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Loskutova E.,Waterford Institute of Technology | Nolan J.,Waterford Institute of Technology | Nolan J.,Institute of Vision Research | Howard A.,University of Cambridge | And 2 more authors.
Nutrients | Year: 2013

Three dietary carotenoids, lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ) accumulate at the central retina (macula), where they are collectively referred to as macular pigment (MP). MP's pre-receptoral absorption of blue light and consequential attenuation of the effects of chromatic aberration and light scatter are important for optimal visual function. Furthermore, antioxidant activity of MP's constituent carotenoids and the same blue light-filtering properties underlie the rationale for its putative protective role for age-related macular degeneration (AMD). Supplementation with L, Z and MZ augments MP and enhances visual performance in diseased and non-diseased eyes, and may reduce risk of AMD development and/or progression. © 2013 by the authors; licensee MDPI, Basel, Switzerland.


Sabour-Pickett S.,Dublin Institute of Technology | Sabour-Pickett S.,Waterford Institute of Technology | Nolan J.M.,Waterford Institute of Technology | Nolan J.M.,Institute of Vision Research | And 4 more authors.
Molecular Nutrition and Food Research | Year: 2012

There is a consensus that age-related macular degeneration (AMD) is the result of (photo)-oxidative-induced retinal injury and its inflammatory sequelae, the latter being influenced by genetic background. The dietary carotenoids, lutein (L), zeaxanthin (Z), and meso-zeaxanthin (meso-Z), accumulate at the macula, where they are collectively known as macular pigment (MP). The anatomic (central retinal), biochemical (anti-oxidant) and optical (short-wavelength-filtering) properties of this pigment have generated interest in the biologically plausible rationale that MP may confer protection against AMD. Level 1 evidence has shown that dietary supplementation with broad-spectrum anti-oxidants results in risk reduction for AMD progression. Studies have demonstrated that MP rises in response to supplementation with the macular carotenoids, although level 1 evidence that such supplementation results in risk reduction of AMD and/or its progression is still lacking. Although appropriately weighted attention should be accorded to higher levels of evidence, the totality of available data should be appraised in an attempt to inform professional practice. In this context, the literature demonstrates that supplementation with the macular carotenoids is probably the best means of fortifying the anti-oxidant defences of the macula, thus putatively reducing the risk of AMD and/or its progression. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Dennison J.L.,Waterford Institute of Technology | Stack J.,Waterford Institute of Technology | Beatty S.,Waterford Institute of Technology | Beatty S.,Institute of Vision Research | And 2 more authors.
Experimental Eye Research | Year: 2013

This study compares invivo measurements of macular pigment (MP) obtained using customized heterochromatic flicker photometry (cHFP; Macular Metrics Densitometer™), dual-wavelength fundus autofluorescence (Heidelberg Spectralis® HRA+OCT MultiColor) and single-wavelength fundus reflectance (Zeiss Visucam® 200). MP was measured in one eye of 62 subjects on each device. Data from 49 subjects (79%) was suitable for analysis. Agreement between the Densitometer and Spectralis was investigated at various eccentricities using a variety of quantitative and graphical methods, including: Pearson correlation coefficient to measure degree of scatter (precision), accuracy coefficient, concordance correlation coefficient (ccc), paired t-test, scatter and Bland-Altman plots. The relationship between max MP from the Visucam and central MP from the Spectralis and Densitometer was investigated using regression methods. Agreement was strong between the Densitometer and Spectralis at all central eccentricities (e.g. at 0.25° eccentricity: accuracy=0.97, precision=0.90, ccc=0.87). Regression analysis showed a very weak relationship between the Visucam and Densitometer (e.g. Visucam max on Densitometer central MP: R2=0.008, p=0.843). Regression analysis also demonstrated a weak relationship between MP measured by the Spectralis and Visucam (e.g. Visucam max on Spectralis central MP: R2=0.047, p=0.348). MP values obtained using the Heidelberg Spectralis are comparable to MP values obtained using the Densitometer. In contrast, MP values obtained using the Zeiss Visucam are not comparable with either the Densitometer or the Spectralis MP measuring devices. Taking cHFP as the current standard to which other MP measuring devices should be compared, the Spectralis is suitable for use in a clinical and research setting, whereas the Visucam is not.© 2013 Elsevier Ltd.


