Macular Pigment, Cognition, and Visual Function in Younger Healthy Adults in Ghana.

BACKGROUND: Macular pigment optical density (MPOD) remains an indispensable biomarker to measure fruit and vegetable intake, with a biologically plausible correlation to vision and cognition. However, evidence in the sub-Saharan regions, including Ghana, is lacking. OBJECTIVE: This study explored dietary carotenoid intake on MPOD and its influence on cognitive and visual function in a healthy Ghanaian sample. METHODS: The MPOD of 301 healthy subjects (aged 21.1±1.9 years) was evaluated using the customized Macular DensitometerTM. A battery of cognitive tests and standard vision assessments were employed to assess cognition and visual function, respectively. Dietary lutein and zeaxanthin (L and Z) were estimated based on a twenty-four-hour repeated dietary recall. RESULTS: The mean MPOD at 0.5° and 1.0° eccentricities were 0.37±0.16 and 0.34±0.15 optical density units, respectively. Dietary intake of L (4.06±10.54 mg/day) was considerably higher than Z (0.33±2.25 mg/day), with cumulative L+Z estimated at 4.39±11.58 mg/day. MPOD was not significantly influenced by demographic, dietary, and visual measures (p≥0.05). However, after statistical adjustment, we found a small but statistically significant positive relationship between F-A-S phonemic verbal fluency (Unstandardized co-efficient (ß) = 0.002, p = 0.016) and the never consumed alcohol category (ß= 0.062, p = 0.02) with MPOD. CONCLUSION: The findings in this population showed significant positive relationships between measures of cognition and no alcohol intake, with MPOD. These findings necessitate dietary education to augment carotenoid intake and limit alcohol intake for better cognitive functioning.

Contrast sensitivity functions measured using simple optics and computer testing.

PURPOSE: Contrast sensitivity function (CSF) testing is a common approach to assessing clinical changes to specific aspects of spatial vision. Different stimulus presentations and testing procedures, however, yield significant differences in CSF curves that are more a feature of the method than the observer. In this study, we designed a simple optical device for measuring CSF that could be directly calibrated and compared with a commonly used computer-based system. METHODS: Twenty-one participants (M = 28.95 ± 10.34 years; 66.7% female; 81.0% non-Hispanic White; best corrected visual acuity 6/9 or better) provided photopic CSFs (from measurements at 1.6, 3.2, 8, 16 and 24 cycles per degree, with spatial frequency presentation randomised) using both the Metropsis test platform and a simple optical device over two test sessions (one session/method, randomised, counterbalanced) separated by 1-7 days. The optical system used 520 nm lasers that were made Lambertian using two integrating spheres with a 3.5° circular exit port. These beams were combined with a beam splitter that allowed constant measurement of light output and contrast modulation using sine-wave gratings on glass. In Metropsis, 2° Gabor stimuli were presented for 0.5 s with either a vertical or a horizontal orientation via a two-alternative forced choice paradigm with contrast modulated until four (first) and eight (last) reversals were complete. RESULTS: Both methods took approximately the same amount of time to generate a CSF and yielded curves that were consistent with past studies using similar methods but different from each other. The optical system showed a 3.5 times higher maximum sensitivity and yielded higher test-retest reliability. CONCLUSIONS: Using simple optics to measure CSF yields low noise, high sensitivity and reliability. The ability to calibrate the stimuli directly is an advantage over computer-based methods.

The Effects of a Blue-Light Filtering Versus Clear Intraocular Implant on Color Appearance.

