The Relationship Between Caffeine Intake and Dry Eye Disease.

PURPOSE: The aim of this study was to determine the association between caffeine intake and dry eye disease (DED) in the large, population-based LifeLines cohort in the Netherlands. METHODS: DED was cross-sectionally assessed in 85,302 participants (59% female participants) using the Women's Health Study dry eye questionnaire. Dietary caffeine was calculated from the intake of coffee, tea, cola, and energy drinks. Logistic regression was used to investigate the relationship between DED and caffeine, correcting for demographic variables, smoking status, alcohol intake, and 48 comorbidities of DED. RESULTS: The mean (SD; range) age of participants was 50.7 years (12.4; 18-96), and 50,339 (59%) were female. The mean (SD) caffeine intake was 285 (182) mg/d. After correcting for demographics, body mass index, smoking status, and alcohol intake, higher caffeine intake was associated with a decreased risk of Women's Health Study-defined DED [odds ratio (OR) 0.971 per 100 mg/d, 95% CI, 0.956-0.986, P < 0.0005]. When additionally adjusting for medical comorbidities, no significant effect was observed (OR 0.985, 95% CI, 0.969-1.001, P = 0.06). Caffeine's effect on DED was similar in male and female participants and independent of sleep quality and stress at work. Decaffeinated coffee intake was significantly associated with an increased risk of DED, when adjusted for caffeinated coffee, demographics, alcohol intake, smoking status, and comorbidities (OR 1.046 per cup/d, 95% CI, 1.010-1.084, P = 0.01). None of the beverages were significantly associated with the risk of DED, when correcting for intake of the other caffeinated beverages, demographics, smoking status, alcohol intake, and all comorbidities. CONCLUSIONS: Dietary caffeine intake does not seem to be a risk factor for DED in the general population.

Temporal dynamics of the relationship between change in depressive symptoms and cannabis use in adolescents receiving psychosocial treatment for cannabis use disorder.

AIMS: Cannabis use disorder (CUD) and depression frequently co-occur in youth. How depressive symptoms change over the course of CUD treatment and how they impact substance use treatment outcomes is unknown. In the current study, we examine the temporal relationships between cannabis use and depression in adolescents receiving evidence-based treatments for CUD as part of a multisite clinical trial. DESIGN: Six hundred adolescents (age 12-18) with a CUD were randomly assigned to substance use treatment from one of five evidence-based psychosocial interventions. We assessed self-reported cannabis use frequency and depressive symptoms at baseline (BL) and again at 3-, 6-, 9, and 12-months. A bivariate latent change model assessed bidirectional effects of baseline levels and time-lagged changes in depressive symptoms and cannabis use on depression and cannabis use outcomes. FINDINGS: Depressive symptoms (72%) and major depressive disorder (MDD) (18%) were common at BL. Both depression and cannabis use decreased over time and change in cannabis use was significantly associated with change in depressive symptoms (b = 1.22, p = .003). Time-lag analyses showed that within-subject change in depression (from one time point to the next) was predicted by previous depression (b = -0.71, p < .001) but not cannabis use (p = .068), and change (decrease) in cannabis use was predicted by previous (greater) depressive symptoms (b = -1.47, p < .001) but not cannabis use (p = .158), respectively. CONCLUSION: These findings indicate an enduring relationship between decreasing cannabis use and decreasing depression among adolescents lasting for 9-months after receiving psychosocial interventions for CUD. The presence of depressive symptoms did not appear to interfere with substance use treatment or attenuate improvements in cannabis use frequency. A decrease in cannabis use was not contingent upon a reduction in depressive symptoms. These findings are limited by the possibility of regression to the mean for both cannabis use and depressive symptoms, and the lack of a nonintervention control group.

Genetic and Dietary Factors Influencing the Progression of Nuclear Cataract.

