Increase In Macular Pigment Optical Density Research Articles

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

BackgroundMultiple 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. ObjectivesThis study aimed to investigate the efficacy of 4-mo lutein supplementation on carotenoid status and cognition in persons with relapse-remitting MS (RRMS). MethodsA 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. ResultsThere 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. ConclusionsLutein 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.

The level and efficacy of lutein in patients with age-related macular degeneration: a comprehensive systematic review and meta-analysis.

BackgroundLutein has been linked with various visual performance disorders, including age-related macular degeneration (AMD). However, previous studies evaluating the association between serum lutein and the risk of AMD showed results, and the efficacy of lutein intake in AMD patients remains unclear.MethodsTo comprehensively estimate the relationship between lutein and AMD, a systematic review and meta-analysis was conducted by searching eligible randomized clinical trials (RCT) and case-control studies to study the association between lutein and AMD on the Cochrane Library, MEDLINE, Elsevier, PubMed, Web of Knowledge, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biomedical Database (CBM) databases until April 2020. The weighted mean difference (WMD) with 95% confidence interval (95% CI) was adopted as the primary effect estimate. Meta-analysis was conducted using STATA 12.0.ResultsNine studies with 855 participants were included in this meta-analysis. The NOS scoring of five case-control studies ranged 5–9. For RCTs, two studies were rated with a low risk of bias, one study with a moderate risk of bias and one with a high risk of bias. The results increased significantly in macular pigment optical density (MPOD) (WMD =0.069; 95% CI: 0.040–0.098, P=0.000) among AMD patients taking lutein supplementation, while there was no difference in circulating lutein levels between AMD patients and controls (WMD =0.00; 95% CI: −0.01 to 0.00, P=0.310). Subgroup analysis suggested that the dose and duration of supplementation could significantly influence the MPOD level in AMD patients. In particular, we observed a larger increase in MPOD of AMD patients using a higher dose (20 mg/d) and longer treatment (>6 months).ConclusionsAlthough current evidence does not support circulating lutein as a biomarker for early screening of the high-risk AMD population, this study is the first meta-analysis to explore the relationship between lutein in blood and AMD patients. Given that lutein has a high safety profile as indicated by many studies, it is reasonable to give the current analysis result that high dose (20 mg/d) and long duration (>6 months) of lutein intake could be beneficial to AMD patients.

The ALGOVUE Clinical Trial: Effects of the Daily Consumption of Eggs Enriched with Lutein and Docosahexaenoic Acid on Plasma Composition and Macular Pigment Optical Density

Background. Carotenoids and docosahexaenoic acid (DHA) were identified as essential components for eye health and are both naturally present in eggs. Objective. We aimed to evaluate the effect of the daily consumption of two eggs enriched with lutein/zeaxanthin and DHA on macular pigment optical density (MPOD) and on circulating xanthophyll and fatty acid concentrations in healthy participants. Methods. Ninety-nine healthy volunteers consumed either two standard eggs or two enriched eggs per day for 4 months. MPOD was measured at baseline (V0) and at follow-up (V4) using a modified confocal scanning laser ophthalmoscope (primary outcome). Blood samples were collected to determine total plasma and lipoprotein fatty acids and lutein/zeaxanthin compositions at V0 and V4 (secondary outcomes). Results. A slight but significant increase in MPOD was observed for all study participants consuming two eggs per day for 4 months at all eccentricities (0.5°, 1°, 2°, and 4°). Plasma and lipoprotein lutein, zeaxanthin, and DHA concentrations significantly increased in both groups but were greater in the enriched group (for the enriched group (V0 vs. V4): lutein, 167 vs. 369 ng/mL; zeaxanthin, 17.7 vs. 29.2 ng/mL; DHA, 1.89 vs. 2.56% of total fatty acids). Interestingly, lutein from high-density lipoprotein (HDL) was strongly correlated with MPOD at 0.5 and 1° eccentricities (rho = 0.385, p = 0.008, and rho = 0.461, p = 0.001, respectively). Conclusions. MPOD was slightly increased in both groups. Lutein, zeaxanthin, and DHA plasma concentrations were strongly enhanced in the enriched group compared with the standard group. A significant correlation was found between MPOD level and lutein concentration in HDL.

Macular pigment optical density change analysis in primary open-angle glaucoma and pseudoexfoliation glaucoma.

