Publications by authors named "Debra A Schaumberg"

78 Publications

The Effect of Lutein/Zeaxanthin Intake on Human Macular Pigment Optical Density: A Systematic Review and Meta-Analysis.

Adv Nutr 2021 Jun 22. Epub 2021 Jun 22.

Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Lutein, zeaxanthin, and meso-zeaxanthin are the only carotenoids found in the human macula and may have a role in visual function. These carotenoids are reported to protect the retina, and thus vision, as antioxidants and by acting as a blue light filter. Our objective was to determine a minimum concentration of lutein/zeaxanthin intake that is associated with a statistically significant and/or clinically important change in macular pigment optical density (MPOD) among adults with healthy eyes. We searched Ovid MEDLINE, CENTRAL, and the Commonwealth of Agriculture Bureau for English-language studies through to July 2020. Two reviewers screened results to identify studies that evaluated supplements or dietary sources of lutein/zeaxanthin on MPOD among adults with healthy eyes. One reviewer extracted data and assessed strength of evidence, which was confirmed by a second reviewer. Two independent reviewers assessed the risk of bias. Meta-analyses were stratified by total lutein/zeaxanthin dose. We included 46 studies (N = 3189 participants; mean age = 43 y; 42% male). There was no statistically significant change in MPOD among studies evaluating <5 mg/d of total lutein/zeaxanthin intake which primarily assessed dietary interventions for 3-6 mo (pooled mean difference, 0.02; 95% CI: -0.01 to 0.05). The pooled mean increase in MPOD was 0.04 units (95% CI: 0.02 to 0.07) among studies evaluating 5 to <20 mg/d of lutein/zeaxanthin and was 0.11 units (95% CI: 0.06 to 0.16) among studies evaluating ≥20 mg/d of lutein/zeaxanthin for 3-12 mo. MPOD increased with lutein/zeaxanthin intake, particularly at higher doses, among adults with healthy eyes. The effects of lutein/zeaxanthin intake at doses <5 mg/d or from dietary sources is less clear. Increased lutein/zeaxanthin intake can help with maintaining ocular health. Future research is needed to determine the minimum dose and duration of lutein/zeaxanthin intake that is associated with a clinically important change in MPOD or visual function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/advances/nmab071DOI Listing
June 2021

Effect of Vitamin D and ω-3 Fatty Acid Supplementation on Risk of Age-Related Macular Degeneration: An Ancillary Study of the VITAL Randomized Clinical Trial.

JAMA Ophthalmol 2020 12;138(12):1280-1289

Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Importance: Observational studies suggest that higher intake or blood levels of vitamin D and marine ω-3 fatty acids may be associated with lower risks of age-related macular degeneration (AMD). However, evidence from randomized trials is limited.

Objective: To evaluate whether daily supplementation with vitamin D3, marine ω-3 fatty acids, or both prevents the development or progression of AMD.

Design, Setting, And Participants: This was a prespecified ancillary study of the Vitamin D and Omega-3 Trial (VITAL), a nationwide, placebo-controlled, 2 × 2 factorial design randomized clinical trial of supplementation with vitamin D and marine ω-3 fatty acids for the primary prevention of cancer and cardiovascular disease. Participants included 25 871 men and women in the US. Randomization was from November 2011 to March 2014, and study pill-taking ended as planned on December 31, 2017.

Interventions: Vitamin D3 (cholecalciferol), 2000 IU per day, and marine ω-3 fatty acids, 1 g per day.

Main Outcomes And Measures: The primary end point was total AMD events, a composite of incident cases of AMD plus cases of progression to advanced AMD among participants with AMD at baseline, based on self-report confirmed by medical record review. Analyses were conducted using the intention-to-treat population.

Results: In total, 25 871 participants with a mean (SD) age of 67.1 (7.0) years were included in the trial. Of them, 50.6% were women, 71.3% were self-declared non-Hispanic White participants, and 20.2% were Black participants. During a median (range) of 5.3 (3.8-6.1) years of treatment and follow-up, 324 participants experienced an AMD event (285 incident AMD and 39 progression to advanced AMD). For vitamin D3, there were 163 events in the treated group and 161 in the placebo group (hazard ratio [HR], 1.02; 95% CI, 0.82-1.27). For ω-3 fatty acids, there were 157 events in the treated group and 167 in the placebo group (HR, 0.94; 95% CI, 0.76-1.17). In analyses of individual components for the primary end point, HRs comparing vitamin D3 groups were 1.09 (95% CI, 0.86-1.37) for incident AMD and 0.63 (95% CI, 0.33-1.21) for AMD progression. For ω-3 fatty acids, HRs were 0.93 (95% CI, 0.73-1.17) for incident AMD and 1.05 (95% CI, 0.56-1.97) for AMD progression.

Conclusion And Relevance: Neither vitamin D3 nor marine ω-3 fatty acid supplementation had a significant overall effect on AMD incidence or progression.

Trial Registration: ClinicalTrials.gov Identifier: NCT01782352.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaophthalmol.2020.4409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596682PMC
December 2020

Estimated Prevalence and Incidence of Dry Eye Disease Based on Coding Analysis of a Large, All-age United States Health Care System.

Am J Ophthalmol 2019 06 2;202:47-54. Epub 2019 Feb 2.

Evidera|PPD, Waltham, Massachusetts, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA; Department of Ophthalmology & Visual Sciences, University of Utah School of Medicine, Salt Lake City, Utah, USA.

Purpose: To assess overall prevalence, annual prevalence, and incidence of dry eye disease (DED) in a large, representative population in the United States.

Design: Prevalence and incidence study.

Methods: Retrospective analysis using the Department of Defense (DOD) Military Health System (MHS) data on beneficiary medical claims from United States DOD military and civilian facilities, January 1, 2003 through March 31, 2015.

Patient Population: Using an algorithm, medical diagnostic codes indicative of DED and prescriptions for cyclosporine ophthalmic emulsion identified a DED population from 9.7 million MHS beneficiaries (DOD service members, retirees, and dependents, aged 2-80+ years).

Main Outcome Measures: DED overall prevalence (2003-2015), annual prevalence (2005-2012), and annual incidence (2008-2012) stratified by sex, age group, and International Statistical Classification of Diseases and Related Health Problems, Ninth Revision diagnosis code grouping.

