The effect of lutein and zeaxanthin supplementation on metabolites of these carotenoids in the serum of persons aged 60 or older

PURPOSE: To investigate the effect of lutein supplementation at doses of 2.5, 5.0, and 10 mg/d for 6 months on distribution of these carotenoids and their metabolites in the serum of elderly human subjects, with and without age-related macular degeneration. To determine whether supplementation with lutein can interact with the serum levels of other dietary carotenoids, retinol, and alpha-tocopherol. METHODS: Forty-five subjects received daily supplements of lutein (containing 5% zeaxanthin) for 6 months and were followed up for another 6 months after supplementation. Blood was collected at various intervals and lutein, zeaxanthin, and their metabolites in the sera were quantified by normal-phase high-performance liquid chromatography (HPLC)-UV/visible detection. Other dietary carotenoids, retinol, and alpha-tocopherol were identified and quantified on a C18 reversed phase HPLC column. RESULTS: After 6 months of supplementation with 10 mg of lutein, the increases in the mean serum levels from baseline were: 210 to 1000 nM/L (P < 0.0001) for lutein and 56 to 95 nM/L (P < 0.0001) for zeaxanthin. Similarly, the mean concentrations (nM/L) of carotenoid metabolites increased from 49 to 98 (P < 0.0001) for 3-hydroxy-beta,epsilon-caroten-3'-one (3'-oxolutein); 31 to 80 (P < 0.0001) for 3'-hydroxy-epsilon,epsilon-caroten-3-one; and 19 to 25 (P < 0.0001) for epsilon,epsilon-carotene-3,3'-dione. The serum levels of these carotenoids gradually decline within 6 months after supplementation. CONCLUSIONS: The increase in the serum levels of lutein/zeaxanthin correlates with increases in the serum levels of their metabolites that have previously been identified in the ocular tissues. Elderly human subjects with and without AMD can safely take supplements of lutein up to 10 mg/d for 6 months with no apparent toxicity or side effects.     

Macular Pigment Imaging in AREDS2 Participants: An Ancillary Study of AREDS2 Subjects Enrolled at the Moran Eye Center

Purpose. Age-Related Eye Disease Study 2 (AREDS2) is a randomized, placebo-controlled study designed to determine whether supplementation with 10 mg of lutein and 2 mg of zeaxanthin per day can slow the rate of progression of age-related macular degeneration (AMD). Although some biomarkers of response to carotenoid supplementation such as serum concentrations are part of the AREDS2 protocol, measurement of carotenoid concentrations in the eye and other tissues is not. In this approved ancillary study, macular pigment optical density (MPOD), macular pigment distributions, and skin carotenoid levels at enrollment and at each annual visit were measured to assess baseline carotenoid status and to monitor response to assigned interventions. Methods. All subjects enrolled at the Moran Eye Center had MPOD and macular pigment spatial distributions measured by dual-wavelength autofluorescence imaging and total skin carotenoids measured by resonance Raman spectroscopy. Results. Baseline MPOD in enrolled subjects was unusually high relative to an age-matched control group that did not consume carotenoid supplements regularly, consistent with the high rate of habitual lutein and zeaxanthin consumption in Utah AREDS2 subjects prior to enrollment. MPOD did not correlate with serum or skin carotenoid measurements. Conclusions. Useful information is provided through this ancillary study on the ocular carotenoid status of AREDS2 participants in the target tissue of lutein and zeaxanthin supplementation: The macula. When treatment assignments are unmasked at the conclusion of the study, unique tissue-based insights will be provided on the progression of AMD in response to long-term, high-dose carotenoid supplementation versus diet alone. (ClinicalTrials.gov number, NCT00345176.).     

