Zeaxanthin Supplementation Research Articles

Ocular Effects of Prenatal Carotenoid Supplementation in the Mother and Her Child: The Lutein and Zeaxanthin in Pregnancy (L-ZIP) Randomized Trial - Report Number 2

PurposeLutein and zeaxanthin are xanthophyll carotenoids that have been promoted to enhance maternal health and infant visual and neurodevelopment. In this study, we determined the effects of prenatal lutein and zeaxanthin supplementation on systemic and ocular carotenoid status in the mother and her newborn infant (NCT03750968). This report focuses on the ocular effects of prenatal carotenoid supplementation. DesignA prospective randomized clinical trial with 47 subjects randomly assigned by 1:1 allocation to receive standard-of-care prenatal vitamins along with 10 mg lutein and 2 mg zeaxanthin softgel (Carotenoid Group) or standard-of-care prenatal vitamins with a placebo softgel (Control Group) starting in the first trimester. SubjectsWe enrolled low-risk pregnancy subjects aged 18 years and above from the obstetrics and gynecology clinic of the University of Utah Hospital. MethodsMaternal macular, skin, and serum carotenoid concentrations were measured using autofluorescence imaging, resonance Raman spectroscopy, and high-performance liquid chromatography, respectively. Infants’ ocular carotenoids and retinal architecture were measured by blue light reflectance imaging and spectral domain optical coherence tomography, respectively. Main Outcome MeasuresChanges in maternal and infant macular pigment, skin, and serum carotenoid status over the study period. Differences in infants’ retinal maturity indicators between the two study groups. ResultsFollowing supplementation, there was a statistically significant increase in maternal macular pigment optical volume (p < 0.001) in the Carotenoid Group relative to the Control Group at all study time points, and there was no detectable maternal ocular carotenoid depletion. Infant skin and serum carotenoids increased significantly in the Carotenoid Group compared to the Control Group. As exploratory endpoints, infants in the Carotenoid Group had a 20% increase in macular pigment optical density (p = 0.242) and more mature foveal parameters compared to those in the Control Group. ConclusionPrenatal carotenoid supplementation significantly increased maternal and infant systemic carotenoids and caused a pattern of increased infant ocular carotenoid status, which may benefit both mothers and their infants’ ocular development and function. This study provides important data to design and power a future multicenter study of prenatal carotenoid supplementation in higher-risk pregnancies.

The Effects of Lycopene, Lutein and Zeaxanthin Supplement to Layer Hen Diets on Performance and Egg Quality Parameters

Amaç: Bu çalışmada yumurta tavuklarında renk maddesi olarak kullanılan likopen (Lİ), lutein (LU) ve zeaksantin (ZE) ilavesinin yumurta sarısının rengi, performans ve yumurta kalite kriterleri üzerine etkileri incelenmiştir. &#x0D; &#x0D; Materyal ve Metot: Çalışmada, 40 haftalık yaşta 192 adet beyaz yumurtacı tavuk rastgele her biri 16 tekerrürden oluşan 4 gruba ayrılmış ve renk maddesi içermeyen yemler ile beslenen kontrol (K) grubu 80’er ppm Lİ, LU veya ZE ilaveli yemlerin tüketildiği gruplar ile karşılaştırılmıştır. Çalışmanın 15. ve 30. günlerinde performans ve yumurta kalite kriterleri ölçülmüş ve renk maddelerinin bu parametreler üzerine etkileri incelenmiştir.&#x0D; &#x0D; Bulgular: Yeme renk maddesi ilavesinin canlı ağırlık, yem tüketimi, yumurta verimi ve yemden yararlanma oranı üzerine önemli bir etkisi bulunmamıştır (P&gt;0.05). Yumurta ağırlığı incelendiğinde 15. günde Lİ, 30. günde ise LU en yüksek değerleri vermiştir (P

Prevention Surpasses Treatment: 5-year Follow-Up, Cost-Utility, and Cost-Benefit of Zeaxanthin Therapy for Neovascular Age-Related Macular Degeneration.