Feeney J.,Trinity College Dublin | Finucane C.,Trinity College Dublin | Savva G.M.,Trinity College Dublin | Cronin H.,Trinity College Dublin | And 5 more authors.
Neurobiology of Aging | Year: 2013

Macular pigment (MP) is comprised of the carotenoids lutein (L), zeaxanthin (Z), and meso-zeaxanthin (MZ), which selectively accumulate at the macula (central retina) of the eye and are neuroprotective. These carotenoids are also present in the brain, and evidence suggests a close correlation between retinal and brain concentrations. We investigated the relationship between MP and cognitive function in 4453 adults aged ≥50 years as part of The Irish Longitudinal Study on Aging. Macular pigment optical density (MPOD) was determined using customized heterochromatic flicker photometry-a quick and noninvasive way of measuring the concentration of the pigment. Lower MPOD was associated with poorer performance on the mini-mental state examination (p= 0.026) and on the Montreal cognitive assessment (p= 0.016). Individuals with lower MPOD also had poorer prospective memory (p= 0.011), took longer time to complete a trail-making task (p= 0.003), and had slower and more variable reaction times on a choice reaction time task (p= 0.000 and 0.001). These associations were only slightly attenuated following adjustment for physical and mental health. There was no significant association between MPOD and verbal fluency, word recall, visual reasoning, or picture memory. Overall, the findings support the theory that xanthophyll carotenoids impact on cognitive function, underscoring the need for exploration of novel, noninvasive biomarkers for cognitive vulnerability and preventive strategies. © 2013 Elsevier Inc.


Nolan J.M.,Waterford Institute of Technology | Nolan J.M.,Institute of Vision Research | Akkali M.C.,Waterford Institute of Technology | Loughman J.,Dublin Institute of Technology | And 5 more authors.
Experimental Eye Research | Year: 2012

This study was designed to investigate the impact of macular carotenoid supplementation on the spatial profile of macular pigment (MP) in subjects where the profile does not exhibit the typical central peak (i.e. peaked MP at foveal epicentre). Thirty one healthy subjects with such atypical MP spatial profiles were assigned to one of three intervention groups: Group 1: (n = 10), 20 mg/day lutein (L), 2 mg/day zeaxanthin (Z); Group 2: (n = 10), 10 mg/day meso-zeaxanthin (MZ), 10 mg/day L, 2 mg/day Z; Group 3: (n = 10), 17 mg/day MZ, 3 mg/day L, 2 mg/day Z. Subjects were instructed to take one capsule daily over an 8-week period. MP at 0.25°, 0.5°, 1°, 1.75°and 3° was measured using customized-heterochromatic flicker photometry at baseline, four weeks and 8 weeks. Over the study period, we report no statistically significant increase in MP at any eccentricity in Group 1 (p > 0.05, for all eccentricities). There was a trend towards an increase in MP at all eccentricities in Group 2, with a significant increase found at 0.25° and 0.50° (p = 0.000 and p = 0.016, respectively). There was a statistically significant increase evident in MP at 0.25° in Group 3 (p = 0.005), but at no other eccentricity (p > 0.05, for all other). We report that the typical central peak of MP can be realised in subjects with atypical spatial profiles, following supplementation with a preparation containing all three macular carotenoids, but not with a supplement lacking MZ. The implications of our findings, in terms of visual performance and/or a (photo)-protective effect, warrant additional study. © 2012 Elsevier Ltd.


