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Thomas Kohnen,1 Billy R Hammond2 1Department of Ophthalmology, Goethe University, Frankfurt, Germany; 2Vision Sciences Laboratory, University of Georgia, Athens, GA, USACorrespondence: Thomas Kohnen, Department of Ophthalmology, Goethe University Frankfurt, Theodor-Stern-Kai 7, Frankfurt, 60590, Germany, Tel +49-69 6301-6739/-3945, Email thomas.kohnen@kgu.deAbstract: Blue light–filtering (BLF) intraocular lenses (IOLs) are designed to mimic the healthy natural adult crystalline lens. Studies that evaluated the relative merit of ultraviolet-only IOL design (ie, blocking wavelengths < 400 nm) versus BLF IOL design (ie, filtering wavelengths ~400– 475 nm in addition to blocking wavelengths < 400 nm) on protection and function of the visual system suggest that neither design had a deleterious impact on visual acuity or contrast sensitivity. A BLF design may reduce some aspects of glare, such as veiling and photostress. BLF has been shown in many contexts to improve visual performance under conditions that are stressed by blue light, such as distance vision impaired by short-wave dominant haze. Furthermore, some data (mostly inferential) support the notion that BLF IOLs reduce actinic stress. Biomimetic BLF IOLs represent a conservative approach to IOL design that provides no harm for visual acuity, contrast sensitivity, or color vision while improving vision under certain circumstances (eg, glare).Keywords: age-related macular degeneration, blue light filtration, cataract surgery, intraocular lens, visual function

Billy R Hammond,1 Vidhyapriya Sreenivasan,2 Rajaraman Suryakumar2 1Department of Psychology, Vision Sciences Laboratory, University of Georgia, Athens, GA, USA; 2Alcon Vision LLC, Fort Worth, TX, USACorrespondence: Billy R HammondVision Sciences Laboratory, Brain and Behavioral Sciences Program, University of Georgia, Athens, GA 30602-3013, USATel +1 706-542-4812Email bhammond@uga.eduAbstract: Filtration of high-energy short-wave visible light (blue light) to improve vision and protect against damage has evolved both in aquatic animals and terrestrial species. In humans, pigments in the inner layer of the macula absorb wavelengths between 400 and 520 nm and function to improve visual performance. In patients who undergo cataract surgery, replacing cataractous lenses with artificial intraocular lenses (IOLs) that do not mimic normal healthy adult lenses could result in preventable negative visual effects, including glare disability. Blue light–filtering (BLF) IOLs were designed to filter short-wave light in addition to ultraviolet light and mimic the natural crystalline lens. Current studies indicate that BLF IOLs may provide protection from blue light–induced retinal damage and slow the development and progression of age-related macular degeneration. Additionally, BLF IOLs have been shown to improve chromatic contrast, reduce photostress recovery time, reduce glare disability and discomfort, and generally improve visual performance under glare conditions. Although a number of concerns have been raised about the relative risks versus the benefits of BLF IOLs, recent studies reported no adverse effects on visual function or contrast under photopic conditions, no long-term effects on color vision, and no detrimental effects on circadian rhythms with BLF IOLs. Based on the current understanding of the field, evidence suggests that BLF IOLs would be returning the eye to a more natural state compared with non-BLF lenses.Keywords: blue light filtration, intraocular lens, cataract surgery

BACKGROUND: Lutein and zeaxanthin are the only carotenoids in the macular region of the retina (referred to as macular pigment [MP]). Foods that are rich in lutein and zeaxanthin can increase MP density. Response to dietary lutein and zeaxanthin in other tissues has not been studied. OBJECTIVE: The objective of this study was to examine tissue responses to dietary lutein and zeaxanthin and relations among tissues in lutein and zeaxanthin concentrations. DESIGN: Seven subjects consumed spinach and corn, which contain lutein and zeaxanthin, with their daily diets for 15 wk. At 0, 4, 8, and 15 wk and 2 mo after the study, serum, buccal mucosa cells, and adipose tissue were analyzed for carotenoids, and MP density was measured. RESULTS: Serum and buccal cell concentrations of lutein increased significantly from baseline during dietary modification. Serum zeaxanthin concentrations were greater than at baseline only at 4 wk, whereas buccal cell and adipose tissue concentrations of zeaxanthin did not change. Adipose tissue lutein concentrations peaked at 8 wk. Changes in adipose tissue lutein concentration were inversely related to the changes in MP density, suggesting an interaction between adipose tissue and retina in lutein metabolism. To investigate the possibility of tissue interactions, we examined cross-sectional relations among serum, tissue, and dietary lutein concentrations, anthropometric measures, and MP density in healthy adults. Significant negative correlations were found between adipose tissue lutein concentrations and MP for women, but a significant positive relation was found for men. CONCLUSION: Sex differences in lutein metabolism may be an important factor in tissue interactions and in determining MP density. Copyright © 2000 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Introduction: Supplementation with dietary neuro-pigments lutein (L) and zeaxanthin (Z) has been shown to improve many aspects of visual and cognitive function in adults. In this study, we tested whether a similar intervention could improve such outcomes in preadolescent children., Methods: Sixty children (age range 5-12 years) were randomized in a 2:1 ratio in this double-blind, placebo-controlled clinical trial. Subjects were supplemented with gummies containing either a combination of 10 mg lutein and 2 mg zeaxanthin (LZ) or placebo for 180 days. Macular pigment optical density (MPOD) was the primary endpoint. The secondary endpoints included serum levels of L and Z, and brain-derived neurotrophic factor (BDNF), critical flicker fusion (CFF), eye strain and fatigue using visual analogue scales (VAS), Children's Sleep Habits Questionnaire-Abbreviated (CSHQ-A), and Creyos Health cognitive domains like attention, focus/concentration, episodic memory and learning, visuospatial working memory, and visuospatial processing speed. Safety was assessed throughout the study on the basis of physical examination, vital signs, clinical laboratory tests, and monitoring of adverse events., Results: The LZ group showed significant increases in MPOD at all visits post-supplementation, with significant increases as early as day 42 compared to placebo. The LZ group showed significant increases in serum lutein levels, reduced eye strain and fatigue, and improved cognitive performance (focus, episodic memory and learning, visuospatial working memory) at days 90 and 180 compared to placebo. Further, the LZ group showed significant increases in processing speed (CFF), attention, visuospatial processing, and serum Z and BDNF levels on day 180 compared to placebo. No safety concerns were observed., Conclusions: Supplementing LZ resulted in increased MPOD levels, along with increased serum levels of L, Z, and BDNF. These changes were associated with improved visual and cognitive performances and reduction in eye strain and eye fatigue in the children receiving LZ gummies. The investigational product was safe and well tolerated., Trial Registration: http://ctri.nic.in/ Identifier CTRI/2022/05/042364., (© 2024. The Author(s).)

