Oral Lutein Supplementation Enhances Macular Pigment Density and Contrast Sensitivity but Not in Combination With Polyunsaturated Fatty Acids.

Purpose It has been shown that lutein and zeaxanthin accumulate in the macula where they enhance contrast sensitivity and may reduce the risk of progression to advanced age-related macular degeneration (AMD). Furthermore, omega-3 long-chain polyunsaturated fatty acids (PUFA) might further reduce this risk. However, controversy exists regarding whether PUFA may reduce the bioavailability of lutein. Methods This was a prospective 12-month, randomized, open label study evaluating the effect of supplementation with lutein, other antioxidants, and minerals on contrast sensitivity (CS) and macular pigment optical density (MPOD) in patients with age-related maculopathy. A total of 79 patients were randomized to either lutein (10 mg) and antioxidant supplement or lutein and antioxidant supplement in combination with PUFA. Patients received supplementation for a period of 6 months and were followed for a total of 12 months. Results Serum lutein and zeaxanthin increased significantly by the first follow-up visit at 1 month, and remained elevated throughout the intervention period of 6 months in the lutein-only group but not in the lutein+PUFA group. Macular pigment optical density and CS increased significantly in the lutein-only group (P < 0.005) but not in the lutein+PUFA group (P = 0.059) compared to baseline. Best-corrected visual acuity remained unchanged during the entire study period in both groups. Conclusions Addition of PUFA may reduce the bioavailability of lutein and therefore lessen the beneficial effect on macular pigment and CS. This needs to be considered when prescribing lutein supplements to patients with low lutein levels. (ClinicalTrials.gov number, NCT00563979.).

Apparent motion photometry:evaluation and reliability of a novel method for the measurement of macular pigment

Background/aims Macular pigment is thought to protect the macula against exposure to light and oxidative stress, both of which may play a role in the development of age-related macular degeneration. The aim was to clinically evaluate a novel cathode-ray-tube-based method for measurement of macular pigment optical density (MPOD) known as apparent motion photometry (AMP). Methods The authors took repeat readings of MPOD centrally (0°) and at 3° eccentricity for 76 healthy subjects (mean (±SD) 26.5±13.2 years, range 18–74 years). Results The overall mean MPOD for the cohort was 0.50±0.24 at 0°, and 0.28±0.20 at 3° eccentricity; these values were significantly different (t=-8.905, p<0.001). The coefficients of repeatability were 0.60 and 0.48 for the 0 and 3° measurements respectively. Conclusions The data suggest that when the same operator is taking repeated 0° AMP MPOD readings over time, only changes of more than 0.60 units can be classed as clinically significant. In other words, AMP is not suitable for monitoring changes in MPOD over time, as increases of this magnitude would not be expected, even in response to dietary modification or nutritional supplementation.

Clinical evaluation of the MPS 9000 Macular Pigment Screener

Background/aims The MPS 9000 uses a psychophysical technique known as heterochromatic flicker photometry to measure macular pigment optical density (MPOD). Our aim was to determine the measurement variability (noise) of the MPS 9000. Methods Forty normally sighted participants who ranged in age from 18 to 50 years (25.4±8.2 years) were recruited from staff and students of Aston University (Birmingham, UK). Data were collected by two operators in two sessions separated by 1 week in order to assess test repeatability and reproducibility. Results The overall mean MPOD for the cohort was 0.35±0.14. There was no significant negative correlation between MPS 9000 MPOD readings and age (r=-0.192, p=0.236). Coefficients were 0.33 and 0.28 for repeatability, and 0.25 and 0.26 for reproducibility. There was no significant correlation between mean and difference MPOD values for any of the four pairs of results. Conclusions When MPOD is being monitored over time then any change less than 0.33 units should not be considered clinically significant as it is very likely to be due to measurement noise. The size of the coefficient appears to be positively correlated with MPOD.