We aimed to investigate whether macular pigment optical density (MPOD) has a diagnostic value by comparing MPOD and retinal nerve fiber layer (RNFL), ganglion cell layer++ (GCL++) of patients with primary open-angle glaucoma (POAG) and pseudoexfoliation (PEX) glaucoma and normal individuals. We included in the study 54 eyes of 34 patients with diagnosis POAG, 40 eyes of 25 patients with PEX glaucoma and 40 eyes of 20 normal individuals. The MPOD measurements of the cases were performed in the MPOD mode of the fundus fluorescein angiography (Carl Zeiss Visucam Meditec, Germany) device while the pupils were in dilated status. RNFL and GCL++ measurements of all individuals included in the study were done by swept source optical coherence tomography (DRI Triton swept source optical coherence tomography; Topcon, Tokyo, Japan). Intraocular pressures of all three groups were measured by Applanation tonometer. The relationship between MPOD, RNFL and GCL++ values were examined. Patients with additional ophthalmic disease, intraocular surgery, history of chronic drug use, and smokers were excluded in the study. MPOD mean and MPOD max values were significantly higher in patients with PEX glaucoma than POAG and control group (p < 0.05). MPOD mean and MPOD max measurements were not different when compared to POAG patients and control group (p > 0.05). RNFL and GCL++ measurements were found significantly thinner in patients with POAG and PEX glaucoma compared to the control group (p < 0.001). There was no correlation between MPOD values and RNFL or GCL++. MPOD max values show a very high correlation with age in a statistically significant positive direction (r = 0.90, p < 0.001). The average age of PEX glaucoma group was higher than the control group (p = 0.006). There was no age difference between the PEX glaucoma group and the POAG group (p > 0.05). Also, there was no difference in age between POAG and control groups. In POAG and PEX glaucoma groups, mean intraocular pressure values are significantly higher than the control group. In our study, no MPOD change was observed in the POAG group, while a statistically significant increase in MPOD was found in the PEX glaucoma group. As a result of these findings, we think that PEX syndrome also affects the posterior segment. Well-organized, large, prospective, and randomized studies should be developed for preventive treatment to the negative effects of PEX syndrome on all eye tissues.

Effects of Lutein Supplementation in Japanese Patients with Unilateral Age-Related Macular Degeneration: The Sakai Lutein Study

This prospective randomized double-masked study investigated the effects of 20 mg lutein supplementation with two different capsules (beeswax or glycerol fatty acid esters) for 6 months on the fellow eyes of 39 Japanese patients with unilateral age-related macular degeneration, and assessed the factors associated with baseline plasma lutein concentration via lifestyle interviews. Macular pigment optical density (MPOD), determined with the two-wavelength autofluorescence method, increased over time in the beeswax group (ANOVA, p = 0.0451), although the increase from 3 months to 6 months was only marginally significant. No significant increase was observed in the glycerol fatty acid esters group (ANOVA, p = 0.7396). Plasma lutein concentrations significantly increased at 3 and 6 months from baseline in both groups (both p < 0.01). In a multiple regression model, age was negatively associated with higher plasma lutein concentration (p = 0.0305), while consumption of green vegetables was positively associated with baseline plasma lutein concentration (p = 0.0322). In conclusion, a significant increase in MPOD was not fully confirmed with 6 months intake duration despite a significant increase in plasma lutein concentrations. Consumption of green vegetable was confirmed to be associated with plasma lutein concentration after adjusting for other potential factors including age.

Practical application of ophthalmic nutraceuticals in patients with dry form of age-related macular degeneration

To conduct a placebo-controlled clinical monitoring of visual functions in patients with dry AMD while taking a drug Complex that corresponds to the AREDS 2 formula. The study included 90 people in 3 equivalent parallel groups, two of which were represented by patients with AMD who took the Complex for 3-6 months or Placebo for 3 months. The third group included healthy subjects of the same age. In addition to standard eye examination, participants underwent evaluation of the macular pigment optical density (MPOD), spatial-frequency contrast sensitivity (CS), photostress test, and reading parameters on the Salzburg Reading Desk device. The changes of blood plasma antioxidant activity (AOA) were also evaluated in the main group. By day 90 of the study, patients of the main group showed statistically significant (p<0.001) growth of MPOD from 0.24±0.13 to 0.32±0.1, reduction of photostress recovery time from 68.2±17.8 to 57.3±17.5 seconds, improvement of high-spatial-frequency CS - from 25.0±8.2 to 30.6±6.8 dB, increase of near visual acuity logMAR from 0.22±0.04 to 0.19±0.03 and reading speed, and decrease of reading mistakes. Statistically significant (p<0.05) reduction of in AOA was seen during the observation period from 1.52±0.16 to 1.68±0.16. Patients of the main group who received the Complex for 180 days demonstrated additional improvements of visual functions. The drug Complex corresponding to the AREDS 2 formula contributes to a significant increase in MPOD, improvements of visual functions and overall antioxidant status of patients, which confirms the feasibility of its use in patients with dry AMD.

