Continuous microalgal culture module and method of culturing microalgae containing macular pigment.

This study established and investigated continuous macular pigment (MP) production with a lutein (L):zeaxanthin (Z) ratio of 4-5:1 by an MP-rich Chlorella sp. CN6 mutant strain in a continuous microalgal culture module. Chlorella sp. CN6 was cultured in a four-stage module for 10 days. The microalgal culture volume increased to 200 L in the first stage (6 days). Biomass productivity increased to 0.931 g/L/day with continuous indoor white light irradiation during the second stage (3 days). MP content effectively increased to 8.29 mg/g upon continuous, indoor white light and blue light-emitting diode irradiation in the third stage (1 day), and the microalgal biomass and MP concentrations were 8.88 g/L and 73.6 mg/L in the fourth stage, respectively. Using a two-step MP extraction process, 80 % of the MP was recovered with a high purity of 93 %, and its L:Z ratio was 4-5:1.

Effect of Antioxidant Supplementation on Macular Pigment Optical Density and Visual Functions: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

Antioxidants are bioactive molecules that function to scavenge free radicals and balance oxidative stress. Although all antioxidants can act as reactive oxygen species scavengers, their efficacy on eye health may vary. Moreover, the comparative effectiveness and potential additive effect between groups of antioxidants, hitherto, have not been systematically studied. A systematic review and network meta-analysis were conducted to investigate the comparative or additive effect of dietary antioxidant supplements on eye health. Four databases (PubMed, Embase, CINAHL, and Cochrane) were searched, and relevant randomized controlled trials were identified. Out of 60 articles selected for systematic review, 38 were included in the network meta-analysis, categorized into 8 distinct antioxidant-supplemented groups and placebo. All groups significantly increased macular pigment optical density and contrast sensitivity at low spatial frequency, whereas only the antioxidant mixture + lutein (L) + fatty acid combination exhibited significant improvements in visual acuity (hazard ratio = -0.15; 95% confidence interval: -0.28, -0.02) and L + zeaxanthin combination for photostress recovery time (hazard ratio = -5.75; 95% confidence interval: -8.80, -1.70). Especially, the L + zeaxanthin + fatty acid combination was ranked best for macular pigment optical density (surface under the cumulative ranking: 99.3%) and second best for contrast sensitivity at low spatial frequency (67.7%). However, these findings should be interpreted with caution due to low quality of evidence, primarily influenced by indirectness and potential publication bias. Overall, antioxidant supplementation was estimated to improve eye health parameters, whereas different combinations of antioxidants may also have varying effects on improving visual health from multiple perspectives. This study was registered at PROSPERO as CRD42022369250.

Macular Pigment Assessment in Indian Population Using Degree of Polarization Threshold: Impact of Diet on Macular Pigment Density.

Purpose: To determine macular pigment (MP) density scores in healthy Indians and examine correlations with demographic and lifestyle variables. Methods: We observed 484 Indians without an ocular pathology. Body mass index (BMI) and self-reported lifestyle factors (sunglasses usage, physical activity, and smoking) were noted. MP density was assessed as the threshold of perception of the shadow of their macular pigments on their retina using a new MP assessment tool (MP-eye). Lutein and zeaxanthin intake was assessed using a prevalidated questionnaire regionally designed for the Indian diet. Clusters of participants were created for statistical analysis based on MP-eye scores secondarily to detect any relevant effects in very low, low, medium, and high ranges of MPs. Results: Data analyzed included 235 males and 249 females with mean age of 36.1 ± 12.9 years (range, 14-72). The median MP-eye score was 6 (range, 0-10, with 10 being high). Most were non-smokers (413, 85.3%) and did not use sunglasses (438, 90.5%), and 314 (64.9%) had low physical activity. Diabetes was present in 62 participants (12.8%) and hypertension in 53 (10.9%). Advancing age (r = -0.209; P < 0.000) and BMI (r = -0.094; P = 0.038) had weak negative correlation with MP-eye scores. Hypertension was less prevalent (7/88) in the cluster with the highest median MP-eye score (P = 0.033). Dietary intake of MPs and other lifestyle factors did not correlate significantly with MP-eye score overall or when analyzed in clusters. Conclusions: MP-eye scores of an Indian population were normally distributed. Higher age, high BMI, and presence of hypertension were weakly associated with lower MP-eye scores. The impact of diet on MPs requires further evaluation. Translational Relevance: This normative regional database enables risk stratification of macular degeneration.

