Environmental and Nutritional Determinants of Macular Pigment in a Mexican Population.

Purpose: The carotenoids lutein (L), zeaxanthin (Z), and meso-zeaxanthin deposit at the macula as macular pigment (MP) and provide visual benefits and protection against macular diseases. The present study investigated MP, its nutritional and environmental determinants, and its constituent carotenoids in serum from a Mexican sample, in healthy participants and with metabolic diseases. Additionally, we compared these variables with an Irish sample. Methods: MP was measured in 215 subjects from a rural community in Mexico with dual-wavelength autofluorescence imaging reported as MP optical volume (MPOV). Dietary intake and serum concentrations of L and Z were evaluated. Results: The mean MPOV was 8429 (95% confidence interval, 8060-8797); range. 1171-15,976. The mean L and Z serum concentrations were 0.25 ± 0.15 µmol/L and 0.09 ± 0.04 µmol/L, respectively. The MPOV was positively correlated with L and Z serum concentrations (r = 0.347; P < 0.001 and r = 0.311; P < 0.001, respectively), but not with L + Z dietary estimates. Subjects with daily sunlight exposure of more than 50% were found to have significantly higher MPOV than those with less than 50% (P = 0.005). MPOV and serum concentrations of L and Z were significantly higher in the Mexican sample compared with the Irish sample, but this difference was not reflected in dietary analysis. Conclusions: These new data from a Mexican sample provide evidence of the multifactorial interactions and environmental determinants of MP such as sunlight exposure and dietary patterns. These findings will be essential for future studies in Mexico for eye health, visual function, and ocular pathology.

Effects of macular xanthophyll supplementation on brain-derived neurotrophic factor, pro-inflammatory cytokines, and cognitive performance.

PURPOSE: Oxidative and inflammatory processes play a major role in stress-induced neural atrophy. There is a wide body of literature linking oxidative and inflammatory stress with reductions in neurotrophic factors, stress resilience, and cognitive function. Based on their antioxidant and anti-inflammatory capacity, we investigated the effect of the dietary carotenoids lutein and zeaxanthin, along with the zeaxanthin isomer meso-zeaxanthin (collectively the "macular xanthophylls" [MXans]) on systemic brain-derived neurotrophic factor (BDNF) and anti-oxidant capacity (AOC), and the pro-inflammatory cytokines TNF-α, IL-6, and IL-1ß. To investigate higher-order effects, we assessed cognitive performance. METHODS: 59 young (18-25 yrs.), healthy subjects participated in a 6-month, double-blind, placebo-controlled trial to evaluate the effects of MXan supplementation on the aforementioned serum parameters and cognitive performance. Subjects were randomly assigned to one of three groups: placebo, 13 mg, or 27 mg/day total MXans; all measures were taken at baseline and 6 months. Blood was obtained via fasting blood draw, and MXan concentration in the retina (termed macular pigment optical density [MPOD]) was measured via customized heterochromatic flicker photometry. Serum BDNF and cytokines were assessed via ELISA. Serum antioxidant capacity (AOC) and serum MXan concentrations were quantified via colorimetric microplate assay, and high-performance liquid chromatography, respectively. Cognitive performance was measured via a computer-based assessment tool (CNS Vital Signs). RESULTS: BDNF, MPOD, serum MXans, and AOC all increased significantly versus placebo in both treatment groups over the 6-month study period (p < .05 for all). IL-1ß decreased significantly versus placebo in both treatment groups (p = .0036 and p = .006, respectively). For cognitive measures, scores for composite memory, verbal memory, sustained attention, psychomotor speed, and processing speed all improved significantly in treatment groups (p < .05 for all) and remained unchanged in the placebo group. Several measures were found to be significantly associated in terms of relational changes over the course of the study. Notably, change in BDNF was related to change in IL-1ß (r = -0.47; p < .001) and MPOD (r = 0.44; p = .0086). Additionally, changes in serum MXans were strongly related to AOC (r = 0.79 & 0.61 for lutein and zeaxanthin isomers respectively; p < .001). For cognitive scores, change in BDNF was correlated to change in composite memory (r = 0.32; p = .014) and verbal memory (r = 0.35; p = .007), whereas change in MPOD was correlated with change in both psychomotor speed (r = 0.38; p = .003), and processing speed (r = 0.35; p = .007). Change in serum lutein was found to be significantly correlated to change in verbal memory (r = 0.41; p < .001), composite memory (r = 0.31; p = .009), and sustained attention (r = 0.28; p = .036). Change in serum zeaxanthin isomers was significantly correlated with change in verbal memory (r = 0.33; p = .017). Lastly, change in AOC was significantly associated with verbal memory (r = 0.34; p = .021), composite memory (r = 0.29; p = .03), and sustained attention (r = 0.35; p = .016). No significant relational changes in any cognitive parameter were found for the placebo group. CONCLUSIONS: Six months of daily supplementation with at least 13 mg of MXans significantly reduces serum IL-1ß, significantly increases serum MXans, BDNF, MPOD, and AOC, and improves several parameters of cognitive performance. Findings suggest that increased systemic antioxidant/anti-inflammatory capacity (and not necessarily deposition of the carotenoids in neural tissues), may explain many of the effects determined in this study. The significant relationship between change in BDNF and IL-1ß over the course of the study suggests that regular consumption of MXans interrupts the inflammatory cascade that can lead to reduction of BDNF. Changes in MPOD and BDNF appear to account for enhancement in cognitive parameters that involve speed of processing and complex processing, respectively. ISRCTN Clinical Trial Registration: ISRCTN16156382.