Effects of lutein supplementation in age-related macular degeneration.

The purpose of this meta-analysis was to evaluate the effects of lutein supplementation on macular pigment optical density (MPOD) in randomized controlled trials involving patients with age-related macular degeneration (AMD). A comprehensive search of the literature was performed in PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and Wan Fang database through December 2018. Nine randomized controlled trials involving 920 eyes (855 with AMD) were included. Meta-analysis suggested that lutein supplementation (10 or 20 mg per day) was associated with an increase in MPOD (mean difference (MD) 0.07; 95% confidence interval (CI) 0.03 to 0.10), visual acuity (MD 0.28; 95%CI 0.06 to 0.50) and contrast sensitivity (MD 0.26; 95%CI 0.22 to 0.30). Stratified analyses showed the increase in MPOD to be faster and greater with higher dose and longer treatment. The available evidence suggests that dietary lutein may be beneficial to AMD patients and the higher dose could make MPOD increase in a shorter time.

Macular pigment density variation after supplementation of lutein and zeaxanthin using the Visucam® 200 pigment module: Impact of age-related macular degeneration and lens status

To assess the evolution of macular pigment optical density (MPOD) following supplementation with various macular formulations obtained with the Visucam® 200, and to study the factors affecting MPOD measurements. In this prospective, randomized, double-masked multicenter study, patients were divided into 2 groups: group A (patients without retinal pathology who underwent cataract surgery 1 month previously) and group B (patients with neovascular age-related macular degeneration [AMD] in one eye). In each group, half of the patients were randomly assigned to receive a food supplementation either with or without carotenoids (5mg of Lutein and 1mg of Zeaxanthin). Outcome measures included MPOD responses obtained with the Visucam® 200 for one year. In total, 126 subjects (52 men, 74 women) with a mean age of 75.3±7.61 years were enrolled. Mean MPOD values at the time of inclusion were statistically lower in group A (0.088 density unit [DU]) compared to group B (0.163 DU, P<0.05). No statistically significant increase in MPOD was noted in either group, even after discontinuation of the supplementation. By multiple regression analysis, age, female gender, lens status and the presence of AMD seemed to significantly affect MPOD measurements. No significant improvement in MPOD seems to be detected with the Visucam® 200 after carotenoid supplementation. The MPOD measurement seems to be highly affected by cataract extraction and the presence of AMD.

Lutein, Zeaxanthin and Meso-zeaxanthin Supplementation Associated with Macular Pigment Optical Density.

The purpose of this study was to evaluate the effects of lutein, zeaxanthin and meso-zeaxanthin on macular pigment optical density (MPOD) in randomized controlled trials (RCTs) among patients with age-related macular degeneration (AMD) and healthy subjects. Medline, Embase, Web of Science and Cochrane Library databases was searched through May 2016. Meta-analysis was conducted to obtain adjusted weighted mean differences (WMD) for intervention-versus-placebo group about the change of MPOD between baseline and terminal point. Pearson correlation analysis was used to determine the relationship between the changes in MPOD and blood xanthophyll carotenoids or baseline MPOD levels. Twenty RCTs involving 938 AMD patients and 826 healthy subjects were identified. Xanthophyll carotenoids supplementation was associated with significant increase in MPOD in AMD patients (WMD, 0.07; 95% CI, 0.03 to 0.11) and healthy subjects (WMD, 0.09; 95% CI, 0.05 to 0.14). Stratified analysis showed a greater increase in MPOD among trials supplemented and combined with meso-zeaxanthin. Additionally, the changes in MPOD were related with baseline MPOD levels (rAMD = −0.43, p = 0.06; rhealthy subjects = −0.71, p < 0.001) and blood xanthophyll carotenoids concentration (rAMD = 0.40, p = 0.07; rhealthy subjects = 0.33, p = 0.05). This meta-analysis revealed that lutein, zeaxanthin and meso-zeaxanthin supplementation improved MPOD both in AMD patients and healthy subjects with a dose-response relationship.