Application of Lutein and Zeaxanthin in nonproliferative diabetic retin

AIM: To compare serum Lutein and Zeaxanthin (L/Z) concentrations between patients with nonproliferative diabetic retinopathy (NDR) and normal subjects, and to explore the effect of L/Z supplementation on serum L/Z level and visual function in NDR patients METHODS: Subjects were divided into three groups: 30 NDR patients supplied with Lutein 6mg/d and Zeaxanthin 0.5mg/d for three months (DR Group), 30 NDR patients without L/Z supplementation (DR Control Group) and 30 normal subjects (Control Group). Serum L/Z concentrations were measured by liquid high-resolution chromatography (HPLC). Visual acuity was recorded at baseline, 1 month, 2 months and 3 months post initial supplementation. Serum L/Z concentration were measured at baseline, 1 month and 2 months post initial supplementation. Contrast sensitivity (CS) and fovea thickness were recorded at baseline and 3 months post initial supplementation. RESULTS: Mean serum lutein concentrations in DR group were 0.0686±0.0296μg/mL and zeaxanthin concentration was 0.0137±0.0059μg/mL. The L/Z level of DR group was significantly lower compared to the control group( lutein: 0.2302±0.1308μg/mL,zeaxanthin: 0.0456±0.0266μg/m,P = 0.000). The concentration of lutein and zeaxanthin in the DR control group at base line was 0.0714±0.0357μg/mL and 0.0119±0.0072μg/mL, respectively. There was no significant change of L/Z concentration in the DR control group during the study. Serum L/Z concentrations of DR group increased significantly after supplementation（F=109.124,P=0.000;F=219.207,P=0.000）.Visual acuity improved significantly after medication. Compared with pre-medication, the average CS values of 1.5cpd, 3cpd and 6cpd after three months increased significantly (P=0.030,0.013,0.008) and the foveal thickness decreased. (P=0.05) CONCLUSION: Serum L/Z concentrations in DR patients are significantly lower than those in normal subjects, and L/Z intake can improve the visual acuity, CS and macular edema in DR patients, suggesting that L/Z supplementation might be targeted as potential potential therapeutic agents in treating NDR.     

Effect of dietary zeaxanthin on tissue distribution of zeaxanthin and lutein in quail

PURPOSE: The xanthophyll carotenoids (lutein and zeaxanthin) are hypothesized to delay progression of age-related macular degeneration. The quail has a cone-dominant retina that accumulates carotenoids. The purpose of these experiments was to characterize the carotenoid composition of retina, serum, liver, and fat in quail and to determine whether dietary enrichment with zeaxanthin alters zeaxanthin or lutein concentrations in these tissues. METHODS: Quail were fed for 6 months with a commercial turkey diet (T group; n = 8), carotenoid-deficient diet (C- group; n = 8), or a carotenoid-deficient diet supplemented with 35 mg 3R,3'R-zeaxanthin per kilogram of food, (Z+ group; n = 8). Zeaxanthin was derived from Sphingobacterium multivorum (basonym Flavobacterium). Carotenoids in serum, retina, liver, and fat were analyzed by HPLC. RESULTS: As in the primate fovea, the retina accumulated zeaxanthin, lutein, and cryptoxanthin, and preferentially absorbed zeaxanthin (P < 0.005). In contrast, lutein was preferentially absorbed by liver (P < 0.01) and fat (P < 0.0001). In supplemented females, zeaxanthin increased approximately 4-fold in retina, and 74-, 63- and 22-fold in serum, liver, and fat, respectively. In males, zeaxanthin was elevated approximately 3-fold in retina, and 42-, 17-, and 12-fold in serum, liver, and fat, respectively. Birds fed the Z+ diet absorbed a higher fraction of dietary lutein into serum, but lutein was reduced in the retina (P < 0.05). CONCLUSIONS: Xanthophyll profiles in quail mimic those in primates. Dietary supplements of zeaxanthin effectively increased zeaxanthin concentrations in serum, retina, liver, and fat. The robust response to zeaxanthin supplementation identifies the quail as an animal model for exploration of factors regulating delivery of dietary carotenoids to the retina.     