Background: Carotenoids are plant pigments with light filtering and antioxidant properties that deposit in human tissues, including retina and skin. Descriptive characteristics and covariates of carotenoid status in macula and skin have been examined in adults; however, similar studies in children are limited. Thus, this study aimed to delineate how factors of age, sex, race, weight status, and dietary carotenoid intake relate to macular and skin carotenoids in children., Methods: Children (7-13 y, N = 375) completed heterochromatic flicker photometry to assess macular pigment optical density (MPOD). Participants underwent anthropometrics to measure weight status (BMI percentile [BMI%]), and parent/guardian provided demographic information. Subsample data were available for skin carotenoids (N = 181), assessed using reflection spectroscopy, and dietary carotenoids (N = 101) using the Block Food Frequency Questionnaire. Relationships between skin and macular carotenoids were assessed using partial Pearson's correlations controlling for age, sex, race, and BMI%. Relationships between dietary carotenoids and macular and skin carotenoids were assessed using stepwise linear regression including age, sex, race, and BMI% in the model., Results: Mean MPOD was 0.56 ± 0.22 and skin carotenoid score was 282 ± 94.6. There was no significant correlation between MPOD and skin carotenoids (r = 0.02, P = 0.76). BMI% was negatively associated with skin (stdβ = -0.42, P < 0.001), but not macular carotenoids (stdβ = -0.04, P = 0.70). Neither MPOD nor skin carotenoids were associated with age, sex, or race (all P > 0.10). MPOD was positively associated with energy-adjusted reported lutein + zeaxanthin intake (stdβ = 0.27, P = 0.01). Skin carotenoids were positively associated with energy-adjusted reported carotenoid intake (stdβ = 0.26, P = 0.01)., Conclusions: The mean MPOD values in children were higher than what has been reported in adult populations. Previous studies in adult samples report an average MPOD of 0.21. Although macular and skin carotenoids were not related, they were associated with dietary carotenoids relevant to the respective tissues; however, skin carotenoids may be more susceptible negative influence from higher weight status., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate associations between baseline macular pigment optical density (MPOD) and retinal layer thicknesses in eyes with and without manifest primary open-angle glaucoma (POAG) in the Carotenoids in Age-Related Eye Disease Study 2 (CAREDS2)., Methods and Analysis: MPOD was measured at CAREDS baseline (2001-2004) via heterochromatic flicker photometry (0.5° from foveal centre). Peripapillary retinal nerve fibre layer (RNFL), macular ganglion cell complex (GCC), ganglion cell layer (GCL), inner plexiform layer (IPL), and RNFL thicknesses were measured at CAREDS2 (2016-2019) via spectral-domain optical coherence tomography. Associations between MPOD and retinal thickness were assessed using multivariable linear regression., Results: Among 742 eyes (379 participants), manifest POAG was identified in 50 eyes (32 participants). In eyes without manifest POAG, MPOD was positively associated with macular GCC, GCL and IPL thicknesses in the central subfield (P-trend ≤0.01), but not the inner or outer subfields. Among eyes with manifest POAG, MPOD was positively associated with macular GCC, GCL, IPL and RNFL in the central subfield (P-trend ≤0.03), but not the inner or outer subfields, and was positively associated with peripapillary RNFL thickness in the superior and temporal quadrants (P-trend≤0.006)., Conclusion: We observed a positive association between MPOD and central subfield GCC thickness 15 years later. MPOD was positively associated with peripapillary RNFL superior and temporal quadrant thicknesses among eyes with manifest POAG. Our results linking low MPOD to retinal layers that are structural indicators of early glaucoma provide further evidence that carotenoids may be protective against manifest POAG., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Introduction: The mortality-morbidity paradox refers to the inconsistency in survival and disease between males and females: females live longer but tend to suffer greater age-related disease and disability. Many aspects of the latter can be targeted by lifestyle interventions, such as changes in dietary behavior. Methods: The relevant literature is reviewed. Conclusion: Dietary intake of the pigmented carotenoids appears to be particularly important for issues such as visual and cognitive loss. This may be due to the highly selective presence of a fraction of carotenoids, namely lutein (L) and zeaxanthin (Z), in specific tissues of the eye and brain. At those sites, L and Z have been shown to directly improve function and prevent central nervous system degeneration. On the palliative side, retinal LZ reduce glare disability, discomfort and photostress, improve chromatic contrast and visual range (e.g., the ability to see through blue atmospheric haze). These effects on input reflect changes in neural output such as improved visual processing speed, problem solving, memory and executive function (presumably due, also, to local effects in areas such as the hippocampus and frontal cortex). These effects on function throughout the central nervous system are mirrored by effects on disease progression. As potent antioxidants/anti-inflammatory agents, and "blue-blockers" within the retina, the pigments prevent loss that precedes neurodegenerative diseases such as age-related macular degeneration and some forms of dementia.

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., (© 2023 The Authors. Ophthalmic and Physiological Optics published by John Wiley & Sons Ltd on behalf of College of Optometrists.)

Purpose: One common complaint with natural opacified lenses is the deleterious effects of higher-order ocular aberrations and intraocular scatter, such as halos and starbursts, which are not always remedied with surgery and intraocular lens (IOL) implantation. Blue-light filtering (BLF) IOL filter scatter-prone short-wave light. Here, we determine whether BLF IOL reduce halo and starburst size., Methods: This study was a case-control design, between- and within-subjects (contralateral implantation). Sixty-nine participants with either the BLF IOL ( n  = 25; AlconSN60AT), clear IOL ( n  = 24; AlconSA60AT or WF), or both ( n  = 20) IOL participated. Participants were exposed to a point source of broadband simulated sunlight, which created the appearance of halos/starbursts. Dysphotopsia was measured as the diameter of broadband light-induced halos and starbursts., Results: A case-control analysis. Halo size was significantly larger ( t [35.05] = 2.98, p  = 0.005) in participants with the clear control lens ( M  = 3°55' ± 2°48'), compared to the BLF IOL ( M  = 1°84' ± 1°34'). Starburst size was not significantly different between groups. Contralateral analysis. Halo size was significantly smaller ( t  = -3.89, p  = .001) in test eyes with the BLF ( M  = 3°16' ± 2°35') compared to the fellow control eyes ( M  = 5°42' ± 3°17'). Starburst size was also significantly smaller ( t  = -2.60, p  < 0.018) in BLF test eyes ( M  = 9°57' ± 4°25') than the fellow eye with the clear IOL ( M  = 12°33' ± 5°25')., Conclusions: BLF IOL filter short-wave light and mimic retinal screening by the young, natural crystalline lens. Such filtering can reduce some deleterious effects of bright light by decreasing ocular diffusion/halos and starbursts.

Visual range is quantified by assessing how far one can see clearly (an ability crucial to many athletes). This ability tends to vary significantly across individuals despite similar personal characteristics. We hypothesize that the primary driver of these differences is the individual response to scattered short-wave light in the environment moderated by the dietarily derived retinal pigments lutein and zeaxanthin., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine.)

