Jessica Dennison

Macular Pigment, Visual Function, and Macular Disease among Subjects with Alzheimer's Disease: An Exploratory Study

BACKGROUND The macula (central retina) contains a yellow pigment, comprising the dietary carotenoids lutein (L), zeaxanthin (Z), and meso-zeaxanthin, known as macular pigment (MP). The concentrations of MPs constituent carotenoids in retina and brain tissue correlate, and there is a biologically-plausible rationale, supported by emerging evidence, that MPs constituent carotenoids are also important for cognitive function. OBJECTIVE To investigate if patients with Alzheimers disease (AD) are comparable to controls in terms of MP and visual function. METHODS 36 patients with moderate AD and 33 controls with the same age range participated. MP was measured using dual-wavelength autofluorescence (Heidelberg Spectralis®); cognitive function was assessed using a battery of cognition tests (including Cambridge Neuropsychological Test Automated Battery). Visual function was recorded by measuring best corrected visual acuity (BCVA) and contrast sensitivity (CS). Serum L and Z concentrations (by HPLC) and age-related macular degeneration (AMD, by retinal examination) status were also assessed. RESULTS In the AD group, central MP (i.e., at 0.23°) and MP volume were significantly lower than the control group (p < 0.001 for both), as were measures of BCVA, CS, and serum L and Z concentrations (p < 0.05, for all). CONCLUSION AD patients were observed to exhibit significantly less MP, lower serum concentrations of L and Z, poorer vision, and a higher occurrence of AMD when compared to control subjects. A clinical trial in AD patients designed to investigate the impact of macular carotenoid supplementation with respect to MP, visual function, and cognitive function is merited.

Enrichment of Macular Pigment Enhances Contrast Sensitivity in Subjects Free of Retinal Disease: Central Retinal Enrichment Supplementation Trials - Report 1.

PURPOSE The high-performance visual function associated with central vision is mediated by the macula (the central retina), which accumulates three diet-derived pigments (the carotenoids lutein [L], zeaxanthin [Z], and meso-zeaxanthin [MZ]). Our study sought to investigate the impact on visual function, including contrast sensitivity (CS), of supplementation with these naturally occurring carotenoids, in individuals with low retinal concentrations. METHODS Subjects consumed daily a formulation containing 10 mg L, 2 mg Z, and 10 mg MZ (active group; n = 53) or placebo (n = 52) for a period of 12 months. Study visits were at baseline, 3, 6, and 12 months. Contrast sensitivity at 6 cycles per degree (cpd) was the primary outcome measure (POM). Secondary outcome measures included CS at other spatial frequencies, best-corrected visual acuity (BCVA), glare disability, photostress recovery, and light scatter. Macular pigment optical density (MPOD) was measured using dual-wavelength autofluorescence, and serum carotenoid concentrations were analyzed using high performance liquid chromatography (HPLC). RESULTS Compared to placebo, statistically significant improvements from baseline CS were detected at 6 (P = 0.002) and 1.2 (P = 0.004) cpd in the active group. Additionally, improvements in CS were commensurate with the observed increases in retinal concentrations of these carotenoids (r = 0.342, P = 0.002 at 6 cpd). CONCLUSIONS These results indicate that dietary fortification with the macular carotenoids can have meaningful effects on visual function.

The Impact of Supplemental Macular Carotenoids in Alzheimer's Disease: A Randomized Clinical Trial

BACKGROUND Patients with Alzheimers disease (AD) exhibit significantly less macular pigment (MP) and poorer vision when compared to control subjects. OBJECTIVE To investigate supplementation with the macular carotenoids on MP, vision, and cognitive function in patients with AD versus controls. METHODS A randomized, double-blind clinical trial with placebo and active arms. 31 AD patients and 31 age-similar control subjects were supplemented for six months with either Macushield (10 mg meso-zeaxanthin [MZ]; 10 mg lutein [L]; 2 mg zeaxanthin [Z]) or placebo (sunflower oil). MP was measured using dual-wavelength autofluorescence (Heidelberg Spectralis®). Serum L, Z, and MZ were quantified by high performance liquid chromatography. Visual function was assessed by best corrected visual acuity and contrast sensitivity (CS). Cognitive function was assessed using a battery of cognition tests, including the Cambridge Neuropsychological Test Automated Battery (CANTAB)). RESULTS Subjects on the active supplement (for both AD and non-AD controls) exhibited statistically significant improvement in serum concentrations of L, Z, MZ, and MP (p < 0.001, for all) and also CS at (p = 0.039). Also, for subjects on the active supplement, paired samples t-tests exhibited four significant results (from five spatial frequencies tested) in the AD group, and two for the non-AD group, and all indicating improvements in CS. We found no significant changes in any of the cognitive function outcome variables measured (p > 0.05, for all). CONCLUSION Supplementation with the macular carotenoids (MZ, Z, and L) benefits patients with AD, in terms of clinically meaningful improvements in visual function and in terms of MP augmentation.