Deep learning-based correction of cataract-induced influence on macular pigment optical density measurement by autofluorescence spectroscopy.

PURPOSE: Measurements of macular pigment optical density (MPOD) using the autofluorescence spectroscopy yield underestimations of actual values in eyes with cataracts. Previously, we proposed a correction method for this error using deep learning (DL); however, the correction performance was validated through internal cross-validation. This cross-sectional study aimed to validate this approach using an external validation dataset. METHODS: MPODs at 0.25°, 0.5°, 1°, and 2° eccentricities and macular pigment optical volume (MPOV) within 9° eccentricity were measured using SPECTRALIS (Heidelberg Engineering, Heidelberg, Germany) in 197 (training dataset inherited from our previous study) and 157 eyes (validating dataset) before and after cataract surgery. A DL model was trained to predict the corrected value from the pre-operative value using the training dataset, and we measured the discrepancy between the corrected value and the actual postoperative value. Subsequently, the prediction performance was validated using a validation dataset. RESULTS: Using the validation dataset, the mean absolute values of errors for MPOD and MPOV corrected using DL ranged from 8.2 to 12.4%, which were lower than values with no correction (P < 0.001, linear mixed model with Tukey's test). The error depended on the autofluorescence image quality used to calculate MPOD. The mean errors in high and moderate quality images ranged from 6.0 to 11.4%, which were lower than those of poor quality images. CONCLUSION: The usefulness of the DL correction method was validated. Deep learning reduced the error for a relatively good autofluorescence image quality. Poor-quality images were not corrected.

Lutein and Zeaxanthin Supplementation Improves Dynamic Visual and Cognitive Performance in Children: A Randomized, Double-Blind, Parallel, Placebo-Controlled Study.

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.

Measuring macular pigment optical density using reflective images of confocal scanning laser system.

PURPOSE: To develop a method to measure the macular pigment optical density (MPOD) using scanning laser ophthalmoscopic images in young adults and children. STUDY DESIGN: Cross-sectional study. METHODS: Blue light reflectance fundus images of 32 healthy subjects were used. A profile of the linear reflectance changes across the center of the fovea on a grayscale fundus image was generated. The ratio of the macula-to-periphery reflection was designated as the peak value of the MPOD (MPOD[FR]) based on established fundamentals. In the MPOD profile, the basal width of the pixels at MPOD < 0 (wMP) and width at one-half value of the MPOD[FR] (wMP0.5) were determined. The MOPD at eccentricity of 0.5° was measured by heterochromatic flicker photometry (MPOD[HFP]), and the correlation between the MPOD[FR] and MPOD[HFP] was evaluated. RESULTS: The MPOD[FR] ranged from 0.17 to 0.73 with a mean of 0.40 ± 0.13. The wMP ranged from 88 to 173 pixels with a mean of 121.7 ± 24.2 pixels, and the wMP0.5 ranged from 38 to 83 pixels with a mean of 54.1 ± 10.3 pixels. A significant correlation was found between the MPOD[FR] and MPOD[HFP] (r = 0.41, P = 0.02). CONCLUSIONS: This simplified method can provide accurate and reliable values of the MPOD comparable to heterochromatic flicker photometry. Obtaining the fundus images in this fast and easy way should be suitable for children thus enabling clinicians to determine the MPODs for children.

Changes in macular pigment optical density after full-thickness macular hole closure using inverted flap technique.

Full-thickness macular hole (FTMH) is a debilitating retinal disorder, particularly in its advanced forms, necessitating surgical intervention for vision restoration. This case report details the successful closure of a large FTMH using the inverted flap technique, highlighting the essential role of multimodal imaging, and particularly macular pigment optical density (MPOD) assessment, in preoperative and postoperative evaluation. A 55-year-old patient presented with severe vision loss in one eye due to a large FTMH. Surgery was performed by an expert vitreoretinal surgeon, resulting in significant postoperative improvements in visual acuity and retinal architecture. Multimodal imaging, including MPOD assessment, played a pivotal role in preoperative evaluation and postoperative monitoring. The notable increase in MPOD following successful surgery suggests its potential role as a valuable adjunctive biomarker associated with a good visual prognosis following this type of macular hole surgical interventions.

