The unfolded protein response in amyotrophic later sclerosis: results of a phase 2 trial.

Strong evidence suggests that endoplasmic reticulum stress plays a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS) through altered regulation of proteostasis. Robust preclinical findings demonstrated that guanabenz selectively inhibits endoplasmic reticulum stress-induced eIF2α-phosphatase, allowing misfolded protein clearance, reduces neuronal death and prolongs survival in in vitro and in vivo models. However, its safety and efficacy in patients with ALS are unknown. To address these issues, we conducted a multicentre, randomized, double-blind trial with a futility design. Patients with ALS who had displayed an onset of symptoms within the previous 18 months were randomly assigned in a 1:1:1:1 ratio to receive 64 mg, 32 mg or 16 mg of guanabenz or placebo daily for 6 months as an add-on therapy to riluzole. The purpose of the placebo group blinding was to determine safety but not efficacy. The primary outcome was the proportion of patients progressing to higher stages of disease within 6 months as measured using the ALS Milano-Torino staging system, compared with a historical cohort of 200 patients with ALS. The secondary outcomes were the rate of decline in the total revised ALS functional rating scale score, slow vital capacity change, time to death, tracheotomy or permanent ventilation and serum light neurofilament level at 6 months. The primary assessment of efficacy was performed using intention-to-treat analysis. The treatment arms using 64 mg and 32 mg guanabenz, both alone and combined, reached the primary hypothesis of non-futility, with the proportions of patients who progressed to higher stages of disease at 6 months being significantly lower than that expected under the hypothesis of non-futility and a significantly lower difference in the median rate of change in the total revised ALS functional rating scale score. This effect was driven by patients with bulbar onset, none of whom (0/18) progressed to a higher stage of disease at 6 months compared with those on 16 mg guanabenz (4/8; 50%), the historical cohort alone (21/49; 43%; P = 0.001) or plus placebo (25/60; 42%; P = 0.001). The proportion of patients who experienced at least one adverse event was higher in any guanabenz arm than in the placebo arm, with higher dosing arms having a significantly higher proportion of drug-related side effects and the 64 mg arm a significantly higher drop-out rate. The number of serious adverse events did not significantly differ between the guanabenz arms and the placebo. Our findings indicate that a larger trial with a molecule targeting the unfolded protein response pathway without the alpha-2 adrenergic related side-effect profile of guanabenz is warranted.

Stereochemistry of Astaxanthin Biosynthesis in the Marine Harpacticoid Copepod Tigriopus Californicus.

The harpacticoid copepod Tigriopus californicus has been recognized as a model organism for the study of marine pollutants. Furthermore, the nutritional profile of this copepod is of interest to the aquafeed industry. Part of this interest lies in the fact that Tigriopus produces astaxanthin, an essential carotenoid in salmonid aquaculture. Here, we study for the first time the stereochemistry of the astaxanthin produced by this copepod. We cultured T. californicus with different feeding sources and used chiral high-performance liquid chromatography with diode array detection (HPLC-DAD) to determine that T. californicus synthesizes pure 3S,3'S-astaxanthin. Using meso-zeaxanthin as feed, we found that the putative ketolase enzyme from T. californicus can work with ß-rings with either 3R- or 3S-oriented hydroxyl groups. Despite this ability, experiments in the presence of hydroxylated and non-hydroxylated carotenoids suggest that T. californicus prefers to use the latter to produce 3S,3'S-astaxanthin. We suggest that the biochemical tools described in this work can be used to study the mechanistic aspects of the recently identified avian ketolase.

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.

Macular response to supplementation with differing xanthophyll formulations in subjects with and without age-related macular degeneration.

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.

Determinants of patient satisfaction and function related to vision following cataract surgery in eyes with no visually consequential ocular co-morbidity.

