Lutein supplementation over a one-year period in early AMD might have a mild beneficial effect on visual acuity: the CLEAR study.

PURPOSE: We investigated the effect of daily supplementation with lutein (L) capsules on macular pigment optical density (MPOD) and visual acuity (VA) in patients with early age-related macular degeneration (AMD). METHODS: A randomized, double-blind, placebo-controlled, two-center investigation of the effects of L supplementation in early AMD was conducted. The duration of the trial was 12 months. The centers were Manchester, United Kingdom and Maastricht, the Netherlands. L capsules (10 mg Ester) or a placebo (P) were taken daily. There were 72 patients (mean age 70.5 ± 8.7) assigned randomly to either L (n = 36) or P (n = 36) groups. MPOD using a flicker-based technique (MPS9000) and best corrected VA (LogMAR) were measured at the beginning and at 4-month intervals over the duration of the 12-month supplementation period. Blood serum samples were collected to monitor compliance. RESULTS: At the end of the trial, an overall increase in the mean MPOD level was found for the L group from 0.38 ± 0.19 to 0.53 ± 0.22 optical density (OD) units. According to a mixed design ANOVA, this was statistically significant (P < 0.001). No change in MPOD was found for the P group. There was no significant change in VA in the L group (n = 36). The P group (n = 36) showed a statistically significant deterioration from 0.05 ± 0.13 to 0.09 ± 0.13 (P < 0.05). When comparing the change in VA over the supplementation period, there was a significant difference between the two groups (P < 0.05). To avoid ceiling effects, 2 subgroups of patients with VA worse than 0.06 at baseline were reanalyzed. In the L subgroup (n = 19) a mean improvement in VA from 0.23 ± 0.12 at baseline to 0.16 ± 0.10 at visit 4 was observed (P < 0.05). In the P subgroup (n = 14), there was a small deterioration from 0.18 ± 0.13 to 0.19 ± 0.12 (P = 0.70). The improvement in VA in the L subgroup was compared to the deterioration in VA in the P group and this effect reached statistical significance (P < 0.05). CONCLUSIONS: L supplementation increases MPOD levels in early stage AMD patients. According to the VA measurements, the progress of the disease might be slowed in some patients with augmented levels of MP. (ClinicalTrials.gov number NCT01042860.).

The association between macular pigment optical density and CFH, ARMS2, C2/BF, and C3 genotype.

Age-related macular degeneration (AMD) is the most common cause of blindness in older people in developed countries, and risk for this condition may be classified as genetic or environmental, with an interaction between such factors predisposing to this disease. This study investigated the relationship between AMD risk genes, macular pigment optical density (MPOD), which may protect against AMD, and serum concentrations of the macular carotenoids, lutein (L) and zeaxanthin (Z). This was a cross-sectional study of 302 healthy adult subjects. Dietary intake of L and Z was assessed by food frequency questionnaire, and MPOD was measured by customized heterochromatic flicker photometry. We also calculated MPOD Area as the area of MP under the spatial profile curve, to reflect MP across the macula. Serum L and Z were measured by HPLC. Genotyping of tag SNPs in the genes CFH, ARMS2, C3, C2 and BF was undertaken with multiplex polymerase chain reaction (PCR) and primer extension methodology (ABI Snapshot, ABI Warrington UK) on DNA extracted from peripheral blood. The mean ± SD (range) age of the subjects in this study was 48 ± 11 (21-66) years. There was a statistically significant association between CFH genotype and family history of AMD, with subjects having two non-risk CFH haplotypes (n = 35), or one non-risk and one protective CFH haplotype (n = 33), being significantly more likely to have a negative family history of AMD (Pearson Chi square: p = 0.001). There was no significant association between the AMD risk genes investigated and either MPOD (One way ANOVA: p > 0.05) or serum concentrations of L or Z (One way ANOVA: p > 0.05, for both). Subjects who were homozygous for risk alleles of both CFH and ARMS2 (n = 4) had significantly lower MPOD at 0.5° and 1° retinal eccentricity (Independent samples t test: p < 0.05) and lower MPOD Area which approached statistical significance (Independent samples t test: p = 0.058), compared to other subjects (n = 291). In conclusion, this study did not detect an association between individual AMD risk genotypes and the putatively protective MP, or serum concentrations of its constituent carotenoids. However, the combination of homozygous risk alleles at both CFH and ARMS2 loci was associated with significantly lower MPOD centrally, despite comparable serum concentrations of the macular carotenoids. These findings suggest that the maculae of subjects at very high genetic risk of AMD represent a hostile environment for accumulation and/or stabilization of MP.

