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W G Christen

Publications and source records attributed to W G Christen.

At least 37 records · Page 2Linked to original sources
PubMed1999

Prospective cohort study of antioxidant vitamin supplement use and the risk of age-related maculopathy.

In a prospective cohort study, the authors examined whether self-selection for antioxidant vitamin supplement use affects the incidence of age-related maculopathy. The study population consisted of 21,120 US male physician participants in the Physicians' Health Study I who did not have a diagnosis of age-related maculopathy at baseline (1982). During an average of 12.5 person-years of follow-up, a total of 279 incident cases of age-related maculopathy with vision loss to 20/30 or worse were confirmed by medical record review. In multivariate analysis, as compared with nonusers of supplements, persons who used vitamin E supplements had a possible but nonsignificant 13% reduced risk of age-related maculopathy (relative risk = 0.87, 95 percent confidence interval (CI) 0.53-1.43), while users of multivitamins had a possible but nonsignificant 10% reduced risk (relative risk = 0.90, 95% CI 0.68-1.19). Users of vitamin C supplements had a relative risk of 1.03 (95% CI 0.71-1.50). These observational data suggest that among persons who self-select for supplemental use of antioxidant vitamin C or E or multivitamins, large reductions in the risk of age-related maculopathy are unlikely. Randomized trial data are accumulating to enable reliable detection of the existence of more plausible small-to-moderate benefits of these agents alone and in combination on age-related maculopathy.

Adult↗
PubMed1999

Determinants of retinopathy progression in type 1 diabetes mellitus.

PURPOSE: To determine the risk factors for retinopathy progression in type 1 (insulin-dependent) diabetes mellitus in a prospective cohort study. SUBJECTS AND METHODS: Subjects were 485 participants in the Sorbinil Retinopathy Trial, a randomized trial of aldose reductase inhibition among patients aged 18 to 56 years with type 1 diabetes mellitus (duration of 1 to 15 years) and no or only mild retinopathy. Retinopathy progression, assessed by seven-field stereoscopic fundus photography, was defined as worsening by two or more levels on a standardized grading scale at the end of follow-up (median, 41 months). RESULTS: The relative risks for retinopathy progression according to successively greater quintiles of total glycosylated hemoglobin level at baseline, after adjusting for age, diabetes duration, sorbinil assignment, and other variables, were 1.0, 2.0, 1.6, 3.7, and 4.4 (P trend <0.0001). Risk increased with greater baseline diastolic blood pressure: 1.0 for <70 mm Hg, 1.2 for 70 to 79 mm Hg, and 1.8 for > or =80 mm Hg (P for trend = 0.04). Diastolic blood pressure was a significant risk factor for progression in participants with mild baseline retinopathy (P for trend <0.02) but not in those without retinopathy at entry. Systolic blood pressure, by comparison, was not associated with progression. Baseline total cholesterol level was a marginally significant predictor of retinopathy progression when examined as a categorical variable (relative risks for increasing quartiles; 1.0, 1.6, 1.8, 1.9; P for trend = 0.03) but not when it was examined as a continuous variable or when hypercholesterolemic patients were compared with those with normal levels. Furthermore, when cholesterol levels were updated in subsequent visits, it was not a significant predictor of progression, and low density lipoprotein (LDL) cholesterol levels did not predict progression no matter how analyzed. Smoking was not associated with progression of retinopathy. CONCLUSIONS: Levels of hyperglycemia and diastolic blood pressure predicted progression of retinopathy in type 1 diabetes mellitus. We found only a suggestion of an association between total cholesterol level (but not of LDL cholesterol level) and progression of retinopathy; resolution of this issue will require additional studies with larger sample sizes and longer follow-up.

Adult↗
PubMed1999

Elevated vitreous interleukin-10 level is not diagnostic of intraocular-central nervous system lymphoma.