We assessed the effect of a contact lens that filters short-wavelength (SW) visible light on color appearance. These effects were modeled and measured by direct comparison to a clear contact lens. Sixty-one subjects were enrolled, and 58 completed as cohort; 31 were 18 to 39 years old (mean ± SD, 29.6 ± 5.6), 27 were 40 to 65 years old (50.1 ± 8.1). A double-masked contralateral design was used; participants randomly wore a SW-filtering contact lens on one eye and a clear control lens on the other eye. Subjects then mixed three primaries (including a short-wave primary, strongly within the absorbance of the test lens) until a perceived perfect neutral white was achieved with each eye. Color appearance was quantified using chromaticity coordinates measured with a spectral radiometer within a custom-built tricolorimeter. Color vision in natural scenes was simulated using hyperspectral images and cone fundamentals based on a standard observer. Overall, the chromaticity coordinates of matches that were set using the SW-filtering contact lens (n = 58; x = 0.345, y = 0.325, u' = 0.222, v' = 0.470) and clear contact lens (n = 58; x = 0.344, y = 0.325, u' = 0.223, v' = 0.471) were not significantly different, regardless of age group. Simulations indicated that, for natural scenes, the SW-filtering contact lens that was evaluated changes L/(L+M) and S/(L+M) chromatic contrast by no more than -1.4% to +1.1% and -36.9% to +5.0%, respectively. Tricolorimetry was used to measure color appearance in subjects wearing a SW-filtering lens in one eye and a clear lens in the other, and the results indicate that imparting a subtle tint to a contact lens, as in the SW-filtering lens that was evaluated, does not alter color appearance for younger or older subjects. A model of color vision predicted little effect of the lens on chromatic contrast for natural scenes.

Objectives: Glare discomfort (GDC) is the slight pain (discomfort) that arises when exposed to light that exceeds one's adaptive state. Such light can also cause a temporary loss in visual function (photostress, PS). We tested the hypothesis that filtering with a high-energy visible (HEV) light-filtering contact lens can reduce GDC and speed PS recovery time., Methods: Sixty-one subjects were randomized and fit with study lenses and 58 subjects completed as cohort (20-65 years of age). A double-masked, randomized, contralateral design was used (HEV filter on one eye; control lens on the other). Participants were given a 5-s exposure to a broadband white photostressor. Video images were analyzed, and palpebral fissure size during exposure was measured, as was PS recovery time to a 2-degree mid-wave target., Results: The HEV-filtering test lens was statistically superior ( P <0.0001) to the clear comparison contact lens with respect to the magnitude of squint (44.9% squint reduction) and photostress recovery time (24.3% faster recovery)., Conclusions: High-energy visible light-filtering contacts can reduce GDC and speed PS recovery. Filtering HEV light before it is incident upon the retina is a natural strategy (e.g., by the lens and macular pigment) for attenuating some of the deleterious effects of bright broadband light., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Contact Lens Association of Opthalmologists.)

Objectives: We assessed the effects of a HEV-filtering contact lens on positive dysphotopsia (halos and starbursts) and a behavioral index of scatter measured using two-point light thresholds. These effects were assessed by direct comparison to a clear (i.e., non-HEV filtering) contact lens tested in the fellow eye., Methods: Sixty-one subjects were randomized and fit with study lenses and 58 subjects completed the study. A double-masked contralateral design was used. Subjects were randomized to test lens-OD, control lens-OS, or vice versa. Participants were exposed to a point source of broadband simulated sunlight (a 403-nm condition was also tested) that created the appearance of halos/starbursts. The degree of dysphotopsia was measured as the diameter of broadband and violet-induced halos, and broadband light-induced starbursts. Two-point thresholds were assessed as the minimum resolvable distance between two pinpoints of light., Results: The HEV-filtering lens was statistically superior ( P <0.0001) to the clear lens in all the conditions tested. The HEV-filtering lens significantly reduced halo diameter by 30%, starburst diameter by 23%, and resolvable distance in the two-point condition by 18% (white) and 30% (violet)., Conclusions: HEV-filtering contact lenses can reduce some deleterious effects of bright broadband light by decreasing light scatter, halos, and starbursts., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Contact Lens Association of Opthalmologists.)

Lutein and zeaxanthin (L + Z) are carotenoids that accumulate in neural tissue and potentially confer benefits to cognition. Whereas cross-sectional studies have revealed positive associations between macular carotenoids (MC) and cognition, no studies have investigated whether L + Z supplementation impacts MC and cognition in childhood. Accordingly, the Integrated Childhood Ocular Nutrition Study aims to investigate the impact of L + Z supplementation over 9-months on academic abilities, attentional control, memory, and MC among preadolescent children. Children 8-10 years (N = 288) will enroll in a 9-month double-blind, placebo-controlled, randomized trial. The study is registered and approved as a clinical trial on the U.S. National Library of Medicine http://ClinicalTrials.gov registry (NCT05177679). Participants will be randomized into an active (10 mg lutein+2 mg zeaxanthin) or waitlist placebo-controlled group. Primary outcomes include hippocampal-dependent memory, attentional inhibition, and academic achievement using a spatial reconstruction task, an Eriksen flanker task, and the Kaufman Test of Academic and Educational Achievement 3rd edition, respectively. Secondary outcomes include event-related brain potentials of attentional resource allocation and information processing speed (i.e., P3/P300 amplitude and latency) recorded during the flanker task. Macular pigment optical density (MPOD) will be assessed using heterochromatic flicker photometry. Cognitive assessments will be completed prior to and after completion of the supplementation period. MPOD will be quantified prior to, at the mid-point of (4-5 months), and after (9 months) the supplementation period. It is hypothesized that L + Z supplementation will improve cognition and academic achievement. Further, benefits for cognition and achievement are anticipated to be mediated by increases in MC among treatment group participants., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

In the United States, women, while having a longer life expectancy than men, experience a differential risk for chronic diseases and have unique nutritional needs based on physiological and hormonal changes across the life span. However, much of what is known about health is based on research conducted in men. Additional complexity in assessing nutritional needs within gender include the variations in genetics, body compositions, hormonal milieus, underlying chronic diseases, and medication usage, with this list expanding as we consider these variables across the life course. It is clear women experience nutrient shortfalls during key periods of their lives, which may differentially impact their health. Consequently, as we move into the era of precision nutrition, understanding these sex- and gender-based differences may help optimize recommendations and interventions chosen to support health and weight management. Recently, a scientific conference was convened with content experts to explore these topics from a life-course perspective at biological, physiological, and behavioral levels. This publication summarizes the presentations and discussions from the workshop and provides an overview of important nutrition and related lifestyle considerations across the life course. The landscape of addressing female-specific nutritional needs continues to grow; now more than ever, it is essential to increase our understanding of the physiological differences between men and women, and determine how these physiological considerations may aid in optimizing nutritional strategies to support certain personal goals related to health, quality of life, sleep, and exercise performance among women., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Purpose: Higher order ocular aberrations (e.g. entopic scatter) arising from cornea and lens, decreases retinal image contrast by dispersing part of the image-forming optics over a broad retinal surface. Selective filtering of the light that is most susceptible to aberration (high-energy "blue" light) may reduce some of the behavioral effects. This was tested by comparing the performance of a blue-light filtering (BLF) vs a clear intraocular lens implant (IOL)., Methods: 52 participants with IOL (BLF: AlconSN60AT; clear: AlconSA60AT; N  = 98 test eyes; M  = 67.33 ±   7.48 years; 58.8% Female; 25.5% non-White) were recruited. Our outcome measure was based on the minimum resolvable distance between two points of light (two-point thresholds), formed using broadband xenon or isolated short-wave energy (425 nm). Iris color was measured by visual inspection and comparison against standard images., Results: In the broadband condition, patients with BLF IOL had smaller two-point thresholds ( M  = 17.17 ± 5.71 mm; F [1,48] = 2.60; p  = 0.045) than clear controls ( M  = 20.93 ± 10.22 mm). Similar improvements were found in the short-wave condition ( M BLF = 17.02 ± 5.30; M clear =21.42 ± 10.99; p  = 0.04). In the contralateral broadband comparison, eyes with the BLF had significantly smaller two-point thresholds ( M  = 18.10 ± 10.47 mm; t = -2.90, p  < 0.001) than the clear IOL ( M  = 20.89 ± 10.61 mm). Similar effects were seen in the short-wave condition ( M BLF = 18.23 ± 9.88; M clear = 21.06 ± 10.47; p  = 0.001). Darker iris color was related to reduced scatter across IOL types, in both shortwave ( F [2,48] = 4.62, p  = 0.02) and broadband ( F [2,48] = 5.27, p  = 0.009) conditions., Conclusions: Anterior screening, be it by a darker iris or a BLF IOL, is directly related to decreases in two-point light thresholds.