Determinants of macular pigment optical density and its relation to age-related maculopathy: results from the Muenster Aging and Retina Study (MARS).

PURPOSE: The controversial protective effect of macular pigment (MP), consisting of lutein (L) and zeaxantin (Z), in age-related maculopathy (ARM) and its late-stage, age-related macular degeneration (AMD) is discussed. Determinants of MP optical density (MPOD) and its relation to ARM were investigated. METHODS: MPOD was accessed at eccentricities of 0.5° and 2.0° from the fovea in 369 participants in the 2.6-year follow-up examination of the prospective Muenster Aging and Retina Study using dual-wavelength analysis of autofluorescence images. ARM was graded from standardized fundus photographs according to the International Classification System. RESULTS: MPOD at 0.5° and 2.0° between pairs and within single eyes was strongly correlated (P < 0.001). Smoking and body mass index showed moderately inverse associations with MPOD at 2.0°, and age was positively related to MPOD at both eccentricities. Serum L, measured at the baseline examination, was significantly associated with MPOD measured at follow-up. Likewise, use of L/Z-containing supplements raised MPOD. Crude mean MPOD increased with ascending stage of ARM. However, adjustment for influential factors and exclusion of L supplement users removed differences of mean MPOD between ARM stages. Considering further the accompanying eye, study eyes with ARM had significantly higher MPOD when the contralateral eye had AMD. CONCLUSIONS: MPOD levels showed a high degree of intraindividual concordance and interindividual variability. Long-standing serum L levels, and in particular L supplementation, were the strongest determinants of MPOD. The hypothetical inverse association between MPOD and ARM stage was not confirmed.

Augmentation of macular pigment following supplementation with all three macular carotenoids: an exploratory study.

PURPOSE: At the macula, the carotenoids meso-zeaxanthin (MZ), lutein (L), and zeaxanthin (Z) are collectively referred to as macular pigment (MP). This study was designed to measure serum and macular responses to a macular carotenoid formulation. MATERIALS AND METHODS: Ten subjects were recruited into this study (five normal and five with early age-related macular degeneration [AMD]). Subjects were instructed to consume a formulation containing 7.3 mg of MZ, 3.7 mg of L, and 0.8 mg of Z everyday over an eight-week period. The spatial profile of MP optical density (i.e., MPOD at 0.25 degrees , 0.5 degrees , 1 degrees , and 1.75 degrees ) was measured using customized heterochromatic flicker photometry, and a blood sample was collected at each study visit in order to analyze serum concentrations of MZ, L, and Z. RESULTS: There was a significant increase in serum concentrations of MZ and L after two weeks of supplementation (p < 0.05). Baseline serum carotenoid analysis detected a small peak eluting at the same time as MZ in all subjects, with a mean +/- SD of 0.02 +/- 0.01 micromol/L. We report significant increases in MPOD at 0.25 degrees , 0.5 degrees , 1 degree , and average MPOD across its spatial profile after just two weeks of supplementation (p < 0.05, for all). Four subjects (one normal and three AMD) who had an atypical MPOD spatial profile (i.e., central dip) at baseline had the more typical MPOD spatial profile (i.e., highest MPOD at the center) after eight weeks of supplementation. CONCLUSION: We report significant increases in serum concentrations of MZ and L following supplementation with MZ, L, and Z and a significant increase in MPOD, including its spatial profile, after two weeks of supplementation. Also, this study has detected the possible presence of MZ in human serum pre-supplementation and the ability of the study carotenoid formulation to rebuild central MPOD in subjects who have atypical profiles at baseline.

Measurement of macular pigment: Raman spectroscopy versus heterochromatic flicker photometry.