OBJECTIVE: Diagnosis of intraocular-central nervous system (CNS) lymphoma is commonly made by identifying malignant lymphocytes in the vitreous. However, such cells are in the minority in the vitreous cellular infiltrate (most are reactive lymphocytes), and therefore lack of cytologic support from biopsied vitreous samples in patients suspected of having intraocular-CNS lymphoma may occur. Recent data suggest that interleukin-10 (IL-10) levels are elevated in the serum and vitreous of patients with non-Hodgkin's lymphoma, whereas IL-12 and IL-6 levels are elevated in patients with uveitis of non-neoplastic etiology. The authors evaluated the usefulness of measuring vitreous levels of IL-6, -10, and -12 in the diagnosis of intraocular-CNS lymphoma. DESIGN: Prospective case series. PARTICIPANTS: Seventeen patients with intraocular inflammation who underwent a diagnostic or therapeutic vitrectomy: 4 patients with intraocular-CNS lymphoma and 13 patients with uveitis unrelated to a neoplasm. INTERVENTION: Eighteen vitreous specimens were obtained prospectively. Concentrations of IL-6, -10, and -12 were measured by enzyme immunosorbent assay, and relative ratios of the interleukins were calculated. Cytopathologic examination and flow cytometry of vitreous cells were also performed. MAIN OUTCOME MEASURES: The ratio of IL-10/IL-12 and IL-10/IL-6 was calculated to assess any association of intraocular-CNS lymphoma and high vitreous IL-10 relative to IL-6 and IL-12 levels. RESULTS: The IL-10/IL-6 and IL-10/IL-12 ratio was greater than 1 in 8 of 14 vitreous specimens obtained from 13 patients with non-neoplastic uveitis. One of the four specimens from patients with cytologically proven intraocular-CNS lymphoma had vitreous IL-10/IL-6 and IL-10/IL-12 ratios of less than 1. CONCLUSION: Although a helpful diagnostic tool, an elevated vitreous IL-10 to IL-6 or IL-12 ratio is not always associated with intraocular-CNS lymphoma.

Central Nervous System Neoplasms↗
PubMed1999

High levels of plasma C-reactive protein and future risk of age-related cataract.

PURPOSE: Chronic intraocular inflammation, with or without systemic inflammation, is associated with increased risk of cataract. Whether systemic inflammation alone is associated with cataract is unknown. This study examined the association between plasma C-reactive protein (CRP), a marker of systemic inflammation, and risk of cataract. METHODS: In the Physicians' Health Study, we recently analyzed plasma CRP levels in baseline blood specimens from 543 men who later developed cardiovascular disease, and 543 who did not. These data provided a cost-efficient means to explore whether baseline plasma CRP is associated with future risk of age-related cataract. After excluding 252 men with prior diagnosis of cataract or missing data, we followed the remaining 834 men defined by baseline CRP level for 11 years for incident cataract. We used proportional hazards regression models, stratified by cardiovascular disease status. RESULTS: Baseline CRP was significantly higher among men who later developed cataract than levels among those who remained free of cataract, P = 0.02 (median 1.53 versus 1.23 mg/L). In a multivariable model adjusted for cardiovascular disease, randomized aspirin and beta carotene assignments, age, diabetes, cigarette smoking, alcohol consumption, body mass index, exercise, and parental history of myocardial infarction, the levels of CRP remained significantly associated with development of cataract (P = 0.001); but the association was less significant in a model using log CRP levels (P = 0.038). In exploratory analyses of a threshold effect, the excess risk was significant only among men with levels at or above the 97.5th centile (6.17 mg/L); compared to those with lower levels, the relative risk in these men was 3.00 (95% confidence interval, 1.53 to 5.91; P = 0.002). Relative risks associated with CRP levels at or above versus below the 85th, 90th, and 95th percentiles were not significant (relative risks 1.29, 1.50, and 1.77, respectively). CONCLUSIONS: Overall, our results suggest that elevated levels of CRP are associated with future risk of cataract in these apparently healthy men. This early report raises the possibility that systemic inflammation may play a role in the pathogenesis of age-related cataract.

