Macular Pigment Spatial Profile Research Articles

Macular pigment profile characteristics and stability over periods of up to 25 years

This study compares the foveal and total retinal macular pigment (MP) amount in healthy subjects and examines the stability of MP spatial distribution profiles, measured almost annually for periods of up to 25 years.Measurements of MP spatial distribution profiles were made by 51 subjects using the psychophysical technique of minimum motion photometry, utilizing a moving bichromatic grating (test 460 nm, comparison 580 nm). Two foveal fields (0.9° and 2.2° diameter) and 11 annular segments (eccentricities from 0.8° to 7.5°) were used. The total amount of MP within the central 15 degrees was estimated by numerical integration and compared with foveal values. Four subjects with widely different MP profiles underwent almost annual testing for periods of 19–25 years. Eleven of the same subjects and 19 others underwent 2‐wavelength autofluorescence (AF) assessment of MP using a scanning laser ophthalmoscope (incident radiation 488 nm and 514 nm), allowing quantification of the peak relative optical density, distribution and total complement of MP over the central 21 degrees.Detailed examinations revealed widely different MP distribution profiles using motion photometry and/or 2‐wavelength fundus autofluorescence. There was a lack of correlation between peak MP optical density at the fovea and assessments of the total complement of MP within the central 15 or 21 degrees. Serial psychophysical assessments over periods of 19–25 years in 4 cases demonstrated a high degree of stability at all macular locations including the fovea; plots of peak MP optical density against time showed minimal positive and negative gradients (<0.0003).The total amount of macular pigment cannot be accurately estimated from foveal or central values. Widely different MP distribution profiles in healthy subjects demonstrate a high degree of long‐term stability, relevant to investigations that aim to monitor MP or fundus autofluorescence in disease or in studies that aim to modify MP through dietary supplementation.

The Differential Contribution of Macular Pigments and Foveal Anatomy to the Perception of Maxwell’s Spot and Haidinger’s Brushes

The relationship of macular pigments and foveal anatomy to the perception of Maxwell's spot (MS) and Haidinger's brushes (HB) entoptic phenomena were investigated. Dual-wavelength-autofluorescence and OCT were used to define macular pigment density and foveal anatomy in 52 eyes. MS was generated by alternating unpolarized red/blue and red/green uniform field illumination. HB was generated by alternating the linear polarization axis of a uniform blue field. In Experiment 1, horizontal widths of MS and HB were measured using a micrometer system and compared with macular pigment densities and OCT-defined morphometry. MS radius (mean 1.4°) was significantly less than HB radius (mean 1.6°), with the spatial extent of both phenomena falling between the boundaries of the foveola and foveal pit. Multiple regression showed MS and HB radii to be significantly associated with the macular pigment spatial profile radius. HB radius, but not MS radius, was also significantly associated with foveolar morphometry. Experiment 2 compared perceptual profiles of MS with macular pigment distribution patterns and demonstrated close agreement. The size and appearance of MS is a direct indicator of macular pigment density and distribution. Measures of HB radii are less specific, with dependence on both macular pigment density and foveal structure.

Spatial distribution of macular pigment estimated by autofluorescence imaging in elderly Japanese individuals

To determine the spatial distribution types of macular pigment (MP) in elderly Japanese individuals and to consider their origin. Observational case series. Local MP optical density (MPOD) at some eccentricities and MP volume were measured using the MPOD module of a MultiColor Spectralis in 96 pseudophakic eyes of 96 participants (age range, 52-86years; mean age, 72.8 ± 8.3years). The MP distribution types were determined from the MP spatial profiles. The retinal thickness (RT) at the foveal center, at both 0.5° and 0.9° eccentricities, and the foveal width were measured using optical coherence tomography. The mean local MPOD at the foveal center was 0.79. Spatial distribution was classified into four types: central peak (24.0%), ring-like (40.6%), intermediate (22.9%), and central dip (12.5%). The ring-like type was the most frequent in these Japanese participants. The central-peak type showed lower MPOD than did the other types in the area outside 0.9°. The ring-like type occurred frequently in eyes with small RT at 0.5° and wider foveal width. A rough contour of the Müller cell cone was found more frequently in the central-dip type than in the other types. The present characteristics of the different distribution patterns could be explained by the hypothesis that MP presents mainly in the Müller cell cone within 0.5° and in Müller cells in the outer and inner plexiform layers in the area outside 0.5°. The anatomic characteristics of Müller cells at the fovea and parafovea likely affect the MP distribution.