Oral administration of zeaxanthin (Zx) 20mg daily in patients with unilateral neovascular age-related macular degeneration (nAMD) treated with triple therapy (photodynamic therapy/intravitreal bevacizumab/intravitreal dexamethasone) reduced fellow-eye 2-year nAMD incidence from 23 to 6% (p = 0.02) in a prior clinical trial. We questioned the long-term benefit and thus analyzed case-control 5-year patient data of trial participants and additional participants with 5-year follow-up, also performing cost-utility and cost-benefit analyses. Consecutive, unilateral nAMD patient outcomes for those taking 20mg Zx supplementation orally for ≥ 5years were compared with the Comparison of AMD Treatments Trials (CATT) 5-year historical controls for fellow-eye nAMD conversion. Eleven-year mean life expectancy, cost-utility and cost-benefit models were undertaken employing a 3% discount rate and 2020 US real dollars. Among 227 consecutive patients with nAMD/Zx-supplementation, 202 (90%) had 5-year follow-up. The fellow-eye nAMD 5-year conversion incidence using a Kaplan-Meier cumulative event estimate was 22% (49/227), versus 48% (167/348) with CATT control data (p < 0.0001). An 11-year cost-utility model with estimates for years 6-11 demonstrated a 0.42 (7.7%) QALY (quality-adjusted life-year) gain, including 3months of life saved per patient due to decreased nAMD fellow-eye conversion. This yielded a direct ophthalmic medical cost perspective, incremental cost-utility ratio (CUR) of -$576/QALY and a societal cost perspective CUR of -$125,071/QALY. Zx supplementation for all 2020 US unilateral nAMD cases would have theoretically saved society, primarily patients, $6.0 billion over 11years, a 1531% return on investment (ROI), or 31.3% annual ROI, on Zx costs. Oral zeaxanthin supplementation for unilateral nAMD patients appears to decrease fellow-eye long-term incidence and is cost-effective and financially rewarding. It is dominant vs. no supplementation in patients presenting with unilateral nAMD. ClinicalTrials.gov identifier, NCT01527435.

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

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 invivo 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. 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. Twenty-one patients completed the follow up period. Serum L and Z concentrations significantly increased during supplementation (mean difference 244.8ng/ml; 95% CI: 81.26-419.9, and 77.1ng/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 277.3ps (interquartile range 230.2-339.1) to 261.0ps (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). 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).

Associations between blood antioxidant levels and femoral neck strength

BackgroundStudies have confirmed that antioxidants contribute to a lower risk of osteoporosis, which is an independent factor for femoral neck fracture (FNF). However, the associations between blood antioxidant levels and femoral neck strength remain unclear.ObjectiveOur aim was to test the hypothesis that levels of blood antioxidants are positively associated with composite indices of bone strength in femoral neck, which integrate the bending strength index (BSI), compressive strength index (CSI), and impact strength index (ISI), in a population of middle-aged and elderly individuals.MethodsThis cross-sectional study utilized data from the Midlife in the United States (MIDUS) study. Blood levels of antioxidants were measured and analyzed.ResultsIn total, data from 878 participants were analyzed. Results of Spearman correlation analyses indicated that blood levels of 6 antioxidants (total lutein, zeaxanthin, alpha-carotene, 13-cis-beta-carotene, trans-beta-carotene and total lycopene) were positively associated with CSI, BSI, or ISI in middle-aged and elderly individuals. Conversely, blood gamma-tocopherol and alpha-tocopherol levels were negatively associated with CSI, BSI, or ISI scores. Furthermore, linear regression analyses suggested that only blood zeaxanthin levels remained positively associated with CSI (odds ratio, OR 1.27; 95% CI: 0.03, 2.50; p = 0.045), BSI (OR, 0.54; 95% CI: 0.03–1.06; p = 0.037), and ISI (OR, 0.06; 95% CI: 0.00, 0.13; p = 0.045) scores in the study population after adjusting for age and sex.ConclusionsOur results indicated that elevated blood zeaxanthin levels were significantly and positively associated with femoral neck strength (CSI, BSI, or ISI) in a population of middle-aged and elderly individuals. These findings suggest that zeaxanthin supplementation may reduce FNF risk independently.

