Do lutein, zeaxanthin, and macular pigment optical density differ with age or age-related maculopathy?

Background and aims Current age-related macular disease (ARMD) treatment includes antioxidant supplementation. Lutein (L) and zeaxanthin (Z) are antioxidants that make up macularpigment within the retina and may reduce the risk of developing ARMD. Ageing and smoking are leading risk factors for developing ARMD. We investigated differences in dietary, supplemental and retinal L and Z, and smoking habits in healthy younger eyes (HY), healthy older eyes (HO) and eyes with an early form of ARMD called age-related maculopathy (ARM). Methods HO, HY and ARM groups were assessed for dietary intakes of L and Z using food diaries. Smoking habits and self-administered quantities of L and Z were obtained via questionnaire. Retinal L and Z levels (macularpigmentopticaldensity, or MPOD) were determined using heterochromatic flicker photometry. Results No significant difference was demonstrated for dietary L and Z intake (?2 = 4.983, p = 0.083) or for MPOD between groups (F = 0.40, p = 0.67). There was a significant difference between the HY (mean ± sd: 1.20 ± 2.99), HO (4.51 ± 7.05) ARM groups (9.15 ± 12.28) for pack years smoked (?2 = 11.61, p = 0.03). Conclusions Our results do not support the theory that ARM develops as a result of L and Z deficiency. Higher pack years smoked may be a factor in disease development. Dietary and supplementary L and Z levels must be obtained when assessing MPOD between groups or over time.

New investigations into macular pigment optical density

Macular pigment (MP) is the collective name for three carotenoids, lutein, zeaxanthin and meso-zeaxanthin, which are found at high concentrations in the central macula. The macular carotenoids, like all carotenoids, are entirely of dietary origin. The term ‘macular pigment optical density’ (MPOD) refers to the peak concentration of MP in the retina, which varies from one individual to the next and is measurable in vivo. On account of its blue-light-filtering and antioxidant properties, MP has become a subject of interest with respect to age-related macular degeneration (AMD), the hypothesis being that MP helps to protect against AMD; the higher the MPOD, the lower the risk for AMD. Recently, a new MPOD-measuring device, the MPS 9000 (MPS), entered the ophthalmic market. Using this device, the research described here aimed to contribute new information to the MP literature. A second MPOD instrument, the Macular Pigment Reflectometer, was also used at times, but a reliability study (included in the thesis) demonstrated that it was unsuitable for use on its own. First, a series of exploratory investigations were undertaken to maximize the accuracy and consistency of MPOD measurements taken with the MPS; a protocol was established that substantially improved repeatability. Subsequently, a series of MPOD-based studies were conducted on anisometropia, South Asian race, blue-light-filtering contact lenses, and dietary modification with kale. The principle findings were as follows: interocular MPOD differences were not attributable to interocular refractive error differences; young adults of South Asian origin had significant gender-related MPOD differences (males>females, p<0.01), and they also had significantly higher MPOD than Caucasians (p<0.0005); wearing blue-light-filtering contact lenses for eight months did not affect MPOD; and dietary modification with kale for 16 weeks did not increase MPOD. This body of research adds new insights to MP knowledge, which in turn may contribute to MP knowledge in the context of AMD.

Macular pigment optical density is related to blood glutathione levels in healthy individuals

Purpose. To assess the relationship between macular pigment optical density (MPOD) and blood markers for antioxidant defense in otherwise healthy volunteers. Methods. Forty-seven healthy volunteers were subjected to blood analysis to detect the level of circulating glutathione in its reduced (GSH) and oxidized (GSSG) forms. The level of MPOD was measured using heterochromatic flicker photometry. Systemic blood pressure (BP) parameters, heart rate (HR), body mass index (BMI), and plasma levels of total, HDL, and LDL cholesterol and triglycerides (TGs) were also determined. Results. A simple correlation model revealed that the level of MPOD correlated significantly and positively with both GSH (P < 0.001) and t-GSH (P < 0.001) levels but not with those of GSSG (P > 0.05). Age, sex, systemic BP parameters, HR, BMI, and plasma levels of cholesterol and TGs did not have any influence on either MPOD or glutathione levels (all P > 0.05). In addition, a forward stepwise multiple regression analysis showed MPOD to have a significantly and independent correlation with GSH levels (ß = 0.63; P < 0.001). Conclusions. In otherwise healthy older individuals, there is a positive correlation between local and systemic antioxidant defense mechanisms.

Measuring macular pigment optical density in vivo:a review of techniques

Macular pigment has been the focus of much attention in recent years, as a potential modifiable risk factor for age-related macular degeneration. This interest has been heightened by the ability to measure macular pigment optical density (MPOD) in vivo.