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.

The relation between visual processing speed (critical flicker fusion thresholds [CFF] and psychomotor reaction time) and higher-level cognitive function was assessed using a cross-sectional sample ( n  = 51) of 7 to 13-year-old preadolescent children. Data on visual processing speed (CFF and psychomotor reaction time) and cognitive function (Woodcock-Johnson III Tests of Cognitive Abilities) were collected. Woodcock-Johnson III composite standard scores (brief intellectual ability [BIA], cognitive efficiency, processing speed, and executive processes) were calculated to control for age in the cognitive variables. CFF was related to cognitive efficiency, r (46) = 0.26, p  = 0.036, and executive processes, r (44) = 0.25, p  = 0.05, and showed a trend toward relating to processing speed, r (46) = 0.19, p  = 0.09. Both psychomotor reaction time measures (fixed and variable) were related to executive processes and global intelligence (BIA) such that higher cognitive scores were associated with shorter reaction times, r s ranged from -0.25 to -0.29, p s < 0.05. In addition, fixed reaction time was related to cognitive efficiency, r (47) = -0.26, p  < 0.05. The small nature of many of these relations suggests that visual processing speed is only one of many possible influences on the higher cognitive function of children.

Background: High macular pigment optical density (MPOD) has been associated with improved eye health and better cognitive functions. Genetic variations have been associated with MPOD in adults. However, these associations between genetic variations and MPOD have not been studied in children., Objectives: This was a secondary analysis of the FK2 (Fitness Improves Thinking in Kids 2) trial (n = 134, 41% male). The aim was to determine differences in MPOD among children (aged 7-9 y) based on genetic variants that either are biologically relevant to lutein (L) and zeaxanthin (Z) accumulation or have been associated with MPOD in adults., Methods: MPOD was measured using customized heterochromatic flicker photometry via a macular densitometer. DXA was used to assess whole-body and visceral adiposity. DNA was extracted from saliva samples and was genotyped for 26 hypothesis-driven single nucleotide polymorphisms and 75 ancestry-informative markers (AIMs). Habitual diet history was obtained via 3-d food logs completed by parents (n = 88). General linear models were used to compare MPOD between different genotypes. Principal component analysis was performed for the AIMs to account for ethnic heterogeneity., Results: Children carrying ≥1 minor allele on β-carotene-15,15'-monooxygenase (BCO1)-rs7501331 (T allele) (P = 0.045), cluster of differentiation 36(CD36)-rs1527483 (T allele) (P = 0.038), or CD36-rs3173798 (C allele) (P = 0.001) had significantly lower MPOD (range: 14.1%-26.4%) than those who were homozygotes for the major alleles. MPOD differences based on CD36-rs3173798 genotypes persisted after adjustment for dietary L and Z intake., Conclusions: The findings indicate that genetic variations of CD36 and BCO1 contribute to MPOD in children. The influence of genetic variation in CD36-rs3173798 persisted after adjusting for variation in dietary intake.This trial was registered at clinicaltrials.gov as NCT01619826., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Objective: The visual effects of wearing a photochromic contact lens (test) were directly compared with a nonphotochromic contact lens (control). Positive dysphotopsia (halos, starbursts) and intraocular scatter (behaviorally determined) were assessed. Both younger and middle-aged subjects were evaluated to examine the influence of age., Methods: Fifty-four subjects (18-62 years) were tested using a contralateral design. Subjects were fit with a photochromic contact lens on one eye and a nonphotochromic contact lens on the other eye, randomly assigned. Testing occurred with and without photochromic activation (darkened) by use of a violet activator (365 nm, half-bandwidth 20 nm). The extent of dysphotopsia (halos and spokes) was measured using an aperture (∼4 mm) that created a bright point source of light 45 inches from the plane of the eye. Between the point source and subject, a centering precision caliper was used to measure lateral spread. Two-point thresholds were determined by measuring the minimum distance between two points of broadband xenon light., Results: The photochromic contact lens produced smaller halo diameters than the control contact lens, both activated (41% on average) and inactivated (21% on average), and age strata was a significant factor (P<0.001) with the older group showing a greater reduction. The photochromic contact lens produced smaller starburst diameters than the control contact lens, both activated (37% on average) and inactivated (23% on average), and age strata was a significant factor (P=0.001) with the older group showing a greater reduction. The two-point thresholds were reduced (25% activated, 9% inactivated) on average but the age effect was not significant (P<0.10)., Conclusions: The senofilcon A lens with photochromic additive reduced the extent of positive dysphotopsia compared with the same lens without the additive, regardless whether the lens was activated or not. The visual benefit was greatest with the older subjects., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Contact Lens Association of Opthalmologists.)

Intraocular scatter, with its associated functional manifestations, is a leading cause of automotive accidents and a significant biomarker of covert and overt ocular disease (e.g., diseases of the cornea and lens). Nearly all current methods of measuring the behavioral consequences of light scatter, however, suffer from various limitations mostly reflecting a lack of construct and content validity: to wit, the measures do not adequately reflect real world conditions (e.g., artificial light vs. sunlight) or everyday tasks (e.g., recognition under visually demanding conditions). This protocol describes two novel, ecologically valid methods of measuring the behavioral effects of intraocular scatter by quantifying scatter geometry and visual recognition under glare conditions. The former was measured by assessing the diameter of halos and spokes that resulted from a bright point source. Light spread (essentially, the point spread function determined using Rayleigh criteria) was quantified by determining the minimum perceivable distance between two small points of broad-band light. The latter was done based on the identification of letters formed using apertures through which bright light was shone.