The effects of Lutein and Zeaxanthin (Lute-genreg;) supplementation, with and without natural mixed carotenoids on Central Foveal Thickness and its relationship with Macular Pigment Optical Density in healthy adult subjects: a randomized, double-blind, placebo-controlled study

The fovea is a specialised part of the retina which accumulates macular carotenoids. Isomeric carotenoids like lutein, zeaxanthin and meso-zeaxanthin with antioxidant properties are the principal components of macular pigment (MP) accounting for the yellowish colour of the macular area of the retina. MP blocks short wavelength (blue) light that would otherwise damage photoreceptors and pigment epithelial cells causing irreversible changes to the eye architecture. The concentration of MP peaks at the fovea and is visible on the inner and outer plexiform layers of the parafoveal area, thereby protecting retinal damage, which is measured through the relationship between CFT (central foveal thickness) and MPOD (macular pigment optical density). The objective of this clinical study was to assess the effect of Lutein and Zeaxanthin (Lute-gen®) supplementation, with and without natural mixed carotenoids on central foveal thickness, and its relationship with macular pigment optical density (MPOD) in healthy adult subjects. A total of 93 subjects were randomized in a double-blind, placebo-controlled, parallel, three-arm study which was followed up for 180 days. Data obtained post the study period was subjected to advanced statistical analysis to determine the efficacy of Lutein and Zeaxanthin (Lute-gen®) with and without natural mixed carotenoids on central foveal thickness (CFT) and its relationship with MPOD to determine the physiological status of the eye health. Lutein and Zeaxanthin (Lute-gen®) supplementation, with natural mixed carotenoids (P=0.003) and without natural mixed carotenoids (P=0.012) showed statistically significant improvements in the CFT levels when compared to baseline. On the other hand, the placebo arm (P=0.11) did not show any significant change in CFT levels when CFT measurements were performed on both the eyes. Our study showed a significant positive correlation between MPOD and CFT suggesting MPOD is strongly correlated with CFT. These studies on the relationship between MPOD and CFT can contribute to a stronger understanding on the relationship between scavenging radicals and antioxidant activities of lutein, zeaxanthin and other mixed carotenoids on eye health.

The Effect of Dietary Supplementations on Delaying the Progression of Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis.

Purpose: Age-related macular degeneration (AMD) is a neurodegenerative ophthalmic disease. The purpose of this systematic review (SR) and meta-analysis was to evaluate if dietary supplementation alone or in combinations might delay the progression of any of the stages of AMD. Methods: A SR and meta-analysis identifying cohort studies and randomized controlled trials (RCTs) evaluating the effect of supplements in patients diagnosed with AMD. PubMed, Scopus, Web of Science, CINAHL, and Cochrane were searched through 8th October 2021. Results: Twenty studies, examining 5634 participants ranging from 55 to 80 years, were included in the SR. Eight studies were selected for meta-analysis (414 and 216 subjects in the intervention and control groups). Lutein and zeaxanthin plus n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) supplementation showed significant improvements in best-corrected visual acuity (BCVA) (SMD: −1.99, 95% CI: −3.33, −0.65) compared to the control group. Multifocal electroretinogram results (mfERG) were significantly improved overall (SMD: 4.59, 95% CI: 1.75, 7.43) after lutein plus zeaxanthin supplementation. Conclusions: Combinations of lutein and zeaxanthin with n-3 LC-PUFA might be beneficial in preventing AMD progression and deterioration of visual function. Our results encourage initiating further studies with combinations of n-3 LC-PUFA, lutein, and zeaxanthin especially in early AMD patients.