Results: DED prevalence was 5.28% overall, 7.78% among female beneficiaries, 2.96% among male beneficiaries and increased with age from 0.20% for ages 2-17 years, to 11.66% for individuals aged 50+ years. Annual prevalence increased from 0.8% to 3.0% overall, from 1.4% to 4.5% in female beneficiaries, and from 0.3% to 1.6% in male beneficiaries. Annual prevalence increased across age groups starting at age 18-39, 0.1%-0.6%, to age 50+, 1.8%-6.0%. Annual incidence increased from 0.6% to 0.9% overall, from 0.8% to 1.2% in female beneficiaries, and from 0.3% to 0.6% in male beneficiaries. Across age groups, annual incidence increased starting at age 18-39 (0.2%-0.3%), to age 50+ (1.0%-1.6%).

Conclusions: DED overall prevalence, annual prevalence, and incidence were found to increase over time for all demographics. These findings highlight the continued importance of research and therapeutic development for this common condition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajo.2019.01.026DOI Listing
June 2019

Serum lipids in adults with late age-related macular degeneration: a case-control study.

Lipids Health Dis 2019 Jan 8;18(1). Epub 2019 Jan 8.

Longitudinal Studies Section, National Institute on Aging, Baltimore, MD, USA.

Background: Lipids are implicated in the pathogenesis of age-related macular degeneration (AMD). The relationship between systemic lipids and AMD has not been well characterized. The objective was to investigate the relationship between serum lipids and AMD in older adults using a lipidomic approach.

Methods: In a case-control study, 240 adults, aged ≥66 years, a third each having geographic atrophy, neovascular AMD, or no signs of AMD, were selected from a population-based sample of participants in the Age Gene/Environment Susceptibility-Reykjavik Study. The exposure was serum lipids and risk factors for AMD. The outcome was late AMD, assessed through fundus images taken through dilated pupils using a 45-degree digital camera and grading for neovascular AMD and geographic atrophy using the modified Wisconsin Age-Related Maculopathy Grading System.

Results: Of 177 serum lipid species measured, there were no significant differences in serum lipids between controls and those with geographic atrophy or neovascular AMD, respectively. Adults with neovascular AMD had higher total serum lysophosphatidylcholine (LPC) (P = 0.004) and serum LPC 18:0 (P = 0.0002) compared to those with geographic atrophy.

Conclusion: Late AMD was not characterized by alterations in systemic lipids compared with normal controls. These findings suggest that there may be differences in the LPC pathway between adults with neovascular AMD and geographic atrophy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12944-018-0954-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6323843PMC
January 2019

Evaluation of comparative effectiveness research: a practical tool.

J Comp Eff Res 2018 05 21;7(5):503-515. Epub 2018 Feb 21.

Center for Observational Research & Data Sciences, Bristol-Myers Squibb, Uxbridge, UB8 1DH, UK.

Comparative effectiveness research (CER) guidelines have been developed to direct the field toward the most rigorous study methodologies. A challenge, however, is how to ensure the best evidence is generated, and how to translate methodologically complex or nuanced CER findings into usable medical evidence. To reach that goal, it is important that both researchers and end users of CER output become knowledgeable about the elements that impact the quality and interpretability of CER. This paper distilled guidance on CER into a practical tool to assist both researchers and nonexperts with the critical review and interpretation of CER, with a focus on issues particularly relevant to CER in oncology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2217/cer-2018-0007DOI Listing
May 2018

TFOS DEWS II Sex, Gender, and Hormones Report.

Ocul Surf 2017 07 20;15(3):284-333. Epub 2017 Jul 20.

School of Optometry and Vision Science, University of New South Wales, Sydney, Australia.

One of the most compelling features of dry eye disease (DED) is that it occurs more frequently in women than men. In fact, the female sex is a significant risk factor for the development of DED. This sex-related difference in DED prevalence is attributed in large part to the effects of sex steroids (e.g. androgens, estrogens), hypothalamic-pituitary hormones, glucocorticoids, insulin, insulin-like growth factor 1 and thyroid hormones, as well as to the sex chromosome complement, sex-specific autosomal factors and epigenetics (e.g. microRNAs). In addition to sex, gender also appears to be a risk factor for DED. "Gender" and "sex" are words that are often used interchangeably, but they have distinct meanings. "Gender" refers to a person's self-representation as a man or woman, whereas "sex" distinguishes males and females based on their biological characteristics. Both gender and sex affect DED risk, presentation of the disease, immune responses, pain, care-seeking behaviors, service utilization, and myriad other facets of eye health. Overall, sex, gender and hormones play a major role in the regulation of ocular surface and adnexal tissues, and in the difference in DED prevalence between women and men. The purpose of this Subcommittee report is to review and critique the nature of this role, as well as to recommend areas for future research to advance our understanding of the interrelationships between sex, gender, hormones and DED.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtos.2017.04.001DOI Listing
July 2017

Prevalence of Diagnosed Dry Eye Disease in the United States Among Adults Aged 18 Years and Older.

Am J Ophthalmol 2017 Oct 10;182:90-98. Epub 2017 Jul 10.

Shire, Lexington, Massachusetts; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Department of Ophthalmology & Visual Sciences, University of Utah School of Medicine, Salt Lake City, Utah.

Purpose: To provide current estimates of the prevalence of diagnosed dry eye disease (DED) and associated demographics among US adults aged ≥18 years.

Design: Cross-sectional, population-based survey.

Methods: Data were analyzed from 75 000 participants in the 2013 National Health and Wellness Survey to estimate prevalence/risk of diagnosed DED overall, and by age, sex, insurance, and other demographic factors. We weighted the observed DED prevalence to project estimates to the US adult population and examined associations between demographic factors and DED using multivariable logistic regression.

Results: Based on weighted estimates, 6.8% of the US adult population was projected to have diagnosed DED (∼16.4 million people). Prevalence increased with age (18-34 years: 2.7%; ≥75 years: 18.6%) and was higher among women (8.8%; ∼11.1 million) than men (4.5%; ∼5.3 million). After adjustment, there were no substantial differences in prevalence/risk of diagnosed DED by race, education, or US census region. However, there was higher risk of diagnosed DED among those aged 45-54 years (odds ratio [OR]: 1.95; 95% confidence interval [CI]: 1.74-2.20) and ≥75 years (OR: 4.95; 95% CI: 4.26-5.74), vs those aged 18-34 years. Risk was also higher among women vs men (OR: 2.00; 95% CI: 1.88-2.13) and insured vs uninsured participants (OR: 2.12; 95% CI: 1.85-2.43 for those on government and private insurance vs none).

Conclusions: We estimate that >16 million US adults have diagnosed DED. Prevalence is higher among women than men, increases with age, and is notable among those aged 18-34 years.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajo.2017.06.033DOI Listing
October 2017

Dietary intake of α-linolenic acid and risk of age-related macular degeneration.