Macular pigment and lutein supplementation in ABCA4-associated retinal degenerations

PURPOSE: To determine macular pigment (MP) optical density (OD) in patients with ABCA4-associated retinal degenerations (ABCA4-RD) and the response of MP and vision to supplementation with lutein. METHODS: Patients with Stargardt disease or cone-rod dystrophy and known or suspected disease-causing mutations in the ABCA4 gene were included. All patients had foveal fixation. MPOD profiles were measured with heterochromatic flicker photometry. Serum carotenoids, visual acuity, foveal sensitivity, and retinal thickness were quantified. Changes in MPOD and central vision were determined in a subset of patients receiving oral supplementation with lutein for 6 months. RESULTS: MPOD in patients ranged from normal to markedly abnormal. As a group, patients with ABCA4-RD had reduced foveal MPOD, and there was a strong correlation with retinal thickness. Average foveal tissue concentration of MP, estimated by dividing MPOD by retinal thickness, was normal in patients, whereas serum concentration of lutein and zeaxanthin was significantly lower than normal. After oral lutein supplementation for 6 months, 91% of the patients showed significant increases in serum lutein, and 63% of the patients' eyes showed a significant augmentation in MPOD. The retinal responders tended to be female and to have lower serum lutein and zeaxanthin, lower MPOD, and greater retinal thickness at baseline. Responding eyes had significantly lower baseline MP concentration than did nonresponding eyes. Central vision was unchanged after the period of supplementation. CONCLUSIONS: MP is strongly affected by the stage of ABCA4 disease leading to abnormal foveal architecture. MP could be augmented by supplemental lutein in some patients. There was no change in central vision after 6 months of lutein supplementation. Long-term influences of this supplement on the natural history of these macular degenerations require further study.     

叶黄素干预对早期年龄相关性黄斑变性患者视功能的影响

目的：探讨叶黄素干预对早期年龄相关性黄斑变性(age-related macular degeneration,AMD)患者视功能的影响。

方法：采用随机双盲空白对照的方法,将200例早期AMD患者随机分为叶黄素干预组(20mg/d)和安慰剂对照组。分别于基线、12、24、36、48wk进行问卷调查、血清叶黄素密度及视功能检查。

结果：叶黄素干预组12、24、36、48wk的血清叶黄素密度比安慰剂对照组高(P<0.05),血清叶黄素密度较基线升高(P<0.05)。叶黄素干预组24、48wk的对比敏感度(contrast sensitivity,CS)的低(3c/d)、中(6c/d)频段,黄斑色素光学密度(macular pigment optical density,MPOD),最佳矫正视力(best-spectacle corrected visual acuity,BCVA)高于安慰剂对照组(P<0.05); CS的低、中频段高于基线(P<0.05),MPOD、BCVA与基线比较差异无统计学意义(P>0.05)。

结论：叶黄素干预可改善早期AMD患者的视功能。     

Kurz- und mittelfristige Änderungen der makulären Pigmentdichte infolge der Supplementation mit Lutein und Zeaxanthin sowie Koantioxidanzien

Background

How long do the elevated concentrations of macular pigment persist after stopping supplementation with lutein and zeaxanthin?

Methods

One hundred eight (108) probands with and without age-related macular degeneration (68 female, 40 male, age 51–87 years) received a supplement containing 12 mg lutein and 1 mg zeaxanthin once per day (Ocuvite lutein) for 6 months. Analysis of macular pigment optical density (MPOD) was performed during the period of supplementation and again 3, 6, and 9 months following discontinuation of the supplement. A control group of 28 subjects received no dietary supplement.

Results

At baseline, the mean MPOD at 0.5° was 0.50 in the supplemented group. Following supplementation, values rose, and 3 months after discontinuation of supplementation the highest levels of MPOD0.5°(0.59 ODU) were detected (increase of +0.1 ODU, (p<0.001). Six months after supplement discontinuation, a slight decrease of mean MPOD0.5° appeared (to 0.54 ODU), followed again by a slight increase 3 months later (to 0.57 ODU). An increment of MPOD0.5° in the control group was not significant (0.03 ODU, p=0.15).