Purpose: More than a dozen studies have investigated whether blue-light filtering (BLF) intraocular lens (IOL) implants influence color vision, generally finding they do not. These studies have not tested color vision per se; rather, they have measured color vision deficiencies or chromatic discrimination. Here, we used additive trichromatic colorimetry to assess color appearance in participants with BLF and clear IOL. Methods: Seventy-six participants were recruited from two populations: older participants (n = 52) with BLF and clear IOL (n = 98 eyes; M = 67.33 ± 7.48 years; 58.8% female; 25.5% non-White), and young adult control participants (n = 24; M = 21.0 ± 5.13 years; 70.8% female; 41.5% non-White). Participants used a custom-built tricolorimeter to mix three primaries until a perceived perfect neutral white was achieved. Color appearance, expressed as chromaticity coordinates, was measured with a spectral radiometer (ILS950). Results: Between subjects, the BLF IOL chromaticity coordinates (x = 0.34, y = 0.35, u' = 0.21, v' = 0.48) were not significantly different from the clear IOL (x = 0.34, y = 0.33, u' = 0.22, v' = 0.48). BLF and clear IOL were also not different within-contralateral subjects (n = 21; BLF x = 0.34, y = 0.33, u' = 0.22, v' = 0.47; clear x = 0.34, y = 0.33, u' = 0.21, v' = 0.48). Both IOL groups differed from young adults (v'[0.45; P = 0.001], x[0.31; P = 0.008], and y[ 0.30, P < 0.000], but not u'[0.21]). Conclusions: One advantage of geometric representation of color space is the ability to specify the appearance (rather than spectral composition) of any light mixture by specific coordinates. Using this system, only minor differences in color appearance were found between a BLF, clear IOL, and young natural lens. Translational Relevance: When color perception is directly measured, the BLF and clear IOL are not meaningfully different.

Stimulus edge effects in the measurement of macular pigment using heterochromatic flicker photometry.

Heterochromatic flicker photometry (HFP) is the most common technique of measuring macular pigment optical density (MPOD). Some data strongly suggest that HFP samples MPOD specifically at the edge of center-fixated circular stimuli. Other data have led to the conclusion that HFP samples over the entire area of the stimulus. To resolve this disparity, MPOD was measured using HFP and a series of solid discs of varying radii (0.25 to 2.0 deg) and with thin annuli corresponding to the edge of those discs. MPOD assessed with the two methods yielded excellent correspondence and linearity: Y=0.01+0.98X , r=0.96. A second set of experiments showed that if a disc stimulus is adjusted for no-flicker (the standard procedure) and simply reduced in size, no flicker is observed despite the higher level of MPOD in the smaller area. Taken together, these results confirm that MPOD is determined at the edge of the measuring stimulus when using stimulus sizes in the range that is in dispute (up to a radius of 0.75 deg). The basis for this edge effect can be explained by quantitative differences in the spatial-temporal properties of the visual field as a function of angular distance from the fixation point.

Photopigment self-screening and the determination of macular pigment absorbance using heterochromatic flicker photometry.

PURPOSE: Heterochromatic flicker photometry (HFP) is commonly used to determine macular pigment optical density (MPOD). Since HFP in this application is a locus comparison method, an identical relative spectral response at each locus is required for a perfect measure. We know this requirement cannot be strictly true since the optical density of photopigments increases as the foveal center is approached. Thus, the self-screening effect would result in an underestimate of MPOD. An earlier study concluded that the underestimate is on the order of 30%. We examined this issue by manipulating photopigment optical density, and consequently the degree of selfscreening. METHODS: A continuously exposed, 470 nm, background bleached cone photopigments over a range from 0 to 80%. MPOD was determined 10' and 30' from the foveal center. Two subjects were used in the main experiment. Five additional subjects were studied with just the 0% and 80% bleach levels. Spectral measures were obtained at 0% and 70% bleach levels for the two primary subjects. RESULTS: Subjects in the main experiment showed MPOD estimates that increased with increasing bleaching. The effect, however, was small: one observer's MPOD increased 0.08 and 0.02 for the 10' and 30' loci, respectively; the other observer's values were 0.04 and 0.01 for the same loci. Comparable values were obtained for the other five subjects using the 0% and 80% bleach conditions. Spectral measures were consistent with the findings of the main experiment. CONCLUSIONS: When self-screening is nearly abolished (80% bleach), a relatively small underestimation is revealed for the unbleached state. For the 1° target we show about 2-3% underestimation. Our 20' target reveals a larger underestimate (8-9%), consistent with longer photoreceptor outer-segments nearer the foveal center. We conclude that HFP yields values essentially independent of self-screening for targets of 1° diameter or greater. Smaller targets are less than 10% underestimated for near-zero bleach conditions.