The role of macular pigment assessment in clinical practice:a review

This review compares the results of studies that have investigated the impact of lutein and zeaxanthin supplementation on macular pigment optical density (MPOD) with those that have investigated the reliability of techniques used to measure macular pigment optical density. The review will focus on studies that have used heterochromatic flicker photometry for measurement of macular pigment optical density, as this is the only technique that is currently available commercially to clinicians. We identified articles that reported on supplementation with lutein and/or zeaxanthin and/or meso-zeaxanthin on macular pigment optical density measurement techniques published in peer-reviewed journals, through a multi-staged, systematic approach. Twenty-four studies have investigated the repeatability of MPOD measurements using heterochromatic flicker photometry. Of these, 10 studies provided a coefficient of repeatability or data from which the coefficient could be calculated, with a range in values of 0.06 to 0.58. The lowest coefficient of repeatability assessed on naïve subjects alone was 0.08. These values tell us that, at best, changes greater than 0.08 can be considered clinically significant and at worst, only changes greater than 0.58 can be considered clinically significant. Six studies assessed the effect of supplementation with up to 20 mg/day lutein on macular pigment optical density measured using heterochromatic flicker photometry and the mean increase in macular pigment optical density ranged from 0.025 to 0.09. It seems reasonable to conclude that the chance of eliciting an increase in macular pigment optical density during six months of daily supplementation with between 10 and 20 mg lutein that is of sufficient magnitude to be detected by using heterochromatic flicker photometry on an individual basis is small. Commercially available heterochromatic flicker photometers for macular pigment optical density assessment in the clinical environment appear to demonstrate particularly poor coefficient of repeatability values. Clinicians should exercise caution when considering the purchase of these instruments for potential monitoring of macular pigment optical density in response to supplementation in individual patients.

Clinical evaluation of the Macuscope macular pigment densitometer

Background/aims. The MacuScope uses a psychophysical technique called heterochromic flicker photometry to measure macular pigment optical density (MPOD). Our aim was to determine the measurement variability (noise) of the MacuScope. Methods. Thirty-eight normally sighted participants who ranged in age from 19 to 46 years (25.7±7.6 years) were recruited from staff and students of Aston University. Data were collected by two operators, HB and JA, in two sessions separated by 1 week in order to assess test repeatability and reproducibility. Results. The overall mean MPOD for the cohort was 0.47±0.14. There was a significant negative correlation between MacuScope MPOD readings and age (r=-0.368, p=0.023). Coefficients were 0.45 and 0.58 for repeatability, and 0.49 and 0.36 for reproducibility. For each pair of results, there was a significant positive correlation between mean and difference MPOD values. Conclusions. If MPOD is being monitored over time then any change less than 0.58 units should not be considered clinically significant as it is very likely to be due to instrument noise. The size of the coefficient appears to be positively correlated with MPOD.

Authors' response:clinical evaluation of the MPS 9000 macular pigment screener

As a research group with no commercial interest in any macular pigment optical density (MPOD) measurement devices or nutritional supplements, we feel that we were well-placed to carry out an independent clinical assessment of the reliability of the MPS 9000 (Tinsley Precision Instruments, Redhill, Surrey, UK). Our study was prompted by the fact that we could not find any reported coefficient of repeatability value within the literature, and none was provided by the manufacturer.1 We had planned to use this instrument in our own research studies investigating the impact of nutritional supplementation on MPOD. For this purpose, we needed …