Am J Clin Nutr 2017 06 3;105(6):1483-1492. Epub 2017 May 3.

Departments of Nutrition.

The relation between α-linolenic acid (ALA), a plant-derived omega-3 (n-3) fatty acid, and age-related macular degeneration (AMD) is unclear. European researchers reported that ≤40% of ALA can be present as forms. We aimed to evaluate the associations between intake of ALA and intermediate and advanced AMD. Seventy-five thousand eight hundred eighty-nine women from the Nurses' Health Study and 38,961 men from Health Professionals Follow-Up Study were followed up from 1984 to 2012 and from 1986 to 2010, respectively. We assessed dietary intake by a validated food-frequency questionnaire at baseline and every 4 y thereafter. One thousand five hundred eighty-nine incident intermediate and 1356 advanced AMD cases (primarily neovascular AMD) were confirmed by medical record review. The multivariable-adjusted HR for intermediate AMD comparing ALA intake at the top quintile to the bottom quintile was 1.28 (95% CI: 1.05, 1.56; -trend = 0.01) in the analyses combining 2 cohorts. The HR in each cohort was in the positive direction but reached statistical significance only in the women. However, the positive association was apparent only in the pre-2002 era in each cohort and not afterward (-time interaction = 0.003). ALA intake was not associated with advanced AMD in either time period. Using gas-liquid chromatography, we identified both ALA (mean ± SD: 0.13% ± 0.04%) and ALA isomers (0.05% ± 0.01%) in 395 erythrocyte samples collected in 1989-1990. In stepwise regression models, mayonnaise was the leading predictor of erythrocyte concentrations of ALA and one isomer of ALA. We also found ALA in mayonnaise samples. A high intake of ALA was associated with an increased risk of intermediate AMD before 2002 but not afterward. The period before 2002 coincides with the same time period when ALA was found in food and participants' blood; this finding deserves further study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3945/ajcn.116.143453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5445670PMC
June 2017

Dietary Intakes of Eicosapentaenoic Acid and Docosahexaenoic Acid and Risk of Age-Related Macular Degeneration.

Ophthalmology 2017 05 30;124(5):634-643. Epub 2017 Jan 30.

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Global Medical Affairs, Ophthalmics, Shire, Lexington, Massachusetts; Center for Translational Medicine, John A. Moran Eye Center, University of Utah School of Medicine, Salt Lake City, Utah.

Purpose: To evaluate the associations between intakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the intermediate and advanced stages of age-related macular degeneration (AMD).

Design: Prospective cohort study.

Participants: We followed 75 889 women from the Nurses' Health Study and 38 961 men from the Health Professionals Follow-Up Study who were at least 50 years old, from 1984 to 2012 and 1986 to 2010, respectively. Cohort participants are mostly white (≥95%).

Methods: We assessed dietary intake by a validated food frequency questionnaire (FFQ) at baseline and every 4 years. We calculated cumulative average intakes of EPA and DHA from FFQs and also computed predicted erythrocyte and plasma scores directly from food intake using regression models. Cox proportional hazards models were used to compute the associations with AMD outcomes.

Main Outcome Measures: We confirmed 1589 incident intermediate and 1356 advanced AMD cases (primarily neovascular AMD) with a visual acuity of 20/30 or worse, owing primarily to AMD, by medical record review.

Results: For intermediate AMD, the pooled hazard ratio (HR) between the 2 cohorts for DHA comparing the extreme quintiles of intake was 0.78 (95% confidence interval [CI], 0.66-0.92; P trend, 0.008) and for EPA + DHA was 0.83 (95% CI, 0.71-0.98; P trend, 0.03). The pooled HR for fatty fish, comparing ≥5 servings per week to almost never, was 0.61 (95% CI, 0.46-0.81; P trend, <0.001). For advanced AMD, the pooled HR for DHA was 1.01 (95% CI, 0.84-1.21; P trend, 0.75) and for fatty fish was 0.80 (95% CI, 0.59-1.08; P trend, 0.11). Secondary analyses using predicted erythrocyte and plasma scores of EPA and DHA yielded slightly stronger inverse associations for intermediate AMD and similar results for advanced AMD.

Conclusions: Higher intakes of EPA and DHA may prevent or delay the occurrence of visually significant intermediate AMD. However, the totality of current evidence for EPA and DHA and advanced AMD is discordant, though there was no association with advanced AMD in the present study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ophtha.2016.12.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5401792PMC
May 2017

Cadmium and lead exposure and risk of cataract surgery in U.S. adults.

Int J Hyg Environ Health 2016 11 19;219(8):850-856. Epub 2016 Jul 19.

Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI 48109-2029, USA; Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI 48109-2029, USA. Electronic address:

Cataract is a major cause of visual dysfunction and the leading cause of blindness. Elevated levels of cadmium and lead have been found in the lenses of cataract patients, suggesting these metals may play a role in cataract risk. This study aimed to examine the associations of blood lead, blood cadmium and urinary cadmium with cataract risk. We identified 9763 individuals aged 50 years and older with blood lead and cadmium levels, and a randomly selected subgroup of 3175 individuals with available urinary cadmium levels, from the National Health and Nutrition Examination Surveys (NHANES) from 1999 to 2008 (mean age=63years). Participants were considered to have cataract if they self-reported prior cataract surgery in NHANES's vision examination. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using survey logistic regression models. We identified 1737 cataract surgery cases (the weighted prevalence=14.1%). With adjustment for age, race/ethnicity, gender, education, diabetes mellitus, body mass index, cigarette smoking (serum cotinine and pack-years) and urine hydration, every 2-fold increase in urinary cadmium was associated with a 23% higher risk of cataract surgery (OR=1.23, 95% CI: 1.04, 1.46, p=0.021). We found no associations of cataract surgery with blood cadmium (OR=0.97, 95% CI: 0.89, 1.07) and blood lead (OR=0.97, 95% CI: 0.88, 1.06). Mediation analysis showed that for the smoking-cadmium-cataract pathway, the ratio of smoking's indirect effect to the total effect through cadmium was more than 50%. These results suggest that cumulative cadmium exposure may be an important under-recognized risk factor for cataract. However, these findings should be interpreted with a caution because of inconsistent results between urinary cadmium and blood cadmium.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5086441PMC
http://dx.doi.org/10.1016/j.ijheh.2016.07.012DOI Listing
November 2016

Contribution of the Nurses' Health Study to the Epidemiology of Cataract, Age-Related Macular Degeneration, and Glaucoma.

Am J Public Health 2016 Sep 26;106(9):1684-9. Epub 2016 Jul 26.