Macular Pigment Optical Density and Measures of Macular Function: Test-Retest Variability, Cross-Sectional Correlations, and Findings from the Zeaxanthin Pilot Study of Response to Supplementation (ZEASTRESS-Pilot).

We report on the short-term test-retest baseline variability in macular function tests in ZEASTRESS-Pilot participants (n = 18), on their cross-sectional correlation with macular pigment optical density (MPOD), and on the effects of four months (FUV4) of 20 mg/day zeaxanthin (ZX), followed by a four-month washout (FUV8; n = 24, age 50–81 years old). Outcomes included: MPOD at 0.5 and 2.0 deg eccentricity (MPOD-0.5 and -2.0); contrast sensitivity (CS); pattern-reversal electroretinogram (PERG) amplitude; dark-adapted 650 nm foveal cone sensitivity (DA650-FCS); and 500 mn parafoveal rod sensitivity (DA500-PFRS). All measures of macular function showed close test-retest correlation (Pearson’s r range: 0.744–0.946) and low coefficients of variation (CV range: 1.13%–4.00%). MPOD correlated in a complex fashion with macular function. Following supplementation, MPOD-0.5 and MPOD-2.0 increased at both FUV4 and FUV8 (p ≤ 0.0001 for all measures). Continued, delayed MPOD increase and a small, but significant (p = 0.012), CS increase was seen at FUV8 only in females. PERGs increased significantly at FUV4 (p = 0.0006), followed by a partial decline at FUV8. In conclusion, following ZX supplementation, MPOD increased significantly. There was no effect on DA-650 FCS or DA-500 PFRS. Both CS and PERG amplitudes increased following supplementation, but the effect varied between males and females. Additional studies appear warranted to confirm and characterize further these inter-gender differences.

The effect of nutritional supplementation on the multifocal electroretinogram in healthy eyes.

Previous studies have demonstrated an increase in macular pigment optical density (MPOD) with lutein (L)-based supplementation in healthy eyes. However, not all studies have assessed whether this increase in MPOD is associated with changes to other measures of retinal function such as the multifocal ERG (mfERG). Some studies also fail to report dietary levels of L and zeaxanthin (Z). Because of the associations between increased levels of L and Z, and reduced risk of AMD, this study was designed to assess the effects of L-based supplementation on mfERG amplitudes and latencies in healthy eyes. Multifocal ERG amplitudes, visual acuity, contrast sensitivity, MPOD and dietary levels of L and Z were assessed in this longitudinal, randomized clinical trial. Fifty-two healthy eyes from 52 participants were randomly allocated to receive a L-based supplement (treated group), or no supplement (non-treated group). There were 25 subjects aged 18-77 (mean age ± SD; 48 ± 17) in the treated group and 27 subjects aged 21-69 (mean age ± SD; 43 ± 16) in the non-treated group. All participants attended for three visits: visit one at baseline, visit two at 20 weeks and visit three at 40 weeks. A statistically significant increase in MPOD (F = 17.0, p ≤ 0.001) and shortening of mfERG ring 2 P1 latency (F = 3.69, p = 0.04) was seen in the treated group. Although the results were not clinically significant, the reported trend for improvement in MPOD and mfERG outcomes warrants further investigation.

Long term effects of lutein, zeaxanthin and omega-3-LCPUFAs supplementation on optical density of macular pigment in AMD patients: the LUTEGA study