Cataract, macular characteristics and assessing lens opacities

Age-related macular degeneration and cataract are very common causes of visual impairment in the elderly. Macular pigment optical density is known to be a factor affecting the risk of developing age-related macular degeneration but its behaviour due to light exposure to the retina and the effect of macular physiology on this measurement are not fully understood. Cataract is difficult to grade in a way which reflects accurately the visual status of the patient. A new technology, optical coherence tomography, which allows a cross sectional slice of the crystalline lens to be imaged has the potential to be able to provide objective measurements of cataract which could be used for grading purposes. This thesis set out to investigate the effect of cataract removal on macular pigment optical density, the relationship between macular pigment optical density and macular thickness and the relationship between cortical cataract density as measured by optical coherence tomography and other measures of cataract severity. These investigations found: 1) Macular pigment optical density in a pseudophakic eye is reduced when compared to a fellow eye with age related cataract, probably due to differences in light exposure between the eyes. 2) Lower macular pigment optical density is correlated with thinning of the entire macular area, but not with thinning of the fovea or central macula. 3) Central macular thickness decreases with age. 4) Spectral domain optical coherence tomography can be used to successfully acquire images of the anterior lens cortex which relate well to slit lamp lens sections. 5) Grading of cortical cataract with spectral domain optical coherence tomography instruments using a wavelength of 840nm is not well correlated with other established metrics of cataract severity and is therefore not useful as presented as a grading method for this type of cataract.

Investigation of Genetic Variation in Scavenger Receptor Class B, Member 1 (SCARB1) and Association with Serum Carotenoids

Objective: To investigate association of scavenger receptor class B, member 1 (SCARB1) genetic variants with serum carotenoid levels of lutein (L) and zeaxanthin (Z) and macular pigment optical density (MPOD).
Design: A cross-sectional study of healthy adults aged 20 to 70.
Participants: We recruited 302 participants after local advertisement.
Methods: We measured MPOD by customized heterochromatic flicker photometry. Fasting blood samples were taken for serum L and Z measurement by high-performance liquid chromatography and lipoprotein analysis by spectrophotometric assay. Forty-seven single nucleotide polymorphisms (SNPs) across SCARB1 were genotyped using Sequenom technology. Association analyses were performed using PLINK to compare allele and haplotype means, with adjustment for potential confounding and correction for multiple comparisons by permutation testing. Replication analysis was performed in the TwinsUK and Carotenoids in Age-Related Eye Disease Study (CAREDS) cohorts.
Main Outcome Measures: Odds ratios for MPOD area, serum L and Z concentrations associated with genetic variations in SCARB1 and interactions between SCARB1 and gender.
Results: After multiple regression analysis with adjustment for age, body mass index, gender, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, smoking, and dietary L and Z levels, 5 SNPs were significantly associated with serum L concentration and 1 SNP with MPOD (P<0.01). Only the association between rs11057841 and serum L withstood correction for multiple comparisons by permutation testing (P<0.01) and replicated in the TwinsUK cohort (P = 0.014). Independent replication was also observed in the CAREDS cohort with rs10846744 (P = 2×10-4), an SNP in high linkage disequilibrium with rs11057841 (r2 = 0.93). No interactions by gender were found. Haplotype analysis revealed no stronger association than obtained with single SNP analyses.
Conclusions: Our study has identified association between rs11057841 and serum L concentration (24% increase per T allele) in healthy subjects, independent of potential confounding factors. Our data supports further evaluation of the role for SCARB1 in the transport of macular pigment and the possible modulation of age-related macular degeneration risk through combating the effects of oxidative stress within the retina.
Financial Disclosure(s): Proprietary or commercial disclosures may be found after the references. Ophthalmology 2013;120:1632–1640 © 2013 by the American Academy of Ophthalmology.

The Effect of nutritional supplementation on subjective and objective measures of visual and retinal function:a random controlled trial