Repeatability of the macular pigment spatial profile: A comparison of objective versus subjective classification.

PurposeClassification of macular pigment (MP) spatial profile phenotypes varies and is often based on subjective visualisation. We investigated repeatability of MP optical density (MPOD) comparing an objective versus subjective profiling system.MethodsThe coefficient of repeatability (CoR) was calculated for point MPOD values (0–3.8°) obtained by dual‐wavelength fundus autofluorescence (FAF) from two scans obtained in a single visit of 40 healthy individuals (39 ± 9 years). For each individual's dataset, the MP profile was classified as exponential, ring‐like or central dip using an objective method (based on deviations away from an exponential fit), as well as by subjective visual profiling. Existing FAF images of 88 monozygotic (MZ) and 69 dizygotic (DZ) twin pairs were reanalysed using the objective profiling method and concordance and heritability of ring‐like profiles determined.ResultsThe CoR was 0.23 at 0° and 0.06 at 0.8°. Agreement of objective profiling between scans was excellent (κ = 0.85, 95% CI 0.69 to 1.00; p < 0.0005). Subjective profiling showed moderate agreement between scans (κ = 0.48, 95% CI 0.23 to 0.73; p < 0.0005). Agreement between objective and subjective classification was low (κ = 0.23, 95% CI 0.04 to 0.42; p = 0.02). Concordance for the ring‐like profile using objective profiling was 0.74 for MZ compared to 0.36 for DZ twins. Heritability was calculated as 81.5% (95% confidence interval 61.1–93.1%).ConclusionCompared to visual assessment, objective MP profiling is a more reliable method and should be considered in future observational and interventional studies. In addition, MP profile phenotypes showed high heritability.

Is macular pigment spatial profile a clinical biomarker in children of AMD parents?

SummaryA central dip in macular pigment (MP) has shown to be more prevalent with age, in AMD patients, and in smokers. We investigated clinical and genetic biomarkers in non‐smoking children of AMD parents (n = 131) over 40 years of age without AMD pathology in relation to their MP spatial profile. MP peak and volume were obtained with ARIS (Visual Pathways, Inc, Prescott, AZ USA) while spatial profiles for both eyes were classified visually and objectively. We explored risk factors including serum carotenoids and in‐vivo skin carotenoids, and cardiovascular biomarkers including omega‐3 fatty acids EPA and DHA, methylenetetrahydrofolate reductase C677T and A1298C in this well‐nourished Caucasian study group. Objectively, a central dip appeared more prevalent in children of AMD patients (41%) when compared to a healthy population. Those with central dip showed increased mean MP peak and volume, decreased serum L, Z, EPA and DHA, and decreased skin carotenoids in comparison to no dip. Identifying biomarkers in children genetically susceptible to AMD and introducing lifestyle changes such as nutrient repletion could provide invaluable advice to those associated with increased risk of AMD.

Classification and heritability of macular pigment spatial profile phenotypes using two‐wavelength fundus autofluorescence