Loughman J.,Dublin Institute of Technology | Loughman J.,University of KwaZulu - Natal | Nolan J.M.,Waterford Institute of Technology | Nolan J.M.,Institute of Vision Research | And 6 more authors.
Investigative Ophthalmology and Visual Science | Year: 2012

Purpose. To investigate changes in macular pigment optical density (MPOD) and visual performance following supplementation with different macular carotenoid formulations. Methods. 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. Results. 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). Conclusions. 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. © 2012 The Association for Research in Vision and Ophthalmology, Inc.


Thurnham D.I.,University of Ulster | Nolan J.M.,Waterford Institute of Technology | Howard A.N.,Howard Foundation | Howard A.N.,University of Cambridge | Beatty S.,Institute of Vision research
Graefe's Archive for Clinical and Experimental Ophthalmology | Year: 2015

Purpose: Our aim was to investigate the macular response to three different supplements containing lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ) in normal subjects and those with age-related macular degeneration (AMD). Materials and Methods: Macular pigment optical density (MPOD) and serum xanthophyll concentrations were measured in normal (n = 31) and AMD subjects (n = 32), randomly assigned to: group 1 (20 mg L, 2 mg Z, 0.3 mg MZ), group 2 (10 mg L, 2 mg Z, 10 mg MZ) or group 3 (3 mg L, 2 mg Z, 17 mg MZ). MPOD was measured at baseline, 2, 4, 6 and 8 weeks and at 0.25°, 0.5°, 1.0° and 1.75° of eccentricity using customised heterochromatic flicker photometry and serum xanthophylls by HPLC. Results: MPOD increased significantly at all eccentricities in each group (p < 0.05), except at 1.75° in group 3 (p = 0.242). There was no difference in MPOD measurements between AMD and normal subjects, except for group 2, where AMD subjects exhibited a greater response at 1.75° (p = 0.012). Final serum concentrations of MZ were positively and significantly related to final MPOD values at each eccentricity in all subjects. Targeted analysis of those subjects receiving the MZ-containing supplements exhibited stronger relationships between serum MZ concentrations and MPOD at 0.25° in group 3 than group 2; in group 2 all associations were positive, but only significant at 1.75°. Conclusions: Serum concentrations of MZ were strongly correlated with MPOD after 8 weeks of supplementation with the group 3 formulation, but the inclusion of L in the group 2 formulation may result in greater MPOD augmentation across the spatial profile. © 2014, Springer-Verlag Berlin Heidelberg.


Lee H.,Institute of Vision Research | Chung J.L.,Yonsei University | Kim E.K.,Institute of Vision Research | Kim E.K.,Konyang University | And 3 more authors.
Journal of Cataract and Refractive Surgery | Year: 2012

Purpose: To compare the corneal astigmatism measurements from 6 instruments in preoperative assessment for toric intraocular lens (IOL) implantation. Setting: Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, South Korea. Design: Prospective comparative observational study. Methods: This study included patients with cataract and more than 1.00 diopter (D) of corneal astigmatism. For preoperative evaluation of toric IOL implantation, the net astigmatism was evaluated using manual keratometry, autokeratometry, partial coherence interferometry (PCI) (IOLMaster), corneal topography/ray-tracing aberrometry (iTrace), scanning-slit topography (Orbscan), and Scheimpflug imaging (Pentacam). All net astigmatisms were converted to polar values. Using the astigmatism measurements from manual keratometry as a standard, Bland-Altman analysis, linear mixed-model, and bivariate graphic analysis were performed. Results: The study group comprised 257 eyes of 141 patients. Bland-Altman plots showed good agreement between manual keratometry and each instrument for polar values. There was no significant between-instrument difference in KP(90) and KP(135) in the linear mixed model analysis or in bivariate polar values in bivariate confidence ellipses. Conclusion: The corneal astigmatism measurements from autokeratometry, PCI, corneal topography/ray-tracing aberrometry, scanning-slit topography, and Scheimpflug imaging were comparable to those from manual keratometry and can be used interchangeably with manual keratometry to measure corneal astigmatism. Financial Disclosure: No author has a financial or proprietary interest in any material or method Mentioned © 2012 2012 ASCRS and ESCRS.