A significant proportion of research on the visual system focuses on general principles that apply to samples and/or populations. Many questions, however, are more suited to the specific characteristics of an individual. The visual system, like most systems of the body, is extremely variable with respect to function and susceptibility to disease. Understanding this variation is an important avenue to better measurement, disease prevention and treatment., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To assess the visual effects of wearing both an activated and an inactivated photochromic contact lens, with a direct comparison to a non-photochromic contact lens worn in the fellow eye. This study focused on the visual effects of scatter quantified as the minimum distance between two points of light, and the diameter of the halo and starbursts that surround a bright white point source., Methods: 60 subjects (aged 18-65 years) were measured in a contralateral design where lens type was randomly assigned, one type to each eye. During activated testing, all visual measures of both study lenses were made while each eye was illuminated by a violet (λ max =365, half bandwidth 20nm) activator, which caused steady-state activation of the photochromic lens during the period of testing. Two-point thresholds were determined by measuring the minimum distance between two points of broadband xenon light. Glare geometry was measured using an aperture (∼4mm) that created a bright point source of light 45 inches from the plane of the eye. Between the point source and subject, a centering precision caliper was used to measure lateral spread of halos (diffusion around the source) and visual spokes. The head was stabilized using an adjustable head-rest assembly and the eye was aligned and monitored with a bore camera., Results: Compared to the non-photochromic lens, and based on the stimulus conditions used in these measurements, the activated and inactivated photochromic lens reduced the light spread using the two-point threshold technique by 32% and 19% respectively; the diameter of the halos were reduced by 44% and 16% respectively; and the spokes were narrowed by 39% and 20% respectively. Based on 95% confidence interval testing, these effects were all statistically significant (p<0.05)., Conclusions: These results are consistent with previous data showing that soft contact lenses with a photochromic additive can improve many aspects of visual function, consistent with their level or activation. Our past data focused on visual function under bright light conditions (e.g., glare disability, discomfort, photostress recovery and chromatic contrast) with an activated photochromic. In this study, we found differences even in the inactivated state, using less intense stimuli (10cd/m 2 at the source). This suggests that the photochromic lens improves the effects of light scatter even at lower luminance., (Copyright © 2020 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.)

Significance: Photochromic soft contact lenses contain light-sensitive additives that allow them to darken when exposed to ultraviolet or violet light. One question, however, is whether the lenses influence vision indoors (minimally activated). In this study, we found that the minimally activated lenses improved many aspects of visual function under bright light., Purpose: Photochromic contact lenses were designed to darken when exposed to outdoor sunlight. The filtering that results improves visual function under bright light conditions. Not all bright light exposures occur outdoors. In this study, we tested whether a photochromic contact lens improved visual function under conditions where the lens was minimally activated (i.e., no more than it normally would be in an indoor environment)., Methods: A subject-masked contralateral design was used comparing a photochromic contact lens randomized to one eye against a nonphotochromic contact in the other eye of the same subject. Sixty subjects (mean = 34.90 ± 11.24 years) were tested. The primary endpoints consisted of four visual function outcomes: photostress recovery, glare disability, glare discomfort, and chromatic contrast. Photostress recovery was quantified by measuring the time needed to recover visual acquisition of a grating target after 5 seconds of an intense xenon white flash exposure; glare disability was evaluated as the energy in a surrounding xenon white annulus necessary to veil a central grating target; and glare discomfort was assessed using bioimaging of the squint response. Chromatic contrast was measured as thresholds for a green-yellow (580 nm) grating target superposed on a blue (460 nm) background., Results: The minimally activated photochromic contact demonstrated improved visual performance compared with the nonphotochromic control across all visual functions tested (P < .01)., Conclusions: Even under conditions of exiguous activation (e.g., as would be expected indoors or while driving at night), a photochromic contact will improve many of the more deleterious aspects of bright light.

The carotenoids lutein (L) and zeaxanthin (Z) accumulate in retinal regions of the eye and have long been shown to benefit visual health. A growing literature suggests cognitive benefits as well, particularly in older adults. The present randomized controlled trial sought to investigate the effects of L and Z on brain function using resting state functional magnetic resonance imaging (fMRI). It was hypothesized that L and Z supplementation would (1) improve intra-network integrity of default mode network (DMN) and (2) reduce inter-network connectivity between DMN and other resting state networks. 48 community-dwelling older adults (mean age = 72 years) were randomly assigned to receive a daily L (10 mg) and Z (2 mg) supplement or a placebo for 1 year. Resting state fMRI data were acquired at baseline and post-intervention. A dictionary learning and sparse coding computational framework, based on machine learning principles, was used to investigate intervention-related changes in functional connectivity. DMN integrity was evaluated by calculating spatial overlap rate with a well-established DMN template provided in the neuroscience literature. Inter-network connectivity was evaluated via time series correlations between DMN and nine other resting state networks. Contrary to expectation, results indicated that L and Z significantly increased rather than decreased inter-network connectivity (Cohen's d = 0.89). A significant intra-network effect on DMN integrity was not observed. Rather than restoring what has been described in the available literature as a "youth-like" pattern of intrinsic brain activity, L and Z may facilitate the aging brain's capacity for compensation by enhancing integration between networks that tend to be functionally segregated earlier in the lifespan.

Purpose: To compare the effects of a photochromic contact lens vs. a non-photochromic control lens on visual function., Methods: A subject-masked, prospective contralateral eye design was used. Sixty-one subjects were enroled based on age (using a 2:1 allocation ratio for ages 18-39 and 40-65 years, respectively). The study lenses were senofilcon A with photochromic additive (Test) that filtered over the entire lens, compared to a non-photochromic Control with no tint. The Test lens was partially activated during testing with a steady-state transmittance of approximately 62%. Eligible subjects were tested using both study lenses, with Test and Control lens randomized by eye. Five visual function outcomes were tested: photostress recovery (PSR), glare disability (GD), glare discomfort (GDC), chromatic contrast (CC) and vernier acuity (VA). Iris colour and macular pigment density were assessed as control variables. PSR was measured as the time needed to recover sight of a target after an intense xenon flash exposure; GD was evaluated as the energy needed to veil a central target by a surrounding xenon annulus; GDC was measured using bio-imaging of the squint response and by self-report using a 9-item Likert scale; CC was measured as thresholds for a yellow grating target superposed on a 460-nm background; VA was determined by measuring vernier offsets of light lines through apertures., Results: Based on our stimulus conditions, PSR was 43% faster using the Test vs. the Control. The eye wearing the Test had 38% less squint (GDC) compared to the Control. GD was improved by 36% in the Test vs. Control and CC was enhanced by 48% with the Test. There was no significant difference in VA., Conclusions: There was a beneficial influence on visual function when comparing the photochromic with the non-photochromic contact lens. This benefit was seen specifically with respect to PRT, GDC, GD and CC thresholds., Competing Interests: Declaration of Competing Interest This study was funded by Johnson & Johnson Vision Care, Inc. Authors JRB, JV and YT are employees of Johnson and Johnson Vision Care, Inc. Authors LRH and BRH have received consulting fees by Johnson and Johnson Vision Care, Inc., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A growing literature emphasizes the importance of lifestyle factors such as nutrition in successful aging. The current study examined if one year of supplementation with lutein (L) and zeaxanthin (Z), two nutrients with known antioxidative properties and cognitive benefits, impacted structural brain outcomes in older adults using a double-blind, randomized, placebo-controlled trial design. Community-dwelling older adults (20 males and 27 females) aged 65-87 years ( M  = 71.8 years, SD = 6.04 years) were randomized into supplement ( N  = 33) and placebo groups ( N  = 14) using simple randomization. The supplement group received 10 mg L + 2 mg Z daily for 12 months while the placebo group received a visually identical, inert placebo. L and Z were measured via retinal concentrations (macular pigment optical density or MPOD). Structural brain outcomes, focusing on global and frontal-temporal lobe regions, were acquired using both T1-weighted and DTI MRI sequences. We hypothesized that the supplement group would increase, maintain, or show attenuated loss in hypothesized regions-of-interest (ROIs) while the placebo group would show age-related declines in brain structural integrity over the course of the trial. While results showed age-related declines for frontal and temporal gray and white matter volumes, as well as fornix white matter microstructure across both groups, only minimal differences were found between the supplement and placebo groups. However, exploratory analyses showed that individuals who responded better to supplementation (i.e., showed greater increases in MPOD) showed less decline in global and prefrontal gray matter volume than supplement "nonresponders." While results suggest that one year of L and Z supplementation may have limited effects on structural brain outcomes overall, there may be a subsample of individuals for whom supplementation of L and Z provides greater benefits. ClinicalTrials.gov number, NCT02023645., Competing Interests: During a portion of data collection time, LMRH was employed by Abbott Nutrition while holding a joint appointment at the University of Georgia. No other conflicts of interest exist for the study authors, including CMM, CAL, BRH, and LSM. All statistical analyses were completed independent of the supporting agencies., (Copyright © 2019 Catherine M. Mewborn et al.)