PurposeWe investigated the frequency and heritability of macular pigment (MP) spatial profile phenotypes determined by objective and subjective profile classification based on fundus autofluorescence (FAF).MethodsBetween scans Coefficient of Repeatability (CoR) of MP optical density (MPOD) was calculated from two FAF scans (Spectralis, Heidelberg, Germany) of 40 participants (39 ± 8.6 years) acquired in a single session. We then analyzed two FAF scans acquired in a single session from 314 twins (157 pairs; 39 ± 8.8 years) and classified each MP profile as exponential, ring‐like or central dip by subjective visual assessment. Profiles were also classified objectively based on deviations larger than the CoR away from the exponential fit. We calculated kappa agreement of the profiling methods, case‐wise concordance of non‐exponential profiles for the 88 mono‐ (MZ) and 69 dizygotic (DZ) twin pairs, and profile heritability.ResultsFollowing visual subjective profiling, 64% showed an exponential profile, 27% presented ring‐like and 9% central dip profiles; case‐wise concordance was 0.80 for MZ and 0.41 for DZ twins. Following objective classification, 71% showed an exponential profile, 29% ring‐like profile and no central dip profiles were identified; case‐wise concordance was 0.74 for MZ and 0.36 for DZ twins. Heritability was calculated as 81.5% (95% CI 61.1–93.1). Between scan repeatability of profile classification showed good agreement objectively (κ = 0.85, 95% CI 0.69–1.00; p &lt; 0.0005) and moderate agreement visually (κ = 0.48, 95% CI 0.23–0.73; p &lt; 0.0005). Agreement of subjective versus objective profiling was low (κ = 0.23, 95% CI 0.04–0.42; p = 0.02).ConclusionsMP profiles showed high heritability. Compared to visual assessment, objective profile classification is a more reliable method for future experimental studies using two‐wavelength FAF.

The Spatial Profile of Macular Pigment in Subjects From a Singapore Chinese Population

To examine the spatial profile of macular pigment (MP) and its relationship with serum concentrations of lutein (L) and zeaxanthin (Z) in subjects from a Singapore Chinese population. In this cross-sectional study, the following details were recorded in 95 healthy subjects: sociodemographic, lifestyle information, body mass index (BMI), visual acuity, MP spatial profile using a macular densitometer, and serum L and Z. The mean (SD) age of the population was 42.40 (± 13) years, ranging from 21 to 68 years. Females demonstrated significantly lower MP optical density (MPOD) than males (MPOD: females = 0.52 ± 0.17; males = 0.61 ± 0.21, P = 0.03). MP spatial profile was typical and atypical with central dip in 68 (85%) and 12 (15%) subjects, respectively. Age and BMI were found to be significant predictors for atypical MP spatial profile (age: odds ratio, OR = 1.06, 95% confidence interval, CI = 1.01-1.13, P = 0.04; BMI: OR = 1.17, 95% CI = 1.01-1.34, P = 0.03). A positive relationship was observed between MPOD and serum concentrations of L and Z, but only the latter relationship reached statistical significance (serum L: r = 0.12, P = 0.30; serum Z: r = 0.26, P = 0.02). A central dip in MP spatial profile was observed with older age and higher BMI, the two known risk factors for AMD, suggesting that atypical MP spatial profile may be associated with an increased risk of AMD. Further studies with larger sample sizes are required to confirm these observations.

Macular Pigment Spatial Profiles in South Asian and White Subjects

Variability in central macular pigment optical density (MPOD) has been reported among healthy individuals. These variations seem to be related to risk factors of AMD, such as female sex, smoking, and ethnicity. This study investigates variations in the spatial profiles of MPOD among ethnicities. Using heterochromatic flicker photometry (HFP), MPOD was measured at seven retinal locations in 54 healthy, young South Asian and 19 white subjects of similar age. Macular pigment spatial profiles were classified as either typical exponential, atypical ring-like, or atypical central dip. Central MPOD was significantly greater in South Asian (0.56 ± 0.17) compared with white subjects (0.45 ± 0.18; P = 0.015). Integrated MPOD up to 1.8° (i.e., average MPOD [MPODav(0-1.8)]) was also significantly increased in South Asian (0.34 ± 0.09) compared to white subjects (0.27 ± 0.10; P = 0.003). Average MPOD(0-1.8) was significantly increased in all subjects presenting a ring-like profile (0.35 ± 0.08) or central dip profile (0.39 ± 0.09), compared with typical exponential profiles (0.28 ± 0.09; P < 0.0005). We found a statistically significant association between ethnicity and spatial profile type (P = 0.008), whereby an exponential profile was present in 79% of white compared with 41% of the South Asian subjects. Central MPOD, MPODav(0-1.8), and the prevalence of atypical spatial profiles were significantly increased in South Asian compared with white subjects. Atypical profiles resulted in increased integrated MPOD up to 1.8°, and may therefore offer enhanced macular protection from harmful blue light.

