Jim Stack

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 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.

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.

Foveal anatomic associations with the secondary peak and the slope of the macular pigment spatial profile.

PURPOSE To investigate the reproducibility of the macular pigment (MP) spatial profile by using heterochromatic flicker photometry (HFP) and to relate the MP spatial profile to foveal architecture. METHODS Sixteen healthy subjects (nine had the typical exponential MP spatial profile [group 1]; seven had a secondary peak MP spatial profile [group 2]) were recruited. The MP spatial profile was measured on three separate occasions. Six radiance measurements were obtained at each locus (0.25 degrees , 0.5 degrees , 1 degrees , and 1.75 degrees eccentricity; reference point, 7 degrees ). Foveal architecture was assessed by optical coherence tomography (OCT). RESULTS Subjects who had the typical decline profile, had this profile after averaging repeated measures (group 1). Subjects who had a secondary peak, displayed the secondary peak after repeated measures were averaged (group 2). Mean SD foveal width in group 1 was significantly narrower than mean SD foveal width in group 2 (1306 +/- 240 microm and 1915 +/- 161 microm, respectively; P < 0.01). This difference remained after adjustment for sex (P < 0.001). Foveal width was significantly related to mean foveal MP, with adjustment for sex (r = 0.588, P = 0.021). Foveal profile slope was significantly related to MP spatial profile slope, after removal of an outlier (r = 0.591, P = 0.020). CONCLUSIONS HFP reproducibly measures MP spatial profile. Secondary peaks seen in the MP spatial profile cannot be attributed to measurement error and are associated with wider foveas. The slope of an individuals MP spatial profile is related to foveal slope, with a steeper MP distribution associated with a steeper foveal depression.

Risk factors, microbiological findings, and clinical outcomes in cases of microbial keratitis admitted to a tertiary referral center in Ireland.

Aim: To identify the risk factors for, and to report the microbiological findings and clinical outcomes of, severe microbial keratitis (MK). Methods: This was a retrospective study of all cases of presumed MK admitted to a tertiary referral center over a 2-year period (September 2001 to August 2003). Data recorded included demographic data, details relating to possible risk factors, results of microbiological studies, clinical findings at presentation, and clinical and visual outcomes. Results: Ninety patients were admitted with a diagnosis of presumed MK during the study period. The mean age of patients was 45 ± 32 years, and the male to female ratio was 47:43 (52.2%:47.7%). Predisposing risk factors for MK included contact lens wear (37; 41.1%), anterior segment disease (19; 21.1%), ocular trauma (13; 14.4%), systemic disease (5; 5.6%), and previous ocular surgery (1; 1.1%). Cultured organisms included gram-negative bacteria (17; 51.5%), gram-positive bacteria (11, 33.3%), acanthamoeba (2; 6.1%), and fungi (1; 3%). Visual acuity improved significantly after treatment [mean best-corrected visual acuity (±standard deviation) at presentation: 0.76 (±0.11); mean best-corrected visual acuity at last follow-up: 0.24 (±0.07); P < 0.001]. Secondary surgical procedures were required in 18 (20%) cases, and these included punctal cautery (1; 1.1%), tissue glue repair of corneal perforation (2; 2.2%), tarsorrhaphy (9; 9.9%), Botulinum toxin-induced ptosis (1; 1.1%), penetrating keratoplasty (3; 3.3%), and evisceration (2; 2.2%). Conclusions: Contact lens wear remains a significant risk factor for severe MK. MK remains a threat to vision and to the eye, but the majority of cases respond to prompt and appropriate antimicrobial therapy.

Measurement of Macular Pigment Optical Density Using Two Different Heterochromatic Flicker Photometers

Purpose: To compare macular pigment optical density using two different heterochromatic flicker photometers. Methods: We measured macular pigment optical density in 121 healthy subjects using heterochromatic flicker photometry. Results: The mean (±SD) macular pigment optical density measured using the Maculometer was 0.394 (±0.170), and that using the Densitometer was 0.395 (±0.189). The difference in measurements on each instrument was influenced by age and macular pigment levels. Conclusions: On average, there is no difference in measurements provided by these two instruments. The Maculometer tends to underestimate macular pigment in older subjects and/or those with higher macular pigment compared with the Densitometer.

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.

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.

Sustained supplementation and monitored response with differing carotenoid formulations in early age-related macular degeneration

PurposeTo compare the impact of sustained supplementation using different macular carotenoid formulations on macular pigment (MP) and visual function in early age-related macular degeneration (AMD).Patients and methodsSixty-seven subjects with early AMD were randomly assigned to: Group 1 (20 mg per day lutein (L), 0.86 mg per day zeaxanthin (Z); Ultra Lutein), Group 2 (10 mg per day meso-zeaxanthin (MZ), 10 mg per day L, 2 mg per day Z; Macushield; Macuhealth), Group 3 (17 mg per day MZ, 3 mg per day L, 2 mg per day Z). MP was measured using customised heterochromatic flicker photometry and visual function was assessed by measuring contrast sensitivity (CS) and best-corrected visual acuity (BCVA). AMD was graded using the Wisconsin Age-Related Maculopathy Grading System (AREDS 11-step severity scale).ResultsAt 3 years, a significant increase in MP from baseline was observed in all groups at each eccentricity (P<0.05), except at 1.75° in Group 1 (P=0.160). Between 24 and 36 months, significant increases in MP at each eccentricity were seen in Group 3 (P<0.05 for all), and at 0.50° in Group 2 (P<0.05), whereas no significant increases were seen in Group 1 (P>0.05 for all). At 36 months, compared with baseline, the following significant improvements (P<0.05) in CS were observed: Group 2—1.2, 6, and 9.6 cycles per degree (c.p.d.); Group 1—15.15 c.p.d.; and Group 3—6, 9.6, and 15.15 c.p.d. No significant changes in BCVA, or progression to advanced AMD, were observed.ConclusionIn early AMD, MP can be augmented with a variety of supplements, although the inclusion of MZ may confer benefits in terms of panprofile augmentation and in terms of CS enhancement.