Scope: Steady-state visual evoked potentials (SSVEP) can be used to test the topological response of cortical neurons. Studies have shown that a lutein (L) preferentially accumulates within cortical tissue. L, zeaxanthin (Z), and their isomers can be measured directly in retina (macular pigment optical density, MPOD), and retinal L+Z correlate highly with L+Z levels in cortical visual processing areas. The purpose of this study was to determine the relation between MPOD and SSVEP signal power, cross-sectionally and after supplementation with L+Z., Methods and Results: SSVEP to three different driving frequencies of stimulation (5, 10, and 16.6 Hz) were obtained for community-dwelling older adults, at baseline and after 12 months of supplementation with either 12 mg L+Z or placebo. Power was quantified at the driving frequencies. Non-specific activation was quantified within the 10-15 Hz band. MPOD was measured psychophysically. Subjects with low MPOD had reduced power at 16.6 Hz and reduced non-specific activation, compared with subjects with high MPOD. Supplementation significantly improved signal power at 5 and 10 Hz., Conclusion: Past research suggests that L+Z can improve visual memory, visual processing speeds, etc. One possible mechanism for that improvement may be improving signal-to-noise ratio throughout the vision system., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Scope: The neural efficiency hypothesis for lutein (L) and zeaxanthin (Z) suggests that higher levels of L+Z in the central nervous system (CNS) are predictive of stronger stimulus-specific brain responses. Past research suggests that supplementing L+Z can improve neural processing speed and cognitive function across multiple domains, which supports this hypothesis. The purpose of this study is to determine the extent to which CNS L+Z levels predict brain responses using an attentionally taxing task., Methods and Results: Macular pigment optical density (MPOD) is measured at baseline in 85 participants ranging in age from 18-92 years. Brain activation is measured using dense array electroencephalography. Stimuli evoking the signal include a grating array of vertical bars, oscillating at four driving frequencies. Significant stimulus-specific interactions are detected between attend condition, location, and age (p < .002) for unattended image locations, and between age and location (p < .008) for attended locations. Although no differences are found across age by MPOD, this measure is found to be predictive of neural power at parafoveal bar locations (R 2 .080)., Conclusion: CNS L+Z status is related to differences in brain activation in conditions designed to stress visual attention. These differences are strongest for older subjects., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

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.

Age-related changes in the interactive behavior of default mode network (DMN) with other resting state networks are poorly understood. We hypothesized that age would positively correlate with inter-network connectivity in late life and intellectual functioning was expected to moderate this relationship. The sample consisted of 48 community-dwelling older adults with resting state functional magnetic resonance imaging data. Global inter-connectivity between DMN and 9 other resting state networks was calculated using a novel computational framework based on machine learning. Intellectual functioning (intelligence) was estimated using the Wechsler Test of Adult Reading. A significant, positive relationship was found between age and global inter-network connectivity (r = 0.31, p = 0.029). Moderation analyses yielded a significant age × intelligence interaction term (p = 0.003), such that intelligence attenuated the relationship between age and global inter-network connectivity. Taken together, these results suggest that age is positively associated with global DMN desegregation, possibly due to dedifferentiation or compensation. Intellectual functioning moderates this relationship, such that more intelligent older adults maintain a segregated DMN profile., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Lutein (L) and zeaxanthin (Z) are phytonutrients that accumulate in human brain tissue and positively impact cognition. Given their antioxidant and anti-inflammatory properties and their role in stabilizing cell membranes, L&Z may relate to measures of white matter integrity (WMI)., Method: The current study tested the relation of retinal (macular pigment optical density/MPOD) and blood serum concentrations of L&Z to WMI in community-dwelling older adults (n = 54) using diffusion tensor imaging (DTI). Younger adults (n = 38) were recruited as a control group to confirm age-related changes in WMI. A priori analyses focused on four regions of interest (ROIs-genu of the corpus callosum, cingulum, fornix, and uncinate fasciculus). Exploratory whole-brain analyses were also conducted., Results: Consistent with previous literature, age group (young vs. old) negatively predicted WMI globally, in the genu, cingulum, and fornix (p < .001). ROI analysis in the older adult sample showed relations of MPOD and serum L&Z to better WMI in the uncinate fasciculus and cingulum (p < .05, FWE-corrected). Whole-brain analysis suggested associations between L&Z and WMI in both anterior white matter tracts vulnerable to age-related decline and posterior tracts (p < .01, uncorrected)., Conclusions: The current study is among the first to use neuroimaging to measure the relation of L&Z to brain structure in vivo. Results confirm previous findings that L&Z influence white matter integrity, particularly in regions vulnerable to age-related decline. The current study contributes to a growing literature investigating the relationship between diet and neural integrity by identifying white matter tracts that may be associated with modifiable dietary factors in older adults.

Objective: Macular pigment optical density (MPOD) - a non-invasive indicator of retinal xanthophylls and correlate of brain lutein - has been associated with superior cognitive function among adult populations. Given that lutein accumulation in the brain occurs in early life, it is possible that the cognitive implications of greater MPOD may be evident in childhood., Methods: Participants aged 8-9 years (n = 56) completed MPOD measurements via heterochromatic flicker photometry. Academic performance was assessed using the Kaufman Test of Academic and Educational Achievement II (KTEA). Habitual dietary intake of L and Z was measured among a subsample of participants (n = 35) using averaged 3-day food records. Stepwise hierarchical regression models were developed to determine the relationship between MPOD and academic achievement tests, following the adjustment of key covariates including sex, aerobic fitness, body composition, and intelligence quotient (IQ)., Results: The regression analyses revealed that MPOD improved the model, beyond the covariates, for overall academic achievement (ΔR 2  = 0.10, P < 0.01), mathematics (ΔR 2  = 0.07, P = 0.02), and written language composite standard scores (ΔR 2  = 0.15, P < 0.01)., Discussion: This is the first study to demonstrate that retinal L and Z, measured as MPOD, is positively related to academic achievement in children, even after accounting for the robust effects of IQ and other demographic factors. These findings extend the positive associations observed between MPOD and cognitive abilities to a pediatric population. Trail registration: The Fitness Improves Thinking in Kids 2 (FITKids2) trial was registered at www.clinicaltrials.gov as NCT01619826.