Macular pigment optical density in a Thai sample

ABSTRACT Background The aim of this study was to determine macular pigment optical density (MPOD) and identify factors that correlate with its level in Thai subjects. Research design and methods This research was a cross-sectional study. Two hundred and forty eyes of 120 participants with healthy eyes underwent MPOD measurement using VISUCAM 500. Demographic and medical data were collected. Pearson’s correlation coefficient analyzed the relationship between the sum of optical densities (MPOD volume) and various factors. MPOD and its influencing factors were analyzed by stepwise multiple regression. Results The mean age of the participants was 50.7 ± 7.5 years. The mean MPOD was 0.102 ± 0.023 density units. The factors age (r = 0.261, p < 0.01), female gender (r = 0.191, p < 0.05), and consumption of lutein and zeaxanthin (L/Z) supplement (r = 0.168, p < 0.05) were positively associated with MPOD volume. In contrast, normal blood pressure (r = – 0.182, p < 0.05) was negatively associated with MPOD volume. No relationship with smoking, body mass index, lipid profile, and family history of AMD on MPOD values was observed in this study. Conclusions Age, gender and consumption of L/Z supplement were found to be significant predictors of MPOD in Thai subjects.

The Effects of Lutein and Zeaxanthin Supplementation on Cognitive Function in Adults With Self-Reported Mild Cognitive Complaints: A Randomized, Double-Blind, Placebo-Controlled Study.

BackgroundLutein and zeaxanthin are fat-soluble, dietary carotenoids with high concentrations in human brain tissue. There have been a number studies confirming an association between lutein and zeaxanthin and cognitive function.PurposeExamine the effects of lutein and zeaxanthin supplementation on cognitive function in adults with self-reported cognitive complaints.Study DesignTwo-arm, parallel-group, 6-month, randomized, double-blind, placebo-controlled trial.MethodsNinety volunteers aged 40–75 years received either 10 mg of lutein and 2 mg of zeaxanthin, once daily or a placebo. Outcome measures included computer-based cognitive tasks, the Cognitive Failures Questionnaire, Behavior Rating Inventory of Executive Function, Profile of Mood States, and the Patient-Reported Outcomes Measurement Information System-29.ResultsCompared to the placebo, lutein and zeaxanthin supplementation was associated with greater improvements in visual episodic memory (p = 0.005) and visual learning (p = 0.001). However, there were no other statistically-significant differences in performance on the other assessed cognitive tests or self-report questionnaires. Lutein and zeaxanthin supplementation was well-tolerated with no reports of significant adverse effects.ConclusionThe results from this trial suggest that 6-months of supplementation with lutein and zeaxanthin may improve visual memory and learning in community-dwelling adults with self-reported cognitive complaints. However, it had no other effect on other computer-based measures of cognitive performance or self-report measures of cognition, memory, mood, or physical function.

Effect of nettle (Urtica spp.), marigold (Tagetes erecta), alfalfa (Medicago sativa) extracts and synthetic xanthophyll (zeaxanthin) carotenoid supplementations into diets on skin pigmentation and growth parameters of electric yellow cichlid (Labidochromis caeruleus)

This study was conducted to investigate the effects nettle (Urtica spp.), marigold (Tagetes erecta), alfalfa (Medicago sativa) plant extracts and synthetic carotenoid supplementations into diets (150 mg kg−1) on growth parameters and skin coloration of electric yellow cichlids. Five experimental groups included control, nettle, marigold, alfalfa and synthetic xanthophylls (Zeaxanthin; Zeax) treatments in 3 replications in 15 aquariums. Fifteen fish in each aquarium were fed ad-libitum (a total of 225 fish) twice a day for 3 months. Initial weight of the fish was 0.560 g. The weights were monthly measured and fish weights exceeded 2 g at the end of 3rd month (P > .05). The differences in weight gain, specific growth rate, feed consumption, total weight gain, feed conversion ratio and survival rate of the experimental groups were not found to be significant. The color parameters of L *, a *, b*, Hue and Chroma were calculated for all plant extracts. The greatest brightness (L*) value was obtained from the nettle extracts (61.850) and such a value was significantly different from the L* values of the control, zeax and marigold groups (P < .05). Hue (Hab°) angle at the end of the experiments was within yellow color in all groups. Hab° angle was calculated as 99.391° for alfalfa, 98.993° for marigold and 98.800° for nettle groups and they were greater than Zeax (94.881°) and Control (91.090°) groups (P < .05). The greatest chroma (Ch) was obtained from alfalfa extract (27.407) and differences in Ch values of the control and supplementation groups were found to be significant (P < .05). Obtained findings revealed that zeaxanthin supplementation as synthetic xanthophyll source and plant extract supplementations as natural carotenoid source yielded sufficient pigmentation on skin of electric yellow cichlids. Skin color of carotenoid-supplemented groups was brighter and purer as compared to the control group.