Jae H. Kang is with the Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. Juan Wu is with the Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston. Eunyoung Cho is with the Department of Dermatology, Warren Alpert Medical School of Brown University, Providence, RI. Soshiro Ogata is with the Department of Health Promotion Science, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. Paul Jacques, Allen Taylor, and Chung-Jung Chiu are with the Laboratory for Nutrition and Vision Research, Jean Mayer USDA Human Nutrition Center on Aging, Tufts University, Boston. Janey L. Wiggs and Louis R. Pasquale are with the Department of Ophthalmology, Massachusetts Eye and Ear Infirmary and Harvard Medical School. Johanna M. Seddon is with the Ophthalmic Epidemiology and Genetics Service, New England Eye Center, Tufts Medical Center, Tufts University School of Medicine. Susan E. Hankinson is with the Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst. Debra A. Schaumberg is with the Department of Epidemiology, Harvard T. H. Chan School of Public Health.

Objectives: To review the contribution of the Nurses' Health Study (NHS) to understanding the genetic and lifestyle factors that influence the risk of cataract, age-related macular degeneration, and glaucoma.

Methods: We performed a narrative review of the publications of the NHS between 1976 and 2016.

Results: The NHS has helped to elucidate the roles of genetics, lifestyle factors (e.g., cigarette smoking associated with cataract extraction and age-related macular degeneration), medical conditions (e.g., diabetes associated with cataract extraction and glaucoma), and dietary factors (e.g., greater carotenoid intake and lower glycemic diet associated with lower risk of age-related macular degeneration) in the etiology of degree and progression of lens opacities, cataract extraction, age-related macular degeneration, primary open-angle glaucoma, and exfoliation glaucoma.

Conclusions: The findings from the NHS, combined with those of other studies, have provided compelling evidence to support public health recommendations for helping to prevent age-related eye diseases: abstinence from cigarette smoking, maintenance of healthy weight and diabetes prevention, and a healthy diet rich in fruits and vegetables.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2105/AJPH.2016.303317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981799PMC
September 2016

Circulating N-Linked Glycoprotein Acetyls and Longitudinal Mortality Risk.

Circ Res 2016 Apr 7;118(7):1106-15. Epub 2016 Mar 7.

From the Center for Lipid Metabolomics (P.R.L., A.O.A., S.M.), the Cardiovascular Division (P.R.L., P.MR., S.M.) and Division of Preventive Medicine (P.R.L., A.O.A., P.D.C., M.V.M., M.J.V., I.-M.L., R.J.G., P.MR., J.E.B., S.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Harvard Chan School of Public Health, Boston, MA (P.R.L., I-M.L., R.J.G., P.MR., J.E.B.), and Department of Ophthalmology and Visual Sciences, Center for Translational Medicine, John A. Moran Eye Center, University of Utah School of Medicine, Salt Lake City (D.A.S.).

Rationale: Circulating glycoprotein N-acetyl glucosamine residues have recently been associated with incident cardiovascular disease and diabetes mellitus.

Objective: Using a plasma glycan biosignature (GlycA) to identify circulating N-acetyl glycan groups, we examined the longitudinal association between GlycA and mortality among initially healthy individuals.

Methods And Results: We quantified GlycA by 400 MHz (1)H nuclear magnetic resonance spectroscopy in 27,524 participants in the Women's Health Study (NCT00000479). The primary outcome was all-cause mortality. We replicated the findings in an independent cohort of 12,527 individuals in the Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial (NCT00239681). We also undertook secondary examination of cardiovascular disease and cancer mortality in the Women's Health Study. In the Women's Health Study, during 524,515 person-years of follow-up (median, 20.5 years), there were 3523 deaths. Risk factor-adjusted multivariable Cox proportional hazard ratio (95% confidence interval) per SD increment in GlycA for all-cause mortality was significantly increased at 5 years (1.21 [1.06-1.40]) and during maximal follow-up (1.14 [1.09-1.16]). Similar risk for all-cause mortality was observed in the replication cohort (1.33 [1.21-1.45]). In the Women's Health Study, risk of cardiovascular disease mortality was increased at 5 years (1.43 [1.05-1.95]) and during maximal follow-up (1.15 [1.04-1.26]) and of cancer mortality at 5 years (1.23 [1.02-1.47]) and during maximal follow-up (1.08 [1.01-1.16]). Examination of correlations and mortality associations adjusted for high-sensitivity C-reactive protein, fibrinogen, and intercellular adhesion molecule-1, suggested that GlycA reflects summative risk related to multiple pathways of systemic inflammation.

Conclusions: Among initially healthy individuals, elevated baseline circulating glycoprotein N-acetyl methyl groups were associated with longitudinal risk of all-cause, cardiovascular, and cancer mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCRESAHA.115.308078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4836171PMC
April 2016

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

Nat Genet 2016 Feb 21;48(2):134-43. Epub 2015 Dec 21.

Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands.

Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/ng.3448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4745342PMC
February 2016

Long-term Natural History of Dry Eye Disease from the Patient's Perspective.

Ophthalmology 2016 Feb 21;123(2):425-433. Epub 2015 Nov 21.

Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts; Division of Preventive Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts; Department of Ophthalmology & Visual Sciences, Center for Translational Medicine, John A. Moran Eye Center, University of Utah School of Medicine, Salt Lake City, Utah. Electronic address:

Purpose: To describe the natural history of dry eye disease (DED), which chronically affects millions of people in the United States.

Design: This study is based on the Women's Health Study and Physicians' Health Studies, and uses questionnaires and medical records.

Participants: A total of 398 men and 386 women who reported a diagnosis of DED and responded to a questionnaire about change in disease since diagnosis.

Methods: Three subscales were developed using factor analysis of questionnaire responses: ocular surface symptoms, vision-related symptoms, and social impact. We examined correlates of worsening on each subscale, obtained medical records from a subset of 261 study participants, and examined changes in clinical signs of DED over time.

Main Outcome Measures: Worsening in ocular surface symptoms, vision-related symptoms, and social impact plus clinical signs.

Results: The average duration of DED of 10.5 years (standard deviation, 9.5 years). Worsening was reported by 24% for ocular surface symptoms, 29% for vision-related symptoms, and 10% for social impact. Factors associated with worsening on at least 2 of 3 subscales included a previous report of severe DED symptoms (odds ratio [OR], 2.17 for ocular surface symptoms; OR, 2.35 for vision-related symptoms), spending >$20 per month on DED treatments (OR, 1.80 for ocular surface symptoms; OR, 1.99 for vision-related symptoms), history of blepharitis or meibomian gland dysfunction (MGD) (OR, 1.57 for vision-related symptoms; OR, 2.12 for social impact), and use of systemic beta-blockers (OR, 1.62 for ocular surface symptoms; OR, 1.84 for vision-related symptoms; OR, 1.86 for the social impact of DED). Presence of corneal staining based on review of medical records was associated with use of level 2 or higher DED treatments (OR, 1.54; confidence interval [CI], 1.01-2.36), a previous report of severe DED symptoms (OR, 1.79; CI, 1.07-3.00), having a tear break-up test performed (OR, 2.73; CI, 1.72-4.36), and having blepharitis or MGD (OR, 0.59; CI, 0.35-0.98).