Objectives: Data obtained mostly from animal models and ex vivo samples show that a small portion of ultraviolet light (UV, 300-400 nm) penetrates the cornea and crystalline lens and impinges on the human retina. UV transmission to the retina appears to be unique to the young and some older pseudophakes. In this study, we determine the variation in UV transmission in a relatively homogenous sample of young adults., Methods: 42 subjects were tested (M = 19 ± 1.3 years). Absolute thresholds to UV radiation were collected (λmax = 315 nm, 305-325). Macular pigment optical density (MPOD, measured using heterochromatic flicker photometry) and iris color (using a standardized color scale) were also assessed as potential covariates., Results: All of the subjects could detect UV radiation at 315 nm but individual variation was large (over a factor of 30). Higher MPOD and darker iridies were not related to UV sensitivity in this young sample. Males, however, were more sensitive to UV than the females (p<0.05)., Conclusions: The large individual differences in UV reaching the retina of younger individuals suggests equally significant vulnerability to the actinic effects of this highly energetic light., Competing Interests: The authors have declared that no competing interests exist.

Lutein (L) and zeaxanthin (Z) are two xanthophyll carotenoids that have antioxidant and anti-inflammatory properties. Previous work has demonstrated their importance for eye health and preventing diseases such as age-related macular degeneration. An emerging literature base has also demonstrated the importance of L and Z in cognition, neural structure, and neural efficiency. The present study aimed to better understand the mechanisms by which L and Z relate to cognition, in particular, visual-spatial processing and decision-making in older adults. We hypothesized that markers of higher levels of L and Z would be associated with better neural efficiency during a visual-spatial processing task. L and Z were assessed via standard measurement of blood serum and retinal concentrations. Visual-spatial processing and decision-making were assessed via a judgment of line orientation task (JLO) completed during a functional magnetic resonance imaging (fMRI) scan. The results demonstrated that individuals with higher concentrations of L and Z showed a decreased blood-oxygen-level dependent (BOLD) signal during task performance (i.e., "neural efficiency") in key areas associated with visual-spatial perception, processing, decision-making, and motor coordination, including the lateral occipital cortex, occipital pole, superior and middle temporal gyri, superior parietal lobule, superior and middle frontal gyri, and pre- and post-central gyri. To our knowledge, this is the first investigation of the relationship of L and Z to visual-spatial processing at a neural level using in vivo methodology. Our findings suggest that L and Z may impact brain health and cognition in older adults by enhancing neurobiological efficiency in a variety of regions that support visual perception and decision-making., Competing Interests: The authors declare no conflict of interest. During a portion of data collection time, author L.M.R.-H. was employed by Abbott Nutrition while holding a joint appointment at the University of Georgia. BRH has consulted for Abbott Nutrition. No other conflicts of interest exist for the study authors, including C.M.M., C.A.L., T.L.R., M.A.G., D.P.T., K.R.J., and L.S.M. All statistical analyses were completed independent of the supporting agencies.

The macular carotenoids lutein (L) and zeaxanthin (Z) are obtained via diet and accumulate in the central retina where they are referred to as macular pigment. The density of this biomarker (macular pigment optical density; MPOD) has been positively correlated with cognitive functioning via measures of global cognition, processing speed, and visual-spatial abilities, among others. Although improvements in cognitive function have been found in adults, much less is known about how L and Z intake may support or improve cognitive functioning during periods of rapid developmental change, such as childhood and pre-adolescence. This study examined the relationship between MPOD and cognitive functioning in 51 7-13-year-old children (51% female). MPOD was measured using heterochromatic flicker photometry (HFP) optimized for this age group. Cognitive function was assessed using the Woodcock-Johnson III (composite standard scores were obtained for Brief Intellectual Ability, Verbal Ability, Cognitive Efficiency, Processing Speed, and Executive Processes). In this sample, MPOD was significantly related to Executive Processes, r (47) = 0.288, p < 0.05, and Brief Intellectual Ability, r (47) = 0.268, p < 0.05. The relationship to Cognitive Efficiency was positive and trending but not significant, r (49) = 0.206, p = 0.074. In general, these data are consistent with those of adults showing a link between higher carotenoid status and improved cognitive functioning., Competing Interests: The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Objectives: The present study constitutes the first randomized controlled trial to investigate the relation of lutein (L) and zeaxanthin (Z) to brain function using functional magnetic resonance imaging (fMRI). It was hypothesized that L and Z supplementation in older adults would enhance neural efficiency (i.e., reduce activation) and cognitive performance on a verbal learning task relative to placebo., Methods: A total of 44 community-dwelling older adults (mean age=72 years) were randomly assigned to receive either placebo or L+Z supplementation (12 mg/daily) for 1 year. Neurocognitive performance was assessed at baseline and post-intervention on an fMRI-adapted task involving learning and recalling word pairs. Imaging contrasts of blood-oxygen-level-dependent (BOLD) signal were created by subtracting active control trials from learning and recall trials. A flexible factorial model was employed to investigate the expected group (placebo vs. supplement) by time (baseline vs. post-intervention) interaction in pre-specified regions-of-interest., Results: L and Z appeared to buffer cognitive decline on the verbal learning task (Cohen's d=.84). Significant interactions during learning were observed in left dorsolateral prefrontal cortex and anterior cingulate cortex (p < .05, family-wise-error corrected). However, these effects were in the direction of increased rather than decreased BOLD signal. Although the omnibus interaction was not significant during recall, within-group contrasts revealed significant increases in left prefrontal activation in the supplement group only., Conclusions: L and Z supplementation appears to benefit neurocognitive function by enhancing cerebral perfusion, even if consumed for a discrete period of time in late life. (JINS, 2018, 24, 77-90).

Background: Past studies have suggested that higher lutein (L) and zeaxanthin (Z) levels in serum and in the central nervous system (as quantified by measuring macular pigment optical density, MPOD) are related to improved cognitive function in older adults. Very few studies have addressed the issue of xanthophylls and cognitive function in younger adults, and no controlled trials have been conducted to date to determine whether or not supplementation with L + Z can change cognitive function in this population. Objective: The purpose of this study was to determine whether or not supplementation with L + Z could improve cognitive function in young (age 18-30), healthy adults. Design: A randomized, double-masked, placebo-controlled trial design was used. Fifty-one young, healthy subjects were recruited as part of a larger study on xanthophylls and cognitive function. Subjects were randomized into active supplement ( n = 37) and placebo groups ( n = 14). MPOD was measured psychophysically using customized heterochromatic flicker photometry. Cognitive function was measured using the CNS Vital Signs testing platform. MPOD and cognitive function were measured every four months for a full year of supplementation. Results: Supplementation increased MPOD significantly over the course of the year, vs. placebo ( p < 0.001). Daily supplementation with L + Z and increases in MPOD resulted in significant improvements in spatial memory ( p < 0.04), reasoning ability ( p < 0.05) and complex attention ( p < 0.04), above and beyond improvements due to practice effects. Conclusions: Supplementation with L + Z improves CNS xanthophyll levels and cognitive function in young, healthy adults. Magnitudes of effects are similar to previous work reporting correlations between MPOD and cognition in other populations., Competing Interests: Authors L.M.R.-H. and B.R.H. have received honoraria from Abbott Nutrition for presentation of research findings and L.R.H. was employed by Abbott Nutrition for a portion of the data collection period. Author J.H.B. was an employee of Abbott Nutrition. No other authors have conflicts of interest to disclose.