The primary objective of LUTEGA is to determine the long-term effect of a supplementation with fixed combination of lutein, zeaxanthin, omega-3-longchain-polyunsaturated-fatty-acids (O-3-LCPUFAs) and antioxidants on macular pigment optical density (MPOD) in patients with non-exudative age-related macular degeneration (AMD). The LUTEGA study is a double-blind, placebo-controlled clinical trial. 172 patients with non-exudative AMD were enrolled and randomized to three treatment arms. Supplementation included either once (dosage D1) or twice daily (dosage D2) of 10 mg L / 1 mg Z/ O-3-LCPUFAs (thereof 100 mg DHA, 30 mg EPA)/ antioxidants, or placebo (P). After best-corrected visual acuity (BCVA) test, blood sample was collected and MPOD was measured using the 1-wavelength-reflection method and recording reflection images at 480 nm (modified Visucam(NM/FA), Carl Zeiss Meditec, Germany). During 1 year of intervention, AMD patients were followed up after 1, 3, 6 and 12 months. 145 AMD patients (D1 = 50, D2 = 55, P = 40) completed the study. After 12 months of intervention, the MPOD parameters (volume, area, maxOD, meanOD) increased significantly in treatment arms D1 and D2 (p < 0.001). Volume of MPOD showed the highest within-group difference and increased significantly in D1 and D2, and decreased significantly in P (p = 0.041). Between-group comparison of absolute changes of all MPOD parameters were significantly different between D1 and P as well as D2 and P with p < 0.001 at end point (t = 12). BCVA, measured in log MAR, improved in D1 and in D2 (p < 0.001). After 12 months of intervention, the mean improvement in BCVA was significant in D2 (p = 0.006) and D1 (p = 0.038) compared to P. The supplementation of L, Z, O-3-LCPUFAs and antioxidants resulted in considerable increase in MPOD. There was no difference in accumulation of MPOD between both dosages. Thus, we believe that the used supplementation with L and Z seems to reach a saturation level in retinal cell structure. Additionally, the constant supplementation of L, Z, O-3-LCPUFAs and antioxidants in AMD patients seems to be useful, because MPOD reduces without supplementation. We conclude that the supplementation caused an increase of MPOD, which results in an improvement and stabilization in BCVA in AMD patients. Thus, a protective effect on the macula in AMD patients is assumed.

The Impact of Macular Pigment Augmentation on Visual Performance Using Different Carotenoid Formulations

To investigate changes in macular pigment optical density (MPOD) and visual performance following supplementation with different macular carotenoid formulations. Thirty-six subjects (19 male, 17 female; mean SD, age 51 13 years) were recruited into this single-masked placebo-controlled study, and were randomly assigned to one of the following three intervention (supplementation) groups: (1) group 1 (20 mg lutein [L] and 2 mg zeaxanthin [Z]); (2) group 2 (10 mg L, 2 mg Z, and 10 mg meso-zeaxanthin [MZ]); and group 3 (placebo). Outcomes measures included visual performance and MPOD response. Data were collected at baseline, at 3 months, and at 6 months. At 3 and 6 months, a statistically significant increase in MPOD was found at all eccentricities (other than the most peripheral 3° location) in group 2 (P < 0.05 for all), whereas no significant increase in MPOD was demonstrable at any eccentricity for subjects in groups 1 and 3. Statistically significant improvements in visual performance measures including visual acuity and contrast sensitivity with and without glare were observed for group 2 only. Only mesopic contrast sensitivity at one spatial frequency improved significantly by 6 months (P < 0.05) for group 1. No improvements in any parameters of visual performance were observed for subjects supplemented with placebo (P > 0.05 for all). These results suggest that supplementation with all three macular carotenoids potentially offered advantages over preparations lacking MZ, both in terms of MPOD response and visual performance enhancement.

The Heritability of Macular Response to Supplemental Lutein and Zeaxanthin: A Classic Twin Study

Antioxidant supplements may reduce age-related macular degeneration (AMD) progression. The macular carotenoids are of particular interest because of their biochemical, optical, and anatomic properties. This classic twin study was designed to determine the heritability of macular pigment (MP) augmentation in response to supplemental lutein (L) and zeaxanthin (Z).A total of 322 healthy female twin volunteers, aged 16-50 years (mean 40 ± 8.7) was enrolled in a prospective, nonrandomized supplement study. Macular pigment optical density (MPOD) measurements using two techniques (2-wavelength fundus autofluorescence [AF] and heterochromatic flicker photometry [HFP]), and serum concentrations of L and Z, were recorded at baseline, and at 3 and 6 months following daily supplementation with 18 mg L and 2.4 mg Z for a study period of 6 months.At baseline, mean MPOD was 0.44 density units (SD 0.21, range 0.04-1.25) using HFP, and 0.41 density units (SD 0.15) using AF. Serum L and Z levels were raised significantly from baseline following 3 months' supplementation (mean increase 223% and 633%, respectively, P < 0.0001 for both), with no MPOD increase. After 6 months' supplementation, a small increase in MPOD was seen (mean increase 0.025 ± 0.16, P = 0.02, using HFP). Subdivision of baseline MPOD into quartiles revealed that baseline levels made no difference to the treatment effect. Genetic factors explained 27% (95% confidence interval [CI] 7-45) of the variation in MPOD response. Distribution profiles of macular pigment did not change in response to supplementation.MPOD response to supplemental L and Z for a period of 6 months was small (an increase over baseline of 5.7% and 3.7%, measured using HFP and AF, respectively), and was moderately heritable. Further study is indicated to investigate the functional and clinical impact of supplementation with the macular carotenoids.