Lutein across the Lifespan: From Childhood Cognitive Performance to the Aging Eye and Brain.

Lutein is a non-provitamin A dietary carotenoid found in dark green leafy vegetables, corn, eggs, and avocados. Among the carotenoids, lutein and its isomer, zeaxanthin, are the only 2 that cross the blood-retina barrier to form macular pigment in the retina. Lutein also preferentially accumulates in the human brain across multiple life stages. A variety of scientific evidence supports a role for lutein in visual as well as cognitive function across the lifespan. The purpose of this review is to summarize the latest science on lutein's role in the eye and the brain across different ages.

Visual Performance in the "Real World": Contrast Sensitivity, Visual Acuity, and Effects of Macular Carotenoids.

Visual acuity (VA) is compared to contrast sensitivity (CS) testing in assessing "real-world" visual performance, and it is recommended that both should be measured routinely in the clinic. The role of nutritional intervention in improving visual performance is reviewed and emphasized. A brief history and illustration of both VA and CS, within the scope of visual performance, is presented. Parameters for effective CS testing in the clinic, and guidelines for interpretation of results, including a new model for understanding the visual impact of changes in CS, are also presented. Relevant research that supports the use of the macular carotenoids lutein, zeaxanthin, and meso-zeaxanthin to enhance visual performance is reviewed with suggested guidelines for supplementation. CS testing is easily performed at a single intermediate target size and is an excellent tool for the accurate assessment of a patient's overall visual experience. Research continues to uncover the strong link between nutrition and visual performance; the macular carotenoids appear to be especially effective in this regard, and their benefits to visual performance now importantly include contrast sensitivity. Clinicians can provide an improved level of care by incorporating into the examination protocol CS testing and, where appropriate, nutritional counseling and intervention.

Mobile Telephone Use and Reaction Time in Drivers With Glaucoma.