The Effects of Lutein and Zeaxanthin Supplementation on Brain Morphology in Older Adults: A Randomized, Controlled Trial.

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.

Idiopathic Macular Telangiectasia Type 2 and Its Relationship with Macular Pigment Optical Density

Idiopathic macular telangiectasia type 2 (IMT2) is a relatively uncommon clinical condition with an estimated prevalence of 1% within the general population. This condition can be challenging to precisely identify in early stages but advancements in clinical imaging to include fluorescein angiography and optical coherence tomography angiography (OCTA) can allow for timely diagnosis and prompt intervention that may leads to improved long-term clinical outcomes. Emerging literature has recognized the role of macular pigment (MP) in IMT2 in terms of Henle fiber layer deposition mechanisms and potential mitigation of inflammatory and oxidative stress. Primary care optometrists are in a unique position to facilitate early detection and manage through close evaluation and individualized lutein and zeaxanthin supplementation. Keywords: Idiopathic macular telangiectasia type 2; Macular pigment; Spectral domain optical coherence tomography angiography

Daily zeaxanthin supplementation prevents atrophy of the retinal pigment epithelium (RPE) in a mouse model of mitochondrial oxidative stress.

Oxidative damage is implicated in the pathogenesis of age-related macular degeneration (AMD). The dry form of AMD (geographic atrophy) is characterized by loss of RPE, photoreceptors, and macular pigments. The cumulative effects of oxidative stress impact mitochondrial function in RPE. In Sod2flox/floxVMD2-cre mice, the RPE specific deletion of Sod2, the gene for mitochondrial manganese superoxide dismutase (MnSOD), leads to elevated oxidative stress in retina and RPE, and causes changes in the RPE and underlying Bruch’s membrane that share some features of AMD. This study tested the hypothesis that zeaxanthin supplementation would reduce oxidative stress and preserve RPE structure and function in these mice. Zeaxanthin in retina/RPE/choroid and liver was quantified by LC/MS, retinal function and structure were evaluated by electroretinogram (ERG) and spectral domain optical coherence tomography (SD-OCT), and antioxidant gene expression was measured by RT-PCR. After one month of supplementation, zeaxanthin levels were 5-fold higher in the retina/RPE/choroid and 12-fold higher in liver than in unsupplemented control mice. After four months of supplementation, amplitudes of the ERG a-wave (function of rod photoreceptors) and b-wave (function of the inner retina) were not different in supplemented and control mice. In contrast, the c-wave amplitude (a measure of RPE function) was 28% higher in supplemented mice than in control mice. Higher RPE/choroid expression of antioxidant genes (Cat, Gstm1, Hmox1, Nqo1) and scaffolding protein Sqstm1 were found in supplemented mice than in unsupplemented controls. Reduced nitrotyrosine content in the RPE/choroid was demonstrated by ELISA. Preliminary assessment of retinal ultrastructure indicated that supplementation supported better preservation of RPE structure with more compact basal infoldings and intact mitochondria. We conclude that daily zeaxanthin supplementation protected RPE cells from mitochondrial oxidative stress associated with deficiency in the MnSOD and thereby improved RPE function early in the disease course.

Protective role of carotenoids in the visual cycle.