The influence of filtering by the macular carotenoids on contrast sensitivity measured under simulated blue haze conditions.

PURPOSE: Distant objects are often obscured as a result of wavelength-dependent scattering in the atmosphere. This scattered light, which is mostly short-wave, effectively forms a veiling luminance (or background light) against which a target must be detected and discriminated. The macular pigment (MP) carotenoids could reduce the effective background intensity by selectively filtering out short wavelengths which would increase the contrast of the object in the retinal image, thus improving visibility. This Visibility hypothesis was originally posited by Wooten and Hammond (2002). This study represents a first empirical test of the hypothesis. METHODS: Five young healthy subjects were evaluated. MP optical density (OD) was measured using HFP. Visibility was assessed by measuring contrast sensitivity thresholds at 8 cycles/deg (CST) using an optical system that passed xenon-light through the sine-wave grating. Blue haze was simulated using an ecologically valid broad-spectrum filter. Changes in MP density were simulated using a variable path length filter with an oil-based carotenoid solution that mimicked the absolute absorption spectrum of MP. RESULTS: The average baseline CST was 0.004. Adding 0.25OD of simulated MP lowered the average threshold to 0.003 (25%). An additional 0.25OD decreased thresholds an additional 10% and the effect reached a plateau at about 0.50. DISCUSSION: The largest improvement (about 25%) in contrast occurred with the initial, and relatively modest, addition of 0.25OD units of simulated MP suggesting that the largest improvements may be linked to initial increases in MPOD.

A practical method of measuring the human temporal contrast sensitivity function.

One of the more significant indicators of neural age-related loss and disease is reduced temporal processing speed. It would, therefore, be useful to have an accurate and practical device that measures the full range of an individual's temporal processing abilities (characterized as the temporal contrast sensitivity function, TCSF). 70 subjects (15-84 yrs) were tested. A small tabletop device utilizing electronic control of light-emitting diodes (LEDs) was constructed that delivered a 1-degree, 660 nm test (the modulation depth of which could be adjusted directly by the subject) centered within a 10-degree 660 nm surround. The method provided a TCSF that had a shape consistent with past studies (peaking around 8 Hz). Also consistent with past work, the largest age-decline was found at the highest frequencies and for the central fovea (r = 0.47, p<0.0001, ~2 Hz per decade). Psychophysical assessment of temporal vision offers an easy and dynamic measure of central visual function.

Consumption of 2 and 4 egg yolks/d for 5 wk increases macular pigment concentrations in older adults with low macular pigment taking cholesterol-lowering statins.

BACKGROUND: Lutein and zeaxanthin may reduce the risk of dry, age-related macular degeneration because of their photo-oxidative role as macular pigment. OBJECTIVE: The present study evaluated serum lutein, zeaxanthin, and macular pigment optical density (MPOD) responses at 0.25 degrees , 0.5 degrees , and 1 degree retinal eccentricities to the consumption of 2 and 4 egg yolks/d by older adults taking cholesterol-lowering medications. DESIGN: Subjects consumed foods containing 2 followed by 4 egg yolks/d for 5 wk each with a 4-wk egg-free period at baseline and between the 2 interventions. RESULTS: Changes in MPOD (n = 37) with egg yolk consumption were inversely associated (P < 0.05) with baseline MPOD. Subjects with low-baseline MPOD (defined as MPOD < or =0.5 at 0.25 degrees , < or =0.4 at 0.5 degrees , and < or =0.35 at 1 degrees ) showed increases of < or =50% (P < 0.05) with 4 egg yolks at the 3 retinal eccentricities. MPOD increased by 31% (P = 0.059) at 0.5 degrees with 2 egg yolks. Serum lutein increased by only 16% and 24% (P < 0.05) compared with increases of 36% and 82% (P < 0.001) in serum zeaxanthin (n = 52) after consumption of 2 and 4 egg yolks, respectively. Serum HDL cholesterol increased by 5% (P < 0.05) after consumption of 2 and 4 egg yolks. Serum LDL cholesterol did not change with either egg yolk treatment. CONCLUSIONS: Consumption of 4 egg yolks/d, and possibly of 2 egg yolks/d, for 5 wk benefited macular health in older adults with low MPOD. Serum HDL cholesterol increased without an increase in LDL cholesterol in this study population, most of whom were taking cholesterol-lowering statins.