Importance: Combining mobile telephone use with driving is not unusual. However, distracted driving limits driving performance because of limited capacity for persons to divide attention. Objectives: To investigate the frequency of mobile telephone use while driving and to assess whether patients with glaucoma had a disproportionate decrease in driving performance while conversing on a mobile telephone compared with healthy participants. Design, Setting, and Participants: Cross-sectional study of surveys collected from 112 patients with glaucoma and 70 control participants investigating mobile telephone use while driving. A randomly selected subgroup of 37 patients with glaucoma and 28 controls drove in a driving simulator to investigate peripheral event detection performance during distracted driving at the Visual Performance Laboratory, Duke University, Durham, North Carolina. Data collection was performed from December 1, 2016, through April 30, 2017. Exposures: Participants answered a survey and submitted to a driving simulation test with and without mobile telephone use. Main Outcomes and Measures: Survey answers were collected, and distracted driving performance, assessed by reaction time to peripheral stimuli, was analyzed. Results: Of the 182 participants who answered the survey, the 112 participants with glaucoma included 56 women (50.0%) and had a mean (SD) age of 73.6 (9.6) years. The 70 controls included 49 women (70.0%) and had a mean (SD) age of 68.4 (10.9) years. When asked about mobile telephone use while driving, 30 patients with glaucoma (26.8%) admitted rarely using and 2 (1.8%) sometimes using it. In the control group, 20 participants (28.6%) admitted rarely using and 2 (2.9%) sometimes using the telephone while driving (P = .80). Reaction times to peripheral stimuli were significantly longer among patients with glaucoma compared with controls during mobile telephone use (median [interquartile range], 1.86 [1.42-2.29] seconds vs 1.14 [0.98-1.59] seconds; P = .02). Compared with driving performance while not using a mobile telephone, the mean (SD) increase of 0.85 (0.60) second in reaction time while conversing on the mobile telephone among patients with glaucoma was significantly greater than the mean (SD) increase of 0.68 (0.83) second for controls (P = .03). Conclusions and Relevance: This study's findings indicate that patients with glaucoma use mobile telephones while driving as frequently as healthy participants. However, the findings also suggest that patients with glaucoma may experience a greater decline than healthy participants in their ability to detect peripheral events while driving when also talking on a mobile telephone. Patients with glaucoma should be informed that they may have a higher driving risk that may be worsened by distractions, such as mobile telephone use.

Visual Crowding in Glaucoma.

Purpose: Crowding refers to the phenomenon in which objects that can be recognized when viewed in isolation are unrecognizable in clutter. Crowding sets a fundamental limit to the capabilities of the peripheral vision and is essential in explaining performance in a broad array of daily tasks. Due to the effects of glaucoma on peripheral vision, we hypothesized that neural loss in the disease would lead to stronger effects of visual crowding. Methods: Subjects were asked to discriminate the orientation of a target letter when presented with surrounding flankers. The critical spacing value (scritical), which was required for correct discrimination of letter orientation, was obtained for each quadrant of the visual field. scritical values were correlated with standard automated perimetry (SAP) mean sensitivity (MS) and optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) thickness measurements. Results: The study involved 13 subjects with mild glaucomatous visual field loss and 13 healthy controls. Glaucomatous eyes had significantly greater (worse) scritical than controls (170.4 ± 27.1 vs. 145.8 ± 28.0 minimum of visual angle, respectively; P = 0.007). scritical measurements were significantly associated with RNFL thickness measurements (R2 = 26%; P < 0.001) but not with SAP MS (P = 0.947). Conclusions: In glaucoma patients, a pronounced visual crowding effect is observed, even in the presence of mild visual field loss on standard perimetry. scritical was associated with the amount of neural loss quantified by OCT. These results may have implications for understanding how glaucoma patients are affected in daily tasks where crowding effects may be significant.

Supplementation with macular carotenoids reduces psychological stress, serum cortisol, and sub-optimal symptoms of physical and emotional health in young adults.

PURPOSE: Oxidative stress and systemic inflammation are the root cause of several deleterious effects of chronic psychological stress. We hypothesize that the antioxidant and anti-inflammatory capabilities of the macular carotenoids (MCs) lutein, zeaxanthin, and meso-zeaxanthin could, via daily supplementation, provide a dietary means of benefit. METHODS: A total of 59 young healthy subjects participated in a 12-month, double-blind, placebo-controlled trial to evaluate the effects of MC supplementation on blood cortisol, psychological stress ratings, behavioural measures of mood, and symptoms of sub-optimal health. Subjects were randomly assigned to one of three groups: placebo, 13 mg, or 27 mg / day total MCs. All parameters were assessed at baseline, 6 months, and 12 months. Serum MCs were determined via HPLC, serum cortisol via ELISA, and macular pigment optical density (MPOD) via customized heterochromatic flicker photometry. Behavioural data were obtained via questionnaire. RESULTS: Significant baseline correlations were found between MPOD and Beck anxiety scores (r = -0.28; P = 0.032), MPOD and Brief Symptom Inventory scores (r = 0.27; P = 0.037), and serum cortisol and psychological stress scores (r = 0.46; P < 0.001). Supplementation for 6 months improved psychological stress, serum cortisol, and measures of emotional and physical health (P < 0.05 for all), versus placebo. These outcomes were either maintained or improved further at 12 months. CONCLUSIONS: Supplementation with the MCs significantly reduces stress, cortisol, and symptoms of sub-optimal emotional and physical health. Determining the basis for these effects, whether systemic or a more central (i.e. brain) is a question that warrants further study.