Discussion

Supplementation of lutein and zeaxanthin leads to an increase of MPOD0.5°. This effect outlasts the duration of intake, and 9 months after supplementation was stopped, the mean MPOD0.5° was still elevated compared with baseline levels. A longer follow-up subsequent to stopping supplementation might clarify whether the values decrease over time or whether a plateau of elevated MPOD levels is reached. High doses of lutein and zeaxanthin seem to be necessary to increase macular pigment density in the retina; afterwards, the amount of carotenoids needed to maintain high concentrations seems to be covered by daily food.     

Lutein improves visual function in some patients with retinal degeneration: a pilot study via the Internet.

PURPOSE: The purpose of this article is to examine the effects of lutein supplementation on visual acuity, central visual-field area, and subjective visual disturbances in retinitis pigmentosa (RP) and related retinal degenerations, in an international study population recruited via an Internet mailing list. METHODS: Sixteen participants (13 with RP, three with other retinal degenerations) completed a 26-week program of lutein supplementation (40 mg/day for 9 weeks, 20 mg/day thereafter); 10 participants also took 500-mg docosahexaenoic acid (DHA)/day, vitamin B complex, and digestive enzymes. Ten participants previously taking vitamin A and/or beta-carotene continued those supplements throughout the study. Participants self-tested their visual acuity on their computer screen and their central visual-field extent on a wall chart, weekly for 14 weeks, bi-weekly thereafter. RESULTS: Mean visual acuity improved by 0.7 dB and mean visual-field area by 0.35 dB. Improvements started 2 to 4 weeks after supplementation began, and plateaued at 6 to 14 weeks. Visual acuity gains were strongly correlated with eye color: 1.2 dB in seven blue-eyed participants, but 0.3 dB in seven dark-eyed participants. Participants who received previous supplements showed greater benefits in central visual-field area (0.55 dB) than those not receiving previous supplements (no change). No significant effects of age, sex, disease stage, or study supplement were found. CONCLUSIONS: Short-term vision improvements after lutein supplementation--previously reported in age-related macular degeneration--also occur in RP, especially in blue-eyed individuals; vitamin A may increase visual field benefits.     

Lutein and antioxidants in the prevention of age-related macular degeneration

Demographic developments in Europe and North America are causing an increase of age-related diseases. Age-related macular degeneration (AMD) is one of the leading causes of severe central visual acuity loss in elderly people and seems to be an economic problem, too. There is evidence that oxidative damage is an important factor for exacerbation of AMD. Macular pigment with its antioxidative effect may serve as"natural sunglasses" filtering the blue light acting as a possible source of photooxidative damage to the neurosensory retina. The macular pigment consists mostly of lutein and zeaxanthin. These micronutrients from the group of carotenoids, as is the case for vitamins (vitamins C, E, and beta-carotene), cannot be synthesized in mammals and that is the reason why the role of micronutrition or its supplementation and its correlation to AMD progression has been discussed for years.The results of currently published studies are often contradictory. At present there are no results from randomized controlled studies confirming that supplementation of lutein and zeaxanthin can reduce the risk for AMD. Several epidemiological studies investigating the impact of antioxidants and omega-3 fatty acids on the incidence of AMD provided conflicting results.Up to now, AREDS is the largest randomized controlled study investigating the effect of supplementation of antioxidants, zinc, and copper on the progression of AMD. AREDS showed a significant effect of this supplementation in some particular groups of patients with AMD. The supplementation of lutein and omega-3 fatty acids is not toxic but a positive effect has not been proven by randomized studies.     