Macular pigment density and age-related maculopathy in the Carotenoids in Age-Related Eye Disease Study. An ancillary study of the women's health initiative.

PURPOSE: To examine the association between intermediate age-related macular degeneration (AMD) and the optical density of macular pigment (MPOD), which is composed of lutein and zeaxanthin from the diet. DESIGN: Cross-sectional cohort study. PARTICIPANTS: We included 1698 of 2005 women ages 54 to 86 years and participating in the Carotenoids in Age-Related Eye Disease Study, an ancillary study of the Women's Health Initiative. METHODS: The MPOD was measured noninvasively by heterochromatic flicker photometry. Fundus photographs were taken to document prevalent AMD. MAIN OUTCOME MEASURES: Intermediate AMD (n = 305) and two subtypes-large drusen (n = 233) and pigmentary abnormalities (n = 157). RESULTS: After adjusting for covariates, the odds ratio (OR) and 95% confidence interval (CI) for AMD among women in quintile (Q) 5 (n = 339) versus 1 (n = 340) for MPOD was 1.4 (0.9, 2.1). However, after excluding women with possible unstable diets and recent supplement use due to chronic disease history, associations reversed (OR Q2-5 vs. 1, 0.8; 95% CI, 0.5-1.2), but remained nonsignificant. Associations also differed between middle-aged (54-69 years) and older (> or =70 years) women (P-interaction = 0.09), but less so, after excluding women who were likely to have unstable diets: adjusted ORs (95% CI) were 0.5 (0.3-1.0; P = 0.08) for intermediate AMD among middle-aged women (n = 516) with MPOD in Q2 to Q5 versus 1 and 1.0 (0.5-2.0; P = 0.90) for older women (n = 422). CONCLUSIONS: The MPOD is not cross-sectionally associated with AMD. The inconsistency of relationships across age groups and in subgroups of women who are likely to have more stable diets suggests that cross-sectional associations may be biased and highlights the need to study these relationships prospectively.

Using scotopic and photopic flicker to measure lens optical density.

Many applications require knowledge of lens absorption. Measuring lens optical density (OD), however, is often difficult and time-consuming. For example, psychophysical measurement typically requires a long period of dark adaptation (e.g. about 40 min) and assessment of absolute scotopic thresholds. In this study, we examined efficient scotopic and photopic methods for measuring lens OD. In Experiment 1, 30 subjects were tested using a Maxwellian-view optical system. Relative scotopic thresholds were obtained after 15 min of dark adaptation using slow-rate (2 Hz) flicker photometry. A 3 degrees test stimulus, presented at 10 degrees nasal, was used that alternated between measuring wavelengths (420 and 460 nm) and a reference field (540 nm). The results showed that the relative scotopic method produces values that are consistent with published lens spectral curves. In Experiment 2, relative photopic measures (i.e. no dark adaptation period) were also obtained at 406 nm in natural view and compared with lens data obtained in Maxwellian view at 407 nm using the absolute scotopic method. The photopic method compared well with the absolute scotopic values obtained on the same subjects. Taken together, the two experiments showed that a relative method can yield valid lens density estimates. Using a relative rather than an absolute method reduces the time needed for dark adaptation and is an easier task for subjects to perform and may therefore be preferable when expeditious measures are desirable.

Compensation for light loss resulting from filtering by macular pigment: relation to the S-cone pathway.