Macular Carotenoid Supplementation Improves Visual Performance, Sleep Quality, and Adverse Physical Symptoms in Those with High Screen Time Exposure.

The dramatic rise in the use of smartphones, tablets, and laptop computers over the past decade has raised concerns about potentially deleterious health effects of increased "screen time" (ST) and associated short-wavelength (blue) light exposure. We determined baseline associations and effects of 6 months' supplementation with the macular carotenoids (MC) lutein, zeaxanthin, and mesozeaxanthin on the blue-absorbing macular pigment (MP) and measures of sleep quality, visual performance, and physical indicators of excessive ST. Forty-eight healthy young adults with at least 6 h of daily near-field ST exposure participated in this placebo-controlled trial. Visual performance measures included contrast sensitivity, critical flicker fusion, disability glare, and photostress recovery. Physical indicators of excessive screen time and sleep quality were assessed via questionnaire. MP optical density (MPOD) was assessed via heterochromatic flicker photometry. At baseline, MPOD was correlated significantly with all visual performance measures (p < 0.05 for all). MC supplementation (24 mg daily) yielded significant improvement in MPOD, overall sleep quality, headache frequency, eye strain, eye fatigue, and all visual performance measures, versus placebo (p < 0.05 for all). Increased MPOD significantly improves visual performance and, in turn, improves several undesirable physical outcomes associated with excessive ST. The improvement in sleep quality was not directly related to increases in MPOD, and may be due to systemic reduction in oxidative stress and inflammation.

Contrast Sensitivity and Lateral Inhibition Are Enhanced With Macular Carotenoid Supplementation.

Purpose: Once deposited in the retina, the so-called macular carotenoids lutein (L), zeaxanthin (Z), and mesozeaxanthin (MZ) have been shown to enhance visual performance. The purpose of our study was to investigate whether increasing macular pigment optical density (MPOD) could enhance lateral inhibitory processes, and thereby improve contrast sensitivity (CS). Methods: A total of 59 young (18-25 years), healthy individuals participated in this 1-year, double-masked, placebo-controlled study. MPOD was assessed via heterochromatic flicker photometry. Lateral inhibition sensitivity (LIS) was determined with a computer-based, user-adjustable Hermann grid. CS (at 8 cycles/degree) was determined with a two-alternative, forced-choice procedure. Subjects received either the placebo (n = 10), 12 mg total macular carotenoids (n = 24), or 24 mg total macular carotenoids (n = 25). Results: MPOD, LIS, and CS increased significantly in treatment groups between baseline and 6 months, and between 6 and 12 months (P < 0.05 for all) versus placebo. The relationships between changes in MPOD and both LIS and CS were significant at 6 and 12 months (P < 0.05 for both). Changes in CS and LIS over the 12-month study period were found to be significantly related (r = 0.41; P = 0.0014). Conclusions: Increases in MPOD led to enhanced lateral inhibitory processes, which correspond to improved CS. Because optical filtering has the same net effect on dark versus light bars, it cannot explain these improvements. Improvement in CS with increases in MPOD therefore appears to involve enhancement of the fundamental physiological systems that give rise to edge detection.

Macular carotenoid supplementation improves disability glare performance and dynamics of photostress recovery.