Effects of Lutein Supplementation on Macular Pigment Optical Density and Visual Acuity in Patients with Age-Related Macular Degeneration

There is evidence from several large-scale clinical trials that reduced intake of lutein, a major component of the macular pigment, is a risk factor for the development of AMD. In the present study (LISA; Lutein Intervention Study Austria) it was hypothesized that lutein supplementation increases macular pigment optical density (MPOD). In addition, an investigation was conducted into whether lutein supplementation improves visual acuity (VA) and macular function (mean differential light threshold; MDLT), as assessed with microperimetry. One hundred twenty-six patients with AMD (AREDS [Age-related Eye Disease Study] stages 2, 3, and 4) were included in this randomized (2:1), placebo-controlled, double-masked parallel group study. Lutein or placebo was administered for 6 months. MPOD was measured with a custom-built reflectometer. VA was assessed with ETDRS (Early Treatment Diabetic Retinopathy Study) charts, and MDLT was assessed with a microperimeter. Lutein significantly increased MPOD by 27.9% ± 2.9% (P < 0.001 versus placebo). No significant effect of lutein supplementation on MDLT or VA was seen, although a tendency toward an increase was seen for both parameters (MDLT, P = 0.096 versus placebo; VA, P = 0.070 versus placebo). A significant correlation was found, however, between the increase in MPOD after 6 months and the increase in MDLT after 6 months (r = 0.25, P = 0.027), as well as between the increase in MPOD after 6 months and the increase in VA after 6 months (r = 0.27, P = 0.013). The present study demonstrates that lutein supplementation increases MPOD, as assessed with an objective The correlation between the change in MPOD and the change in VA and MDLT indicates that patients who show a pronounced increase in MPOD also benefit in terms of visual function. (ClinicalTrials.gov number, NCT00879671.).

The impact of macular pigment augmentation on visual performance in normal subjects: COMPASS

This study was conducted to investigate whether augmentation of macular pigment (MP) enhances visual performance (VP). 121 normal subjects were recruited. The active (A) group consumed 12 mg of lutein (L) and 1 mg of zeaxanthin (Z) daily. MP optical density (MPOD) was assessed by customized heterochromatic flicker photometry. VP was assessed as best corrected visual acuity (BCVA), mesopic and photopic contrast sensitivity (CS), glare disability, photostress, and subjective visual function. Subjects were assessed at baseline; 3; 6; 12 months (V1, V2, V3 and V4, respectively). Central MPOD increased significantly in the A group ( p < 0.05) but not in the placebo group ( p > 0.05). This statistically significant increase in MPOD in the A group was not, in general, associated with a corresponding improvement in VP ( p > 0.05, for all variables), with the exception of a statistically significant time/treatment effect in “daily tasks comparative analysis” ( p = 0.03). At V4, we report statistically significant differences in mesopic CS at 20.7 cpd, mesopic CS at 1.5 cpd under high glare conditions, and light/dark adaptation comparative analysis between the lower and the upper MP tertile groups ( p < 0.05) Further study into the relationship between MP and VP is warranted, with particular attention directed towards individuals with low MP and suboptimal VP.