PURPOSE: Macular pigment (MP) filters short-wavelength light before it reaches the visual pigments. At peak absorbance (460 nm), transmission of light through MP can range from almost 100% transmission to as little as 3%. As a result of the uneven topographic distribution of MP, spatial nonuniformities in visual perception would result if the visual system did not compensate for filtering differences across the central retina. This study characterizes compensation for different densities of MP. METHODS: Sixteen young subjects (aged 24-40 years) with a wide range of MP density were studied. Increment thresholds were measured at 440 and 500 nm in the center of the fovea and at 6 degrees to 7 degrees eccentricity using conditions chosen to isolate the pi-1 mechanism. For six of the subjects, increment thresholds were also obtained for eccentricities of 1 degrees , 1.75 degrees , and 3 degrees . MP density was measured using heterochromatic flicker photometry at the same locations as the increment thresholds. RESULTS: Peak sensitivity of the short-wavelength pathway across the central retina was constant despite MP density differences as large as 1.0 log unit. CONCLUSIONS: These results suggest that the visual system increases gain of the S-cone pathway to offset light absorption by MP.

Predictors of optical density of lutein and zeaxanthin in retinas of older women in the Carotenoids in Age-Related Eye Disease Study, an ancillary study of the Women's Health Initiative.

BACKGROUND: Lifestyle, diet, and physical and health predictors of xanthophyll carotenoids in the retina are poorly understood. OBJECTIVE: We aimed to investigate the predictors of the density of lutein and zeaxanthin in the macula of the retina. DESIGN: Macular pigment optical density (MPOD) was measured by heterochromatic flicker photometry. Relations to dietary lutein and zeaxanthin and to other predictors were measured in 1698 women aged 53-86 y. The women were members of observational study cohorts of the Women's Health Initiative at Iowa City, IA, Madison, WI, or Portland, OR, and participated in the Carotenoids in Age-Related Eye Disease Study (2001-2004). RESULTS: MPOD at 0.5 degrees from the foveal center was 30% higher in women in the highest quintile for lutein and zeaxanthin intake [x (+/-SD): 0.40 +/- 0.21] than in women in the lowest quintile (0.31 +/- 0.21) and 20% higher after adjustment for other predictors. Dietary intake of lutein, zeaxanthin, fiber, and polyunsaturated fatty acids (% of energy) together explained 3% of the variability in MPOD. Higher waist circumference and diabetes, which are related to lower MPOD, together with study site explained an additional 5% of variation. The total explained variability increased to 12% when lutein and zexanthin concentrations obtained from the serum, which were collected 4-7 y earlier, were added to the model. CONCLUSIONS: MPOD is directly related to dietary intake of lutein and zeaxanthin but even more strongly to serum concentrations, which may reflect unmeasured physical and medical factors that influence the uptake, distribution, and utilization of lutein and zeaxanthin. Higher abdominal body fat and diabetes are related to lower MPOD. Unknown predictors of retinal carotenoids remain.

Resonance Raman spectroscopic measurement of carotenoids in the skin and retina.

Carotenoid pigments within the skin and retina are measured using resonance Raman spectroscopy (RS). These RS instruments are unique in that they have been designed to obtain vibrational spectra in normal and diseased subjects using noninvasive procedures. Raman spectra have traditionally been used as a means of identifying a given chemical within some substrate. The new generation of RS instruments, however, has been designed to quantify the amount of carotenoids within the retina and skin. These amounts are typically reported in nonstandardized units called Raman counts (RC). These RCs are dependent on many factors intrinsic to their measurement, such as the specific optics used for stimulation and acquisition. The question of whether RCs can be used to derive valid quantitative measures of the carotenoid pigments in vivo is discussed.

CFF thresholds: relation to macular pigment optical density.

PURPOSE: Only two small studies have evaluated the relation between individual differences in macular pigment (MP) levels and visual health prior to retinal disease. In this study, we assess the relation between MP and a general measure of visual health, the critical flicker fusion (CFF) threshold. METHODS: A total of 134 subjects were assessed. CFF values were determined psychophysically using a 570 nm, circular 1-degree test field centrally fixated. MP optical density was measured using flicker photometry and a 1-degree circular 458 nm test field centrally fixated. Personal characteristics were determined by questionnaire. RESULTS: Similar to past studies, we found a significant decline in CFF values with age (r = -0.56). There was a significant positive relationship (r = 0.30, p < 0.001) between MP density and CFF values that was independent of age. CONCLUSIONS: These results are consistent with a protective effect of MP on visual health across the lifespan.