Improving the repeatability of heterochromatic flicker photometry for measurement of macular pigment optical density

Background: Heterochromatic flicker photometry (HFP) is a psychophysical technique used to measure macular pigment optical density (MPOD). We used the MPS 9000 (MPS) HFP device. Our aim was to determine if the repeatability of the MPS could be improved to make it more suitable for monitoring MPOD over time. Methods: Intra-session repeatability was assessed in 25 participants (aged 20-50 years). The resulting data was explored in detail, e.g., by examining the effect of removal and adjustment of data with less than optimal quality parameters. A protocol was developed for improved overall reliability, which was then tested in terms of inter-session repeatability in a separate group of 27 participants (aged 19-52 years). Results: Removal and adjustment of data reduced the intra-session coefficient of repeatability (CR) by 0.04, on average, and the mean individual standard deviation by 0.004. Raw data observation offered further insight into ways of improving repeatability. The proposed protocol resulted in an inter-session CR of 0.08. Conclusions: Removal and adjustment of less than optimal data improved repeatability, and is therefore recommended. To further improve repeatability, in brief we propose that each patient perform each part of the test twice, and a third time where necessary (described in detail by the protocol). Doing so will make the MPS more useful in research and clinical settings. © 2012 Springer-Verlag.

Macular pigment optical density in young adults of South Asian origin

Purpose: To assess the range of macular pigment optical density (MPOD) in a healthy group of young adults of South Asian origin; to investigate whether any dietary factors or personal characteristics were related to inter-subject variations in MPOD; and to compare the mean MPOD of the South Asian group with the mean MPOD of a white group. Methods: Heterochromatic flicker photometry was used to measure the MP levels of 169 healthy volunteers, of which 117 were Asian and 52 were white. In addition, the Asian participants completed a questionnaire pertaining to the various physical, ocular, lifestyle, dietary and environmental factors that may be associated with MPOD or age-related macular degeneration (AMD). Results: The mean MPOD of the Asian subjects was 0.43±0.14. The male participants had a higher mean MPOD than the females (0.47±0.13 vs 0.41±0.14, p<0.01). Possible associations also emerged between MPOD and form of refractive correction, and iris colour. No MPOD associations were found for the other variables examined in the questionnaire. The mean MPOD of the white subject group was 0.33±0.13, which was significantly lower than the Asian group (p<0.0005). Conclusions: This study adds to the currently limited information on MPOD in South Asians, and while a comparison between Asians and Whites was not the main focus here, highly significant differences between these two ethnicities were revealed. This provokes the possibility that South Asian individuals could have a lower risk for AMD, and it warrants further study.

The effect of ocular nutritional supplements on macular pigment optical density

This thesis describes the investigation of the effects of ocular supplements with different levels of nutrients on the macular pigment optical density (MPOD) in participants with healthy eyes. Abstract A review of the literature highlighted that ocular supplements are produced in various combinations of nutrients and concentrations. The ideal concentrations of nutrients such as lutein (L) have not been established. It was unclear whether different stages of eye disease require different concentrations of key nutrients, leading to the design of this study. The primary aim was to determine the effects of ocular supplements with different concentrations of nutrients on the MPOD of healthy participants. The secondary aim was to determine L and zeaxanthin (Z) intake at the start and end of the study through completion of food diaries. The primary study was split into two experiments. Experiment 1 was an exploratory study to determine sample size and experiment 2 the main study. Statistical power was calculated and a sample size of 38 was specified. Block stratification for age, gender and smoking habit was applied and from 101 volunteers 42 completed the study, 31 with both sets of food diaries. Four confounders were accounted for in the design of the study; gender, smoking habit, age and diet. Further factors that could affect comparability of results between studies were identified during the study and were not monitored; ethnicity, gastro-intestinal health, alcohol intake, body mass index and genetics. Comparisons were made between the sample population and the Sheffield general population according to recent demographic results in the public domain. Food diaries were analysed and shown to have no statistical difference when comparing baseline to final results. The average L and Z intake for the 31 participants who returned both sets of food diaries was initially 1.96mg and 1.51mg for the final food diaries. The effect of the two ocular supplements with different levels of xanthophyll (6mg lutein/zeaxanthin and 10mg lutein only) on MPOD was not significantly different over a four-month period.

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 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 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.

The effect of simulated cataract light scatter on retinal vessel oximetry

To assess the impact of light scatter, similar to that introduced by cataract on retinal vessel blood oxygen saturation measurements using poly-bead solutions of varying concentrations. Eight healthy, young, non-smoking individuals were enrolled for this study. All subjects underwent digital blood pressure measurements, assessment of non-contact intraocular pressure, pupil dilation and retinal vessel oximetry using dual wavelength photography (Oximetry Module, Imedos Systems, Germany). To simulate light scatter, cells comprising a plastic collar and two plano lenses were filled with solutions of differing concentrations (0.001, 0.002 and 0.004%) of polystyrene microspheres (Polysciences Inc., USA). The adopted light scatter model showed an artifactual increase in venous optical density ratio (p=0.036), with the 0.004% condition producing significantly higher venous optical density ratio values when compared to images without a cell in place. Spectrophotometric analysis, and thus retinal vessel oximetry of the retinal vessels, is altered by artificial light scatter. © 2013 Elsevier Ltd.