PURPOSE: To investigate subjectively reported outcomes following cataract surgery and the relationships between such outcomes in the context of falling thresholds for cataract surgery. SETTING: Large, private, non-refractive cataract practice, Institute of Eye Surgery, Whitfield Clinic, Waterford, Ireland METHODS: Pre-operative, intra-operative and post-operative data of 2552 eyes undergoing phacoemulsification and implantation of the Tecnis(R) ZCB00 1-piece intraocular lens (IOL) by a single surgeon between July 2009 and October 2013 was analysed. Patients without visually consequential ocular co-morbidity completed two validated questionnaires, designed to assess subjectively perceived visual functioning and identify symptoms of dysphotopsia following cataract surgery. RESULTS: 54.8 % of questionnaire respondents were entirely satisfied (satisfaction 10/10) post-operatively, with 83.7 % reporting satisfaction of ≥7/10. Satisfaction was positively associated with patient age and negatively associated with spectacle dependence, dysphotopsia, and function related to vision (NEI VF-11) score. The mean (±standard deviation[SD]) dysphotopsia score was 1.36 (±1.9; scale 0-10), with 40 % of respondents reporting no dysphotopsia symptoms and 9.8 % reporting clinically meaningful dysphotopsia. The mean (±SD) National Eye Institute visual function-11 (NEI VF-11) score was 0.33 (±0.53; scale 0-4) and reduced function related to vision was associated with increasing severity of dysphotopsia symptoms. When linear regression was applied, 17.5 % of the variation in functionality was attributable to symptoms of dysphotopsia. CONCLUSION: Dysphotopsia is an important determinant of a patient having difficulty with vision-related tasks following cataract surgery, and patient satisfaction is positively associated with patient age and negatively associated with spectacle in dependence, dysphotopsia and function related to the vision (NEI VF-11) score.

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.

Secondary outcomes in a clinical trial of carotenoids with coantioxidants versus placebo in early age-related macular degeneration.

PURPOSE: To report the secondary outcomes in the Carotenoids with Coantioxidants in Age-Related Maculopathy trial. DESIGN: Randomized double-masked placebo-controlled clinical trial (registered as ISRCTN 94557601). PARTICIPANTS: Participants included 433 adults 55 years of age or older with early age-related macular degeneration (AMD) in 1 eye and late-stage disease in the fellow eye (group 1) or early AMD in both eyes (group 2). INTERVENTION: An oral preparation containing lutein (L), zeaxanthin (Z), vitamin C, vitamin E, copper, and zinc or placebo. Best-corrected visual acuity (BCVA), contrast sensitivity (CS), Raman spectroscopy, stereoscopic colour fundus photography, and serum sampling were performed every 6 months with a minimum follow-up time of 12 months. MAIN OUTCOME MEASURES: Secondary outcomes included differences in BCVA (at 24 and 36 months), CS, Raman counts, serum antioxidant levels, and progression along the AMD severity scale (at 12, 24, and 36 months). RESULTS: The differential between active and placebo groups increased steadily, with average BCVA in the former being approximately 4.8 letters better than the latter for those who had 36 months of follow-up, and this difference was statistically significant (P = 0.04). In the longitudinal analysis, for a 1-log-unit increase in serum L, visual acuity was better by 1.4 letters (95% confidence interval, 0.3-2.5; P = 0.01), and a slower progression along a morphologic severity scale (P = 0.014) was observed. CONCLUSIONS: Functional and morphologic benefits were observed in key secondary outcomes after supplementation with L, Z, and coantioxidants in persons with early AMD.

Investigation of genetic variation in scavenger receptor class B, member 1 (SCARB1) and association with serum carotenoids.