In industrialised countries age-related macular disease (ARMD) is the leading cause of visual loss in older people. Because oxidative stress is purported to be associated with an increased risk of disease development the role of antioxidant supplementation is of interest. Lutein is a carotenoid antioxidant that accumulates within the retina and is thought to filter blue light. Increased levels of lutein have been associated with reduced risk of developing ARMD and improvements in visual and retinal function in eyes with ARMD. The aim of this randomised controlled trial (RCT) was to investigate the effect of a lutein-based nutritional supplement on subjective and objective measures of visual function in healthy eyes and in eyes with age-related maculopathy (ARM) – an early form of ARMD. Supplement withdrawal effects were also investigated. A sample size of 66 healthy older (HO), healthy younger (HY), and ARM eyes were randomly allocated to receive a lutein-based supplement or no treatment for 40 weeks. The supplemented group then stopped supplementation to look at the effects of withdrawal over a further 20 weeks. The primary outcome measure was multifocal electroretinogram (mfERG) N1P1 amplitude. Secondary outcome measures were mfERG N1, P1 and N2 latency, contrast sensitivity (CS), Visual acuity (VA) and macular pigment optical density (MPOD). Sample sizes were sufficient for the RCT to have an 80% power to detect a significant clinical effect at the 5% significance level for all outcome measures when the healthy eye groups were combined, and CS, VA and mfERG in the ARM group. This RCT demonstrates significant improvements in MPOD in HY and HO supplemented eyes. When HY and HO supplemented groups were combined, MPOD improvements were maintained, and mfERG ring 2 P1 latency became shorter. On withdrawal of the supplement mfERG ring 1 N1P1 amplitude reduced in HO eyes. When HO and HY groups were combined, mfERG ring 1 and ring 2 N1P1 amplitudes were reduced. In ARM eyes, ring 3 N2 latency and ring 4 P1 latency became longer. These statistically significant changes may not be clinically significant. The finding that a lutein-based supplement increases MPOD in healthy eyes, but does not increase mfERG amplitudes contrasts with the CARMIS study and contributes to the debate on the use of nutritional supplementation in ARM.

The effect of nutritional supplementation on the multifocal electroretinogram in healthy eyes

BACKGROUND: Previous studies have demonstrated an increase in macular pigment optical density (MPOD) with lutein (L)-based supplementation in healthy eyes. However, not all studies have assessed whether this increase in MPOD is associated with changes to other measures of retinal function such as the multifocal ERG (mfERG). Some studies also fail to report dietary levels of L and zeaxanthin (Z). Because of the associations between increased levels of L and Z, and reduced risk of AMD, this study was designed to assess the effects of L-based supplementation on mfERG amplitudes and latencies in healthy eyes. METHODS: Multifocal ERG amplitudes, visual acuity, contrast sensitivity, MPOD and dietary levels of L and Z were assessed in this longitudinal, randomized clinical trial. Fifty-two healthy eyes from 52 participants were randomly allocated to receive a L-based supplement (treated group), or no supplement (non-treated group). RESULTS: There were 25 subjects aged 18-77 (mean age ± SD; 48 ± 17) in the treated group and 27 subjects aged 21-69 (mean age ± SD; 43 ± 16) in the non-treated group. All participants attended for three visits: visit one at baseline, visit two at 20 weeks and visit three at 40 weeks. A statistically significant increase in MPOD (F = 17.0, p ≤ 0.001) and shortening of mfERG ring 2 P1 latency (F = 3.69, p = 0.04) was seen in the treated group. CONCLUSIONS: Although the results were not clinically significant, the reported trend for improvement in MPOD and mfERG outcomes warrants further investigation.

Macular pigment density at the site of altered fundus autofluorescence

The purpose of our study was to determine whether abnormalities of increased or decreased fundus autofluorescence (FAF) are associated with local changes in macular pigment (MP) optical density in patients with age-related maculopathy (ARM) and macular degeneration (ARMD).

Heritability of the spatial distribution and peak density of macular pigment:a classical twin study

Purpose: To elucidate the heritability of peak density and spatial width of macular pigment (MP) using a Classical Twin Study.

Methods: Fundus autofluorescence images were obtained at 488?nm from 86 subjects or 43 twin pairs (21 monozygotic (MZ) and 22 dizygotic (DZ)) (27 male, 59 female) aged from 55 to 76 years (mean 62.2±5.3 years). The relative topographic distribution of MP was measured using a grey scale of intensity (0-255 units) in a 7° eccentricity around the fovea. Relative peak MP density (rPMPD) and relative spatial distribution of MP (rSDMP) were used as the main outcome measure in the statistical analysis.