PURPOSE: To determine the heritability of nuclear cataract progression and to explore prospectively the effect of dietary micronutrients on the progression of nuclear cataract. DESIGN: Prospective cohort study. PARTICIPANTS: Cross-sectional nuclear cataract and dietary measurements were available for 2054 white female twins from the TwinsUK cohort. Follow-up cataract measurements were available for 324 of the twins (151 monozygotic and 173 dizygotic twins). METHODS: Nuclear cataract was measured using a quantitative measure of nuclear density obtained from digital Scheimpflug images. Dietary data were available from EPIC food frequency questionnaires. Heritability was modeled using maximum likelihood structural equation twin modeling. Association between nuclear cataract change and micronutrients was investigated using linear and multinomial regression analysis. The mean interval between baseline and follow-up examination was 9.4 years. MAIN OUTCOME MEASURES: Nuclear cataract progression. RESULTS: The best-fitting model estimated that the heritability of nuclear cataract progression was 35% (95% confidence interval [CI], 13-54), and individual environmental factors explained the remaining 65% (95% CI, 46-87) of variance. Dietary vitamin C was protective against both nuclear cataract at baseline and nuclear cataract progression (ß = -0.0002, P = 0.01 and ß = -0.001, P = 0.03, respectively), whereas manganese and intake of micronutrient supplements were protective against nuclear cataract at baseline only (ß = -0.009, P = 0.03 and ß = -0.03, P = 0.01, respectively). CONCLUSIONS: Genetic factors explained 35% of the variation in progression of nuclear cataract over a 10-year period. Environmental factors accounted for the remaining variance, and in particular, dietary vitamin C protected against cataract progression assessed approximately 10 years after baseline.

Optic disc planimetry, corneal hysteresis, central corneal thickness, and intraocular pressure as risk factors for glaucoma.

PURPOSE: To determine whether corneal hysteresis and central corneal thickness are independent risk factors for glaucoma. DESIGN: A cross-sectional population-based cohort study. METHODS: Associations were tested between corneal hysteresis, measured in 1754 population-based subjects from the TwinsUK cohort, and glaucoma-related endophenotypes, including intraocular pressure (IOP), vertical cup-to-disc ratio, optic disc area, and optic disc cup area. Corneal hysteresis, IOP, and central corneal thickness (CCT) were measured; optic disc photographs were analyzed; and multivariable linear regression analysis was performed. RESULTS: Data were available on 1645 individuals. Multiple regression analysis showed corneal hysteresis to be significantly negatively associated with age (beta coefficient = -0.03, P < .00005) and IOP (beta coefficient = -0.06, P < .00005). Corneal hysteresis was also found to be associated with CCT (beta coefficient = 0.02, P < .0005). There was no significant association between corneal hysteresis and optic disc area (P = .6), cup area (P = .77), vertical cup-to-disc ratio (P = .51), or spherical equivalent (P = .08). CCT was also found to be significantly associated with IOP (beta coefficient = 3.3, P < .0005) and corneal hysteresis (beta coefficient = 9.4, P < .0005), but not with age (P = .59) or spherical equivalent (P = .16). CONCLUSION: In this large cohort of healthy British twins, we found no relationship between corneal hysteresis or CCT and quantitative measures of optic disc cupping, suggesting that corneal hysteresis and CCT are not independent risk factors for glaucoma.

Candidate gene study of macular response to supplemental lutein and zeaxanthin.

Supplementation with carotenoids is proposed to protect against age-related macular degeneration. There is, however, considerable variability in retinal macular pigment response, which may be due to underlying genetic variation. The purpose of this study was to determine whether genetic factors, which have been previously associated with cross-sectional macular pigment levels in the retina or serum lutein, also influence response to supplementation. To this end we conducted an association study in 310 subjects from the TwinsUK cohort between variants in 8 candidate genes and serum lutein and retinal macular pigment optical density (MPOD) levels before and after supplementation. Four variants were associated with MPOD response to supplementation (p < 0.05): rs11057841 (SCARB1), rs4926339 (RPE65), rs1929841 (ABCA1) and rs174534 (FADS1). We also confirmed previous associations between rs6564851 near BMCO1 (p < 0.001) and rs11057841 within SCARB1 (p = 0.01) and baseline measures of serum lutein; while the latter was also associated with MPOD response, none of the BMCO1 variants were. Finally, there was evidence for association between variants near RPE65 and ELOVL2 and changes in lutein concentration after supplementation. This study is the first to show association between genetic variants and response to carotenoids supplementation. Our findings suggest an important link between MP response and the biological processes of carotenoids transport and fatty acid metabolism.

The heritability of macular response to supplemental lutein and zeaxanthin: a classic twin study.