Lutein und Antioxidantien zur Prävention der AMD

Demographic developments in Europe and North America are causing an increase of age-related diseases. Age-related macular degeneration (AMD) is one of the leading causes of severe central visual acuity loss in elderly people and seems to be an economic problem, too. There is evidence that oxidative damage is an important factor for exacerbation of AMD. Macular pigment with its antioxidative effect may serve as“natural sunglasses” filtering the blue light acting as a possible source of photooxidative damage to the neurosensory retina. The macular pigment consists mostly of lutein and zeaxanthin. These micronutrients from the group of carotenoids, as is the case for vitamins (vitamins C, E, and β-carotene), cannot be synthesized in mammals and that is the reason why the role of micronutrition or its supplementation and its correlation to AMD progression has been discussed for years. The results of currently published studies are often contradictory. At present there are no results from randomized controlled studies confirming that supplementation of lutein and zeaxanthin can reduce the risk for AMD. Several epidemiological studies investigating the impact of antioxidants and ω-3 fatty acids on the incidence of AMD provided conflicting results. Up to now, AREDS is the largest randomized controlled study investigating the effect of supplementation of antioxidants, zinc, and copper on the progression of AMD. AREDS showed a significant effect of this supplementation in some particular groups of patients with AMD. The supplementation of lutein and ω-3 fatty acids is not toxic but a positive effect has not been proven by randomized studies.     

Chronic ingestion of (3R,3'R,6'R)-lutein and (3R,3'R)-zeaxanthin in the female rhesus macaque

PURPOSE: To investigate how supplementation of the monkey's diet with high doses of lutein (L), zeaxanthin (Z), or a combination of the two affects the plasma levels and ocular tissue deposition of these carotenoids and their metabolites over time and to determine whether these high doses can cause ocular toxicity. METHODS: Eighteen female rhesus monkeys were divided into groups of control (n = 3 control), L-treated (n = 5, 9.34 mg lutein/kg and 0.66 mg zeaxanthin/kg), Z-treated (n = 5, 10 mg zeaxanthin/kg), and L/Z-treated (n = 5, lutein and zeaxanthin, each 0.5 mg/kg). After 12 months of daily supplementation, one control animal, two L-treated animals, two Z-treated animals, and all the L/Z-treated animals were killed. The rest of the monkeys were killed after an additional six months without supplementation. Plasma and ocular tissue carotenoid analyses, fundus photography, and retina histopathology were performed on the animals. RESULTS: Supplementation of monkeys with L and/or Z increased the mean plasma and ocular tissue concentrations of these carotenoids and their metabolites. The mean levels of L and Z in the retinas of the L- and Z-treated animals after 1 year increased significantly over baseline. High dose supplementation of monkeys with L or Z did not cause ocular toxicity and had no effect on biomarkers associated with kidney toxicity. CONCLUSIONS: The mean levels of L and Z in plasma and ocular tissues of the rhesus monkeys increase with supplementation and in most cases correlate with the levels of their metabolites. Supplementation of monkeys with L or Z at high doses, or their combination does not cause ocular toxicity.     

Macular pigment and lutein supplementation in retinitis pigmentosa and Usher syndrome.

PURPOSE. To determine macular pigment (MP) in patients with inherited retinal degeneration and the response of MP and vision to supplementation of lutein. METHODS. Patients with retinitis pigmentosa (RP) or Usher syndrome and normal subjects had MP optical density profiles measured with heterochromatic flicker photometry. Serum carotenoids, visual acuity, foveal sensitivity, and retinal thickness (by optical coherence tomography [OCT]) were quantified. The effects on MP and central vision of 6 months of lutein supplementation at 20 mg/d were determined. RESULTS. MP density in the patients as a group did not differ from normal. Among patients with lower MP, there was a higher percentage of females, smokers, and light-colored irides. Disease expression tended to be more severe in patients with lower MP. Inner retinal thickness by OCT correlated positively with MP density in the patients. After supplementation, all participants showed an increase in serum lutein. Only approximately half the patients showed a statistically significant increase in MP. Retinal nonresponders had slightly greater disease severity but were otherwise not distinguishable from responders. Central vision was unchanged after supplementation. CONCLUSIONS. Factors previously associated with lower or higher MP density in normal subjects showed similar associations in RP and Usher syndrome. In addition, MP in patients may be affected by stage of retinal disease, especially that leading to abnormal foveal architecture. MP could be augmented by supplemental lutein in many but not all patients. There was no change in central vision after 6 months of lutein supplementation, but long-term influences on the natural history of these retinal degenerations require further study.     