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 Ringlike Structure of Macular Pigment in Age-Related Maculopathy: Results from the Muenster Aging and Retina Study (MARS)

The role of macular pigment (MP) in age-related maculopathy (ARM) is still not clearly understood. Recent studies have reported on variations in the spatial distribution of MP optical density (MPOD) including a secondary peak ("ring") in the slope of the MPOD profile. The authors investigated in a cross-sectional manner the presence of ringlike structures, their determinants, and their relationship with ARM. In all, 369 participants of the Muenster Aging and Retina Study were examined using dual-wavelength analysis of autofluorescence images. ARM was graded using digital fundus photographs according to the International Classification System. A ringlike structure was observed in 73 (19.8%) study participants. The MP maximum of the ring was located on average at 0.85° and the minimum at 0.48° from the center of the fovea. Their concordance between pairs of eyes was highly significant. MPOD measured at eccentricities of 0°, 0.25°, and 0.5° from the fovea was significantly lower in eyes with ringlike structure, whereas it was significantly higher at 1.0° and 2.0° than that in eyes without the ring. Ringlike structures were significantly more common in females and never smokers and were found significantly less often in eyes with ARM than in healthy eyes, even after adjustment for influential factors (adjusted odds ratio, 0.347; 95% confidence interval, 0.196-0.617). Ringlike structures in the MP spatial profile are fairly common, show a high degree of bilaterality, and appeared inversely related with ARM.

Recovery of macular pigment spectrum in vivo using hyperspectral image analysis

We investigated the feasibility of a novel method for hyperspectral mapping of macular pigment (MP) in vivo. Six healthy subjects were recruited for noninvasive imaging using a snapshot hyperspectral system. The three-dimensional full spatial-spectral data cube was analyzed using non-negative matrix factorization (NMF), wherein the data was decomposed to give spectral signatures and spatial distribution, in search for the MP absorbance spectrum. The NMF was initialized with the in vitro MP spectrum and rank 4 spectral signature decomposition was used to recover the MP spectrum and optical density in vivo. The recovered MP spectra showed two peaks in the blue spectrum, characteristic of MP, giving a detailed in vivo demonstration of these absorbance peaks. The peak MP optical densities ranged from 0.08 to 0.22 (mean 0.15+∕-0.05) and became spatially negligible at diameters 1100 to 1760 μm (4 to 6 deg) in the normal subjects. This objective method was able to exploit prior knowledge (the in vitro MP spectrum) in order to extract an accurate in vivo spectral analysis and full MP spatial profile, while separating the MP spectra from other ocular absorbers. Snapshot hyperspectral imaging in combination with advanced mathematical analysis provides a simple cost-effective approach for MP mapping in vivo.

A Central Dip in the Macular Pigment Spatial Profile Is Associated with Age and Smoking

To investigate the relationship between specific macular pigment (MP) spatial profiles and risk factors for age-related macular degeneration (AMD). The MP spatial profile of 484 healthy subjects was measured with customized heterochromatic flicker photometry (cHFP) and categorized into one of two profile types: typical exponential or atypical "central dip." Data on risk factors for AMD were obtained with a general health and lifestyle questionnaire. Dietary and serum concentrations of lutein (L) and zeaxanthin (Z) were also assessed. The presence of the central dip MP spatial profile was significantly more common in older subjects (the mean ± SD age of subjects with a central dip MP spatial profile was 46.9 ± 12 years, whereas the mean age of subjects with a typical MP spatial profile was 41.8 ± 12 years; P = 0.004) and in current cigarette smokers (P = 0.031). Also, there was a significant age-related decline in central MP optical density (MPOD; 0.25° retinal eccentricity), but in the men only (r = -0.146, P = 0.049). A central dip in the MP spatial profile, seen in older subjects and in cigarette smokers, may represent an undesirable feature of macular pigmentation. Further research is needed in this area.

