Twelve-month clinical outcomes after implantation of a new, modular, anterior shape-changing fluid optic intraocular lens.

PURPOSE: To report the initial safety and effectiveness profile for an anterior shape-changing, modular IOL, Juvene IOL (JIOL), for the treatment of aphakia and presbyopia after removal of the natural crystalline lens due to cataract. SETTING: 2 private practices in Monterrey and Tijuana, Mexico. DESIGN: Exploratory prospective multicenter open-label noncomparative clinical trial. METHODS: A convenience sample of patients aged 50 to 80 years with planned cataract surgery was recruited to undergo unilateral or bilateral implantation with the JIOL. Patients were required to complete an informed consent and be able to dilate to at least 6.0 mm pharmacologically, be in good overall health, and have no significant eye health history to qualify. Visual acuities, defocus curves, and contrast sensitivity were measured for all patients 12 months postoperatively. RESULTS: 51 of 58 eyes completed the 12-month visit. Intraoperative complication rates were extremely low (n = 1; missed base lens tab). The most frequent adverse events (AEs) were prolonged inflammation (N = 6) and cystoid macular edema (N = 4); all AEs were resolved without sequelae by the 12-month visit. The mean monocular logMAR corrected distance visual acuity, distance-corrected intermediate visual acuity, and distance-corrected near visual acuity were 0.01, 0.08, and 0.24, respectively. Defocus testing showed visual acuity > 20/40 from approximately +1.00 through -2.00 diopters. Binocular implantation (n = 16) provided superior performance over monocular implantation. CONCLUSIONS: The JIOL offers a new solution to treat presbyopia, providing clear functional vision performance across a range of distances with an acceptable initial safety profile.

Effects of a Lutein and Zeaxanthin Intervention on Cognitive Function: A Randomized, Double-Masked, Placebo-Controlled Trial of Younger Healthy Adults.

Background: Past studies have suggested that higher lutein (L) and zeaxanthin (Z) levels in serum and in the central nervous system (as quantified by measuring macular pigment optical density, MPOD) are related to improved cognitive function in older adults. Very few studies have addressed the issue of xanthophylls and cognitive function in younger adults, and no controlled trials have been conducted to date to determine whether or not supplementation with L + Z can change cognitive function in this population. Objective: The purpose of this study was to determine whether or not supplementation with L + Z could improve cognitive function in young (age 18-30), healthy adults. Design: A randomized, double-masked, placebo-controlled trial design was used. Fifty-one young, healthy subjects were recruited as part of a larger study on xanthophylls and cognitive function. Subjects were randomized into active supplement (n = 37) and placebo groups (n = 14). MPOD was measured psychophysically using customized heterochromatic flicker photometry. Cognitive function was measured using the CNS Vital Signs testing platform. MPOD and cognitive function were measured every four months for a full year of supplementation. Results: Supplementation increased MPOD significantly over the course of the year, vs. placebo (p < 0.001). Daily supplementation with L + Z and increases in MPOD resulted in significant improvements in spatial memory (p < 0.04), reasoning ability (p < 0.05) and complex attention (p < 0.04), above and beyond improvements due to practice effects. Conclusions: Supplementation with L + Z improves CNS xanthophyll levels and cognitive function in young, healthy adults. Magnitudes of effects are similar to previous work reporting correlations between MPOD and cognition in other populations.

A double-blind, placebo-controlled study on the effects of lutein and zeaxanthin on photostress recovery, glare disability, and chromatic contrast.