Association of macular pigment optical density with retinal layer thicknesses in eyes with and without manifest primary open-angle glaucoma.

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.

Influence of macular pigment on the sensitivity to discomfort glare from daylight.

Understanding the factors that influence the human perception of glare is necessary to properly address glare risks in buildings and achieve comfortable visual environments, especially in the workplace. Yet large inter-individual variabilities in glare perception remain unexplained and thus uncovered by the current empirical glare models. We hypothesize that this variability has an origin in the human retina, in particular in the density of macular pigments present in its central area, which varies between individuals. Macular pigments are known to absorb blue light and attenuate chromatic aberration, thus reducing light scatter. This study presents the outcomes of the first experiment ever conducted in a daylit office environment, in which glare sensitivity and macular pigment density were measured and compared for 110 young healthy individuals, along with other ocular parameters. The participants were exposed to different glare conditions induced by the sun filtered through either color-neutral or blue-colored glazing. In neutral daylight conditions with sun disc in the near periphery, neither macular pigment nor any other investigated ocular factors have an impact on discomfort glare perception whereas glare perception in conditions with the blue-colored sun disc in the near periphery was found to be correlated with macular pigment optical density.

Imaging human macular pigments with visible light optical coherence tomography and superluminescent diodes.

We demonstrate superluminescent diodes (SLDs) for visible light optical coherence tomography (OCT) of the human retina. SLDs are less costly than supercontinuum sources and have lower intrinsic excess noise, enabling imaging closer to the shot noise limit. While single SLDs are not broadband, they provide power concentrated at specific wavelengths relevant to retinal function. As a new, to the best of our knowledge, application, we image human macular pigments (MPs), which are thought to both aid vision and protect against advanced age-related macular degeneration. Using the unique depth-resolved capabilities of OCT, we localize MPs in depth to Henle's fibers beneath the foveal pit in the living human retina. Our approach reduces the cost of visible light OCT to nearly that of near-infrared (NIR) OCT while also providing information about clinically relevant MPs which cannot be measured in the NIR.

Impacts of regular consumption of grapes on macular pigment accumulation in Singapore older adults: a randomized controlled trial.

Background: Oxidative stress is a key risk factor for visual impairment and consuming dietary antioxidant-rich foods may help in managing visual impairments. However, a limited number of studies have investigated the effect of dietary antioxidant-rich food including grapes on eye health in older adults. Objectives: To assess the effects on macular pigment accumulation of regular consumption of grapes in Singapore older adults. Methods: This was a 16 week, double-blind, randomized, placebo-controlled trial. Thirty-four Singapore older adults were randomized into regularly consuming either 46 g day-1 of freeze-dried table grape powder (the intervention group) or the same amount of placebo powder (the control group). Macular pigment optical density (MPOD), skin carotenoid status, advanced glycation end product (AGEs) status and dietary lutein intake were assessed every 4 weeks, and plasma lutein concentration, total antioxidant capacity and total phenolic content were measured every 8 weeks. Results: A significant time effect (p = 0.007) was observed for MPOD, and this is largely attributed to the improvement in the MPOD for the intervention group, as a significant increase was observed only in this group (week 0: 0.56 ± 0.04 D.U.; week 16: 0.61 ± 0.04 D.U., p < 0.01). Additionally, a significant increase in plasma total antioxidant capacity (week 0: 0.26 ± 0.13 mM TEAC; week 16: 0.36 ± 0.20 mM TEAC, p < 0.01) and total phenolic content (week 0: 10.50 ± 0.44 mg L-1 GAE; week 16: 12.58 ± 0.55 mg L-1 GAE, p < 0.001) was observed for the intervention group only. In contrast, a significant increase in skin AGE status was observed in the control group (week 0: 2.47 ± 0.24; week 16: 2.99 ± 0.12, p < 0.05) while this was mitigated in the intervention group. There were no differences in dietary lutein intake, plasma lutein concentration and skin carotenoid status between groups throughout the study. Conclusions: Regular intake of grapes may improve eye health in Singapore older adults, specifically in augmenting MPOD, which can be explained by an increase in plasma total antioxidant capacity and phenolic content, and the downregulation of AGEs. This study was registered at clinicatrials.gov as NCT05064865.