OBJECTIVE: To investigate association of scavenger receptor class B, member 1 (SCARB1) genetic variants with serum carotenoid levels of lutein (L) and zeaxanthin (Z) and macular pigment optical density (MPOD). DESIGN: A cross-sectional study of healthy adults aged 20 to 70. PARTICIPANTS: We recruited 302 participants after local advertisement. METHODS: We measured MPOD by customized heterochromatic flicker photometry. Fasting blood samples were taken for serum L and Z measurement by high-performance liquid chromatography and lipoprotein analysis by spectrophotometric assay. Forty-seven single nucleotide polymorphisms (SNPs) across SCARB1 were genotyped using Sequenom technology. Association analyses were performed using PLINK to compare allele and haplotype means, with adjustment for potential confounding and correction for multiple comparisons by permutation testing. Replication analysis was performed in the TwinsUK and Carotenoids in Age-Related Eye Disease Study (CAREDS) cohorts. MAIN OUTCOME MEASURES: Odds ratios for MPOD area, serum L and Z concentrations associated with genetic variations in SCARB1 and interactions between SCARB1 and gender. RESULTS: After multiple regression analysis with adjustment for age, body mass index, gender, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, smoking, and dietary L and Z levels, 5 SNPs were significantly associated with serum L concentration and 1 SNP with MPOD (P<0.01). Only the association between rs11057841 and serum L withstood correction for multiple comparisons by permutation testing (P<0.01) and replicated in the TwinsUK cohort (P = 0.014). Independent replication was also observed in the CAREDS cohort with rs10846744 (P = 2×10(-4)), an SNP in high linkage disequilibrium with rs11057841 (r(2) = 0.93). No interactions by gender were found. Haplotype analysis revealed no stronger association than obtained with single SNP analyses. CONCLUSIONS: Our study has identified association between rs11057841 and serum L concentration (24% increase per T allele) in healthy subjects, independent of potential confounding factors. Our data supports further evaluation of the role for SCARB1 in the transport of macular pigment and the possible modulation of age-related macular degeneration risk through combating the effects of oxidative stress within the retina. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosures may be found after the references.

Concordance of macular pigment measurements obtained using customized heterochromatic flicker photometry, dual-wavelength autofluorescence, and single-wavelength reflectance.

This study compares in vivo 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: R(2) = 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: R(2) = 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.

Serum response to supplemental macular carotenoids in subjects with and without age-related macular degeneration.

Macular pigment (MP) is composed of lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ). The present study reports on serum response to three different MP supplements in normal subjects (n 27) and in subjects with age-related macular degeneration (AMD) (n 27). Subjects were randomly assigned to: Group 1 (20 mg L and 2 mg Z), Group 2 (10 mg L, 2 mg Z and 10 mg MZ) or Group 3 (3 mg L, 2 mg Z and 17 mg MZ). Serum carotenoids were quantified at baseline, and at 4 and 8 weeks using HPLC. Response data for normal and AMD subjects were comparable and therefore combined for analysis. We report response as the average of the 4- and 8-week concentrations (saturation plateau). Serum L increased significantly in Group 1 (0·036 µmol/l per mg (269 %); P< 0·001) and Group 2 (0·079 µmol/l per mg (340 %); P< 0·001), with no significant change in Group 3 (0·006 µmol/l per mg (7 %); P= 0·466). Serum Z increased significantly in Group 1 (0·037 µmol/l per mg (69 %); P= 0·001) and Group 2 (0·015 µmol/l per mg (75 %); P< 0·001), with no significant change in Group 3 ( − 0·0002 µmol/l per mg ( − 6 %); P= 0·384). Serum MZ increased significantly in Group 1 (0·0094 µmol/l (absolute value); P= 0·015), Group 2 (0·005 µmol/l per mg; P< 0·001) and Group 3 (0·004 µmol/l per mg; P< 0·001). The formulation containing all three macular carotenoids (Group 2 supplement) was the most efficacious in terms of achieving the highest combined concentration of the three MP constituent carotenoids in serum, thereby potentially optimising the bioavailability of these compounds for capture by the target tissue (retina).

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.

Comment on Richer et al. Night Vision and Carotenoids (NVC): A Randomized Placebo Controlled Clinical Trial on Effects of Carotenoid Supplementation on Night Vision in Older Adults. Nutrients 2021, 13, 3191.

Richer and colleagues [...].

Intensive production of the harpacticoid copepod Tigriopus californicus in a zero-effluent 'green water' bioreactor.

Aquaculture is looking for substitutes for fishmeal and fish oil to maintain its continued growth. Zooplankton is the most nutritious option, but its controlled mass production has not yet been achieved. In this context, we have developed a monoalgal 'green water' closed-loop bioreactor with the microalgae Tetraselmis chui that continuously produced the harpacticoid copepod Tigriopus californicus. During 145 days of operation, the 2.2 m3 bioreactor produced 3.9 kg (wet weight) of Tigriopus with (dry weight) 0.79 ± 0.29% eicosapentaenoic acid (EPA), 0.82 ± 0.26% docosahexaenoic acid (DHA), 1.89 ± 0,60% 3S,3'S-astaxanthin and an essential amino acid index (EAAI) of 97% for juvenile Atlantic salmon. The reactor kept the pH stable over the operation time (pH 8.81 ± 0.40 in the algae phase and pH 8.22 ± 2.96 in the zooplankton phase), while constantly removed nitrate (322.6 mg L-1) and phosphate (20.4 mg L-1) from the water. As a result of the stable pH and nutrient removal, the bioreactor achieved zero effluent discharges. The upscaling of monoalgal, closed-loop 'green water' bioreactors could help standardize zooplankton mass production to supply the aquafeeds industry.