BACKGROUND: The so-called macular carotenoids (MC) lutein (L), zeaxanthin (Z), and meso-zeaxanthin (MZ) comprise the diet-derived macular pigment (MP). The purpose of this study was to determine effects of MC supplementation on the optical density of MP (MPOD), repeated-exposure photostress recovery (PSR), and disability glare (DG) thresholds. METHODS: This was a double-blind, placebo-controlled trial. Fifty-nine young (mean age = 21.7), healthy volunteers participated in this study. Subjects supplemented their daily diet with either 10 mg L + 2 mg total Z (1 mg Z + 1 mg MZ; n = 24), 20 mg L + 4 mg total Z (2 mg Z + 2 mg MZ; n = 25), or placebo (n = 10) for 12 months. The primary outcome was a composite measure of visual performance in glare, defined by change in DG and PSR. Secondary outcomes included MPOD and visual fatigue. The primary endpoint for outcomes was 12 months. MPOD was assessed with customized heterochromatic flicker photometry. PSR times for an 8 cycle /degree, 15 % contrast Gabor patch target were determined after each of five successive exposures to intense LED lights. DG threshold was defined as the intensity of a ring of lights through which subjects were able to maintain visibility of the aforementioned target. Measures of all parameters were conducted at baseline, 6 months, and 12 months. Repeated-measures ANOVA, and Pearson product-moment correlations were used to determine statistically significant correlations, and changes within and between groups. RESULTS: MPOD for subjects in both supplementation groups increased significantly versus placebo at both 6- and 12-month visits (p < 0.001 for all). Additionally, PSR times and DG thresholds improved significantly from baseline compared to placebo at 6- and 12-month visits (p < 0.001 for all). At baseline, MPOD was significantly related to both DG thresholds (r = 0.444; p = 0.0021) and PSR times (r = -0.56; p < 0.001). As a function of MPOD, the repeated-exposure PSR curves became more asymptotic, as opposed to linear. The change in subjects' DG thresholds were significantly related to changes in PSR times across the study period (r = -0.534; p < 0.001). CONCLUSIONS: Increases in MPOD lead to significant improvements in PSR times and DG thresholds. The asymptotic shape of the repeated-exposure PSR curves suggests that increases in MPOD produce more consistent steady-state visual performance in bright light conditions. The mechanism for this effect may involve both the optical filtering and biochemical (antioxidant) properties of MP. TRIAL REGISTRATION: ISRCTN trial registration number: ISRCTN54990825. Data reported in this manuscript represent secondary outcome measures from the registered trial.

Serum and retinal responses to three different doses of macular carotenoids over 12 weeks of supplementation.

The macular carotenoids lutein (L), zeaxanthin (Z), and mesozeaxanthin (MZ) have been shown to have neuroprotective and visual performance benefits once deposited in retinal tissues. The purpose of this 12-week trial was to determine biweekly the absorption kinetics, efficiency of retinal deposition, and effects on the spatial profile of macular pigment for three levels of L + Z + MZ supplement. This study was a double-blind, placebo-controlled 12-week trial. Twenty-eight healthy subjects, aged 18-25 yrs participated. Subjects were randomly assigned to one of four daily supplementation groups: placebo (safflower oil; n = 5), 7.44 mg total macular carotenoid (n = 7), 13.13 mg total macular carotenoid (n = 8), and 27.03 (n = 8) mg total macular carotenoid. Ratios of the three carotenoids were virtually identical for the three levels of supplement (83% L, 10% Z, 7% MZ). At baseline and every two weeks thereafter over the 12-week study period, a fasting blood draw was conducted and, via heterochromatic flicker photometry, spatial profiles of macular pigment optical density (MPOD) were determined. Compared to placebo, serum concentrations of both L and total Z, for each of the supplement levels, were found to increase significantly from baseline after two weeks of daily ingestion (p < 0.001). Likewise, MPOD increased significantly in all treatment groups (p < 0.001) compared to placebo. Serum responses (L, Z, and L + Z) were linearly related to dose (p < 0.001 for all), but not to retinal response. L: Z serum response ratios decreased exponentially with increases in dose (p = 0.008). The ratio of MPOD change: total serum response was found to be highest for the 13.13 mg level of supplement (p = 0.021), followed by 27.03- and 7.44-mg doses. The very center of the spatial profile of MPOD increased in a fashion commensurate with dose level. Although L serum responses increased with dose, the slope of increase was shallower than for Z. Given the higher levels of L in the supplements, this is suggestive of a compressed response with relatively high doses of L. Although all three doses significantly augmented MPOD, the 13.13 mg/day L + Z supplement level was the most efficient in doing so. The data regarding efficiency may inform recommendations regarding macular carotenoid supplementation for age-related macular degeneration. Lastly (although not statistically significant), the shift toward a more pronounced central peak in the spatial profile of MPOD in all treatment groups suggests that central retinal deposition of Z and MZ was efficient and can be seen after a short period of supplementation, especially with higher (e.g. 27.03 mg) daily doses of macular carotenoids. ISRCTN trial registration number: ISRCTN54990825.

Temporal Visual Mechanisms May Mediate Compensation for Macular Pigment.