Reading ability after photodynamic therapy (PDT) for age-related macular degeneration (AMD) and for high myopia

BACKGROUND: A prospective uncontrolled follow-up of changes in reading ability after PDT with Verteporfin in patients with predominantly classic subfoveal choroidal neovascularization (CNV) due to AMD or high myopia was carried out. PATIENTS AND METHODS: A follow-up time of at least 6 months is documented for 48 patients with AMD and for 22 patients with high myopia. In addition to the usual clinical parameters the need for magnification was measured using standardized reading charts provided by the SZB.A need for magnification higher than 3.2-fold was defined as a severe loss in reading ability.PDT's were repeated every 3 months according to the usual guidelines. RESULTS: Before treatment, the mean reading acuity for patients with AMD was between 20/200 and 20/100.The average need for magnification was between 2.5-fold and 3.2-fold.Reading acuity, need for magnification and the percentage of patients with a need for magnification of 3.2-fold or less remained stable over a 6-12 months follow-up period.High myopic patients initially had a mean reading acuity of 20/200 and a need for magnification of 2.5-fold.After 9 months follow-up, reading acuity showed a mean improvement from 0.2 up to 0.3 ( p<0.05). There was also a trend towards improvement in the need for magnification and the percentage of patients with a need for magnification of 3.2-fold or less improved significantly from 68% to 78% ( p<0.05). CONCLUSION: Reading ability could be stabilized with PDT for predominantly classic subfoveal CNV in patients with high myopia or AMD for at least 9-12 months.The risk of developing a severe loss in reading ability (need for magnification >3.2-fold) was significantly reduced in high myopia and was stable over time in AMD.     

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 microg selenium (Ocuvite Luteintrade mark) 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 degrees) 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 degrees) 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 degrees) at visit 6 and at baseline (visit 1). Quartile 1 (the "non-responder" quartile) displayed no increase in MPOD (at 0.5 degrees), 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 degrees), 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 degrees 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.     

Nutritional manipulation of primate retinas, I: effects of lutein or zeaxanthin supplements on serum and macular pigment in xanthophyll-free rhesus monkeys

PURPOSE: The xanthophylls lutein (L) and zeaxanthin (Z) are the primary components of macular pigment (MP) and may protect the macula from age-related degeneration (AMD). In this study, L or Z was fed to rhesus monkeys reared on xanthophyll-free diets to follow the accumulation of serum carotenoids and MP over time. METHODS: Eighteen rhesus monkeys were fed xanthophyll-free semipurified diets from birth until 7 to 16 years. The diets of six were then supplemented with pure L and six with pure Z at 3.9 micromol/kg per day (2.2 mg/kg per day) for 24 to 56 weeks. At baseline and 4- to 12-week intervals during supplementation, serum carotenoids were measured by HPLC, and MP density was estimated by two-wavelength reflectometry. Serum carotenoids and MP were also measured in monkeys fed a stock diet. RESULTS: Monkeys fed xanthophyll-free diets had no L or Z in serum and no detectable MP. During supplementation, serum L or Z increased rapidly over the first 4 weeks and from 16 weeks onward maintained similar levels, both several times higher than in stock-diet-fed monkeys. The central peak of MP optical density increased to a relatively steady level by 24 to 32 weeks in both L- and Z-fed groups. Rhesus monkeys fed a stock diet had lower blood concentrations of L than those found in humans and other nonhuman primates. CONCLUSIONS: Rhesus monkeys respond to either dietary L or Z supplementation with increases in serum xanthophylls and MP, even after life-long xanthophyll deficiency. These animals provide a potential model to study mechanisms of protection from AMD.     