Exposure to light and accumulation of aberrant visual cycle by-products causes stress in the retina. The physical and chemical properties of carotenoids may provide protection against such scenario. These pigments exist in retinas of many vertebrates, including humans. However, the absence of carotenoids in mice, the preferred ophthalmologic animal model, hindered molecular and biochemical examination of the pigments' role in vision. We established a mouse model that accumulates significant amounts of carotenoids in the retina due to inactivating mutations in the Isx and Bco2 genes. We introduced a robust light damage protocol for the mouse retina using green (532 nm) and blue (405 nm) low-energy lasers. We observed that blue but not green laser light treatment triggered the formation of aberrant retinaldehyde isomers in the retina. The production of these visual cycle by-products was accompanied by morphologic damage in inferior parts of the mouse retina. Zeaxanthin supplementation of mice shielded retinoids from these photochemical modifications. These pigments also reduced the extent of the damage to the retina after the blue laser light insult. Thus, our study discovered a novel role of carotenoids in the visual cycle and indicated that vertebrates accumulate carotenoids to shield photoreceptors from short-wavelength light-induced damage.-Widjaja-Adhi, M. A. K., Ramkumar, S., von Lintig, J. Protective role of carotenoids in the visual cycle.

Treatments for dry age-related macular degeneration and Stargardt disease: a systematic review.

Age-related macular degeneration (AMD) is the leading cause of visual loss in older people. Advanced AMD takes two forms, neovascular (wet) and atrophic (dry). Stargardt disease (STGD) is the commonest form of inherited macular dystrophy. To carry out a systematic review of treatments for dry AMD and STGD, and to identify emerging treatments where future NIHR research might be commissioned. Systematic review. We searched MEDLINE, EMBASE, Web of Science and The Cochrane Library from 2005 to 13 July 2017 for reviews, journal articles and meeting abstracts. We looked for studies of interventions that aim to preserve or restore vision in people with dry AMD or STGD. The most important outcomes are those that matter to patients: visual acuity (VA), contrast sensitivity, reading speed, ability to drive, adverse effects of treatment, quality of life, progression of disease and patient preference. However, visual loss is a late event and intermediate predictors of future decline were accepted if there was good evidence that they are strong predictors of subsequent visual outcomes. These include changes detectable by investigation, but not necessarily noticed by people with AMD or STGD. ClinicalTrials.gov, the World Health Organization search portal and the UK Clinical Trials gateway were searched for ongoing and recently completed clinical trials. The titles and abstracts of 7948 articles were screened for inclusion. The full text of 398 articles were obtained for further screening and checking of references and 112 articles were included in the final report. Overall, there were disappointingly few good-quality studies (including of sufficient size and duration) reporting useful outcomes, particularly in STGD. However we did identify a number of promising research topics, including drug treatments, stem cells, new forms of laser treatment, and implantable intraocular lens telescopes. In many cases, research is already under way, funded by industry or governments. In AMD, the main limitation came from the poor quality of much of the evidence. Many studies used VA as their main outcome despite not having sufficient duration to observe changes. The evidence on treatments for STGD is sparse. Most studies tested interventions with no comparison group, were far too short term, and the quality of some studies was poor. We think that the topics on which the Health Technology Assessment (HTA) and Efficacy Mechanism and Evaluation (EME) programmes might consider commissioning primary research are in STGD, a HTA trial of fenretinide (ReVision Therapeutics, San Diego, CA, USA), a visual cycle inhibitor, and EME research into the value of lutein and zeaxanthin supplements, using short-term measures of retinal function. In AMD, we suggest trials of fenretinide and of a potent statin. There is epidemiological evidence from the USA that the drug, levodopa, used for treating Parkinson's disease, may reduce the incidence of AMD. We suggest that similar research should be carried out using the large general practice databases in the UK. Ideally, future research should be at earlier stages in both diseases, before vision is impaired, using sensitive measures of macular function. This may require early detection of AMD by screening. This study is registered as PROSPERO CRD42016038708. The National Institute for Health Research HTA programme.