Augmentation of Macular Pigment following Implantation of Blue Light–Filtering Intraocular Lenses at the Time of Cataract Surgery

(Photo)-oxidative stress is believed to play a role in the pathogenesis of age-related macular degeneration (AMD), with the threshold for retinal damage being lowest for short-wavelength (blue) light. Macular pigment (MP), consisting of the carotenoids lutein (L), zeaxanthin (Z) and meso-Z, has a maximum absorption at 460 nm and protects the retina from (photo)-oxidative injury. This study was designed to investigate whether the blue light-filtering properties of the Alcon AcrySof Natural intraocular lens (ANIOL) implanted during cataract surgery affects MP optical density (MPOD). Forty-two patients scheduled for cataract surgery were recruited for the study. These patients all had a preoperative best corrected visual acuity rating (BCVAR) of at least 0.5 (logMAR) in the study eye. The patients were randomized to have either the standard Alcon AcrySof three-piece acrylic intraocular lens (AIOL) (controls) or the ANIOL implanted at the time of cataract surgery. The spatial profile of MPOD (i.e., at 0.25 degrees, 0.5 degrees, 1.0 degrees, and 1.75 degrees eccentricity) was measured with customized heterochromatic flicker photometry (cHFP) 1 week before and 1 week after surgery, and at 3, 6, and 12 months after surgery. Serum concentrations of L and Z were also measured at each study visit. There was a highly significant and positive correlation between all MPODs (e.g., at 0.25 degrees) recorded 1 week before and after surgery in eyes with an AIOL implant (r = 0.915, P < 0.01; paired samples t-test, P = 0.631) and in those ANIOL implants (r = 0.868, P < 0.01; paired samples t-test, P = 0.719). Average MPOD across the retina increased significantly with time (after 3 months) in the ANIOL group (repeated-measures, general linear model, P < 0.05), but remained stable in the AIOL group (repeated-measures, general linear model, P > 0.05). There were no significant time or lens effects observed for serum L over the study period (P > 0.05). There was a significant time effect for serum Z over the study period (P < 0.05), but not a significant time/lens interaction (P > 0.05). Customized HFP can reliably measure the MPOD spatial profile in the presence of lens opacity, and cataract surgery does not artifactually alter MPOD readings. This study also provides evidence that implanting an IOL that filters blue light is associated with augmentation of MPOD in the absence of raised serum concentrations of L and Z. However, further and longitudinal study is needed to assess whether the observed increase in MPOD after implantation of blue-filtering IOLs is associated with reduced risk of AMD development and/or progression.

Lutein supplementation ‐ the rationale

Abstract Purpose Photo‐oxidation is believed to play a role in age‐related macular degeneration (AMD). Macular pigment (MP), consisting of lutein (L), zeaxanthin (Z) and meso‐Z, protects the retina from photo‐oxidative damage. We review this rationale and critically appraise the current evidence‐base germane to the use of supplements containing the macular carotenoids in patients with, or at risk of developing, AMD. Methods The evidence supporting a role for MP in the prevention of AMD is primarily available from observational studies and interventional (supplementation) studies. We present data from the following observational and interventional studies: Age‐Related Eye Disease Study (AREDS, I and II); Lutein Antioxidant Supplementation Trial (LAST); LUtein Nutrition effects measured by Autofluorescence (LUNA); Carotenoids in Age‐Related MAculopathy (CARMA). Results The AREDS I demonstrated that patients with AMD exhibited a 25% risk reduction in progression to advanced AMD when supplemented with zinc plus antioxidants. The LAST reported that visual function improved with L supplementation alone, or with L supplementation in combination with other antioxidants. The LUNA study reported a significant increase in MP optical density with 12 mg L and 1 mg Z, combined with co‐antioxidants (p &gt; 0.05). Conclusion In conclusion, we await the outcomes of several randomized controlled trials before a truly meaningful comment can be made upon the potential beneficial effects of supplemental L, Z and meso‐Z in patients with AMD. However, the benefits of the macular carotenoids, if any, relate to the ability of these compounds to protect against chronic and cumulative retinal damage and, therefore, the putative protective effect of this pigment may need to be exerted in the young and middle age.

LAST II: Differential temporal responses of macular pigment optical density in patients with atrophic age-related macular degeneration to dietary supplementation with xanthophylls