Tear biomarkers for Alzheimer's disease screening and diagnosis (the TearAD study): design and rationale of an observational longitudinal multicenter study.

BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia, and due to increasing life expectancy the number of patients is expected to grow. The diagnosis of AD involves the use of biomarkers determined by an amyloid PET scan or cerebrospinal fluid analyses that are either invasive or expensive, and not available in each hospital, thus limiting their usage as a front-line screener. The TearAD study aims to use tear fluid as a potential source for AD biomarkers. In previous reports, we demonstrated that AD biomarkers amyloid-beta and tau, are measurable in tear fluid and are associated with disease severity and neurodegeration. This study aims to validate previous results in a larger cohort and evaluate the diagnostic accuracy of tear biomarkers to discriminate between individuals with and without neurodegeneration as determined by hippocampal atrophy. METHODS: The TearAD study is an observational longitudinal multi-center study that will enroll 50 cognitively healthy controls, 50 patients with subjective cognitive decline, 50 patients with mild cognitive impairment and 50 patients with AD dementia from the memory clinic. Participants will be examined at baseline, after one year, and after two years follow-up. Study assessments include neuropsychological tests and ophthalmic examination. All participants will receive a MRI scan, and a subset of the study population will undergo cerebral spinal fluid collection and an amyloid PET scan. Tear fluid will be collected with Schirmer strips and levels of Aß38, Aß40, Aß42, t-tau and p-tau in tear fluid will be determined using multiplex immunoassays. Blood samples will be collected from all participants. Images of the retina will be obtained with a standard, hyperspectral and ultra-wide field fundus camera. Additionally, macular pigment optical density will be measured with the macular pigment reflectometer, and cross-sectional images of the retina will be obtained through optical coherence tomography imaging. DISCUSSION: The TearAD study will provide insight into the potential diagnostic use of tear biomarkers as a minimally invasive and low cost tool for the screening and diagnosis of AD. TRIAL REGISTRATION: Retrospectively registered at clinicaltrials.gov (NCT05655793).

Macular Pigment Carotenoids and Bisretinoid A2E.

Lutein (L), zeaxanthin (Z), and meso-zeaxanthin (MZ) are the three macular pigments (MP) carotenoids that uniquely accumulate in the macula lutea region of the human retina. L and Z are obtained by humans through dietary intake. The third MP, MZ, is rarely present in diet, and its abundance in the human fovea is due to the metabolic conversion of dietary L by the retinal pigment epithelium's RPE65 enzyme. The major functions of MP in ocular health are to filter high-intensity, phototoxic blue light and to act as effective antioxidants for scavenging free radicals. The pyridinium bisretinoid, N-retinylidene-N-retinylethanolamine (A2E), contributes to drusen formation in dry age-related macular degeneration (AMD) and to the autofluorescent flecks in autosomal recessive Stargardt disease (STGD1). Retinal carotenoids attenuate A2E formation and can directly and indirectly alleviate A2E-mediated oxidative damage. In this chapter, we review these more recently recognized interconnections between MP carotenoids and A2E bisretinoids.

Macular Pigment Optical Density and Skin Carotenoids in a Childhood Sample.

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 (stdß = -0.42, P < 0.001), but not macular carotenoids (stdß = -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 (stdß = 0.27, P = 0.01). Skin carotenoids were positively associated with energy-adjusted reported carotenoid intake (stdß = 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.

Randomized, Placebo-Controlled, Single-Blind Study of Lutein Supplementation on Carotenoid Status and Cognition in Persons with Multiple Sclerosis.