MACULAR PIGMENT DISTRIBUTION RESPONSES TO HIGH-DOSE ZEAXANTHIN SUPPLEMENTATION IN PATIENTS WITH MACULAR TELANGIECTASIA TYPE 2.

To analyze macular pigment (MP) amount and distribution in patients with macular telangiectasia Type 2 receiving oral zeaxanthin supplementation in a randomized, open-label, interventional trial. Eight macular telangiectasia Type 2 patients were randomized to 10 mg or 20 mg of zeaxanthin per day. At each visit, best-corrected visual acuity, contrast sensitivity, fundus biomicroscopy, color fundus photography, autofluorescence imaging, optical coherence tomography, and serum carotenoid levels were tested. Patients were assessed at baseline and after 6, 12, 18, and 24 months of zeaxanthin supplementation. Concentration of MP was analyzed and calculated from autofluorescence imaging obtained at 488-nm excitation wavelength. Serum carotenoid levels were obtained using high-performance liquid chromatography. The majority of patients had definite increases in the intensity of hypofluorescent ring of MP, but none of them deposited MP centrally at the fovea. Although some patients noted subjective improvements in vision, no objective improvements could be documented, and there were no changes in foveal optical coherence tomographic features. Yellowish, hypofluorescent crystals appeared in one patient's macular region with no change in visual acuity. These inner retinal crystals disappeared several months after discontinuing her 20-mg zeaxanthin supplement. Based on the current study, zeaxanthin supplementation does not result in any visual benefit in patients with macular telangiectasia Type 2 and does not reestablish a normal peaked distribution of MP in the fovea. One patient developed a novel, reversible, crystalline maculopathy in response to zeaxanthin supplementation that was reminiscent of canthaxanthin crystalline maculopathy.

Restoration of Central Macular Pigment Dip with Dietary RR Zeaxanthin Supplementation in Patients with AMD

Restoration of Central Macular Pigment Dip with Dietary RR Zeaxanthin Supplementation in Patients with AMD

Lutein and Zeaxanthin Supplement Use and Macular Pigment Change Over 14 years in the Second Carotenoids and Age‐Related Eye Diseases Study (CAREDS2), an Ancillary Study to the Women's Health Initiative

PurposeMacular Pigment (MP), a retinal accumulation of lutein and zeaxanthin (L and Z), may modify risk for age‐related macular degeneration (AMD), a leading cause of blindness. Studies of MP change are limited, and may be influenced by L and Z supplement use. We describe changes in MPOD over 14 years in older women, and the relationship to supplemental L and Z. We describe whether other factors, including diet, lifestyle, and metabolic health, are related to MPOD change, or interact with L and Z supplement use.MethodsPreliminary data for 197 women (ages 70 to 98 years) seen for a 14‐year follow‐up visit were included. MPOD was measured using heterochromatic flicker photometry at 0.5° from the foveal center relative to reference levels at 7°, at baseline (2001–2004) and follow‐up (2016). Daily use of L and Z supplements was assessed by questionnaire at follow‐up. At baseline, waist circumference and body mass index were measured, and diet, lifestyle, and medication use were assessed in questionnaires. Serum L and Z was assessed in specimens from WHI study visits (1994–1998). Prevalent AMD and intraocular lens (IOL) were determined at follow‐up. Relationships between L and Z supplement use and MPOD change and potential interactions were determined by linear regression.ResultsWe observed a MPOD increase of 0.15 density units between baseline and CAREDS2 visits (P &lt; .0001). L and Z supplement use at CAREDS2 was more prevalent than baseline (18% vs. 2%). Consuming &gt;1mg daily, vs. less (including those consuming 0mg) was associated with greater mean (SE) MPOD change since baseline (0.23 ± 0.07 vs. 0.13 ± 0.02; p = .05). Adjustment for confounding strengthened this relationship. In supplement users, the increase in MPOD was greatest with baseline MPOD less than the median, lower healthy eating score, and in those without AMD (Pinteraction &lt; .20). Age, physical activity level, and the presence of an IOL interacted positively with supplement use to predict MPOD change. Physical activity and IOL were directly related to greater MPOD change (P &lt; .01) independent of supplements. Baseline MPOD and serum L and Z were inversely related to MPOD change (P =.05).ConclusionThese results suggest an average increase in MPOD with age that is related to the use of L and Z supplements. Other factors, including AMD status, baseline MPOD, physical activity level, and IOL, may modify this association or independently increase MPOD. Given the relatively small sample size, these results require confirmation in the larger study, once complete.Support or Funding InformationNIH/NEI (R01EY025292)This work was supported in part by an unrestricted grant from Research to Prevent Blindness, Inc. to the UW Madison Department of Ophthalmology and Visual Sciences.