Spectral absorbance and spatial distribution of macular pigment using heterochromatic flicker photometry.

PURPOSE: The validity of the heterochromatic flicker photometric (HFP) technique for measuring macular pigment (MP) was assessed by evaluating the spatial density and spectral absorption curves of normal subjects. METHODS: Standard Maxwellian view optics were used to measure MP spatial density and spectral absorption curves. Four subjects with normal color vision and one protanope were tested. All of the subjects were experienced psychophysical observers. RESULTS: Spatial density profiles for all subjects were nearly symmetric. The width of the spatial distribution, at half maximal density, averaged 0.70 degrees (standard deviation = 0.15). A first-order exponential decay with eccentricity described the distribution profile well (average r = 0.95). The shape of the spectral absorption curves matched an ex vivo template closely at wavelengths greater than approximately 430 nm. Stimulus size did not influence the derived spectral curves. CONCLUSION: Based on data from this study and others, the HFP method appears to be a valid method for measuring MP density in subjects without retinal disease.

Assessment of the validity of in vivo methods of measuring human macular pigment optical density.

PURPOSE: As a result of the putative protective role of lutein and zeaxanthin at the site of the retina (macular pigment [MP]), interest in the noninvasive measurement of these retinal carotenoids is increasing. In principle, any method used to measure MP in vivo should provide spectral absorption curves that match extinction spectra of MP measured ex vivo. METHODS: In this article, we assess published spectral curves with respect to this criterion. RESULTS AND DISCUSSION: Variation in derived MP measures resulting from methodological differences between techniques is noted and discussed.

Macular pigment measurement by heterochromatic flicker photometry in older subjects: the carotenoids and age-related eye disease study.

PURPOSE: To develop a standardized protocol for measuring macular pigment optical density (MPOD) of experimentally naïve subjects by heterochromatic flicker photometry (HFP). METHODS: MPOD in eyes of 54 women, age 50 and 79 years (mean, 66), was studied. The spatial profile of MPOD was measured in the right eye, and two spatial points were also measured in the left eye. Forty-eight of these inexperienced subjects completed the protocol on two separate visits. For a subset of the group, the MPOD at two different wavelengths was measured. RESULTS: The test-retest correlation at 0.5 degrees eccentricity in the right eye was 0.9. On the second visit, more than 90% of the subjects were able to perform the HFP test with results that were consistent with the absorption spectrum of macular pigment. On the first visit, data from the inexperienced subjects deviated more from the expected relationships between the two wavelengths, presumably because they had less skill in performing the task. However, subjects with high or low macular pigment density were distinguished clearly. CONCLUSIONS: Reliable and meaningful measurements of macular pigment density in older subjects can be made using HFP, with a standardized protocol in the limited time available in large epidemiologic studies. This protocol will be made freely available to other researchers on request.

Macular pigment: influences on visual acuity and visibility.

There is increasing evidence that the macular pigment (MP) carotenoids lutein (L) and zeaxanthin (Z) protect the retina and lens from age-related loss. As a result, the use of L and Z supplements has increased dramatically in recent years. An increasing number of reports have suggested that L and Z supplementation (and increased MP density) are related to improved visual performance in normal subjects and patients with retinal and lenticular disease. These improvements in vision could be due either to changes in the underlying biology and/or optical changes. The optical mechanisms, i.e., preferential absorption of short-wave light, underlying these putative improvements in vision, however, have not been properly evaluated. Two major hypotheses are discussed. The acuity hypothesis posits that MP could improve visual function by reducing the effects of chromatic aberration. The visibility hypothesis is based on the idea that MP may improve vision through the atmosphere by preferentially absorbing blue haze (short-wave dominant air light that produces a veiling luminance when viewing objects at a distance).