measure degree of scatter (precision), accuracy coefficient, concordance correlation coefficient (ccc), paired t-test, scatter and Bland–Altman plots. The relationship between max MP from the Visucam and central MP from the Spectralis and Densitometer was investigated using regression methods. Agreement was strong between the Densitometer and Spectralis at all central eccentricities (e.g. at 0.25° eccentricity: accuracy = 0.97, precision = 0.90, ccc = 0.87). Regression analysis showed a very weak relationship between the Visucam and Densitometer (e.g. Visucam max on Densitometer central MP: R2 = 0.008, p = 0.843). Regression analysis also demonstrated a weak relationship between MP measured by the Spectralis and Visucam (e.g. Visucam max on Spectralis central MP: R2 = 0.047, p = 0.348). MP values obtained using the Heidelberg Spectralis are comparable to MP values obtained using the Densitometer. In contrast, MP values obtained using the Zeiss Visucam are not comparable with either the Densitometer or the Spectralis MP measuring devices. Taking cHFP as the current standard to which other MP measuring devices should be compared, the Spectralis is suitable for use in a clinical and research setting, whereas the Visucam is not.

Low macular pigment optical density is associated with lower cognitive performance in a large, population-based sample of older adults

Macular pigment (MP) is comprised of the carotenoids lutein (L), zeaxanthin (Z), and meso-zeaxanthin (MZ), which selectively accumulate at the macula (central retina) of the eye and are neuroprotective. These carotenoids are also present in the brain, and evidence suggests a close correlation between retinal and brain concentrations. We investigated the relationship between MP and cognitive function in 4453 adults aged ≥50 years as part of The Irish Longitudinal Study on Aging. Macular pigment optical density (MPOD) was determined using customized heterochromatic flicker photometry—a quick and noninvasive way of measuring the concentration of the pigment. Lower MPOD was associated with poorer performance on the mini-mental state examination (p = 0.026) and on the Montreal cognitive assessment (p = 0.016). Individuals with lower MPOD also had poorer prospective memory (p = 0.011), took longer time to complete a trail-making task (p = 0.003), and had slower and more variable reaction times on a choice reaction time task (p = 0.000 and 0.001). These associations were only slightly attenuated following adjustment for physical and mental health. There was no significant association between MPOD and verbal fluency, word recall, visual reasoning, or picture memory. Overall, the findings support the theory that xanthophyll carotenoids impact on cognitive function, underscoring the need for exploration of novel, noninvasive biomarkers for cognitive vulnerability and preventive strategies.

Genetic Determinants of Macular Pigments in Women of the Carotenoids in Age-Related Eye Disease Study

To investigate genetic determinants of macular pigment optical density in women from the Carotenoids in Age-Related Eye Disease Study (CAREDS), an ancillary study of the Women's Health Initiative Observational Study. 1585 of 2005 CAREDS participants had macular pigment optical density (MPOD) measured noninvasively using customized heterochromatic flicker photometry and blood samples genotyped for 440 single nucleotide polymorphisms (SNPs) in 26 candidate genes related to absorption, transport, binding, and cleavage of carotenoids directly, or via lipid transport. SNPs were individually tested for associations with MPOD using least-squares linear regression. Twenty-one SNPs from 11 genes were associated with MPOD (P ≤ 0.05) after adjusting for dietary intake of lutein and zeaxanthin. This includes variants in or near genes related to zeaxanthin binding in the macula (GSTP1), carotenoid cleavage (BCMO1), cholesterol transport or uptake (SCARB1, ABCA1, ABCG5, and LIPC), long-chain omega-3 fatty acid status (ELOVL2, FADS1, and FADS2), and various maculopathies (ALDH3A2 and RPE65). The strongest association was for rs11645428 near BCMO1 (βA = 0.029, P = 2.2 × 10(-4)). Conditional modeling within genes and further adjustment for other predictors of MPOD, including waist circumference, diabetes, and dietary intake of fiber, resulted in 13 SNPs from 10 genes maintaining independent association with MPOD. Variation in these single gene polymorphisms accounted for 5% of the variability in MPOD (P = 3.5 × 10(-11)). Our results support that MPOD is a multi-factorial phenotype associated with variation in genes related to carotenoid transport, uptake, and metabolism, independent of known dietary and health influences on MPOD.