BACKGROUND: Multiple sclerosis (MS) is traditionally managed using disease-modifying pharmaceutical therapies as a first line approach for treatment, yet there is increasing interest in lifestyle factors, particularly diet, for managing disease outcomes. Lutein has neuroprotective properties in healthy adults, but no previous research has examined the effects of lutein supplementation in persons with MS. OBJECTIVES: This study aimed to investigate the efficacy of 4-mo lutein supplementation on carotenoid status and cognition in persons with relapse-remitting MS (RRMS). METHODS: A randomized controlled, single-blind research design was used among adults with RRMS (N = 21). Participants were randomized into placebo (n = 9) or treatment (20-mg/d lutein, n = 12) groups with outcomes measured before and after 4 mo. Macular pigment optical density (MPOD) was assessed using heterochromatic flicker photometry. Skin carotenoids were assessed using reflection spectroscopy. Serum lutein was measured using high-performance liquid chromatography. Cognition was assessed via the Eriksen flanker with event-related potentials, spatial reconstruction, and the symbol digit modalities tests. RESULTS: There was a significant group by time interaction for MPOD (F = 6.74, P = 0.02), skin carotenoids (F = 17.30, P < 0.01), and serum lutein (F = 24.10, P < 0.01), whereby the treatment group improved in all carotenoid outcomes. There were no significant group by time interactions for cognitive and neuroelectric outcomes. However, increase in MPOD was positively associated with accuracy during the flanker incongruent trials (r = 0.55, P = 0.03) and the spatial memory task (r = 0.58, P = 0.02) among treatment participants. CONCLUSIONS: Lutein supplementation increases carotenoid status among persons with RRMS. There is no significant effect on cognitive function but change in macular carotenoids is selectively associated with improved attention and memory. This study provides preliminary support for a fully powered study targeting retinal and neural carotenoids for cognitive benefits in persons with MS. This trial was registered at clinicaltrials.gov as NCT04843813.

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

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

Fluorescence lifetime imaging ophthalmoscopy and the influence of oral lutein/zeaxanthin supplementation on macular pigment (FLOS) - A pilot study.

BACKGROUND & AIMS: Oral lutein (L) and zeaxanthin (Z) supplementation enhances macular pigment optical density (MPOD) and plays a protective role in the development of age-related macular degeneration (AMD). Fluorescence lifetime imaging ophthalmoscopy (FLIO) is a novel in vivo retinal imaging method that has been shown to correlate to classical MPOD measurements and might contribute to a metabolic mapping of the retina in the future. Our aim was to show that oral supplementation of L and Z affects the FLIO signal in a positive way in patients with AMD. METHODS: This was a prospective, single center, open label cohort study. Patients with early and intermediate AMD received oral L and Z supplementation during three months, and were observed for another three months after therapy termination. All visits included measurements of clinical parameters, serum L and Z concentration, MPOD measurements using heterochromatic flicker photometry, dual wavelength autofluorescence imaging, and FLIO. Correlation analysis between FLIO and MPOD were performed. RESULTS: Twenty-one patients completed the follow up period. Serum L and Z concentrations significantly increased during supplementation (mean difference 244.8 ng/ml; 95% CI: 81.26-419.9, and 77.1 ng/ml; 95% CI: 5.3-52.0, respectively). Mean MPOD units significantly increased (mean difference 0.06; 95% CI: 0.02-0.09; at 0.5°, 202; 95% CI: 58-345; at 2°, 1033; 95% CI: 288-1668; at 9° of eccentricity, respectively) after three months of supplementation with macular xanthophylls, which included L and Z. Median FLIO lifetimes in the foveal center significantly decreased from 277.3 ps (interquartile range 230.2-339.1) to 261.0 ps (interquartile range 231.4-334.4, p = 0.027). All parameters returned to near-normal values after termination of the nutritional supplementation. A significant negative correlation was found between FLIO and MPOD (r2 = 0.57, p < 0.0001). CONCLUSIONS: FLIO is able to detect subtle changes in MPOD after L and Z supplementation in patients with early and intermediate AMD. Our findings confirm the previous described negative correlation between FLIO and MPOD. Macular xanthophylls seem to contribute to short foveal lifetimes. This study is registered at ClinicalTrials.gov (identifier number NCT04761341).

Macular pigment is inversely related to circulating C-reactive protein concentrations in school-aged children.