PURPOSE: Past studies have shown that higher macular pigment optical density (MPOD) and lutein (L) and zeaxanthin (Z) supplementation are related to improvements in glare disability, photostress recovery, and chromatic contrast. This study assessed those links using a randomized, double-blind, placebo-controlled design. METHODS: The visual effects of 1 year of supplementing L (10 mg/d) and Z (2 mg/d) were investigated. One hundred fifteen young, healthy subjects were recruited and randomized into the study (58 received placebo, 57 L+Z). Several dependent measures were collected at baseline and then once every 3 months: serum L and Z measured by HPLC chromatography; MPOD measured using customized heterochromatic flicker photometry; photostress recovery assessed by measuring the time needed to recover visual acquisition of a grating target after 30 seconds of an intense xenon white flash exposure; glare disability evaluated as the energy in a surrounding annulus necessary to veil a central grating target; and chromatic contrast assessed by measuring thresholds for a yellow grating target superposed on a 460-nm background. RESULTS: Macular pigment optical density increased significantly versus placebo at all eccentricities (10, 30, 60, and 105 minutes from the center of the macula). Serum L and Z also increased significantly by the first follow-up visit (at 3 months), and remained elevated throughout the intervention period of 1 year. Chromatic contrast and photostress recovery time improved significantly versus placebo. Glare disability was correlated with macular pigment density throughout the study period but did not increase significantly in the treated group. CONCLUSIONS: Daily supplementation with L+Z resulted in significant increase in serum levels and MPOD and improvements in chromatic contrast and recovery from photostress. These results are consistent with past studies showing that increasing MPOD leads to improved visual performance. (ClinicalTrials.gov number, NCT00909090.).

Visibility through atmospheric haze and its relation to macular pigment.

PURPOSE: A major factor limiting the visibility of distant targets is veiling attributed to atmospheric scattering, known commonly as haze. It has been suggested that yellow filters (in this case, the macular pigments, MPs) could selectively absorb this haze, thus extending visual range. This study is an empirical test of the visibility hypothesis. METHODS: Twelve subjects had their full contrast sensitivity function (CSF) (represented by six spatial frequencies) assessed in the presence of two background conditions: simulated blue haze and short wave-deficient light. Contrast sensitivity at the peak of the CSF (7.5 cycles per degree) was measured in the presence of the same two backgrounds as the full CSF, with the addition of a broadband xenon background condition in a separate sample of 25 subjects. RESULTS: Simulated blue haze was found to uniformly reduce the CSF in the 12 subjects for whom the full CSF was assessed. Therefore, only the peak was measured in the larger sample of 25 subjects. Macular pigment density was significantly related to energy at threshold for both the haze and xenon backgrounds but not the short wave-deficient background. Thus, subjects with higher levels of MP could withstand more light before losing sight of the target. CONCLUSIONS: This result is consistent with previous modeling of the visibility hypothesis as well as visual range improvements seen when using an artificial MP filter.

Glare disability, photostress recovery, and chromatic contrast: relation to macular pigment and serum lutein and zeaxanthin.

PURPOSE: A large body of research has linked macular lutein and zeaxanthin to reduced risk of degenerative eye disease. The earliest published hypothesis for the role of the pigments was not based on chronic protection but immediate function. Recent data on macular pigment (MP) have shown that screening the foveal cones from short-wave light does, in fact, result in improvements in photostress recovery (PR), glare disability (GD), and chromatic contrast (CC). This study examined those relations on a larger sample. METHODS: A total of 150 young healthy subjects were assessed. Plasma samples were obtained from 100 subjects for HPLC quantification of serum xanthophylls. MP density was measured using customized heterochromatic flicker photometery. GD, PR, and CC were measured in Maxwellian view using a broadband xenon light source. GD was measured by increasing the intensity of an annulus until it veiled a central target. PR was measured as the time necessary to regain sight of a central target after a 5-second exposure to an intense bleaching light. CC was measured as the amount of light necessary in a 460-nm background to lose sight of a central target. RESULTS: MP density was significantly related to serum lutein and zeaxanthin combined (r = 0.31, P = 0.002), GD (r = 0.24, P = 0.0015), PR (r = -0.18, P = 0.01), and CC (r = 0.46, P = 0.00005). CONCLUSIONS: These results confirm earlier reports of a significant relation between variation in macular pigment optical density and immediate effects on visual function. As with many species, intraocular yellow filters in humans appear to improve many aspects of the visual stimulus. (ClinicalTrials.gov number, NCT00909090.).