Conclusions: A proportion of patients with DED experience worsening over time, tending to report with more severe symptoms earlier in the disease. Forthcoming data on the natural history of DED from prospective studies should help clarify some of the limitations of this retrospective study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ophtha.2015.10.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4724500PMC
February 2016

Intakes of Lutein, Zeaxanthin, and Other Carotenoids and Age-Related Macular Degeneration During 2 Decades of Prospective Follow-up.

JAMA Ophthalmol 2015 Dec;133(12):1415-24

Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts7Moran Center for Translational Medicine, John A. Moran Eye Center, Department of Ophthalmology and Visual Sciences, University of Utah School of Medicine, Salt L.

Importance: Despite strong biological plausibility, evidence from epidemiologic studies and clinical trials on the relations between intakes of lutein and zeaxanthin and age-related macular degeneration (AMD) has been inconsistent. The roles of other carotenoids are less thoroughly investigated.

Objective: To investigate the associations between intakes of carotenoids and AMD.

Design, Setting, And Participants: Prospective cohort study, with cohorts from the Nurses' Health Study and the Health Professionals Follow-up Study in the United States. A total of 63,443 women and 38,603 men were followed up, from 1984 until May 31, 2010, in the Nurses' Health Study and from 1986 until January 31, 2010, in the Health Professionals Follow-up Study. All participants were aged 50 years or older and were free of diagnosed AMD, diabetes mellitus, cardiovascular disease, and cancer at baseline.

Main Outcomes And Measures: Predicted plasma carotenoid scores were computed directly from food intake, assessed by repeated food frequency questionnaires at baseline and follow-up, using validated regression models to account for bioavailability and reporting validity of different foods, and associations between predicted plasma carotenoid scores and AMD were determined.

Results: We confirmed 1361 incident intermediate and 1118 advanced AMD cases (primarily neovascular AMD) with a visual acuity of 20/30 or worse by medical record review. Comparing extreme quintiles of predicted plasma lutein/zeaxanthin score, we found a risk reduction for advanced AMD of about 40% in both women and men (pooled relative risk comparing extreme quintiles = 0.59; 95% CI, 0.48-0.73; P for trend < .001). Predicted plasma carotenoid scores for other carotenoids, including β-cryptoxanthin, α-carotene, and β-carotene, were associated with a 25% to 35% lower risk of advanced AMD when comparing extreme quintiles. The relative risk comparing extreme quintiles for the predicted plasma total carotenoid index was 0.65 (95% CI, 0.53-0.80; P for trend < .001). We did not identify any associations of carotenoids, either as predicted plasma score or calculated intake, with intermediate AMD.

Conclusions And Relevance: Higher intake of bioavailable lutein/zeaxanthin is associated with a long-term reduced risk of advanced AMD. Given that some other carotenoids are also associated with a lower risk, a public health strategy aimed at increasing dietary consumption of a wide variety of fruits and vegetables rich in carotenoids may reduce the incidence of advanced AMD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaophthalmol.2015.3590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5119484PMC
December 2015

Priorities and trends in the study of proteins in eye research, 1924-2014.

Proteomics Clin Appl 2015 Dec 16;9(11-12):1105-22. Epub 2015 Sep 16.

Advanced Clinical BioSystems Research Institute, The Heart Institute and Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Purpose: To identify the proteins that are relevant to eye research and develop assays for the study of a set of these proteins.

Experimental Design: We conducted a bibliometric analysis by merging gene lists for human and mouse from the National Center for Biotechnology Information FTP site and combining them with PubMed references that were retrieved with the search terms "eye" [MeSH Terms] OR "eye" [All Fields] OR "eyes" [All Fields].

Results: For human and mouse eye studies, respectively, the total number of publications was 13,525 and 23,895 and the total number of proteins was 4050 and 4717. For proteins in human and mouse eye studies, respectively, 88.7 and 81.7% had five or fewer citations. The top 50 most intensively studied proteins for human and mouse eye studies were generally in the areas of photoreceptors and phototransduction, inflammation, and angiogenesis, neurodevelopment, lens transparency, and cell-cycle and cellular processes. We proposed selected reaction monitoring assays that were developed in silico for the top fifty most intensively studied proteins in human and mouse eye research.

Conclusions And Clinical Relevance: We conclude that scientists engaged in eye research tend to focus on the same proteins. Newer resources and tools in proteomics can expand the investigations to lesser-known proteins of the eye.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/prca.201500006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4695326PMC
December 2015

Vision-Related Quality of Life in Patients with Ocular Graft-versus-Host Disease.

Ophthalmology 2015 Aug 20;122(8):1669-74. Epub 2015 May 20.

Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts. Electronic address:

Purpose: To assess the vision-related quality of life (QOL) in a cohort of patients with ocular graft-versus-host disease (GVHD).

Design: Prospective study.

Participants: Eighty-four patients diagnosed with chronic ocular GVHD.

Methods: We assessed the vision-related QOL with the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25). The symptoms of ocular GVHD were assessed using the Ocular Surface Disease Index (OSDI) and Symptom Assessment in Dry Eye (SANDE) questionnaires.

Main Outcome Measures: We assessed vision-related QOL with the NEI-VFQ-25 and compared the scores obtained from patients with ocular GVHD with those from a healthy population. In the ocular GVHD population, we also evaluated the associations between the NEI-VFQ-25 and the dry eye symptoms measured by the OSDI and SANDE questionnaires, age, duration of disease, best-corrected visual acuity (BCVA), corneal fluorescein staining (CFS), tear break-up time, and Schirmer test.

Results: The mean composite NEI-VFQ-25 score in patients with ocular GVHD was 76.5±17. Compared with healthy subjects, patients with ocular GVHD reported reduced scores on all NEI-VFQ-25 subscales (each P < 0.001) with the exception of color vision (P = 0.11). The NEI-VFQ-25 composite scores significantly correlated with OSDI (R = -0.81, P < 0.001), SANDE (R = -0.56, P < 0.001), CFS (R = -0.36, P = 0.001), and BCVA (R = -0.30, P = 0.004).