Ueyama H.,Shiga University of Medical Science | Muraki-Oda S.,Shiga University of Medical Science | Yamade S.,Shiga University of Medical Science | Tanabe S.,Institute of Vision Research | And 3 more authors.
Biochemical and Biophysical Research Communications | Year: 2012

We have analyzed L/M visual pigment gene arrays in 119 Japanese men with protanopia color vision defect and found that five had a normal gene order of L-M. Among the five men, two (identified as A376 and A642) had apparently normal L genes. To clarify their L gene defect, the whole L or M gene from A376 and control subjects was cloned in an expression vector. Total RNA extracted from the transfected HEK293 cells was analyzed by Northern blot and reverse transcription-polymerase chain reaction. The product from the cloned L gene of A376 was smaller than the normal control due to the absence of exon 3. To investigate such exon-skipping at splicing, minigenes of exon 3 accompanying introns 2 and 3 were prepared from A376, A642, and control subjects. The minigenes of A376 (L) and A642 (L) showed the product lacking exon 3 only, while the minigene of normal control N44 (L) showed the product retaining exon 3 only. Exchanging of introns 2 and 3 between the A376 (L) and N44 (L) minigenes showed that the skipping of exon 3 was caused by the exon itself. Seven differences in exon 3 between A376 (L) and N44 (L) were all within already-known polymorphisms as follows: G 151-3, C 153-1, G 155-3, A 171-1, T 171-3, G 178-1 and G 180-1 in A376 (L) and A642 (L), and A 151-3, A 153-1, C 155-3, G 171-1, G 171-3, A 178-1 and T 180-1 in N44 (L). An in vitro mutagenesis experiment with these nucleotides in the minigenes showed that exon 3 was completely skipped at splicing only in the haplotype observed in A376 (L) and A642 (L). These results suggest that complete skipping of exon 3 at splicing, due to the unique haplotype of the exon, causes loss of expression of L-opsin in these men. © 2012 Elsevier Inc.


Song W.K.,Yonsei University | Lee S.C.,Yonsei University | Lee E.S.,Yonsei University | Kim C.Y.,Yonsei University | Kim S.S.,Institute of Vision Research
Investigative Ophthalmology and Visual Science | Year: 2010

PURPOSE. To assess the relationship between macular retinal thickness and volume and age, sex, and refractive error/axial length with spectral domain-optical coherence tomography (SD-OCT). METHODS. One randomly selected eye of 198 consecutive ophthalmically normal subjects (104 men, 94 women) between July 2008 and January 2009, with corrected visual acuities better than 20/30 were included in this cross-sectional study. Complete ophthalmic examination, axial length measurement with a laser interferometer, and macular cube 512×128 scan by SD-OCT were performed. RESULTS. The mean age was 55.6±16.4 years (range, 17-83), average refractive error was -2.17±4.82 (range, -23.50-3.75), and average axial length was 24.73±1.98 mm (range, 21.52-32.51). The central subfield thickness, average inner macular thickness, and overall macular volume were significantly lower in the female subjects (partial correlation: P=0.009, P=0.027, and P= 0.042, respectively). As age increased, average inner macular thickness, average outer macular thickness, overall average macular thickness, and macular volume decreased significantly (partial correlation: P= 0.002, P= 0.002, P= 0.002, and P= 0.000, respectively). Refractive error had no significant influence in partial correlation analysis. Axial length correlated negatively with average outer macular thickness, overall average macular thickness, and macular volume (partial correlation: P= 0.006, P =0.044, and P=0.003, respectively). CONCLUSIONS. In normal subjects, SD-OCT showed that retinal thickness is related to age, sex, and axial length, with regional variations. © Association for Research in Vision and Ophthalmology.

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