Biomedical subjects

Larry D Hubbard

Publications and source records attributed to Larry D Hubbard.

At least 37 records · Page 2Linked to original sources

PubMed2004

Associations between the metabolic syndrome and retinal microvascular signs: the Atherosclerosis Risk In Communities study.

PURPOSE: To examine the cross-sectional relationship of the metabolic syndrome (hypertension, hyperglycemia, central obesity, and dyslipidemia) and retinal microvascular abnormalities in middle-aged men and women. METHODS: A population-based, cross-sectional study involving 11,265 persons aged 49 to 73 years who had retinal photography from 1993 through 1995. Photographs were graded for presence of retinal microvascular signs (microaneurysms, retinal hemorrhages, arteriovenous nicking, and focal arteriolar narrowing) according to a standardized protocol. To quantify retinal vessel diameters, photographs were digitized and individual arteriolar and venular diameters were measured and summarized. The metabolic syndrome was defined according to the Third Report of the National Cholesterol Education Program Adult Treatment Panel. RESULTS: After adjustment for age, gender, race, education, cigarette smoking and alcohol consumption, persons with the metabolic syndrome were more likely to have retinopathy (odds ratio [OR] 1.68, 95% confidence interval [CI], 1.45-1.96), arteriovenous nicking (OR 1.30, 95% CI, 1.16-1.45), focal arteriolar narrowing (OR 1.24, 95% CI, 1.10-1.38), generalized retinal arteriolar narrowing (OR 1.23, 95% CI, 1.12-1.35), and generalized retinal venular dilatation (OR 1.30, 95% CI, 1.18-1.48) than persons without the metabolic syndrome. Associations for arteriovenous nicking, focal arteriolar narrowing, generalized arteriolar narrowing, and venular dilatation were noted, even in people without diabetes or hypertension. CONCLUSIONS: These data suggest that the metabolic syndrome is associated with microvascular changes in the retina. This finding reflects, in part, the associations of individual syndrome components with retinal microvascular abnormalities.

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PubMed2003

Racial differences in the prevalence of hypertensive retinopathy.

Few population-based data support the hypothesis that hypertensive retinopathy is more common in African Americans than in whites. We examined racial differences in the prevalence of and risk factors for hypertensive retinopathy in a population-based sample of 1860 African Americans and 7874 white persons, aged 49 to 73 years, without diabetes. Retinal photographs were taken of one randomly selected eye and evaluated for the presence of retinopathy (flame and blot-shaped retinal hemorrhages, microaneurysms, and soft exudates) according to standardized protocols by graders masked to participant characteristics. The prevalence of retinopathy was 2 times higher in African Americans than in whites (7.7% versus 4.1%, age- and gender-adjusted odds ratio [OR] 2.03, 95% confidence intervals [CI] 1.65, 2.49). After controlling for 6-year mean arterial blood pressure, use of antihypertensive medications and left ventricular hypertrophy by ECG criteria, the excess prevalence of retinopathy in African Americans was reduced by 40% (adjusted OR 1.61, 95% CI 1.26, 2.06). Further adjustment for other vascular risk factors, common carotid artery intima-media thickness, and serum creatinine levels reduced the excess prevalence in African Americans by another 13% (adjusted OR 1.48, 95% CI 1.08, 2.03). We conclude that hypertensive retinopathy is twice as frequent in African Americans compared with whites without diabetes and that the excess prevalence of retinopathy in African Americans is associated with blood pressure and severity of hypertension.

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PubMed2003

Early age-related maculopathy in the cardiovascular health study.