PURPOSE: There are several techniques for measuring macular pigment (MP) in vivo, of which Raman spectroscopy (RS) is a recently developed objective METHOD: This study reports the reproducibility, test-retest variability, and validity of RS MP readings, by comparing them with heterochromatic flicker photometry (HFP). METHODS: MP was measured with HFP and RS in 120 healthy subjects, and the latter technique was also used on two separate occasions in a sample of 20 subjects to investigate the intersessional variability of readings. Intrasessional reproducibility of RS MP measurements was also calculated. In addition, serum concentrations of lutein (L) and zeaxanthin (Z) were measured and correlated with both RS and HFP MP readings. RESULTS: Mean (+/-SD) MP in the right eye was 0.279 +/- 0.145 and 0.319 +/- 0.155 with RS and HFP, respectively. The differences between corresponding MP readings taken on RS and HFP lay within the Bland-Altman 95% limits of agreement for the two instruments in 93.6% and 94.4% of cases in the right and left eyes, respectively. Intrasessional reproducibility of RS readings, expressed as the coefficient of variation, was 8.42% +/- 7.12%. Ninety-five percent of MP readings taken with RS on two separate occasions lay within the 95% limits of agreement for the two sessions. A positive, but insignificant, relationship was observed between RS and HFP MP readings and serum concentrations of L and Z (RS, P = 0.356; HFP, P = 0.540). CONCLUSIONS: RS, an objective method of measuring MP levels in vivo, exhibits acceptable reproducibility and test-retest variability. The results demonstrated good correlation between RS and HFP measurements of MP, thus authenticating RS against a validated psychophysical technique of measuring MP. However, investigators should use only one of these instruments for the duration of any given study because of differences in the scientific rationale, and the factors that influence RS and HFP measurements of MP.

Macular pigment optical density in a midwestern sample.

OBJECTIVE: To assess the distribution of the macular pigments (MPs) lutein (L) and zeaxanthin (Z) in a healthy sample more representative of the general population than past studies and to determine which dietary factors and personal characteristics might explain the large interindividual differences in the density of these MPs. DESIGN: Prevalence study in a self-selected population. PARTICIPANTS: Two hundred eighty healthy adult volunteers, consisting of 138 men and 142 women, between the ages of 18 and 50 years, recruited from the general population. METHODS: MP optical density was measured psychophysically at 460 nm by use of a 1 degrees test field. Serum was analyzed for carotenoid and vitamin E content with reversed-phase high-performance liquid chromatography. Usual intakes of nutrients over the past year were determined by means of a food frequency questionnaire. MAIN OUTCOME MEASURES: MP optical density. RESULTS: Mean MP optical density measured 0.211 +/- 0.13, which is approximately 40% lower than the average reported in smaller, less representative studies. MP density was 44% lower in the bottom versus the top quintile of serum L and Z concentrations. Similarly, MP density was 33% lower in the bottom compared with the top quintile of L and Z intake. MP density was 19% lower in blue-grey-eyed subjects than in subjects with brown-black irises. When all variables were considered together in a general linear model of determinants of MP, statistically significant (P < 0.05) relationships were found between MP density and serum L and Z, dietary L and Z intake, fiber intake, and iris color. CONCLUSIONS: These data suggest that MP values in this healthy adult population are lower than in smaller select samples. Moreover, these data indicate that MP is related to serum L and Z, dietary L and Z intake, fiber intake, and iris color.

Influence of lutein supplementation on macular pigment, assessed with two objective techniques.

PURPOSE: Macular pigment (MP) may protect against age-related macular degeneration. This study was conducted to determine the extent of changes in the macular pigment density as a consequence of oral supplementation with lutein. A second purpose was to compare two objective measurement techniques. METHODS: In the first technique, reflectance maps were made with a scanning laser ophthalmoscope. Digital subtraction of log reflectance maps and comparison between the foveal area and a 14 degrees temporal site provided MP density estimates. In the second technique, spectral fundus reflectance of the fovea was measured with a fundus reflectometer and analyzed with a detailed optical model, to arrive at MP density values. Eight subjects participated in this study. They took 10 mg lutein per day for 12 weeks. Plasma lutein concentration was measured at 4-week intervals. RESULTS: After 4 weeks, mean blood level of lutein had increased from 0.18 to 0.90 microM. It stayed at this level throughout the intake period and declined to 0.28 microM 4 weeks after termination. Measurement of the density of MP showed a within-subject variation of 10% with MP maps and 17% with spectral reflectance analysis. MP density showed a mean linear 4-week increase of 5.3% (P: < 0.001) and 4.1% (P: = 0. 022), respectively. CONCLUSIONS: Supplementation with lutein significantly increased the density of the MP. Analyzing reflectance maps with a scanning laser ophthalmoscope provided very reliable estimates of MP.