Conclusions: Patients with ocular GVHD experience measurable impairment of vision-related QOL. This study highlights the impact of ocular GVHD on the vision-related QOL, and thus the importance of comprehensive diagnosis and treatment of this condition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ophtha.2015.04.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4516685PMC
August 2015

Comparison of Two Questionnaires for Dry Eye Symptom Assessment: The Ocular Surface Disease Index and the Symptom Assessment in Dry Eye.

Ophthalmology 2015 Jul 8;122(7):1498-503. Epub 2015 Apr 8.

Cornea Service, Massachusetts Eye & Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts. Electronic address:

Purpose: The aim of this study was to compare patient-reported symptoms of dry eye disease (DED) as assessed by the Ocular Surface Disease Index (OSDI), a 12-item symptom frequency-based questionnaire, and the Symptom Assessment iN Dry Eye (SANDE), a 2-item frequency- and severity-based visual analog scale.

Design: Clinic-based evaluation of a diagnostic test.

Participants: A total of 114 patients with DED.

Methods: Patients were administered the OSDI and SANDE questionnaires at baseline and follow-up visits to evaluate DED-related symptoms. The correlations between both questionnaires' scores were evaluated using the Spearman coefficient, and their clinical differences were assessed using Bland-Altman analysis.

Main Outcome Measures: Baseline and follow-up visit OSDI and SANDE dry eye symptom scores.

Results: At the baseline visit, the OSDI and SANDE questionnaire scores were significantly correlated (R = 0.64; P < 0.001). Moreover, a significant correlation was found between changes in the OSDI and SANDE scores from baseline to follow-up visits (R = 0.47; P < 0.001). A Bland-Altman analysis, after score normalization, revealed a difference (bias) of less than 2 centesimal units between the scores of the 2 questionnaires.

Conclusions: Data collected from the SANDE questionnaire showed a significant correlation and negligible score differences with those from the OSDI, suggesting that the SANDE visual analog scale-based questionnaire has the potential to provide clinicians with a short, quick, and reliable measure for DED symptoms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ophtha.2015.02.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4485570PMC
July 2015

Environmental cadmium and lead exposures and age-related macular degeneration in U.S. adults: the National Health and Nutrition Examination Survey 2005 to 2008.

Environ Res 2014 Aug 21;133:178-84. Epub 2014 Jun 21.

Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA; Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA. Electronic address:

Age-related macular degeneration (AMD) is a complex disease resulting from the interplay of genetic predisposition and environmental exposures, and has been linked to oxidative stress and inflammatory mechanisms. Lead and cadmium can accumulate in human retinal tissues and may damage the retina through oxidative stress, and may thereby play a role in the development of AMD. We examined associations between blood lead, blood cadmium, and urinary cadmium concentrations and the presence of AMD in 5390 participants aged 40 years and older with blood lead and blood cadmium measures and a subsample of 1548 with urinary cadmium measures in the 2005-2008 National Health and Nutrition Examination Surveys. AMD was identified by grading retinal photographs with a modification of the Wisconsin Age-Related Maculopathy Grading System. The weighted prevalence of AMD was 6.6% (n=426). Controlling for age, gender, race/ethnicity, education and body mass index, adults in the highest blood cadmium quartile had higher odds of AMD compared to the lowest quartile (odds ratio [OR], 1.56; 95% CI, 1.02-2.40), with a significant trend across quartiles (p-trend=0.02). After further adjustment for pack-years of cigarette smoking, estimates were somewhat attenuated (OR, 1.43; 95% CI, 0.91-2.27; p-trend=0.08). Similar associations were found with urinary cadmium. The association between urinary cadmium and AMD was stronger in non-Hispanic whites (NHW) than in non-Hispanic blacks (NHB) (OR, 3.31; 95% CI, 1.37-8.01 for levels above versus below the median among NHW; OR,1.45; 95% CI, 0.40-5.32 for levels above versus below the median among NHB; p-interaction=0.03). We found no association between blood lead levels and AMD. Higher cadmium body burden may increase risk of AMD, particularly among non-Hispanic white individuals; however, additional studies are needed before firm conclusions can be drawn.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envres.2014.05.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4124906PMC
August 2014

Rare and common variants in extracellular matrix gene Fibrillin 2 (FBN2) are associated with macular degeneration.

Hum Mol Genet 2014 Nov 4;23(21):5827-37. Epub 2014 Jun 4.

The Fred Hollows Foundation, Auckland, New Zealand, School of Social Sciences, University of New South Wales, Sydney, Australia.

Neurodegenerative diseases affecting the macula constitute a major cause of incurable vision loss and exhibit considerable clinical and genetic heterogeneity, from early-onset monogenic disease to multifactorial late-onset age-related macular degeneration (AMD). As part of our continued efforts to define genetic causes of macular degeneration, we performed whole exome sequencing in four individuals of a two-generation family with autosomal dominant maculopathy and identified a rare variant p.Glu1144Lys in Fibrillin 2 (FBN2), a glycoprotein of the elastin-rich extracellular matrix (ECM). Sanger sequencing validated the segregation of this variant in the complete pedigree, including two additional affected and one unaffected individual. Sequencing of 192 maculopathy patients revealed additional rare variants, predicted to disrupt FBN2 function. We then undertook additional studies to explore the relationship of FBN2 to macular disease. We show that FBN2 localizes to Bruch's membrane and its expression appears to be reduced in aging and AMD eyes, prompting us to examine its relationship with AMD. We detect suggestive association of a common FBN2 non-synonymous variant, rs154001 (p.Val965Ile) with AMD in 10 337 cases and 11 174 controls (OR = 1.10; P-value = 3.79 × 10(-5)). Thus, it appears that rare and common variants in a single gene--FBN2--can contribute to Mendelian and complex forms of macular degeneration. Our studies provide genetic evidence for a key role of elastin microfibers and Bruch's membrane in maintaining blood-retina homeostasis and establish the importance of studying orphan diseases for understanding more common clinical phenotypes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/hmg/ddu276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4189898PMC
November 2014

Age-related macular degeneration and the incidence of cardiovascular disease: a systematic review and meta-analysis.

PLoS One 2014 28;9(3):e89600. Epub 2014 Mar 28.

Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America; Moran Center for Translational Medicine, John A. Moran Eye Center, Department of Ophthalmology & Visual Sciences, University of Utah School of Medicine, Salt Lake City, Utah, United States of America; Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America; Schepens Eye Research Institute, Boston, Massachusetts, United States of America.

Importance: Research has indicated some shared pathogenic mechanisms between age-related macular degeneration (AMD) and cardiovascular disease (CVD). However, results from prior epidemiologic studies have been inconsistent as to whether AMD is predictive of future CVD risk.