Supplementation with the carotenoids lutein or zeaxanthin improves human visual performance

BACKGROUND: Macular pigment (MP) is found in diurnal primate species when vision spans a range of ambient illumination and is mediated by cone and rod photoreceptors. The exact role of MP remains to be determined. In this study we investigate two new hypotheses for possible MP functions. OBJECTIVE: As MP absorption coincides partly with that of rhodopsin, MP may reduce rod signal effectiveness in the mesopic range, thus extend the usefulness of cone-mediated vision into the mesopic range. Forward light scatter in the eye can reduce retinal image contrast. If blue light contributes significantly to intraocular scatter, selective blue light absorption by MP could reduce the effects of scatter. DESIGN: We investigated 34 subjects from a carotenoid supplementation trial. The measurements included high mesopic contrast acuity thresholds (CATs), macular pigment optical density (MPOD), wavefront aberrations, and scattered light. The measurements were made after 6 months of daily supplementation with zeaxanthin (Z, OPTISHARP), lutein (L), a combination of the two (C), or placebo (P), and again after a further 6 months of doubled supplementation. RESULTS: The data reveal a trend toward lower CATs in all groups supplemented, with a statistically significant improvement in the lutein group (p = 0.001), although there was no correlation with MPOD. Light scattering in the eye and the root-mean-square wavefront aberrations show decreasing trends as a result of supplementation, but no correlation with MPOD. CONCLUSIONS: The results suggest that supplementation with L or Z increases MPOD at the fovea and at 2.5 degrees , and that supplementation can improve CATs at high mesopic levels and hence visual performance at low illumination.     

Clinical experience in the treatment of neovascular age-related macular degeneration with pegaptanib

BACKGROUND: Intravitreal anti-VEGF therapy with Pegaptanib was effective in neovascular AMD in the VISION study. We report our experience with Macugen for the treatment of occult or minimally classic choroidal neovascularisation (CNV) due to age-related macular degeneration (AMD). PATIENTS AND METHODS: 35 eyes of 35 patients with occult CNV or minimally classic CNV due to neovascular AMD not eligible for PDT were treated with intravitreal injection of 0.3 mg Pegaptanib. An average of 2.74 injections per patient was administered. Before, and every 3 months after treatment, visual acuity, intraocular pressure measurement, angiography and OCT examinations were performed. One month after treatment only visual acuity, intraocular pressure measurement, and OCT examinations were performed. Visual acuity measurements and an eye examination were done on the first and second day after injection, after 4-6 weeks and at months 3 and 6. RESULTS: Intravitreal Pegaptanib was well tolerated and we had no complications. Mean visual acuity was 0.38 +/- 0.23 at baseline, after one month 0.38 +/- 0.26, at 3 months it was 0.39 +/- 0.22 and at 6 months 0.41 +/- 0.26. OCT examinations showed a decrease in central retinal thickness from 277 microm to 254 microm. In 91.4 % of the eyes the visual acuity was stabilised or improved. No patient had an elevated intraocular pressure after 6 months. CONCLUSIONS: Intravitreal therapy with Pegaptanib was safe and effective. The majority of patients showed a stabilisation in all the assessed parameters. In clinical practice unselective VEGF inhibition should be considered carefully for patients with high cardiovascular risk profile or thromboembolic events in the history.     

Macular pigment and visual performance under glare conditions

PURPOSE: Many parameters of visual performance (e.g., contrast sensitivity) are compromised under glaring light conditions. Recent data indicate that macular pigment (MP) is strongly related to improvements in glare disability and photostress recovery based on a filtering mechanism. In this study, we assessed the causality of this relation by supplementing lutein and zeaxanthin for 6 months while measuring MP, glare disability, and photostress recovery. METHODS: Forty healthy subjects (mean age = 23.9) participated in the study. Subjects were followed for 6 months and assessed at baseline, 1, 2, 4, and 6 months. Spatial density profiles of MP were measured using heterochromatic flicker photometry. Disability glare was measured using a 1 degree-diameter circular grating surrounded by a broadband glare source (a xenon-white annulus). The intensity of the annulus (11 degree inner and 12 degree outer diameters) was adjusted by the subject until the grating target was no longer seen. For the photostress recovery experiment, the time required to detect a 1 degree-diameter grating stimulus after a 5-s exposure to a 2.5 muW/cm2, 5 degree-diameter disk was recorded. Subjects were tested under central viewing and eccentric viewing (10 degree temporal retina) conditions. RESULTS: At the baseline time point, MP optical density (OD) at 30' eccentricity ranged from 0.08 to 1.04, and was strongly correlated with improved visual performance in the two glare tasks. After 6 months of lutein (L) and zeaxanthin (Z) supplementation, average MPOD (at 30' eccentricity) had increased from 0.41 to 0.57, and was shown to significantly reduce the deleterious effects of glare for both the visual performance tasks assessed. CONCLUSIONS: MP is strongly related to improvements in glare disability and photostress recovery in a manner strongly consistent with its spectral absorption and spatial profile. Four to 6 months of 12 mg daily L + Z supplementation significantly increases MPOD and improves visual performance in glare for most subjects.     