Macular pigment (MP) is a pre-receptoral filter that is diet derived and deposited in relatively high optical density in the foveal region of the retina. Due to its yellow coloration, MP absorbs light of relatively short wavelengths, ranging from 400 nm to 520 nm. Despite the spectral and spatial nonuniformity imposed upon the sensory retina by MP, perception appears to be relatively uniform across the central visual field. MP therefore offers an opportunity to determine experimentally potential mechanisms responsible for mediating this uniformity. After assessing, in 14 subjects, MP's effects on the temporal sensitivity of both the short-wavelength- and middle-/long-wavelength-sensitive visual pathways, it appears that the visual system compensates for absorption of short-wavelength light by MP by slowing the sampling rate of short-wavelength cones and by increasing the processing speed of middle-/long-wavelength-sensitive cones. This mechanism could work via temporal summation or a temporal neural code, whereby slower response dynamics lead to amplification of relatively weak signals.

Macular Pigment and Visual Performance in Low-Light Conditions.

PURPOSE: By reducing rod intrusion and improving efficiency of neural signaling throughout the visual system, macular pigment (MP) could improve many aspects of visual performance in low-light level conditions. Our study examined this possibility for a variety of visual performance parameters, including spatial resolution, dark adaptation kinetics, and color detection. METHODS: Twenty-seven subjects participated in the study. Spatial profiles of MP optical density (MPOD) were determined by using heterochromatic flicker photometry. Mesopic- and scotopic-adaptation level experiments were conducted in Maxwellian view. RESULTS: Subjects with higher MPOD required significantly lower contrast to detect the mesopic-level resolution targets; this effect became stronger with increasing spatial frequency. Dark adaptation recovery times were significantly faster as a function of MPOD (by nearly 2 minutes for the lowest mesopic-level task [high versus low MPOD]; P < 0.001). Absolute scotopic thresholds were also significantly associated with MPOD (P < 0.001). Macular pigment optical density was inversely associated with detection of yellow (P < 0.001), and, paradoxically, approached a significant positive correlation with the detection of blue (P = 0.06). CONCLUSIONS: Macular pigment appears to enhance visual function in low-light conditions. Based on the results of this study, it can be said that MP extends the range of foveal vision into lower light. Additionally, MP appears to enhance dark adaptation kinetics, which suggests that increased MPOD leads to more efficient photopigment regeneration. The findings of the color detection portion of the study are suggestive of an active compensatory mechanism that offsets absorption by MP in order to maintain normal color perception.

Nitric Oxide and Lutein: Function, Performance, and Protection of Neural Tissue.

The soluble gas neurotransmitter nitric oxide (NO) serves many important metabolic and neuroregulatory functions in the retina and brain. Although it is necessary for normal neural function, NO can play a significant role in neurotoxicity. This is often seen in disease states that involve oxidative stress and inflammation of neural tissues, such as age-related macular degeneration and Alzheimer's disease. The dietary xanthophyll carotenoid lutein (L) is a potent antioxidant and anti-inflammatory agent that, if consumed in sufficient amounts, is deposited in neural tissues that require substantial metabolic demand. Some of these specific tissues, such as the central retina and frontal lobes of the brain, are impacted by age-related diseases such as those noted above. The conspicuous correspondence between metabolic demand, NO, and L is suggestive of a homeostatic relationship that serves to facilitate normal function, enhance performance, and protect vulnerable neural tissues. The purpose of this paper is to review the literature on these points.

Enhancing performance while avoiding damage: a contribution of macular pigment.

PURPOSE: To compare action spectra for visual discomfort in the fovea and the parafovea and to determine the effect of macular pigment (MP). METHODS: Visual discomfort thresholds to lights from 440 to 600 nm were obtained for six young (<35 y), visually normal subjects with a wide range of MP densities (0.10-0.71 at 30' eccentricity). Foveal and parafoveal conditions were assessed. Discomfort thresholds were also obtained for xenon-white light (partially absorbed by MP), and a broadband yellow (outside the absorption band of MP). MP was measured psychophysically using heterochromatic flicker photometry (HFP). RESULTS: For the parafovea, discomfort sensitivity (1/threshold) increased sharply with decreasing wavelength for all subjects. Commensurate with a subject's MP level, MP significantly reduced visual discomfort to short wavelengths (including xenon-white light) for central viewing. CONCLUSIONS: MP simultaneously reduces visual discomfort and protects from light damage at short wavelengths. As a result, MP increases the range of safe and comfortable light levels. Because higher light levels enable improved visual sensitivity for fine detail, these findings indicate that the spectral absorption properties and spatial distribution of MP combine to protect the retina while enhancing visual performance. The action spectrum for visual discomfort closely matches the risk for acute light damage to the retinal pigment epithelium, and it is consistent with a major influence from the intrinsically photosensitive retinal ganglion cells containing melanopsin. We suggest that MP interacts with nonimage-forming retinal input to achieve the dual outcomes of visual discomfort reduction and protection from light damage.