OBJECTIVE: To describe the prevalence of early age-related maculopathy (ARM) and its relation to atherosclerosis, lipids, hypertension, and inflammatory factors in a population studied for cardiovascular disease risk factors and outcomes. DESIGN: Population-based cohort study. PARTICIPANTS: A biracial population of 2361 adults (ranging from 69-97 years of age; 1998 whites and 363 blacks) living in four US counties (Allegheny County, Pennsylvania; Forsyth County, North Carolina; Sacramento County, California; and Washington County, Maryland) were examined during the interval from 1997 to 1998. METHODS: Drusen and other lesions typical of ARM were identified by examining a 45 degrees color fundus photograph of one eye of each participant and classified by means of a modification of the Wisconsin Age-Related Maculopathy Grading System. MAIN OUTCOME MEASURES: Early ARM. RESULTS: Early ARM was present in 15.5% and late ARM in 1.3% of the cohort. The overall prevalence of any ARM was lower in blacks (9.1%) compared with whites (18.2%). While controlling for age, race, gender, and total calories consumed in the diet, factors associated with ARM were cerebral white matter disease as detected by magnetic resonance imaging (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.05, 2.16, P = 0.027), and lower serum total cholesterol (OR, per 10 mg/dl increase 0.95; 95% CI, 0.91, 0.98, P = 0.02). There were no associations between hypertension, blood pressure, common carotid artery plaque, or any systemic inflammatory factors studied and early ARM. CONCLUSIONS: This population-based study documents the higher prevalence of ARM in whites compared with blacks. Although an association was found between signs of white matter disease and early ARM, there was no evidence of an association of ARM with either hypertension or inflammatory factors.

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PubMed2003

The prevalence and risk factors of retinal microvascular abnormalities in older persons: The Cardiovascular Health Study.

PURPOSE: To describe the prevalence of retinal microvascular characteristics and their associations with atherosclerosis in elderly, nondiabetic persons. DESIGN AND PARTICIPANTS: Population-based, cross-sectional study comprising 2050 men and women aged 69 to 97 years without diabetes, living in four communities. METHODS: Participants underwent retinal photography and standardized grading of retinal microvascular characteristics, including retinopathy (e.g., microaneurysms, retinal hemorrhages), focal arteriolar narrowing, and arteriovenous nicking. In addition, calibers of retinal arterioles and venules were measured on digitized photographs to obtain an estimate of generalized arteriolar narrowing. Atherosclerosis and its risk factors were obtained from clinical examination and laboratory investigations. MAIN OUTCOME MEASURES: Prevalence of retinal microvascular abnormalities and their associations with measures of atherosclerosis. RESULTS: The prevalence of retinal microvascular abnormalities was 8.3% for retinopathy, 9.6% for focal arteriolar narrowing, and 7.7% for arteriovenous nicking. All retinal lesions were associated with hypertension (odds ratios [OR] were 1.8 for retinopathy, 2.1 for focal arteriolar narrowing, 1.5 for arteriovenous nicking, and 1.7 for generalized arteriolar narrowing). After controlling for age, gender, race, mean arterial blood pressure, and antihypertensive medication use, retinopathy was associated with prevalent coronary heart disease (OR, 1.7), prevalent myocardial infarction (OR, 1.7), prevalent stroke (OR, 2.0), presence of carotid artery plaque (OR, 1.9), and increased intima-media thickness of the common carotid (OR, 2.3; fourth vs. first quartile) and internal carotid (OR, 1.8; fourth vs. first quartile) arteries. In contrast, focal arteriolar narrowing, arteriovenous nicking, and generalized arteriolar narrowing were not associated with any measures of atherosclerosis. CONCLUSIONS: Retinal microvascular abnormalities are common in older persons without diabetes and are related to hypertension. Retinopathy is associated with prevalent coronary heart disease, stroke, and carotid artery thickening, but focal and generalized arteriolar narrowing and arteriovenous nicking are not related to most measures of atherosclerosis. These data suggest that retinal microvascular abnormalities reflect processes associated with hypertension but distinct from atherosclerosis.

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PubMed2003

Retinal microvascular abnormalities and 10-year cardiovascular mortality: a population-based case-control study.