Monthly consistency of macular pigment optical density and serum concentrations of lutein and zeaxanthin

PURPOSE: This study was undertaken to assess serial month-to-month consistency of macular pigment (MP) optical density and serum concentrations of lutein (L) and zeaxanthin (Z). Four healthy subjects aged between 23 and 51 years volunteered to participate in this study. METHODS: MP optical density (measured psychophysically using heterochromatic flicker photometry [HFP]), and serum concentrations of L and Z (quantified using high-performance liquid chromatography [HPLC]), were recorded every month for 24 consecutive months. RESULTS: Mean MP optical density (+/-SD) was 0.361 (0.086) and 0.369 (0.074) for right and left eyes, respectively. There was no statistically significant seasonal variation in MP optical density for the group (two-way ANOVA: p>0.05). Serum concentrations of L and Z demonstrated a statistically significant subject-season interaction effect (two-way ANOVA: p<0.01). Serial serum concentrations of L and Z were positively correlated within all four subjects (r=0.370 to 0.786), and significantly so for three subjects (p<0.05). There was no obvious relationship, synchronous or lagged, between serum concentrations of L (or Z) and MP optical density (r=-0.036 to 0.368). CONCLUSIONS: MP optical density was relatively stable for all subjects over the 24-month period. Fluctuations in serum concentrations of L and Z, in the absence of dietary modification or supplementation, are associated with stable MP optical density.     

Resonance Raman measurement of macular carotenoids in normal subjects and in age-related macular degeneration patients

PURPOSE: Dietary carotenoids lutein and zeaxanthin may play a protective role against visual loss from age-related macular degeneration (AMD) through antioxidant and light screening mechanisms. We used a novel noninvasive objective method to quantify lutein and zeaxanthin in the human macula using resonance Raman spectroscopy and compared macular pigment levels in AMD and normal subjects. DESIGN: Observational study of an ophthalmology clinic-based population. PARTICIPANTS AND CONTROLS: Ninety-three AMD eyes from 63 patients and 220 normal eyes from 138 subjects. METHODS: Macular carotenoid levels were quantified by illuminating the macula with a low-power argon laser spot and measuring Raman backscattered light using a spectrograph. This technique is sensitive, specific, and repeatable even in subjects with significant macular pathologic features. MAIN OUTCOME MEASURE: Raman signal intensity at 1525 cm(-1) generated by the carbon-carbon double-bond vibrations of lutein and zeaxanthin. RESULTS: Carotenoid Raman signal intensity declined with age in normal eyes (P < 0.001). Average levels of lutein and zeaxanthin were 32% lower in AMD eyes versus normal elderly control eyes as long as the subjects were not consuming high-dose lutein supplements (P = 0.001). Patients who had begun to consume supplements containing high doses of lutein (> or =4 mg/day) regularly after their initial diagnosis of AMD had average macular pigment levels that were in the normal range (P = 0.829) and that were significantly higher than in AMD patients not consuming these supplements (P = 0.038). CONCLUSIONS: These findings are consistent with the hypothesis that low levels of lutein and zeaxanthin in the human macula may represent a pathogenic risk factor for the development of AMD. Resonance Raman measurement of macular carotenoid pigments could play an important role in facilitating large-scale prospective clinical studies of lutein and zeaxanthin protection against AMD, and this technology may someday prove useful in the early detection of individuals at risk for visual loss from AMD.