Objective: To systematically review population-based cohort studies of the association between AMD and risk of total CVD and CVD subtypes, coronary heart disease (CHD) and stroke.

Data Sources: A systematic search of the PubMed and EMBASE databases and reference lists of key retrieved articles up to December 20, 2012 without language restriction.

Data Extraction: Two reviewers independently extracted data on baseline AMD status, risk estimates of CVD and methods used to assess AMD and CVD. We pooled relative risks using random or fixed effects models as appropriate.

Results: Thirteen cohort studies (8 prospective and 5 retrospective studies) with a total of 1,593,390 participants with 155,500 CVD events (92,039 stroke and 62,737 CHD) were included in this meta-analysis. Among all studies, early AMD was associated with a 15% (95% CI, 1.08-1.22) increased risk of total CVD. The relative risk was similar but not significant for late AMD (RR, 1.17; 95% CI, 0.98-1.40). In analyses restricted to the subset of prospective studies, the risk associated with early AMD did not appreciably change; however, there was a marked 66% (95% CI, 1.31-2.10) increased risk of CVD among those with late AMD.

Conclusion: Whereas the results from all cohort studies suggest that both early and late AMD are predictive of a small increase in risk of future CVD, subgroup analyses limited to prospective studies demonstrate a markedly increased risk of CVD among people with late AMD. Retrospective studies using healthcare databases may have inherent methodological limitations that obscure such association. Additional prospective studies are needed to further elucidate the associations between AMD and specific CVD outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0089600PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3969321PMC
June 2015

Serum carboxymethyllysine, an advanced glycation end product, and age-related macular degeneration: the Age, Gene/Environment Susceptibility-Reykjavik Study.

JAMA Ophthalmol 2014 Apr;132(4):464-70

Moran Center for Translational Medicine, Department of Ophthalmology and Visual Sciences, University of Utah School of Medicine, Salt Lake City.

IMPORTANCE Advanced glycation end products have been implicated in the pathogenesis of age-related macular degeneration (AMD). OBJECTIVE To investigate the relationship between serum carboxymethyllysine (CML), a major circulating advanced glycation end product, and AMD in older adults. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional study of a population-based sample of 4907 older adults (aged ≥66 years) in the Age, Gene/Environment Susceptibility-Reykjavik Study in Iceland. EXPOSURES Serum CML and risk factors for AMD. MAIN OUTCOMES AND MEASURES Early or late AMD, assessed through fundus images taken through dilated pupils using a 45° digital camera and grading for drusen size, type, area, increased retinal pigment, retinal pigment epithelial depigmentation, neovascular lesions, and geographic atrophy using the modified Wisconsin Age-Related Maculopathy Grading System. RESULTS Of the 4907 participants, 1025 (20.9%) had early AMD and 276 (5.6%) had late AMD. Mean (SD) serum CML concentrations among adults with no AMD, early AMD, and late AMD (exudative AMD and pure geographic atrophy) were 618.8 (195.5), 634.2 (206.4), and 638.4 (192.0) ng/mL, respectively (to convert to micromoles per liter, multiply by 0.00489; P = .07). Log serum CML (per 1-SD increase) was not associated with any AMD (early and late AMD) (odds ratio = 0.97; 95% CI, 0.90-1.04; P = .44) or with late AMD (odds ratio = 0.94; 95% CI, 0.82-1.08; P = .36) in respective multivariable logistic regression models adjusting for age, sex, body mass index, smoking, and renal function. CONCLUSIONS AND RELEVANCE Higher serum CML concentration had no significant cross-sectional association with prevalent AMD in this large population-based cohort of older adults in Iceland.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaophthalmol.2013.7664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4169215PMC
April 2014

Prospective study of common variants in CX3CR1 and risk of macular degeneration: pooled analysis from 5 long-term studies.

JAMA Ophthalmol 2014 Jan;132(1):84-95

Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Importance: The CX3CR1 gene is implicated as a candidate gene for age-related macular degeneration (AMD) through several lines of evidence. There is uncertainty, however, as to whether common genetic variants in CX3CR1 alter risk of AMD, since prior studies have been inconsistent and mostly limited to evaluation of 2 nonsynonymous variants, T280M (rs3732378) and V249I (rs3732379).

Objective: To determine if common variants in CX3CR1 predict future risk of AMD.

Design, Setting, And Participants: Prospective nested case-control study within 5 large study populations with long-term follow-up. We measured genotypes for T280M, V249I, and 13 other common single-nucleotide polymorphisms (SNPs) of the CX3CR1 gene among people who developed AMD (n = 1110, including 369 with neovascular AMD) and 2532 age- and sex-matched controls.

Main Outcomes And Measures: We determined the incidence rate ratios (RR) and 95% CIs for incidence of AMD for each variant and examined interactions with other AMD-associated variants and modifiable risk factors.

Results: In additive genetic models, we identified nonsignificant associations with AMD for T280M (RR, 0.87; P = .07) and 3 other SNPs, rs2853707 (RR, 0.88; P = .07), rs12636547 (RR, 0.85; P = .10), and rs1877563 (RR, 0.84; P = .06), 1 of which, rs2853707, is positioned in the CX3CR1 promoter region and was associated with neovascular AMD (RR, 0.75; P = .03). We observed that a recessive model was a better fit to the data for some SNPs, with associations between rs11715522 and AMD (RR, 1.27; P = .03) and between rs2669845 (RR, 3.10; P = .04), rs2853707 (RR, 0.48; P = .050), and rs9868689 (RR, 0.31; P = .02) and neovascular AMD. Moreover, in exploratory analyses, we identified a number of possible interactions including between V249I and rs2669845 and dietary intake of ω-3 fatty acids (P = .004 and P = .009, respectively) for AMD; between rs2669845 and obesity (P = .03) for neovascular AMD; between T280M and complement component 3 (C3) R102G for AMD (P = .03); between rs2669845 and Y402H in complement factor H for AMD (P = .04); and between rs2669845, rs2853707, and V249I and C3 R102G for neovascular AMD (P = .008; .04; and .002, respectively).

Conclusions And Relevance: This study failed to identify significant associations between common CX3CR1 variants and AMD after considering the number of SNPs analyzed and multiple comparisons. However, we observed evidence consistent with recessive modes of association and that an effect of CX3CR1 variants may depend on other factors including dietary intake of ω-3 fatty acids, obesity, and genotypes at CFH Y402H and C3 R102G. If replicated in other populations, these findings would support a role for CX3CR1 in AMD but also suggest that its role may involve mechanisms that are independent of the T280M/V249I variations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaophthalmol.2013.5506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4170669PMC
January 2014

Is household air pollution a risk factor for eye disease?