Cognitive Function and Its Relationship with Macular Pigment Optical Density and Serum Concentrations of its Constituent Carotenoids

Abstract Background: Macular pigment (MP) levels correlate with brain concentrations of lutein (L) and zeaxanthin (Z), and have also been shown to correlate with cognitive performance in the young and elderly. Objective: To investigate the relationship between MP, serum concentrations of L and Z, and cognitive function in subjects free of retinal disease with low MP (Group 1, n = 105) and in subjects with AMD (Group 2, n = 121). Methods: MP was measured using customized heterochromatic flicker photometry and dual-wavelength autofluorescence; cognitive function was assessed using a battery of validated cognition tests; serum L and Z concentrations were determined by HPLC. Results: Significant correlations were evident between MP and various measures of cognitive function in both groups (r = –0.273 to 0.261, p≤0.05, for all). Both serum L and Z concentrations correlated significantly (r = 0.187, p≤0.05 and r = 0.197, p≤0.05, respectively) with semantic (animal) fluency cognitive scores in Group 2 (the AMD study group), while serum L concentrations also correlated significantly with Verbal Recognition Memory learning slope scores in the AMD study group (r = 0.200, p = 0.031). Most of the correlations with MP, but not serum L or Z, remained significant after controlling for age, gender, diet, and education level. Conclusion: MP offers potential as a non-invasive clinical biomarker of cognitive health, and appears more successful in this role than serum concentrations of L or Z.

Central Retinal Enrichment Supplementation Trials (CREST): Design and Methodology of the CREST Randomized Controlled Trials

Abstract Purpose: The Central Retinal Enrichment Supplementation Trials (CREST) aim to investigate the potential impact of macular pigment (MP) enrichment, following supplementation with a formulation containing 10 mg lutein (L), 2 mg zeaxanthin (Z) and 10 mg meso-zeaxanthin (MZ), on visual function in normal subjects (Trial 1) and in subjects with early age-related macular degeneration (AMD; Trial 2). Methods: CREST is a single center, double-blind, randomized clinical trial. Trial 1 (12-month follow-up) subjects are randomly assigned to a formulation containing 10 mg L, 10 mg MZ and 2 mg Z (n = 60) or placebo (n = 60). Trial 2 (24-month follow-up) subjects are randomly assigned to a formulation containing 10 mg L, 10 mg MZ, 2 mg Z plus 500 mg vitamin C, 400 IU vitamin E, 25 mg zinc and 2 mg copper (Intervention A; n = 75) or 10 mg L and 2 mg Z plus 500 mg vitamin C, 400 IU vitamin E, 25 mg zinc and 2 mg copper (Intervention B; n = 75). Contrast sensitivity (CS) at 6 cycles per degree represents the primary outcome measure in each trial. Secondary outcomes include: CS at other spatial frequencies, MP, best-corrected visual acuity, glare disability, photostress recovery, light scatter, cognitive function, foveal architecture, serum carotenoid concentrations, and subjective visual function. For Trial 2, AMD morphology, reading speed and reading acuity are also being recorded. Conclusions: CREST is the first study to investigate the impact of supplementation with all three macular carotenoids in the context of a large, double-blind, randomized clinical trial.

The Photobiology of Lutein and Zeaxanthin in the Eye

Lutein and zeaxanthin are antioxidants found in the human retina and macula. Recent clinical trials have determined that age- and diet-related loss of lutein and zeaxanthin enhances phototoxic damage to the human eye and that supplementation of these carotenoids has a protective effect against photoinduced damage to the lens and the retina. Two of the major mechanisms of protection offered by lutein and zeaxanthin against age-related blue light damage are the quenching of singlet oxygen and other reactive oxygen species and the absorption of blue light. Determining the specific reactive intermediate(s) produced by a particular phototoxic ocular chromophore not only defines the mechanism of toxicity but can also later be used as a tool to prevent damage.

The evidence informing the surgeon’s selection of intraocular lens on the basis of light transmittance properties

In recent years, manufacturers and distributors have promoted commercially available intraocular lenses (IOLs) with transmittance properties that filter visible short-wavelength (blue) light on the basis of a putative photoprotective effect. Systematic literature review. Out of 21 studies reporting on outcomes following implantation of blue-light-filtering IOLs (involving 8914 patients and 12 919 study eyes undergoing cataract surgery), the primary outcome was vision, sleep pattern, and photoprotection in 9 (42.9%), 9 (42.9%), and 3 (14.2%) respectively, and, of these, only 7 (33.3%) can be classed as high as level 2b (individual cohort study/low-quality randomized controlled trials), all other studies being classed as level 3b or lower. Of the level 2b studies, only one (14.3%) found in favor of blue-light-filtering IOLs vs ultraviolet (UV)-only filtering IOLs on the basis of an association between better post-operative contrast sensitivity (CS) at select frequencies with the former; however, that study did not measure or report CS preoperatively in either group, and the finding may simply reflect better preoperative CS in the eyes scheduled to be implanted with the blue-light-filtering IOL; moreover, that study failed to measure macular pigment, a natural preceptoral filter of blue-light, augmentation of which is now known to improve CS. In terms of photoprotection, there is no level 2b (or higher) evidence in support of blue filtering IOLs vs UV-only filtering IOLs. On the basis of currently available evidence, one cannot advocate for the use of blue-light-filtering IOLs over UV-only filtering IOLs.