Lutein (L) and zeaxanthin (Z) status can be quantified by measuring their concentrations both in serum and, non-invasively, in retinal tissue. This has resulted in a unique ability to assess their role in a number of tissues ranging from cardiovascular to central nervous system tissue. Recent reports using animal models have suggested yet another role, a developmental increase in bone mass. To test this, we assessed L and Z status in 63 young healthy adults. LZ status was determined by measuring LZ in serum (using HPLC) and retina tissue (measuring macular pigment optical density, MPOD, using customized heterochromatic flicker photometry). Bone density was measured using dual-energy X-ray absorptiometry (DXA). Although serum LZ was generally not related to bone mass, MPOD was significantly related to bone density in the proximal femur and lumbar spine. In general, our results are consistent with carotenoids, specifically LZ, playing a role in optimal bone health., Competing Interests: The authors declare no conflict of interest.

Processing speed, which can be measured behaviorally in various sensory domains, has been shown to be a strong marker of central nervous system health and functioning in adults. Visual temporal processing speed (measured via critical flicker fusion [CFF] thresholds) represents the maximum speed at which the visual system can detect changes. Previous studies of infant CFF development have been limited and inconsistent. The present study sought to characterize the development of CFF thresholds in the first year of life using a larger sample than previous studies and a repeated measures design (in Experiment 2) to control for individual differences. Experiment 1 (n=44 infants and n=24 adults) used a cross-sectional design aimed at examining age-related changes that exist in CFF thresholds across infants during the first year of life. Adult data were collected to give context to infant CFF thresholds obtained under our specific stimulus conditions. Experiment 2 (N=28) used a repeated-measures design to characterize the developmental trajectory of infant CFF thresholds between three and six months of age, based on the results of Experiment 1. Our results reveal a general increase in CFF from three to four and one-half months of age, with a high degree of variability within each age group. Infant CFF thresholds at 4.5months of age were not significantly different from the adult average, though a regression analysis of the data from Experiment 2 predicted that infants would reach the adult average closer to 6months of age. Developmental and clinical implications of these data are discussed., (Published by Elsevier Ltd.)

Background: High levels of xanthophyll carotenoids lutein (L) and zeaxanthin (Z) in the central nervous system have been previously correlated with improved cognitive function in community-dwelling older adults. In this study, we tested the effects of supplementing L and Z on older men and women with a range of baseline cognitive abilities. Objective: The purpose of this study was to determine whether or not supplementation with L+Z could improve cognitive function in community-dwelling, older adults. Design: Double-masked, randomized, placebo-controlled trial. A total of 62 older adults were randomized into groups receiving either 12 mg L+Z or a visually identical placebo. Data from 51 participants ( M = 73.7 years) were available for analysis. Retinal L+Z levels (macular pigment optical density, MPOD) were measured psychophysically using heterochromatic flicker photometry as a biomarker of cortical L+Z levels. Cognitive function was measured using the CNS Vital Signs computerized test platform. Results: Participants receiving the active L+Z supplement had statistically significant increases in MPOD ( p < 0.03) and improvements in complex attention ( p < 0.02) and cognitive flexibility domains ( p < 0.04), relative to participants taking the placebo. A trend was also seen for the executive function domain ( p = 0.073). In male participants only, supplementation yielded improved composite memory ( p = 0.04). Conclusions: Supplementation with L+Z improved cognitive function in community-dwelling, older men and women.

Lutein and zeaxanthin are plant pigments known to preferentially accumulate in neural tissue. Macular Pigment Optical Density (MPOD), a non-invasive measure of retinal carotenoids and surrogate measure of brain carotenoid concentration, has been associated with disease prevention and cognitive health. Superior MPOD status in later adulthood has been shown to provide neuroprotective effects on cognition. Given that childhood signifies a critical period for carotenoid accumulation in brain, it is likely that the beneficial impact would be evident during development, though this relationship has not been directly investigated. The present study investigated the relationship between MPOD and the behavioral and neuroelectric indices elicited during a cognitive control task in preadolescent children. 49 participants completed a modified flanker task while event-related potentials (ERPs) were recorded to assess the P3 component of the ERP waveform. MPOD was associated with both behavioral performance and P3 amplitude such that children with higher MPOD had more accurate performance and lower P3 amplitudes. These relationships were more pronounced for trials requiring greater amounts of cognitive control. These results indicate that children with higher MPOD may respond to cognitive tasks more efficiently, maintaining high performance while displaying neural indices indicative of lower cognitive load. These findings provide novel support for the neuroprotective influence of retinal carotenoids during preadolescence., (Copyright © 2017 Elsevier B.V. All rights reserved.)

One apparent consequence of aging appears to be loss of some aspects of cognitive control. This loss is measurable as early as mid-adulthood. Since, like many aspects of cognition, there is wide variance among individuals, it is possible that behavior, such as one's diet, could drive some of these differences. For instance, past data on older humans and non-human primates have suggested that dietary carotenoids could slow cognitive decline. In this study, we tested how early such protection might manifest by examining a sample ( n = 60) of 25-45 year olds. Carotenoid status was assessed by directly measuring macular pigment optical density (MPOD) which has shown to be highly correlated with the primary carotenoid in brain, lutein. Cognitive control was measured using event-related potentials during the performance of cognitive control tasks designed to tap into different aspects of attentional (i.e., selective attention, attentional inhibition, and response inhibition) control. Our results showed that, across participants, MPOD was related to both age and the P3 component of participants' neuroelectric profile (P3 amplitude) for attentional, but not response, inhibition. Although younger adults exhibited larger P3 amplitudes than their older adult counterparts, older subjects with higher MPOD levels displayed P3 indices similar to their younger adult counterparts in amplitude. Furthermore, hierarchical regression analyses showed that age was no longer a significant predictor of P3 amplitude when MPOD was included as a predictor in the model, suggesting that MPOD may partially contribute to the relationship between age and P3 amplitude. In addition, age and MPOD were shown to have independent associations with intraindividual variability of attentional control, such that younger individuals and individuals with higher MPOD showed less intraindividual variability. These results show a relationship between retinal carotenoids and neuroelectric indices underlying cognitive control. The protective role of carotenoids within the CNS may be evident during early and middle adulthood, decades prior to the onset of older age.

Objectives: To examine the associations of macular pigment carotenoids (lutein, meso-zeaxanthin, and zeaxanthin), aerobic fitness, and central adiposity with hippocampal-dependent relational memory in prepubescent children., Study Design: Children between 7 and 10 years of age (n = 40) completed a task designed to assess relational memory performance and participated in aerobic fitness, adiposity, and macular pigment optical density (MPOD) assessment. Aerobic fitness was assessed via a modified Balke treadmill protocol designed to measure maximal oxygen volume. Central adiposity was assessed via dual-energy x-ray absorptiometry. MPOD was measured psychophysically by the use of customized heterochromatic flicker photometry. Statistical analyses included correlations and hierarchical linear regression., Results: Aerobic fitness and MPOD were associated negatively with relational memory errors (P < .01), whereas central adiposity was associated positively with relational memory errors (P < .05). Hierarchical regression analysis revealed that MPOD accounted for a significant amount of the variance in relational memory performance even after we accounted for aerobic fitness (β = -0.388, P = .007)., Conclusions: Even after we adjusted for aerobic fitness and central adiposity, factors known to relate to hippocampal-dependent memory, MPOD positively and significantly predicted hippocampal-dependent memory performance., Trial Registration: ClinicalTrials.gov: NCT01619826., (Copyright © 2017 Elsevier Inc. All rights reserved.)