The Use of Fixation Suture to Treat Inferonasal Hypertrophic Bleb after Xen Gel Stent Implant: A Case Report.

We report a case of an inferonasal hypertrophic bleb complication which formed 5 months after Xen Gel Stent implantation for intraocular pressure (IOP) control in a primary open-angle glaucoma patient and its management using a fixation suture. The patient underwent an uneventful right-eye phacoemulsification and intraocular lens implantation combined with Xen Gel Stent ab interno implantation surgery. A month after the surgery, a second needling was performed due to a flat bleb and increased IOP. Post-needling slit-lamp examination showed a well-formed diffuse bleb in the superonasal quadrant. Two months after the needling, the patient presented with redness and irritation medially. Upon examination, a large inferonasal bleb was observed together with scarring of a previously formed superior bleb above the Xen Gel Stent implant. Fornix-based conjunctival incision technique was used to release the conjunctival scarring, and a fixation suture was used for the Xen implant in order to change the filtration direction. A Palmberg compression mattress suture was used to stop the inferior filtration. Despite an open conjunctiva surgical revision in the superior quadrant, no additional scaring was formed in the follow-up period of 20 months. There was good post-operative IOP control and formation of superiorly positioned bleb. To our knowledge, this is the first report to describe the use of a fixation suture for treating inferonasal hypertrophic bleb as a late complication of Xen Gel Stent implantation surgery.

Omega-3 fatty acid, carotenoid and vitamin E supplementation improves working memory in older adults: A randomised clinical trial.

BACKGROUND & AIMS: Accumulating evidence suggests that omega-3 fatty acids (ω-3FAs), carotenoids and vitamin E can improve cognitive performance. However, their collective impact on cognition has not yet been investigated in healthy individuals. This study investigated the combined effect of ω-3FA, carotenoid and vitamin E supplementation on the cognitive performance of older adults. METHODS: Cognitively healthy individuals aged ≥65 years consumed daily 1 g fish oil (of which 430 mg docosahexaenoic acid, 90 mg eicosapentaenoic acid), 22 mg carotenoids (10 mg lutein, 10 mg meso-zeaxanthin, 2 mg zeaxanthin) and 15 mg vitamin E or placebo for 24 months in a double-blind, placebo-controlled, randomised clinical trial. RESULTS: Following 24-month supplementation, individuals in the active group (n = 30; aged 69.03 ± 4.41 years; 56.7% female) recorded significantly fewer errors in working memory tasks than individuals receiving placebo (n = 30; aged 69.77 ± 3.74 years; 70% female) (point estimate effect sizes ranged 0.090-0.105). Interestingly, as the cognitive load of the working memory tasks increased, the active group outperformed the placebo group. Statistically significant improvements in tissue carotenoid concentrations, serum xanthophyll carotenoid concentrations and plasma ω-3FA concentrations were also observed in the active group versus placebo (point estimate effect sizes ranged 0.078-0.589). Moreover, the magnitude of change of carotenoid concentrations in tissue, and ω-3FA and carotenoid concentrations in blood were related to the magnitude of change in working memory performance. CONCLUSION: These results support a biologically plausible rationale whereby these nutrients work synergistically, and in a dose-dependent manner, to improve working memory in cognitively healthy older adults. Increasing nutritional intake of carotenoids and ω-3FAs may prove beneficial in reducing cognitive decline and dementia risk in later life. STUDY ID NUMBER: ISRCTN10431469; https://doi.org/10.1186/ISRCTN10431469.

INTERNAL DRAINAGE OF SUBRETINAL FLUID DURING CHANDELIER-ASSISTED SCLERAL BUCKLING.