Adult↗
PubMed1999

A prospective study of alcohol consumption and the risk of age-related macular degeneration.

PURPOSE: Vascular risk factors, including alcohol intake, have been hypothesized to play a role in the development of age-related macular degeneration (AMD). We examined the relationship of alcohol intake with AMD in the Physicians' Health Study (PHS). METHODS: The PHS was a randomized trial of aspirin and beta-carotene among 22,071 U.S. male physicians age 40 to 84 years at entry. A total of 21,041 physicians with complete data on alcohol consumption and no AMD at baseline were included in this analysis. Proportional hazards models were used to estimate relative risks (RR) and 95% confidence interval (CI). RESULTS: During an average follow-up period of 12.5 years, 278 physicians were confirmed by medical record review to have incident AMD resulting in vision loss ( acuity 20/30 or worse). After adjusting for age, randomized treatment assignment, and other potential risk factors, the RR for > or = 1 drink/week versus < 1 drink/week was 0.97 (CI: 0.78-1.21). For categories of alcohol intake, the RRs for those reporting alcohol consumption of < 1 drink/week, 1 drink/week, 2-4 drinks/week, 5-6 drinks/week, and > or = 1 drink/day were 1.00 (referent), 1.00 (0.65-1.55), 0.68 (0.44-1.04), 1.32 (0.89-1.95), and 1.27 (0.93-1.73), respectively. CONCLUSIONS: These prospective data indicate that alcohol intake is not appreciably associated with the risk of incident AMD. However, the width of the confidence intervals are compatible with a possible small effect (reduction or increase) in risk for low to moderate levels of alcohol intake, which warrant further investigation.

Adult↗
PubMed1999

Beta-carotene supplementation: a good thing, a bad thing, or nothing?

Available data from several completed large-scale randomized trials indicate that beta-carotene supplementation for durations up to 12 years has no overall benefit in well-nourished populations on the incidence of cardiovascular disease or the middle-to-late stages of carcinogenesis. Several important questions, however, remain unanswered. The post-trial follow-up of completed trials, together with the results of several ongoing trials of beta-carotene supplementation, will contribute reliable information to the totality of evidence from basic research, animal studies, observational epidemiologic studies, and completed trials, thus allowing more rational clinical decisions for individual patients and policy decisions for the health of the general public.

Antioxidants↗
PubMed1998

A systematic overview of the incidence of posterior capsule opacification.

OBJECTIVE: Reported rates of posterior capsule opacification (PCO) vary widely and are based on various definitions of PCO, varying lengths and intervals of follow-up, and the use of different surgical techniques, intraocular lens (i.o.l.) designs, and methods of IOL implantation. This study was designed to obtain a more precise overall estimate of the incidence of PCO and to explore factors that might influence the rate of PCO development. DESIGN: A meta-analysis. METHODS: Published articles were selected for study based on a computerized MEDLINE search of the literature and a manual search of the bibliographies of relevant articles. Articles meeting selected inclusion criteria were reviewed systematically, and the reported data were abstracted and synthesized using the statistical techniques of meta-analysis. MAIN OUTCOME MEASURE: Pooled estimates of the proportion of eyes developing PCO at three postoperative timepoints--1 year, 3 years, and 5 years--were measured. RESULTS: There is significant heterogeneity among published rates of PCO. The overall pooled estimates (95% confidence limits) of the incidence of PCO were 11.8% (9.3%-14.3%) at 1 year, 20.7% (16.6%-24.9%) at 3 years, and 28.4% (18.4%-38.4%) at 5 years after surgery. There is no evidence of a significant decline in PCO incidence during the study period. CONCLUSIONS: Visually significant PCO develops in more than 25% of patients undergoing standard extracapsular cataract extraction or phacoemulsification with posterior chamber intraocular lens implantation over the first 5 years after surgery. Patient characteristics, surgical techniques, and differences in research design and reporting may account for some of the variability in reported rates. However, no specific factors were identified in the authors' analysis. More precise estimates of incidence and identification of risk factors for PCO will depend on the development of a standardized measurement of PCO and wider adoption of more rigorous study methodology.