Serum and macular response to carotenoid-enriched egg supplementation in human subjects: the Egg Xanthophyll Intervention clinical Trial (EXIT).

The macular carotenoids lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ) accumulate at the macula, where they are collectively referred to as macular pigment (MP). Augmentation of this pigment, typically achieved through diet and supplementation, enhances visual function and protects against progression of age-related macular degeneration. However, it is known that eggs are a rich dietary source of L and Z, in a highly bioavailable matrix. In this single-blind placebo-controlled study, L- and MZ-enriched eggs and control non-enriched eggs were fed to human subjects (mean age 41 and 35 years, respectively) over an 8-week period, and outcome measures included MP, visual function and serum concentrations of carotenoids and cholesterol. Serum carotenoid concentrations increased significantly in control and enriched egg groups, but to a significantly greater extent in the enriched egg group (P<0·001 for L, Z and MZ). There was no significant increase in MP in either study group post intervention, and we saw no significant improvement in visual performance in either group. Total cholesterol increased significantly in each group, but it did not exceed the upper limit of the normative range (6·5 mmol/l). Therefore, carotenoid-enriched eggs may represent an effective dietary source of L, Z and MZ, reflected in significantly raised serum concentrations of these carotenoids, and consequentially improved bioavailability for capture by target tissues. However, benefits in terms of MP augmentation and /or improved visual performance were not realised over the 8-week study period, and a study of greater duration will be required to address these questions.

Measuring Visual Function Using the MultiQuity System: Comparison with an Established Device.

Purpose. To compare measures of visual acuity (VA) and contrast sensitivity (CS) from the Thompson Xpert 2000 and MultiQuity (MiQ) devices. Methods. Corrected distance VA (CDVA) and CS were measured in the right eye of 73 subjects, on an established system (Thompson Xpert) and a novel system (MiQ 720). Regression was used to convert MiQ scores into the Thompson scale. Agreement between the converted MiQ and Thompson scores was investigated using standard agreement indices. Test-retest variability for both devices was also investigated, for a separate sample of 24 subjects. Results. For CDVA, agreement was strong between the MiQ and Thomson devices (accuracy = 0.993, precision = 0.889, CCC = 0.883). For CS, agreement was also strong (accuracy = 0.996, precision = 0.911, CCC = 0.907). Agreement was unaffected by demographic variables or by presence/absence of ocular pathology. Test-retest agreement indices for both devices were excellent: in the range 0.88–0.96 for CDVA and in the range 0.90–0.98 for CS. Conclusion. MiQ measurements exhibit strong agreement with corresponding Thomson measurements, and test-retest results are good for both devices. Agreement between the two devices is unaffected by age or ocular pathology.

Re: Lutein supplementation improves visual performance in Chinese drivers: 1-year randomized, double-blind, placebo-controlled study: The importance of supplementing with all three macular carotenoids

To the Editor: We congratulate Yao et al [1] on their valuable contribution to the area of nutritional supplementation to maximize visual performance. In brief, Yao et al conducted a randomized, double-blind, placebo-controlled trial of patients supplemented with 20mg of lutein daily versus placebo, and found that supplementation with 20 mg of lutein per day resulted in improvements in terms of contrast sensitivity and glare disability, especially under mesopic conditions. Indeed, the findings of Yao et al are consistent with the growing evidence base in this area, which indicates that high levels of macular pigment are required for visual excellence in normal individuals [2]. Macular pigment is made up of three carotenoids, lutein (L), zeaxanthin (Z), and meso-zeaxanthin (MZ), MZ being the dominant carotenoid at the visual center, where visual performance and sensitivity is maximal [3]. A recent randomized, placebocontrolled trial of differing carotenoid formulations versus placebo (also in normal participants), revealed that a formulation containing MZ resulted in the greatest improvements in visual performance (contrast sensitivity, under mesopic and photopic conditions, under and not under conditions of glare), whereas only minimal benefits were noted with the supplementation lacking the centrally dominant carotenoid (MZ); no visual improvements were noted in participants who were supplemented with placebos [4]. The finding that MZ is required in a formulation to maximally improve visual performance is unsurprising, given that 12% of the population has a central dip in the spatial profile of their macular pigment [5], and that in these individuals the normal, centrally peaked spatial profile of macular pigment can only be realized following supplementation with a formulation that contains all three of macular pigment’s constituent carotenoids (MZ, L, andZ in a ratioof 10:10:2) [6]. Also, thenecessityofMZ in a formulation to maximally enhance visual performance is consistent with a recent serum study, where it was shown that a preparation containing all three macular carotenoids was required if serum bioavailability of macular pigment’s constituent carotenoids was to bemaximized, and therefore enhance capture by the target tissue (macula) of these circulating compounds [7]. In summary, and again, we congratulate Yao et al for their excellent piece of work and contribution to this growing area of research. However, we believe that a formulation designed to optimize visual performance should include all three of macular pigment’s constituent carotenoids in a MZ:L:Z ratio of 10:10:2.