PURPOSE: To describe the surgical technique of internal drainage of subretinal fluid as an adjunct to chandelier-assisted scleral buckling for the repair of rhegmatogenous retinal detachment. METHODS: The technique of internal drainage with a sharp needle or cannula through a trocar is described and shown in a Supplemental Digital Content 1 (see Video, http://links.lww.com/ICB/A87). RESULTS: Three patients (3 eyes) underwent scleral buckling for rhegmatogenous retinal detachment repair. Subretinal fluid was drained using the internal drainage approach in all cases. All three patients had successful reattachment of retina with improvement in visual function. No complications were reported related to vitreous loss, retinal incarceration, or redetachment following primary surgery. CONCLUSION: Internal drainage of subretinal fluid during chandelier-assisted scleral buckling is a useful technique that can be considered for repairing rhegmatogenous retinal detachment.

Impact of symptomatic vitreous degeneration on photopic and mesopic contrast thresholds.

CLINICAL RELEVANCE: Contrast thresholds under photopic and mesopic luminance conditions are compromised in subjects with vitreous degeneration. A plausible explanation is needed for the visual discomfort expressed by patients suffering from symptomatic vitreous degeneration. BACKGROUND: The current study investigates the effect of symptomatic vitreous degeneration on photopic and mesopic contrast at high spatial frequencies. METHODS: An age-matched sample of 115 subjects, comprising 30 subjects with symptomatic vitreous floaters (cases) and 85 healthy subjects (controls), was included in this study. Visual acuity and flicker thresholds were measured for all participants. Photopic and mesopic functional contrast thresholds at 10 cycles per degree were measured for all participants to assess the effect of floaters on contrast. Further, to determine the effect of posterior vitreous detachment on contrast, the sample was divided into three groups: cases with posterior vitreous detachment (n = 12); cases without posterior vitreous detachment (n = 18); and controls (n = 85), and their contrast thresholds were compared. RESULTS: Photopic and mesopic contrast thresholds were lower by 37.4% and 27.5%, respectively, when the cases were compared with the controls (p = 0.028 and p < 0.001 for photopic and mesopic contrast thresholds, respectively). Photopic contrast was lower by 64.0% in cases with posterior vitreous detachment compared with controls (p = 0.001). Compared with controls, mesopic contrast was lower in cases with posterior vitreous detachment and in cases without posterior vitreous detachment by 30.3% and 25.6%, respectively (p = 0.014 and p = 0.017 for cases with and without posterior vitreous detachment, respectively). CONCLUSION: : Subjects with vitreous degeneration have diminished photopic and mesopic contrast thresholds compared with controls. This finding highlights the negative impact of vitreous degeneration on the quality of vision.

Supplementation With Carotenoids, Omega-3 Fatty Acids, and Vitamin E Has a Positive Effect on the Symptoms and Progression of Alzheimer's Disease.

BACKGROUND: Preliminary work by our center has reported behavior and functional benefits in patients with Alzheimer's disease (AD) following targeted micronutritional supplementation. OBJECTIVE: To build on the existing exploratory research and investigate the impact of these micronutrients on the natural progression of AD in a randomized controlled trial. METHODS: Patients with mild-moderate AD consumed daily 1 g fish oil (of which 500 mg DHA, 150 mg EPA), 22 mg carotenoids (10 mg lutein, 10 mg meso-zeaxanthin, 2 mg zeaxanthin), and 15 mg vitamin E or placebo for 12 months in a double-blind, placebo-controlled, randomized clinical trial. Carotenoids, ω-3FAs, and vitamin E were quantified in blood. Carotenoids were also measured in skin. AD severity was measured using the mini-mental state examination and dementia severity rating scale tools. Behavior, mood, and memory were measured using an informant-based questionnaire. RESULTS: Following 12 months of supplementation, the active group (n = 50) compared to the placebo group (n = 27), demonstrated statistically significant improvements in skin carotenoid measurements, blood carotenoids, ω-3FAs, and vitamin E concentrations (p < 0.05, for all). The active group also performed better in objective measures of AD severity (i.e., memory and mood), with a statistically significant difference reported in the clinical collateral for memory (p < 0.001). CONCLUSION: Exponential increases in the prevalence of AD and its relentless progressive nature is driving the need for interventions that help to ameliorate symptoms and improve quality of life in AD patients. Given the positive outcomes demonstrated in this trial, this combined micronutrient dietary supplement should be considered in the overall management of AD.

