James Loughman

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°, 0.5°, 1°, and 1.75°) 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 μmol/L. We report significant increases in MPOD at 0.25°, 0.5°, 1°, 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.

The impact of macular pigment augmentation on visual performance using different carotenoid formulations.

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.

The Relationship Between Macular Pigment and Visual Performance

This study was designed to assess whether macular pigment optical density (MPOD) is associated with visual performance. One hundred and forty-two young healthy subjects were recruited. Macular pigment optical density and visual performance were assessed by psychophysical tests including best corrected visual acuity (BCVA), mesopic and photopic contrast sensitivity, glare sensitivity, photostress recovery time (PRT). Measures of central visual function, including BCVA and contrast sensitivity, were positively associated with MPOD (p<0.05, for all). Photostress recovery and glare sensitivity were unrelated to MPOD (p>0.05). A longitudinal, placebo-controlled and randomized supplementation trial will be required to ascertain whether augmentation of MPOD can influence visual performance.

A review of the evidence germane to the putative protective role of the macular carotenoids for age‐related macular degeneration

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.

Augmentation of macular pigment following implantation of blue light-filtering intraocular lenses at the time of cataract surgery.

PURPOSE (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). METHODS 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. RESULTS 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). CONCLUSIONS 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.

Supplementation with All Three Macular Carotenoids: Response, Stability, and Safety

PURPOSE This study was designed to investigate serum and macular response to, and safety of supplementation with, meso-zeaxanthin (MZ), lutein (L), and zeaxanthin (Z), the carotenoids that constitute macular pigment (MP). METHODS Forty-four healthy subjects were recruited into this randomized, placebo-controlled, clinical trial. Subjects consumed one tablet per day containing 10.6 mg MZ, 5.9 mg L, and 1.2 mg Z (intervention, I group) or placebo (P group). The spatial profile of MP optical density (MPOD) was measured with customized heterochromatic flicker photometry (cHFP), and serum concentrations of L and Z were quantified by using high performance liquid chromatography (HPLC). Subjects were assessed at baseline and at 3 and 6 months. Clinical pathology analysis was performed at baseline and 6 months. RESULTS Serum concentrations of L and Z increased significantly in the I group (P = 0.001 and 0.003, respectively) and remained stable in the P group (P > 0.05). There was a significant increase in central MPOD in the I group (0.25°: P = 0.001; 0.5°: P = 0.001), with no significant change in the P group (P > 0.05). Clinical pathology analysis confirmed that all variables remained within the normal reference range, with the exception of total cholesterol and low-density lipoprotein (LDL), which exhibited baseline values outside the accepted normal reference range before supplementation. CONCLUSIONS Subjects supplemented with MZ, L, and Z exhibited significant increases in serum concentrations of these carotenoids and a subsequent increase in central MPOD. Pathology analysis suggested no adverse clinical implications of consuming these carotenoids. (http://isrctn.org number, ISRCTN60816411).

Macular Pigment Optical Density in an Ageing Irish Population: The Irish Longitudinal Study on Ageing.

Purpose: The 3 carotenoids lutein, zeaxanthin, and meso-zeaxanthin, which account for the ‘yellow spot’ at the macula and which are referred to as macular pigment (MP), are believed to play a role in visual function and protect against age-related macular degeneration (AMD) via their optical and antioxidant properties. This study was undertaken to compare MP optical density (MPOD) in a population aged ≧50 years with MPOD values from a normative database of subjects aged 18–60 years. Methods: Seventy-nine subjects were recruited into this pilot study (The Irish Longitudinal Study on Ageing-TILDA). MPOD was measured using heterochromatic flicker photometry. Retinal fundus photographs, lifestyle data and general health data, were also obtained. Results: The mean ± SD age of the 79 subjects recruited into this study was 65 ± 11 years. There was a moderate, but statistically significant, age-related decline in MPOD at 0.5° in the TILDA data (r = –0.251, p = 0.045), which remained upon merging with a normative database of an additional 462 subjects aged between 18 and 67 years (r = –0.179, p = 0.000). Conclusions: We report an inverse association between MPOD and increasing age. Longitudinal data in a larger cohort of participants are required to satisfactorily investigate the relationship between the optical density of this pigment and age, and with risk for development and/or progression of AMD. This pilot study represents a first step in this endeavour.

Macular carotenoid supplementation in subjects with atypical spatial profiles of macular pigment

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.

Changes in intraocular pressure and anterior segment morphometry after uneventful phacoemulsification cataract surgery.

PurposeTo study changes in anterior segment morphometry after uneventful phacoemulsification cataract surgery, and to investigate whether there is a relationship between any observed changes and intraocular pressure (IOP) reduction after the procedure.MethodsThe anterior chamber depth (ACD), anterior chamber volume (ACV), anterior chamber angle (ACA), central corneal thickness (CCT), and IOP were measured in 101 non-glaucomatous eyes before and after uneventful phacoemulsification cataract surgery.ResultsAfter cataract surgery, the mean ACD, ACV, and ACA values increased by 1.08 mm, 54.4 mm3, and 13.1°, respectively, and the mean IOP (corrected for CCT) decreased by 3.2 mm Hg. The predictive value of a previously described index (preoperative ACD/preoperative IOP (corrected for CCT) or CPD ratio) for IOP (corrected for CCT) reduction after cataract surgery was confirmed, reflected in an r2 value of 23.3% between these two parameters (P<0.001). Other indices predictive of IOP reduction after cataract surgery were also identified, including preoperative IOP/preoperative ACV and preoperative IOP/preoperative ACA, reflected in r2 values of 13.7 and 13.7%, respectively (P<0.001 and P<0.001, respectively).ConclusionsOur study confirms the predictive value of the CPD ratio for IOP reduction after cataract surgery, and may contribute to the decision-making process in patients with glaucoma or ocular hypertension. Furthermore, two novel indices of preoperative parameters that are predictive for IOP reduction after cataract surgery were identified, and enhance our understanding of the mechanisms underlying IOP changes after this procedure.

Supplementation with three different macular carotenoid formulations in patients with early age-related macular degeneration.

Purpose: To investigate the impact of three different macular carotenoid formulations on macular pigment optical density and visual performance in subjects with early age-related macular degeneration. Methods: Fifty-two subjects were supplemented and followed for 12 months, 17 of them were in intervention Group 1 (20 mg/day lutein and 2 mg/day zeaxanthin); 21 in Group 2 (10 mg/day meso-zeaxanthin, 10 mg/day lutein, and 2 mg/day zeaxanthin); and 14 in Group 3 (17 mg/day meso-zeaxanthin, 3 mg/day lutein, and 2 mg/day zeaxanthin). The macular pigment optical density was measured using customized heterochromatic flicker photometry, and visual function was assessed using corrected distance visual acuity and by letter contrast sensitivity. Results: A statistically significant increase in the macular pigment optical density was observed at all measured eccentricities in Group 2 (P ⩽ 0.005) and in Group 3 (P < 0.05, for all), but only at 1.75° in Group 1 (P = 0.018). Statistically significant (P < 0.05) improvements in letter contrast sensitivity were seen at all spatial frequencies (except 1.2 cycles per degree) in Group 3, and at low spatial frequencies in Groups 1 and 2. Conclusion: Augmentation of the macular pigment optical density across its spatial profile and enhancements in contrast sensitivity were best achieved after supplementation with a formulation containing high doses of meso-zeaxanthin in combination with lutein and zeaxanthin.