PURPOSE: Antioxidant supplements may reduce age-related macular degeneration (AMD) progression. The macular carotenoids are of particular interest because of their biochemical, optical, and anatomic properties. This classic twin study was designed to determine the heritability of macular pigment (MP) augmentation in response to supplemental lutein (L) and zeaxanthin (Z). METHODS: A total of 322 healthy female twin volunteers, aged 16-50 years (mean 40 ± 8.7) was enrolled in a prospective, nonrandomized supplement study. Macular pigment optical density (MPOD) measurements using two techniques (2-wavelength fundus autofluorescence [AF] and heterochromatic flicker photometry [HFP]), and serum concentrations of L and Z, were recorded at baseline, and at 3 and 6 months following daily supplementation with 18 mg L and 2.4 mg Z for a study period of 6 months. RESULTS: At baseline, mean MPOD was 0.44 density units (SD 0.21, range 0.04-1.25) using HFP, and 0.41 density units (SD 0.15) using AF. Serum L and Z levels were raised significantly from baseline following 3 months' supplementation (mean increase 223% and 633%, respectively, P < 0.0001 for both), with no MPOD increase. After 6 months' supplementation, a small increase in MPOD was seen (mean increase 0.025 ± 0.16, P = 0.02, using HFP). Subdivision of baseline MPOD into quartiles revealed that baseline levels made no difference to the treatment effect. Genetic factors explained 27% (95% confidence interval [CI] 7-45) of the variation in MPOD response. Distribution profiles of macular pigment did not change in response to supplementation. CONCLUSIONS: MPOD response to supplemental L and Z for a period of 6 months was small (an increase over baseline of 5.7% and 3.7%, measured using HFP and AF, respectively), and was moderately heritable. Further study is indicated to investigate the functional and clinical impact of supplementation with the macular carotenoids.

Volatiles from leaves and rhizomes of Fragrant Acorus spp. (Acoraceae).

Three horticultural selections of Acorus gramineus Soland were investigated to determine the chemical composition of their leaves and rhizomes. The variety 'liquorice' was found to contain methylchavicol (49%) which accounts for the unusual anisic odor of this variety, while beta-asarone was the main component of A. christophii (43%) and 'yodo-no-yuki' (20%). The results are compared with calamus oils, and the possible biosynthetic precursors of the main components methylchavicol and beta-asarone are considered.

Volatile organic nitrogen-containing constituents in ambrette seed Abelmoschus moschatus Medik (Malvaceae).

A detailed investigation of the basic fraction of a CO2 extract of ambrette seeds (Abelmoschus moschatus) revealed a total of 58 nitrogen-containing compounds. The identification of these compounds was carried out by GC-MS and NMR. All the identified nitrogen-containing compounds are reported here for the first time in ambrette seeds. Among these are 27 pyrazine derivatives and 12 pyridines, including the tentative identification of four new natural compounds, 1-(6-ethyl-3-hydroxypyridin-2-yl)ethanone (1), 1-(3-hydroxy-5,6-dimethylpyridin-2-yl)ethanone (2), 1-(3-hydroxy-6-methylpyridin-2-yl)ethanone (3), and 1-(3-hydroxy-5-methylpyridin-2-yl)ethanone (4). The odor of the basic fraction was assumed to be due to these pyrazines and pyridines and also the presence of seven thiazoles. The odors described suggest that these N-compounds contribute to what is described in perfumery terms as the "natural and rounded" character of the ambrette extract.

Vertical diplopia following peribulbar anesthesia: the role of hyaluronidase.

PURPOSE: To estimate the incidence of vertical diplopia following peribulbar anesthesia in otherwise uncomplicated cataract surgery and to establish whether the use of hyaluronidase in the peribulbar injection mixture affected the likelihood of this complication. METHODS: Nine hundred forty consecutive phacoemulsification procedures using peribulbar anesthesia were retrospectively reviewed to identify cases of postoperative vertical diplopia. Case notes were reviewed to establish the nature and timing of the onset of diplopia, the anesthetic technique, and whether hyaluronidase was used. The patterns of progression as demonstrated by serial Hess charts were compared. RESULTS: There were 6 cases of vertical diplopia (incidence, 0.64%). All showed an immediate postoperative hypertropia in the injected eye changing during a 4- to 6-week period to hypotropia with restriction of upgaze. All applications of anesthesia were administered by consultant anesthetists, associate specialists, or residents under their direct supervision using 25-mm, 25-gauge needles with 2% lidocaine. Hyaluronidase was included in the injection mixture for 435 (46%) of the cases and was not included for 505 (54%) of the cases. All 6 cases of vertical diplopia occurred in the group in which hyaluronidase was not used, which has a significant association (chi-square test, 5.22; P = .023). CONCLUSION: Hyaluronidase should be included in peribulbar anesthetics to reduce the risk of postoperative vertical diplopia.