A potential mechanism for compensation in the blue-yellow visual channel.

Due to their unique contribution to human vision, the short (S)-wavelength sensitive cones, their anatomical projections and, more recently, the cortical representation of their function, have motivated intense scientific interest. The principal study of the visual channel associated with S-cone projections has been conducted using psychophysical, neurophysiological, and ex vivo anatomical techniques, whereas more recent research on the pathway has employed functional magnetic resonance imaging (fMRI). The purpose of this manuscript is to present a perspective regarding the means by which color signals within this visual channel are processed in the brain, namely how differences in short-wavelength light transmission caused by intraocular, pre-receptoral filtration are compensated for. Recent results from fMRI and psychophysical studies indicate the existence of a frequency-dependent signal amplification mechanism, whereby lower frequencies result in an amplification of S-cone signals. This finding could motivate a future research direction for determining the localization of blue-yellow color processing and neural compensation in the blue-yellow visual channel.

Macular pigment and visual performance in glare: benefits for photostress recovery, disability glare, and visual discomfort.

PURPOSE: One theory of macular pigment's (MP) presence in the fovea is to improve visual performance in glare. This study sought to determine the effect of MP level on three aspects of visual performance in glare: photostress recovery, disability glare, and visual discomfort. METHODS: Twenty-six subjects participated in the study. Spatial profiles of MP optical density were assessed with heterochromatic flicker photometry. Glare was delivered via high-bright-white LEDs. For the disability glare and photostress recovery portions of the experiment, the visual task consisted of correct identification of a 1° Gabor patch's orientation. Visual discomfort during the glare presentation was assessed with a visual discomfort rating scale. Pupil diameter was monitored with an infrared (IR) camera. RESULTS: MP level correlated significantly with all the outcome measures. Higher MP optical densities (MPODs) resulted in faster photostress recovery times (average P < 0.003), lower disability glare contrast thresholds (average P < 0.004), and lower visual discomfort (P = 0.002). Smaller pupil diameter during glare presentation significantly correlated with higher visual discomfort ratings (P = 0.037). CONCLUSIONS: MP correlates with three aspects of visual performance in glare. Unlike previous studies of MP and glare, the present study used free-viewing conditions, in which effects of iris pigmentation and pupil size could be accounted for. The effects described, therefore, can be extended more confidently to real-world, practical visual performance benefits. Greater iris constriction resulted (paradoxically) in greater visual discomfort. This finding may be attributable to the neurobiologic mechanism that mediates the pain elicited by light.

The influence of dietary lutein and zeaxanthin on visual performance.

The idea that normal constituents of the diet can influence visual function is not new. As early as 1782, Buzzi identified the yellow of the macula and Schulze (1866) specifically postulated that the yellow pigments led to improvements in human vision. These pigments were later found to be derived from dietary lutein and zeaxanthin that are known to be oxygenated carotenoids (xanthophylls). Walls and Judd (1933) postulated that these yellow intraocular pigments could improve visual performance by absorbing light scattered both within (for example, glare) and outside of the eye (increasing visual range by absorbing blue light scattered in the atmosphere), and by improving spatial vision through enhancing contrast and reducing chromatic blur. In this article, evidence for these ideas is reviewed with particular emphasis towards more recent data on glare effects.

Spatial profile of macular pigment and its relationship to foveal architecture.