Int J Environ Res Public Health 2013 Oct 25;10(11):5378-98. Epub 2013 Oct 25.

Wilmer Eye Institute, Johns Hopkins Hospital, Baltimore, MD 21287, USA.

In developing countries, household air pollution (HAP) resulting from the inefficient burning of coal and biomass (wood, charcoal, animal dung and crop residues) for cooking and heating has been linked to a number of negative health outcomes, mostly notably respiratory diseases and cancers. While ocular irritation has been associated with HAP, there are sparse data on adverse ocular outcomes that may result from acute and chronic exposures. We consider that there is suggestive evidence, and biological plausibility, to hypothesize that HAP is associated with some of the major blinding, and painful, eye conditions seen worldwide. Further research on this environmental risk factor for eye diseases is warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijerph10115378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3863851PMC
October 2013

Dry eye disease and work productivity loss in visual display users: the Osaka study.

Am J Ophthalmol 2014 Feb 1;157(2):294-300. Epub 2013 Nov 1.

Department of Ophthalmology, School of Medicine, Keio University, Tokyo, Japan.

Purpose: To estimate the impact of dry eye disease (DED) on work performance and productivity in office workers using visual display terminals (VDTs).

Design: Cross-sectional study.

Methods: Six hundred seventy-two Japanese young and middle-aged office workers using VDTs completed a questionnaire that was designed to measured at-work performance deficits and productivity losses using the Japanese version of the Work Limitations Questionnaire, completed by e-mail. Using the Japanese dry eye diagnostic criteria, respondents were classified into 3 groups: definite DED, probable DED, and non DED.

Results: Of the 672 office workers, 553 subjects (82.3%), including 366 men and 187 women, completed the questionnaire and underwent clinical evaluation. As for the total workplace productivity loss, the non DED group demonstrated a loss of 3.56%, those with probable DED demonstrated a loss of 4.06%, and those with definite DED demonstrated a loss of 4.82%, indicating significantly worse performance and productivity (P = .014, trend test). For the 4 subscales, DED was associated with significantly lower on-the-job time management (P = .009, trend test) and combined mental performance and interpersonal functioning (P = .011, trend test). After controlling for age, sex, VDT working hours, and diagnosis of DED, time management, physical demands, and mental and interpersonal functioning showed a significant relationship to DED (each P > .05). Annual DED productivity losses were estimated to be $6160 per employee when measured by total production and $1178 per employee calculated by wage.

Conclusions: This study indicated that there is a significant impact of DED on the total productivity of Japanese VDT users.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajo.2013.10.014DOI Listing
February 2014

Patient reported differences in dry eye disease between men and women: impact, management, and patient satisfaction.

PLoS One 2013 30;8(9):e76121. Epub 2013 Sep 30.

Division of Preventive Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America ; Department of Ophthalmology & Visual Sciences, Center for Translational Medicine, John A. Moran Eye Center, University of Utah School of Medicine, Salt Lake City, Utah, United States of America ; Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States of America ; Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America.

Purpose: Dry eye disease affects women twice as often as men, but there is little information on whether dry eye treatments, treatment satisfaction, or the impact of dry eye disease on patients' lives and vision might differ by sex.

Design: Questionnaire survey of 4000 participants in the Women's Health Study and the Physicians' Health Studies I and II with a prior report of a diagnosis of DED.

Methods: Among participants who re-confirmed a diagnosis of dry eye disease, we assessed symptoms, treatments, patient satisfaction and impact of dry eye disease, and analyzed differences between men and women using regression models.

Results: The final study population consisted of 1,518 women (mean age 70.7 years) and 581 men (mean age 76.7 years), with a mean reported duration of dry eye disease of 10.5 years and 10.1 years, respectively. The frequency and severity of dry eye disease symptoms were higher among women (each P<0.0001), and women reported a greater impact on everyday activities (P<0.0001). Women were more likely to use artificial tears (P<0.0001) use them more often (P<0.0001), and to use Restasis® (P<0.0001), omega-3 fatty acids (P=0.0006), and have punctal occlusion (P=0.005). Women spent more money per month on dry eye treatments (P<0.0001), but reported greater dissatisfaction with treatment side effects (P=0.001), and the amount of time before treatments started working (P=0.03).

Conclusions: These data show that dry eye disease is generally experienced as being more severe among women, having a greater impact on their self-assessed well-being.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0076121PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3786885PMC
June 2014

What is the value of incorporating tear osmolarity measurement in assessing patient response to therapy in dry eye disease?

Am J Ophthalmol 2014 Jan 21;157(1):69-77.e2. Epub 2013 Sep 21.

Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts. Electronic address:

Purpose: To evaluate the correlation between changes in tear osmolarity, symptoms, and corneal fluorescein staining in patients with dry eye disease (DED).

Design: Retrospective, clinic-based cohort study.

Methods: In this single-institution study, we reviewed the charts of 186 patients with DED from whom we had data on tear osmolarity, symptoms, and corneal fluorescein staining from 2 separate visits. Main outcomes included the correlation of the changes between the 2 visits for tear osmolarity (TearLab system), symptoms (Ocular Surface Disease Index), and corneal fluorescein staining (modified Oxford scheme). For tear osmolarity and corneal fluorescein staining the scores from the eye with highest readings were analyzed. The correlations were repeated on subgroups based on proposed cutoffs for DED severity and on patients' treatment.

Results: We found a modest, though statistically significant, correlation between changes in corneal fluorescein staining and symptoms of DED (R = 0.31; P < .001). However, there was no correlation between the recorded change in tear osmolarity and symptoms (R = -0.091; P = .38) or between changes in tear osmolarity and corneal fluorescein staining (R = -0.02; P = .80). This lack of correlation was consistent in all the subgroups studied. A multivariate analysis revealed that changes in corneal fluorescein staining had predictive value on symptom changes, whereas tear osmolarity changes did not.

Conclusions: Changes in tear osmolarity do not correlate significantly with changes in patient symptoms or corneal fluorescein staining in dry eye disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajo.2013.07.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865167PMC
January 2014

The TFOS International Workshop on Contact Lens Discomfort: report of the subcommittee on clinical trial design and outcomes.

Invest Ophthalmol Vis Sci 2013 Oct 18;54(11):TFOS157-83. Epub 2013 Oct 18.

Department of Ophthalmology and Vision Science, University of Louisville, Wilmington, North Carolina.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1167/iovs.13-13189DOI Listing
October 2013
-->