Influence of the dietary carotenoids lutein and zeaxanthin on visual performance: application to baseball.

Macular pigment (MP) is composed of the yellow, blue-absorbing carotenoids lutein and zeaxanthin. Although distributed throughout the visual system, MP is heavily concentrated in the central retinal area (eg, screening the foveal cones). Because light must pass through MP before reaching the receptors, it filters significant amounts of short-wave energy. Individual variation in peak absorbance is large and ranges from 0.0 to 1.6 optical density units depending largely on dietary intake. Several important functions of MP have been proposed. MP may serve to protect the retina from damage by absorbing actinic short-wave light (analogous to internal sunglasses) or by inactivating highly reactive free radicals and oxygen triplicates that are the by-product of light-driven cellular activity. MP may also serve, as proposed more than a century ago, to improve the retinal image through optical mechanisms. Recent data suggest that the MP carotenoids reduce glare discomfort and disability, shorten photostress recovery times, enhance chromatic contrast, and increase visual range (how far one can see in the distance). Lutein and zeaxanthin within the brain might also increase temporal processing speeds. This article reviews the influences of MP on visual function by exploring the implications of these visual improvements for baseball players.

Protein kinase B phosphorylation of PIKfyve regulates the trafficking of GLUT4 vesicles.

Insulin-stimulated glucose uptake involves the recruitment of the glucose transporter 4 isoform (GLUT4) from an intracellular location to the plasma membrane of fat and muscle cells. Although the activation of the PI3-kinase/protein kinase B (PKB) pathway is central to this effect of insulin, the key substrates for PKB that are involved require identification. Here we report that serine318 on the FYVE domain-containing PtdIns3P 5-kinase (PIKfyve) is a novel substrate for PKB, and show that phosphorylation stimulates the PtdIns3P 5-kinase activity of the enzyme. We also demonstrate that PIKfyve is phosphorylated on serine318 in intact cells in response to insulin, in a PI3-kinase-dependent manner, and that PIKfyve colocalises with a highly motile subpopulation of insulin-regulated aminopeptidase (IRAP)/GLUT4 vesicles. Finally, we demonstrate that overexpression of a PIKfyve[S318A] mutant in 3T3-L1 adipocytes enhances insulin-stimulated IRAP/GLUT4 vesicle translocation to the plasma membrane suggesting a role for PKB-dependent phosphorylation of PIKfyve in insulin-regulated IRAP/GLUT4 trafficking. The phosphorylation and activation of PIKfyve by PKB provides a novel signalling paradigm that may link plasma membrane-localised PtdIns(3,4,5)P3 signals via a protein kinase cascade to regulated PtdIns(3,5)P2 production, and thereby to the control of trafficking of other membrane cargos.

Functional consequence of targeting protein kinase B/Akt to GLUT4 vesicles.

We have investigated the role of protein kinase B (Akt) in the insulin-stimulated translocation of vesicles containing the insulin-responsive isoform of glucose transporter (GLUT4) to the plasma membrane of adipocytes. Previous reports have suggested that protein kinase B can bind to intracellular GLUT4 vesicles in an insulin-dependent manner, but the functional consequence of this translocation is not known. In this study we have artificially targeted constitutively active and kinase-inactive mutants of protein kinase B to intracellular GLUT4 vesicles by fusing them with the N-terminus of GLUT4 itself. We examined the effect of these mutants on the insulin-dependent translocation of the insulin-responsive amino peptidase IRAP (a bona fide GLUT4-vesicle-resident protein). A kinase-inactive protein kinase B targeted to GLUT4 vesicles was an extremely effective dominant-negative inhibitor of insulin-stimulated IRAP translocation to the plasma membrane. By contrast, a kinase-inactive protein kinase B expressed in the cytoplasm did not have an effect. The results suggest that protein kinase B has an important functional role at, or in the vicinity of, GLUT4 vesicles in the insulin-dependent translocation of those vesicles to the plasma membrane of adipocytes.