The association between macular pigment optical density and CFH, ARMS2, C2/BF, and C3 genotype.

Age-related macular degeneration (AMD) is the most common cause of blindness in older people in developed countries, and risk for this condition may be classified as genetic or environmental, with an interaction between such factors predisposing to this disease. This study investigated the relationship between AMD risk genes, macular pigment optical density (MPOD), which may protect against AMD, and serum concentrations of the macular carotenoids, lutein (L) and zeaxanthin (Z). This was a cross-sectional study of 302 healthy adult subjects. Dietary intake of L and Z was assessed by food frequency questionnaire, and MPOD was measured by customized heterochromatic flicker photometry. We also calculated MPOD Area as the area of MP under the spatial profile curve, to reflect MP across the macula. Serum L and Z were measured by HPLC. Genotyping of tag SNPs in the genes CFH, ARMS2, C3, C2 and BF was undertaken with multiplex polymerase chain reaction (PCR) and primer extension methodology (ABI Snapshot, ABI Warrington UK) on DNA extracted from peripheral blood. The mean ± SD (range) age of the subjects in this study was 48 ± 11 (21-66) years. There was a statistically significant association between CFH genotype and family history of AMD, with subjects having two non-risk CFH haplotypes (n = 35), or one non-risk and one protective CFH haplotype (n = 33), being significantly more likely to have a negative family history of AMD (Pearson Chi square: p = 0.001). There was no significant association between the AMD risk genes investigated and either MPOD (One way ANOVA: p > 0.05) or serum concentrations of L or Z (One way ANOVA: p > 0.05, for both). Subjects who were homozygous for risk alleles of both CFH and ARMS2 (n = 4) had significantly lower MPOD at 0.5° and 1° retinal eccentricity (Independent samples t test: p < 0.05) and lower MPOD Area which approached statistical significance (Independent samples t test: p = 0.058), compared to other subjects (n = 291). In conclusion, this study did not detect an association between individual AMD risk genotypes and the putatively protective MP, or serum concentrations of its constituent carotenoids. However, the combination of homozygous risk alleles at both CFH and ARMS2 loci was associated with significantly lower MPOD centrally, despite comparable serum concentrations of the macular carotenoids. These findings suggest that the maculae of subjects at very high genetic risk of AMD represent a hostile environment for accumulation and/or stabilization of MP.

Changes in macular pigment optical density and serum concentrations of lutein and zeaxanthin in response to weight loss.

The objective of the present study was to investigate whether weight loss is associated with changes in serum concentrations of lutein (L) and zeaxanthin (Z), and/or macular pigment optical density (MPOD). We recruited 104 overweight subjects into this randomised controlled weight loss study. For the intervention group (I group), weight was assessed weekly and body composition, including BMI (kg/m2) and body fat (kg and percentage), was assessed at baseline, 6 and 12 months. Weight loss was encouraged using dietary and exercise programmes. MPOD was measured by heterochromatic flicker photometry and serum concentrations of L and Z by HPLC (at baseline, 1, 3, 6 and 12 months). The control (C) group was assessed at baseline and 12 months. Repeated-measures ANOVA (RMA) demonstrated significant weight loss in the I group over the study period (P = 0·000). There was no significant weight change in the C group (P = 0·993). RMA of dietary L and Z, serum L and Z, and MPOD demonstrated no significant time or time × group interaction effect in any of these parameters (P>0·05 for all), with the exception of a significant decrease in the dietary intake of Z seen in both groups, over the study period (P < 0·05). There was a positive and significant relationship between body fat loss (kg) and increase in serum concentrations of L in the I group (r 0·521; P = 0·006). Our finding that a reduction in body composition (e.g. fat mass) is related to increases in serum concentrations of L is consistent with the hypothesis that body fat acts as a reservoir for this carotenoid, and that weight loss can positively influence circulating carotenoid levels.