Combination Therapy with Dietary Zeaxanthin for Neovascular Age Related Macular Degeneration. A Randomized Clinical Trial

Purpose: A previous comparative interventional study suggested oral zeaxanthin added to triple therapy of intravitreal bevacizumab, intravitreal corticosteroids and photodynamic therapy with verteporfin for the treatment of neovascular age-related macular degeneration (NVAMD) was comparatively effective and cost-effective. A randomized clinical trial was undertaken to confirm these effects. Methodology: A two-year, triple-blinded, randomized clinical trial enrolled 144 participants (168 eyes) with NVAMD to triple therapy (TT) (intravitreal bevacizumab, reduced-fluence photodynamic therapy and intravitreal dexamethasone) or the same triple therapy with oral zeaxanthin (TTZ) supplementation, 20 mg daily. Data were modeled out to the 11-year life expectancy of the average participant. Results: At 24-months, twenty-seven percent (17/62) of TTZ eyes gained ≥ 15 letters, versus 9% (7/81) of TT eyes (p=0.003). Among unilateral, NVAMD participants, NVAMD developed in 23% (12/53) of TT and 6% (3/47) of TTZ fellow eyes with atrophic age-related macular degeneration (AMD) (p=0.02) by 24 months after baseline. The incremental costutility ratio of oral zeaxanthin supplementation was a remarkably low $30/QALY (quality-adjusted life-year). Zeaxanthin supplementation to TT is cost-effective in every country since the 11-year cost of TTZ ($14,486) exceeds the cost of TT ($14,480) by only $6, yet provides a 0.200 QALY gain. Conclusion: Oral zeaxanthin supplementation of triple therapy for the treatment of neovascular age-related macular degeneration is comparatively effective because it yields improved vision and reduces the incidence of subsequent neovascular age-related macular degeneration in fellow eyes with atrophic age-related macular degeneration by 74%. Oral zeaxanthin supplementation is very cost-effective in the U.S. and worldwide referent to most ophthalmic interventions.

Effect of zeaxanthin on porcine embryonic development during in vitro maturation.

Zeaxanthin is a common carotenoid, which is a powerful antioxidant that protects against damage caused by reactive oxygen species. The aim of the present study was to investigate the effects of zeaxanthin supplementation on in vitro maturation of porcine embryo development. We investigated nuclear maturation, intracellular glutathione (GSH), and reactive oxygen species (ROS) levels during in vitro maturation, and subsequent embryonic development following parthenogenetic activation and in vitro fertilization (IVF). The oocytes were maturated and used at the metaphase II stage. After 42 hours of in vitro maturation, the zeaxanthin-treated group (0.5 mmol/L) showed significant increases in nuclear maturation (89.6%) than the control group (83.4%) (P<0.05). The intracellular GSH levels increased significantly (P<0.05) as zeaxanthin concentrations increased; ROS generation levels decreased with increased zeaxanthin concentrations, but there were no significant differences. There were no significant differences in subsequent embryonic development, cleavage rate, blastocyst stage rate, and total blastocyst cell numbers following parthenogenetic activation and IVF when in vitro maturation media was supplemented with zeaxanthin. These results suggest that treatment with zeaxanthin during in vitro maturation improved the nuclear maturation of porcine oocytes by increasing the intracellular GSH level, thereby slightly decreasing the intracellular ROS level.