Xanthophyll carotenoids (i.e., lutein and zeaxanthin) are plant pigments that selectively deposit in the macula of the eye and provide retinal tissue with protection against photooxidative stress. Although having greater xanthophylls in various tissues is related to lower inflammation in adulthood and infancy, this relationship is underinvestigated in childhood. Thus, this study aimed to elucidate the relationships between macular xanthophyll status and inflammation in school-aged children. We hypothesized that greater macular pigment would be associated with lower systemic concentrations of C-reactive protein (CRP). Forty children (aged 7-12 years) from the East-Central Illinois area were recruited. Data were collected in a convenience sample over multiple visits to the laboratory that occurred over 1 month, including all individuals who provided adequate blood samples for analyses. Macular pigment optical density (MPOD) was assessed using customized heterochromatic flicker photometry. Dietary lutein and zeaxanthin were determined using 7-day diet records. Capillary dried blood spot samples were analyzed for CRP concentrations via enzyme-linked immunosorbent assay. Whole-body percentage fat (%Fat) was measured using dual-energy x-ray absorptiometry. Two-step hierarchical linear regression modelling was used to assess relationships between MPOD and CRP, following adjustment of pertinent covariates and the removal of outliers (N = 3). MPOD was negatively associated with CRP concentrations, after controlling for a priori covariates of age, sex, %Fat, and dietary lutein and zeaxanthin (ß = -0.58, ΔR2 = 0.22, P = .004). Age, sex, dietary lutein and zeaxanthin, and %Fat did not significantly contribute to the model. This study provides novel evidence that macular pigment and peripheral inflammation are inversely related in childhood.

Prenatal Carotenoid Supplementation With Lutein or Zeaxanthin Ameliorates Oxygen-Induced Retinopathy (OIR) in Bco2-/- Macular Pigment Mice.

Purpose: Premature infants at risk of retinopathy of prematurity (ROP) miss placental transfer of the carotenoids lutein (L) and zeaxanthin (Z) during the third trimester. We previously demonstrated that prenatal L and Z supplementation raised carotenoid levels in infants at birth in the Lutein and Zeaxanthin in Pregnancy (L-ZIP) study (NCT03750968). Based on their antioxidant effects and bioavailability, we hypothesized that prenatal maternal supplementation with macular carotenoids would reduce the risk of ROP. To test this hypothesis, we utilized "macular pigment mice" genetically engineered to take up L and Z into the retina in a model of oxygen-induced retinopathy (OIR). Methods: Pregnant Bco2-/- mice were divided into nine experimental subgroups based on the type of supplementation (L, Z, or placebo) and on the maternal supplementation start date corresponding to the three trimesters of human fetal development (E0, E11, and P1). Pups and nursing mothers were exposed to 75% O2 for 5 days (P7-P12) and returned to room air for 5 days (P12-P17). Pups were killed at P12 and P17, and their retinas were analyzed for vaso-obliteration and intravitreal neovascularization. Results: Pups of pregnant mice supplemented with L or Z had significant reductions in areas of vaso-obliteration and intravitreal neovascularization compared to placebo. Prenatal carotenoid supplementation starting at E0 or E11 was significantly more protective against OIR than postnatal supplementation starting at P1. Conclusions: Prenatal supplementation with L and Z was beneficial in a mouse OIR model. We recommend testing prenatal L and Z supplementation in future human clinical trials to prevent ROP.

Assessment of macular pigment optical density of primary open-angle glaucoma patients under topical medication.

BACKGROUND: Glaucoma is a progressive, sight-threatening disease. In this study, we aimed to compare macular pigment optical density (MPOD) measurements of the primary open-angle glaucoma (POAG) patients under topical therapy with the control group. METHODS: This cross-sectional study included 55 eyes of 30 POAG patients and 42 eyes of 22 age- and sex-matched healthy controls. The data of all participants were analyzed retrospectively. Subsequently, patients with POAG were divided into two groups: Group 1 received therapy including prostaglandin analogue (PGA), and group 2 was using anti-glaucomatous drugs other than PGA. All participants underwent detailed ophthalmologic examination, including fundus photography and spectral-domain optical coherence tomography. In addition, MPOD was measured using the Zeiss Visucam 500 fundus camera. Mann-Whitney U test, Independent samples t-test, and one-way multivariate analysis of variance (MANOVA) tests were used to compare the values between and among groups. RESULTS: There was no significant difference in age and sex between POAG and healthy controls (p = 0.229, p = 0.376, respectively). All MPOD values were higher in the glaucoma group than in the control group. MPOD max, MPOD volume, and MPOD area were significantly higher in the POAG group than in the control group (p<0.05 for all). However, there was no significant difference in the mean MPOD (p = 0.083). In addition, in pairwise comparisons, the PGA therapy group had significantly higher MPOD values than the control group (p<0.05 for all). CONCLUSION: MPOD levels increased in patients receiving PGA treatment. In addition, retinal nerve fiber layer thickness was positively correlated with MPOD levels in POAG patients. Therefore, PGAs may have a neuroprotective effect.