Cataract↗
PubMed1998

Low-dose aspirin and risk of cataract and subtypes in a randomized trial of U.S. physicians.

PURPOSE: To examine whether low-dose aspirin (325 mg on alternate days) reduces the risk of age-related cataract and subtypes. This report extends previous findings, including both subtypes and additional newly identified incident cases since the earlier report. METHODS: All 20,979 participants in the Physicians' Health Study, a randomized trial of aspirin and beta-carotene among U.S. male physicians age 40-84 in 1982, who did not report cataract at baseline were included. Average follow-up was five years. The main outcome measure was incident, age-related cataract responsible for a reduction in best-corrected visual acuity to 20/30 or worse, based on self-report confirmed by medical record review. RESULTS: 501 age-related cataracts were diagnosed during follow-up, including 416 with nuclear sclerosis and 212 with a posterior subcapsular component; 318 cataracts progressed to surgical extraction. Overall, there were 245 cataracts in the aspirin group and 256 in the placebo group (relative risk [RR], 0.94; 95% confidence interval [CI], 0.79 to 1.13; P = 0.52). Cataract extractions were 19% less frequent in the aspirin than in the placebo group (RR, 0.81; 95% CI, 0.65 to 1.01; P = 0.06). In subgroup analyses of subtypes, aspirin takers had a lower risk of posterior subcapsular cataract (RR, 0.74; 95% CI, 0.57 to 0.98; P = 0.03) but not nuclear sclerosis (RR, 0.96; 95% CI, 0.79 to 1.16; P = 0.65) cataract. CONCLUSIONS: Overall, these randomized trial data tend to exclude a large benefit of five years of low-dose aspirin therapy on cataract development and extraction. The data are compatible with a modest benefit on cataract extraction for this duration of aspirin therapy. Subgroup analyses raise the possibility of a modest, but potentially important, protective effect of aspirin on posterior subcapsular cataract, a particularly disabling subtype.

Adult↗
PubMed1996

A prospective study of cigarette smoking and risk of age-related macular degeneration in men.

OBJECTIVE: To examine the association between cigarette smoking and the incidence of age-related macular degeneration (AMD) in men. DESIGN: Prospective cohort study with average person-years of follow-up for AMD of 12.2 years. PARTICIPANTS: A total of 21 157 US male physicians participating in the Physicians' Health Study who did not have a diagnosis of AMD at baseline, were followed for at least 7 years, and had known levels of baseline smoking. Based on information reported at baseline, 11% were current smokers, 39% were past smokers, and 50% were never smokers. MAIN OUTCOME MEASURE: Incident AMD, defined as a self-report that was confirmed by medical record, review, first diagnosed after randomization, and responsible for vision loss to 20/30 or worse. RESULTS: A total of 268 incident cases of AMD with vision loss were confirmed. In multivariate analysis, current smokers of 20 or more cigarettes per day, compared with never smokers, had an increased risk of AMD (relative risk [RR], 2.46; 95% confidence interval [CI], 1.60-3.79). Past smokers had a modest elevation in risk of AMD (RR, 1.30; 95% CI, 0.99-1.70). For current smokers of fewer than 20 cigarettes per day, there was a nonsignificant 26% increased risk of AMD (RR, 1.26; 95% CI, 0.61-2.59). CONCLUSIONS: These prospective data provide support for the hypothesis that cigarette smoking increases the risk of developing AMD.

Adult↗
PubMed1996

Antioxidants and age-related eye disease. Current and future perspectives.