PURPOSE: Macular pigment (MP) is composed of two dietary carotenoids, lutein and zeaxanthin, and a carotenoid generated by the retina, meso-zeaxanthin. There is large intersubject variability in peak optical density, spatial profile, and lateral extent of macular pigment, and it has been suggested that foveal architecture may play a role in this variability. This study is an initial investigation of the relationship between the spatial profile of macular pigment and foveal architecture. METHODS: Sixty normal subjects were enrolled (one was eventually excluded). The spatial profile of macular pigment optical density (MPOD) was measured by customized heterochromatic flicker photometry (cHFP). High-resolution macular thickness maps were obtained by optical coherence tomography. Four parameters were analyzed: (1) minimum foveal thickness (MFT) at the intersection of six radial scans; (2) central foveal thickness (CFT) averaged over the central 1 mm of the fovea; (3) foveal width identified as the region lacking a nerve fiber layer; and (4) foveal width measured from crest to crest. Lifestyle and vision information were obtained by questionnaire. RESULTS: The mean +/- SD MPOD at 0.25 degrees eccentricity was 0.49 +/- 0.23 and at 0.5 degrees eccentricity, 0.41 +/- 0.21. A first-order decreasing exponential function accounted for most of the variance of the MP profile averaged across subjects (r(2) = 0.99). MPOD measured at 0.25 degrees was unrelated to both measures of foveal thickness for the entire study group (r = 0.03, P = 0.81, and r = -0.08, P = 0.57, respectively). Similarly, MPOD measured at 0.5 degrees was unrelated to foveal thickness in the entire study group (r = 0.12, P = 0.36 and r = -0.05, P = 0.71, respectively). However, when analyzed separately in the nonwhite subjects, the relationship between MPOD at 0.25 degrees and MFT was positive and significant (r = 0.59, P = 0.01), but remained unrelated to CFT (r = 0.20, P = 0.41). Similarly, in the nonwhite subjects, the relationship between MPOD at 0.5 degrees and MFT was positive and significant (r = 0.68, P < 0.01), but again was unrelated to CFT (r = 0.23, P = 0.32). There was no significant relationship between MPOD and either measure of foveal thickness in the white subjects. In the entire study group, there was a positive and significant relationship between foveal width and MPOD averaged across the fovea (r = 0.41, P < 0.01) and between foveal width and MP integrated across the fovea (r = 0.41, P < 0.01). CONCLUSIONS: Foveal MP was positively and significantly related to foveal width in the entire study group. This relationship may be determined by the greater length of the cone axons (Henle fibers) in wider foveas. MPOD was unrelated to foveal thickness in the white subjects. However, in the nonwhite subjects there was a positive association between MFT and MPOD at the 0.25 degrees and 0.5 degrees eccentricities, suggesting that other personal characteristics modulate the MPOD-retinal thickness relationship.

Macular pigment and visual performance under glare conditions.

PURPOSE: Many parameters of visual performance (e.g., contrast sensitivity) are compromised under glaring light conditions. Recent data indicate that macular pigment (MP) is strongly related to improvements in glare disability and photostress recovery based on a filtering mechanism. In this study, we assessed the causality of this relation by supplementing lutein and zeaxanthin for 6 months while measuring MP, glare disability, and photostress recovery. METHODS: Forty healthy subjects (mean age = 23.9) participated in the study. Subjects were followed for 6 months and assessed at baseline, 1, 2, 4, and 6 months. Spatial density profiles of MP were measured using heterochromatic flicker photometry. Disability glare was measured using a 1 degree-diameter circular grating surrounded by a broadband glare source (a xenon-white annulus). The intensity of the annulus (11 degree inner and 12 degree outer diameters) was adjusted by the subject until the grating target was no longer seen. For the photostress recovery experiment, the time required to detect a 1 degree-diameter grating stimulus after a 5-s exposure to a 2.5 muW/cm2, 5 degree-diameter disk was recorded. Subjects were tested under central viewing and eccentric viewing (10 degree temporal retina) conditions. RESULTS: At the baseline time point, MP optical density (OD) at 30' eccentricity ranged from 0.08 to 1.04, and was strongly correlated with improved visual performance in the two glare tasks. After 6 months of lutein (L) and zeaxanthin (Z) supplementation, average MPOD (at 30' eccentricity) had increased from 0.41 to 0.57, and was shown to significantly reduce the deleterious effects of glare for both the visual performance tasks assessed. CONCLUSIONS: MP is strongly related to improvements in glare disability and photostress recovery in a manner strongly consistent with its spectral absorption and spatial profile. Four to 6 months of 12 mg daily L + Z supplementation significantly increases MPOD and improves visual performance in glare for most subjects.