Background Age-related macular degeneration (ARMD) is the leading cause of vision loss in aging Western societies. The objective of the Lutein Antioxidant Supplementation Trial (LAST) was to determine whether specific dietary interventions increased macular pigment optical density (MPOD) and visual function in patients with atrophic ARMD. The current objective of LAST II is to discern those specific characteristics that increase MPOD, i.e., that might differentiate a responder from a nonresponder. Methods The LAST study was a prospective, 12-month, randomized, double-masked, placebo-controlled trial conducted at an urban midwestern Veterans Administation Hospital from August 1999 to May 2001. Ninety patients with atrophic ARMD entered the study and were assigned randomly to 1 of 3 groups. Patients in group 1 received 10 mg lutein; in group 2, 10 mg lutein in combination with vitamins, minerals, and antioxidants; and in group 3, maltodextrin placebo. Changes in macular MPOD over time were evaluated. Characteristics potentially influencing MPOD included age, weight (body mass index), initial baseline values of macular pigment, and combining xanthophylls with other nutrients. Results MPOD increased with supplementation and declined slightly without supplementation (regression slopes not equal to zero in supplemented groups, P < 0.02). The highest increases in MPOD over time occurred in patients with lower baseline values of MPOD. Statistically significant increases in MPOD density were observed in the lutein group for patients with baseline MPOD ≤0.3 optical density units and up to 0.2 optical density units in the lutein plus antioxidant group. Further analysis found that none of the subjects’ eyes in the lowest quartile of baseline MPOD were in the lowest quartile for change in MPOD. Conclusion Noteworthy is the observation that those individuals with lowest MPOD, and in greatest need of supplementation, were also most likely to benefit from either the lutein or the lutein plus antioxidant supplementation. For those individuals who responded to supplementation, their macular pigment optical density had not ceased to increase at 12 months’ duration of supplementation. The inference is that if a deficiency in macular pigment optical density is accurately diagnosed, effective interventions should be able to re-establish this prophylactic barrier.

Changes in macular pigment optical density and serum concentrations of its constituent carotenoids following supplemental lutein and zeaxanthin: The LUNA study

Macular pigment (MP), consisting of lutein (L) and zeaxanthin (Z), is believed to protect the retina from photo-oxidative damage. The current study investigates, in terms of MP optical density (MPOD) and serum concentrations of its constituent carotenoids, response to supplemental L and Z, and co-antioxidants. An intervention (I) group, consisting of 108 subjects (mean [±SD] age: 71.5 [±7.1] years), of which 92.6% exhibited features of age-related macular degeneration (AMD), received a daily supplement consisting of 12 mg L and 1 mg Z, both provided as ester 120 mg vitamin C, 17.6 mg vitamin E, 10 mg zinc, 40 μg selenium (Ocuvite Lutein™) for a period of 6 months. MPOD was measured, by 2-wavelength autofluorescence (AF), on five occasions during the period of supplementation, and once again 3 months following discontinuation of the supplement. A control (C) group of 28 subjects (mean [±SD] age: 71.0 [±8.1] years), who received no dietary supplementation or modification, was examined at baseline and once again after a mean of 29.4 (±9.3) weeks. At baseline, mean (±SD) MPOD (at 0.5°) was 0.504 (±0.197) and 0.525 (±0.189) in the I and C groups, respectively. There was a statistically significant increase in MPOD (at 0.5°) for the I group (0.1 [±0.009]; p < 0.0008), whereas no significant increase was seen in the C group (0.03 [±0.02]; p > 0.05), over the period of supplementation. In order to classify supplemented subjects into quartiles, in terms of MPOD response, we calculated the difference between MPOD (at 0.5°) at visit 6 and at baseline (visit 1). Quartile 1 (the “non-responder” quartile) displayed no increase in MPOD (at 0.5°), in spite of rises seen in serum concentrations of L and Z. The three “responder” quartiles reached similar final plateaus of MPOD (at 0.5°), reflected in final mean (±SEM) values of 0.59 (±0.04) optical density unit (ODU), 0.64 (±0.03) ODU and 0.64 (±0.03) ODU for quartiles 2, 3 and 4, respectively. Subjects with low baseline MPOD were more likely to exhibit a dramatic rise in MPOD, or to exhibit no rise in MPOD, in response to supplements than subjects with medium to high baseline MPOD values. Supplementation with 12 mg L and 1 mg Z, combined with co-antioxidants, resulted in an increase of MPOD at 0.5° eccentricity in a majority of subjects, including those afflicted with AMD. However, there remains a substantial proportion of subjects for whom, in spite of rises in serum concentrations of L and Z in these subjects, MPOD augmentation in response to supplemental L, Z and co-antioxidants could not be detected over the study period, thus indicating that intestinal malabsorption of these carotenoids is not responsible for the lack of a macular response to such supplements. Further, our results suggest that saturable mechanisms play a role in the retinal capture and/or stabilisation of the macular carotenoids.