Oxidative mechanisms may play an important role in the pathogenesis of age-related eye disease, in particular cataract and macular degeneration, the two most important causes of visual impairment in older adults. For this reason, there is considerable interest in determining whether vitamins and trace minerals with antioxidant properties can be of benefit in preventing the onset or progression of disabling eye disease. Basic research studies have shown that antioxidants can protect against the cumulative effects of oxidative stress in animal models of cataract and macular degeneration. Data from observational epidemiological studies in humans, however, are inconclusive. While results from several studies, primarily cross-sectional and case-control, are compatible with a possible protective role for micronutrients in disease development, data for specific nutrients or specific disease types have often been inconsistent. Further, these observational studies are limited because of the inherent imprecision of dietary exposure data and the likely effects of uncontrolled confounding. Thus, reliable data regarding a potentially important benefit of vitamin supplementation in eye disease will emerge mainly from well-designed, large-scale, randomized trials.

Adult↗
PubMed1996

Systemic drug toxicity trends in immunosuppressive therapy of immune and inflammatory ocular disease.

PURPOSE: To compare the relative toxicities of six systemic immunosuppressive drugs and systemic corticosteroids used to treat patients with severe ocular inflammatory disease and to identify factors influencing their occurrence. METHODS: The authors reviewed the clinical records of 602 patients with ocular inflammatory disease treated with immunosuppressive drug therapy and/or systemic corticosteroids for adverse systemic effects while undergoing therapy. Proportional hazards regression analysis was performed to identify demographic and clinical factors that influence the occurrence of drug toxicity in these patients. RESULTS: Immunosuppressive drug treatment was more likely to result in discontinuation of therapy because of toxic side effects than was corticosteroid treatment. However, unlike many of the side effects of corticosteroid treatment, the side effects of immunosuppressive therapy were reversible with reduction in dosage or discontinuation of the drug. Gastrointestinal symptoms and hematologic abnormalities accounted for the majority of reported side effects of the immunosuppressive medications. Neuro-psychiatric and endocrine side effects were common in patients taking prednisone. In 17 patients treated with prednisone, pathologic fractures developed, which involved the hips and the spine. Female sex and age older than 60 years also were identified as factors associated with intolerance to drug therapy in the authors' study population. Race and type of systemic ocular disease were not significant factors influencing tolerance to drug therapy. CONCLUSION: These findings suggest that when properly administered and monitored for adverse effects, most immunosuppressive agents used in the current study have similar risk profiles with relatively few serious therapeutic mishaps and largely reversible side effects. In contrast, corticosteroids can result in permanent disabilities as a result of long-term treatment.

Adult↗
PubMed1995

Body mass index. An independent predictor of cataract.

OBJECTIVE: To examine whether body mass index is an independent predictor of cataract. (Body mass index is a standardized measure defined as weight in kilograms divided by the square of the height in meters.) DESIGN: Prospective cohort study, with 5 years of follow-up. PARTICIPANTS: A total of 17,764 US male physicians participating in the Physicians' Health Study, aged 40 to 84 years, who were free of cataract, myocardial infarction, stroke, and cancer at baseline and reported complete information about body mass index and other cataract risk factors. MAIN OUTCOME MEASURE: Incident cataract, defined as a self-report, confirmed by medical record review, first diagnosed after randomization, age-related in origin, and responsible for a decrease in best corrected visual acuity to 20/30 or worse. RESULTS: Incident cataract occurred during follow-up in 370 participants. In proportional hazards models that adjusted for potential confounding variables, body mass index had a strong, graded relationship with risk of cataract. Relative to those with body mass index less than 22, relative risks (95% confidence intervals) associated with body mass index of 22 to less than 25, 25 to less than 27.8, and 27.8 or more were 1.54 (1.04 to 2.27), 1.46 (0.98 to 2.20), and 2.10 (1.35 to 3.25), respectively. Relative to any given level of body mass index, a 2-unit higher level predicted a 12% increase in risk of cataract (95% confidence interval, 5% to 19%). Higher body mass index was especially strongly related to risk of posterior subcapsular and nuclear sclerotic cataracts and was also significantly related to risk of cataract extraction. CONCLUSIONS: In a prospective cohort study of apparently healthy men, higher body mass index, a potentially modifiable risk factor, was a determinant of cataract. The leanest men had the lowest rates, consistent with experimental evidence that restriction of energy intake slows development of cataract. Although precise mechanisms are unclear, the effect of body mass index on cataractogenesis is apparently independent of other risk factors, including age, smoking, and diagnosed diabetes.