Results: A significantly higher correlation was found within MZ pairs as compared with that within DZ pairs for rPMPD, (r=0.99, 95% confidence interval (95% CI) 0.93 to 1.00) and 0.22, 95% CI -0.34 to 0.71), respectively, suggesting strong heritability of this trait. When rSDMP was compared, there was no significant difference between the correlations within MZ pairs (r=0.48, 95% CI -0.02 to 0.83) and DZ pairs (r=0.63, 95% CI 0.32 to 0.83), thus rSDMP is unlikely to have a considerable heritable component. In addition, there was no difference between any MP parameter when normal maculae were compared with early age-related macular degeneration (AMD) (rPMPD 0.36 vs 0.34, t=1.18 P=0.243, rSDMP 1.75 vs 1.75, t=0.028 P=0.977).ConclusionsrPMPD is a strongly heritable trait whereas rSDMP has minimal genetic influence and a greater influence by environmental factors. The presence of macular changes associated with early AMD did not appear to influence any of these pigment parameters. © 2012 Macmillan Publishers Limited All rights reserved 0950-222X/12

Simple and objective method for routine detection of the macular pigment xanthophyll

A new simple method for two-dimensional determination of optical density of macular pigment xanthophyll (ODx) in clinical routine is based on a single blue-reflection fundus image. Individual different vignetting is corrected by a shading function. For its construction, nodes are automatically found in structureless image regions. The influence of stray light in elderly crystalline lenses is compensated by a correction function that depends on age. The reproducibility of parameters in a one-wavelength reflection method determined for three subjects (47, 61, and 78 years old) was: maxODx = 6.3%, meanODx = 4.6%, volume = 6%, and area = 6% already before stray-light correction. ODx was comparable in pseudophakic and in an eye with a crystalline lens of the same 11 subjects after stray-light correction. Significant correlation in ODx was found between the one-wavelength reflection method and the two-wavelength autofluorescence method for pseudophakic and cataract eyes of 19 patients suffering from dry age-related macular degeneration (AMD) (R(2) = 0.855). In pseudophakic eyes, maxODx was significantly lower for dry AMD (n = 45) (ODx = 0.491±0.102 ODU) than in eyes with healthy fundus (n = 22) (ODx = 0.615±0.103 ODU) (p = 0.000033). Also in eyes with crystalline lens, maxODx was lower in AMD (n = 125) (ODx = 0.610±0.093 ODU) than in healthy subjects (n = 45) (ODx = 0.674±0.098 ODU) (p = 0.00019). No dependence on age was found in the pseudophakic eyes both of healthy subjects and AMD patients.

[Seasonal fluctuations and influence of nutrition on macular pigment density]

PURPOSE: We have previously reported on measuring macular pigment density (MPD) with a scanning laser ophthalmoscope (HRA, Heidelberg Engineering, Heidelberg, Germany). This study war undertaken to evaluate the variation of MPD over a period of 1 year in healthy subjects. METHOD: We used autofluorescence images recorded with a HRA to evaluate MPD with a 2 degrees circle centered on the fovea. Healthy subjects were included in the study and MPD measurements were repeated every 2 months over a period of 1 year. RESULTS: We included a total of 30 healthy subjects aged 19-34 years (mean: 23+/-2 years). Mean MPD at time point 1 was 0.215+/-0.056 density units (DU), at time point 2 0.235+/-0.051 DU, at time point 3 0.218+/-0.055 DU, at time point 4 0.228+/-0.057 DU, at time point 5 0.225+/-0.053 DU, and at time point 6 0.203+/-0.050 DU. The statistical analysis revealed no significant variation of MPD over the follow-up period of 1 year. CONCLUSION: This study demonstrates that MPD shows no variation over a period of 1 year in healthy subjects.