Correspondence between retinal reflectometry and a flicker-based technique in the measurement of macular pigment spatial profiles

A comparison of macular pigment optical density (MPOD) spatial profiles determined by an optical and a psychophysical technique is presented. We measured the right eyes of 19 healthy individuals, using fundus reflectometry at 0, 1, 2, 4, 6, and 8 deg eccentricity; and heterochromatic flicker photometry (HFP) at 0, 0.5, 1, 2, 3, 4, 5, 6, and 7 deg, and a reference point at 8 deg eccentricity. We found a strong correlation between the two techniques. However, the absolute estimates obtained by fundus reflectometry data were higher than by HFP. These differences could partly be explained by the fact that at 8 deg eccentricity the MPOD is not zero, as assumed in HFP. Furthermore, when performing HFP for eccentricities of <1 deg, we had to assume that subjects set flicker thresholds at 0.4 deg horizontal translation when using a 1-deg stimulus. MPOD profiles are very similar for both techniques if, on average, 0.05 DU is added to the HFP data at all eccentricities. An additional correction factor, dependent on the steepness of the MPOD spatial distribution, is required for 0 deg.

Foveal Anatomic Associations with the Secondary Peak and the Slope of the Macular Pigment Spatial Profile

To investigate the reproducibility of the macular pigment (MP) spatial profile by using heterochromatic flicker photometry (HFP) and to relate the MP spatial profile to foveal architecture. Sixteen healthy subjects (nine had the typical exponential MP spatial profile [group 1]; seven had a secondary peak MP spatial profile [group 2]) were recruited. The MP spatial profile was measured on three separate occasions. Six radiance measurements were obtained at each locus (0.25 degrees , 0.5 degrees , 1 degrees , and 1.75 degrees eccentricity; reference point, 7 degrees ). Foveal architecture was assessed by optical coherence tomography (OCT). Subjects who had the typical decline profile, had this profile after averaging repeated measures (group 1). Subjects who had a secondary peak, displayed the secondary peak after repeated measures were averaged (group 2). Mean SD foveal width in group 1 was significantly narrower than mean SD foveal width in group 2 (1306 +/- 240 microm and 1915 +/- 161 microm, respectively; P < 0.01). This difference remained after adjustment for sex (P < 0.001). Foveal width was significantly related to mean foveal MP, with adjustment for sex (r = 0.588, P = 0.021). Foveal profile slope was significantly related to MP spatial profile slope, after removal of an outlier (r = 0.591, P = 0.020). HFP reproducibly measures MP spatial profile. Secondary peaks seen in the MP spatial profile cannot be attributed to measurement error and are associated with wider foveas. The slope of an individual's MP spatial profile is related to foveal slope, with a steeper MP distribution associated with a steeper foveal depression.

Compensation for light loss due to filtering by macular pigment: relation to hue cancellation

A long-standing question in colour vision research is how the visual system is able to correct for the significant absorbance of short wave light by the crystalline lens and macular pigment (MP). Such compensation must be required in order to maintain colour constancy across the retina where MP levels are changing quickly and dramatically. We studied this compensation mechanism by measuring MP spatial density profiles and hue cancellation functions across the central retina in a sample of six young healthy subjects. Yellow (Y, 575 nm)/blue (B, 440 nm) and red (R, 600 nm)/green (G, 501 nm) cancellation functions were obtained at 0, 1, 1.75, 3 and 7 degrees eccentricity. The MP optical density at 460 nm was measured at these same eccentricities using heterochromatic flicker photometry. One subject was assessed repeatedly over a 4-month period during daily supplementation with 30 mg of lutein (L). Hue cancellation values for the Y/B system did not change across the retina (r = 0.09). In contrast, R/G sensitivity changed as a direct function of MP absorbance (r = 0.99). The Y/B values did not change in the one subject supplemented with 30 mg L daily, despite increases in MP of about 50% over 4 months. Despite large variations in MP across the retina, hue cancellation values for the Y-B system across the central retina were constant. For example, one subject's MP density declined from a central peak of 0.99 to near zero at 7 degrees (near 90% transmission difference) yet thresholds for the Y/B system were unaffected. In contrast, the G lobe of the R/G system was directly correlated with MP density. Taken together, these results confirm that the Y/B system compensates for MP density, but the R/G system does not.