Adult↗
PubMed1994

Antioxidants and eye disease.

Oxidative mechanisms are believed to play an important role in the pathogenesis of age-related eye disease, in particular, cataract and macular degeneration, the two most important causes of visual impairment in older adults. For this reason, there is considerable interest in determining whether vitamins and trace minerals with antioxidant properties can be of benefit in preventing the onset or progression of disabling eye disease. Basic research studies have shown that antioxidants can protect against the cumulative effects of oxidative stress in animal models of cataract and macular degeneration. Data from observational epidemiologic studies in humans, however, are inconclusive. While results from several studies, primarily cross-sectional and case-control, are compatible with a possible protective role for micronutrients in cataract and macular degeneration, data for specific nutrients or specific disease types have often been inconsistent. Further, these observational studies are limited because of the inherent imprecision of dietary exposure data and the likely effects of uncontrolled confounding. Thus, reliable data regarding a potentially important benefit of vitamin supplementation in eye disease will emerge mainly from well-designed, large-scale, randomized trials. Such data are already being collected in the National Eye Institute-sponsored Age Related Eye Disease Study, as well as in the Physicians' Health Study and Women's Health Study.

Aging↗
PubMed1994

The use of vitamin supplements and the risk of cataract among US male physicians.

OBJECTIVES: The purpose of this study was to examine prospectively the association between reported use of vitamin supplements and risk of cataract and cataract extraction. METHODS: The study population consisted of 17,744 participants in the Physicians' Health Study, a randomized trial of aspirin therapy and beta-carotene among US male physicians 40 to 84 years of age in 1982 who did not report cataract at baseline and provided complete information about vitamin supplementation and other risk factors for cataract. Self-reports of cataract and cataract extraction were confirmed by medical record review. RESULTS: During 60 months of follow-up, there were 370 incident cataracts and 109 cataract extractions. In comparison with physicians who did not use any supplements, those who took only multivitamins had a relative risk of cataract of 0.73 after adjustment for other risk factors. For cataract extraction, the corresponding relative risk was 0.79. Use of vitamin C and/or E supplements alone was not associated with a reduced risk of cataract, but the size of this subgroup was small. CONCLUSIONS: These data suggest that men who took multivitamin supplements tended to experience a decreased risk of cataract and support the need for rigorous testing of this hypothesis in large-scale randomized trials in men and women.

Adult↗
PubMed1994

Confirmation of self-reported cataract in the Physicians' Health Study.

Large-scale prospective studies of disease development often rely on self-reported data. To assess the accuracy of self-reports of cataract, we compared the self-reports with medical record data obtained from diagnosing ophthalmologists and optometrists for participants in the Physicians' Health Study, a randomized trial of aspirin and beta-carotene among 22,071 male U.S. physicians aged 40-84 years. A report of cataract, defined as a positive response to a question about whether cataract had ever been diagnosed in either eye and the date of diagnosis, was found to be a very good indicator of lens opacification but was not a good indicator of an incident, age-related opacity that reduced visual acuity. These results indicate that in large prospective studies of clinically significant cataract, where examination of all study participants is not feasible and self-reported data are used, additional documentation to supplement the self-reports should be obtained and strict diagnostic criteria applied to minimize the likely effects of misclassification.

Adult↗