Education Is Positively Associated with Macular Pigment: The Irish Longitudinal Study on Ageing (TILDA)

The three carotenoids lutein, zeaxanthin, and meso-zeaxanthin, are found at the macula and referred to as macular pigment (MP). This study was undertaken to investigate determinants of MP in a large randomly selected sample from the Republic of Ireland (as part of The Irish Longitudinal Study on Ageing [TILDA]).MP optical density (MPOD) was measured using customized heterochromatic flicker photometry in 4373 participants. Sociodemographic and self reported health data was obtained using computer assisted personal interview (CAPI).Mean (SD) MPOD for the study group was 0.203 (0.156) with a range of 0 to 1.01. MPOD was higher for participants with secondary education (mean [SD] = 0.205 [0.148]) than for those with only primary education or no education (mean [SD] = 0.183 [0.113]; P < 0.001). MPOD was also higher for those with tertiary education (mean [SD] = 0.232 [0.231]) compared with primary/no education or secondary education (P < 0.001 for both comparisons).We report that MP is lower amongst those participants of a population-representative study who did not have secondary or third level education when compared with participants who had such education. Given the emerging evidence that MP is important for visual performance and comfort, and given the putative protection that this pigment confers against AMD (especially important in the context of increased risk of AMD in this social group), public health measures aimed at improving diet for this at-risk population need to be considered.

Macular carotenoid supplementation in subjects with atypical spatial profiles of macular pigment

This study was designed to investigate the impact of macular carotenoid supplementation on the spatial profile of macular pigment (MP) in subjects where the profile does not exhibit the typical central peak (i.e. peaked MP at foveal epicentre). Thirty one healthy subjects with such atypical MP spatial profiles were assigned to one of three intervention groups: Group 1: (n = 10), 20 mg/day lutein (L), 2 mg/day zeaxanthin (Z); Group 2: (n = 10), 10 mg/day meso-zeaxanthin (MZ), 10 mg/day L, 2 mg/day Z; Group 3: (n = 10), 17 mg/day MZ, 3 mg/day L, 2 mg/day Z. Subjects were instructed to take one capsule daily over an 8-week period. MP at 0.25°, 0.5°, 1°, 1.75°and 3° was measured using customized-heterochromatic flicker photometry at baseline, four weeks and 8 weeks. Over the study period, we report no statistically significant increase in MP at any eccentricity in Group 1 (p > 0.05, for all eccentricities). There was a trend towards an increase in MP at all eccentricities in Group 2, with a significant increase found at 0.25° and 0.50° (p = 0.000 and p = 0.016, respectively). There was a statistically significant increase evident in MP at 0.25° in Group 3 (p = 0.005), but at no other eccentricity (p > 0.05, for all other). We report that the typical central peak of MP can be realised in subjects with atypical spatial profiles, following supplementation with a preparation containing all three macular carotenoids, but not with a supplement lacking MZ. The implications of our findings, in terms of visual performance and/or a (photo)-protective effect, warrant additional study.

The relation between serum lipids and lutein and zeaxanthin in the serum and retina: results from cross-sectional, case-control and case study designs

BackgroundThe xanthophyll carotenoids lutein (L) and zeaxanthin (Z) are found in and around the macula of the primate retina, where they are termed macular pigment (MP). Dietary L and Z are absorbed with fat in the gut and transported on lipoproteins to the retina. Both MP and serum lipoproteins have been related to risk for neurodegenerative diseases such as age-related macular degeneration (AMD). L and Z are carried on both HDL (related to reduced risk of AMD) and LDL (related to increased risk). The purpose of this set of studies was to analyze the relation between L and Z in the serum and retina with the circulating lipid profile.MethodsIn all experiments, lipoproteins were measured enzymatically from plasma, and MP optical density (MPOD) was measured using customized heterochromatic flicker photometry. Experiment 1: Relations between serum L and Z, MPOD and lipoprotein levels. 108 young, healthy subjects (M = 23.2, SD = 4.12 years) participated. Lipoprotein levels and MPOD were measured. In a subset of 66 participants, serum L and Z levels were also measured using high-performance liquid chromatography. Experiment 2: Relations between lipoprotein levels and MPOD in statin users. 20 subjects (M = 58.05, SD = 11.08 years) taking statin medication and 20 subjects (M = 57.95, SD = 11.03 years) not taking satin were recruited for participation. MPOD and lipoprotein levels were measured. Experiment 3: lowering lipoprotein levels to impact MPOD. One individual (aged 41 years) with high MP density adhered first to an atorvastatin regimen, then, after a wash-out period, to a rosuvastatin regimen.ResultsExperiment 1: HDL were significantly (p < 0.05) related to MPOD (r = 0.33), to serum L (r = 0.36) and to serum Z (r = 0.26). MPOD was also significantly related to total cholesterol (r = 0.19). Experiment 2: MPOD was not lower in statin users when compared to matched non-statin users, but MPOD decreased significantly with increased duration of statin use (r = −0.63). Experiment 3: Administration of a statin regimen reduced MPOD with atorvastatin (p < 0.05) but not with rosuvastatin.ConclusionsSerum xanthophylls, retinal xanthophylls and lipoprotein concentrations are significantly related, and changing lipoprotein levels may impact levels of retinal xanthophylls.