PURPOSE: Retinal microvascular abnormalities reflect persistent arteriolar damage from hypertension and independently predict stroke. We examined their associations with long-term cardiovascular mortality. DESIGN: Population-based, nested, case-control study. POPULATION: Cases were Beaver Dam Eye Study participants (age range, 43-84 years) who died of coronary heart disease or stroke between the baseline examination in 1988 to 1990 and 1999 (n = 413). Nearly 3 controls per case were selected from the baseline cohort, frequency-matched on 5-year age intervals and gender (n = 1198). METHODS: Retinal photographs of cases and controls at baseline were evaluated for retinopathy, focal arteriolar narrowing, and arteriovenous nicking by graders masked to case-control status using standardized protocols. To obtain an estimate of generalized arteriolar narrowing, photographs were digitized and diameters of individual retinal vessels were measured and summarized by a computer program. MAIN OUTCOME MEASURE: Ten-year cardiovascular mortality. RESULTS: After controlling for systolic blood pressure, diabetes, glycosylated hemoglobin levels, and other risk factors, retinopathy was associated with increased cardiovascular mortality, with odds ratios of 1.8 (95% confidence interval [CI], 1.2, 2.7). For other retinal abnormalities, associations with cardiovascular mortality were present only in younger people, with odds ratios of 2.7 (95% CI, 1.0, 7.4) for focal arteriolar narrowing, 1.8 (95% CI, 0.8, 4.5) for arteriovenous nicking, and 1.9 (95% CI, 1.2, 2.9) for generalized arteriolar narrowing in persons 43 to 74 years of age but odds ratios of 1.1, 0.4, and 1.0 for the corresponding retinal abnormalities in persons 75 years and older. CONCLUSIONS: Retinopathy is independently associated with cardiovascular mortality. Associations for other retinal abnormalities were only observed in middle-aged persons. These data support recent studies that suggest retinal microvascular abnormalities provide independent information regarding cardiovascular risk.

Adult↗

PubMed2003

Computer-assisted retinal vessel measurement in an older population: correlation between right and left eyes.

This study assessed the correlation between computer-assisted retinal vessel measurements of right and left eyes, from subjects in a defined, community-based older population. Retinal photographs from participants in the Blue Mountains Eye Study were digitized. All retinal arterioles and venules located 0.5-1.0 disc diameters from the optic disc margin were identified and a computer program measured their diameters. Pearson correlation (R2) statistic was used to assess the correlation in a random subsample of 1546 images. Substantial correlation between right and left eye measurements was found for summary indices of retinal arterioles (R2 = 0.70) and venules (R2 = 0.77). Higher correlation was found for intragrader (R2 0.75-079) than for intergrader assessment (R2 0.67-0.72). Moderate correlation was found in arteriole-to-venule ratio assessed by the same (R2 = 0.57) or different (R2 = 0.52) graders. Measurements from one eye can thus adequately represent the retinal vessel diameters of a person.

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PubMed2003

Correlation between generalized and focal retinal arteriolar narrowing in an older population.

This study aimed to assess the associations between generalized and focal retinal arteriolar narrowing in the Blue Mountains Eye Study population (n = 3654 persons aged 49+ years). Summarized estimates of the average retinal arteriolar diameter, the central retinal arteriolar equivalent (CRAE) and arteriole-to-venule ratio were obtained from right eye photographs of each participant using a computer-assisted method. Focal retinal arteriolar narrowing was graded from retinal photographs of both eyes using a 'light-box' method. The proportion of subjects with focal arteriolar narrowing increased as CRAE decreased from the widest (2.2%) to the narrowest (7.8%) quintile (P for trend = 0.001). A receiver operating characteristic curve was constructed using CRAE to detect focal arteriolar narrowing. With the diagnostic cut point set at the 4th decile of CRAE, the sensitivity and specificity in detecting focal arteriolar narrowing were 64% and 61%,respectively. These data suggest a moderate correlation between generalized (CRAE) and focal arteriolar narrowing. However, no significant association was found between arteriole-to-venule ratio and focal arteriolar narrowing.

Arterioles↗

PubMed2003

Revised formulas for summarizing retinal vessel diameters.

Background/Purpose. Recent findings suggest that an objective assessment of retinal vessel caliber from fundus photographs provide information about the association of microvascular characteristics with macrovascular disease. Current methods used to quantify retinal vessel caliber, introduced by Parr(1,2) and Hubbard,(3) are not independent of scale and are affected by the number of vessels. To improve upon these methods we introduce revised formulas for quantifying vessel caliber. Methods. Revised formulas were estimated using retinal vessel measurements from 44 young adults free of hypertension and diabetes. Comparisons between the two methods were done using digitized photographs from 4926 participants at the baseline examination of the Beaver Dam Eye Study (BDES), an ongoing population-based cohort study initiated in 1987. Individual arterioles and venules were measured using semi-automated computer software from which summary measures were calculated. Results. Correlation coefficients between the Parr-Hubbard and revised formulas were high (Pearson correlation coefficients ranging from 0.94 to 0.98). Both arteriolar and venular caliber significantly increased with an increasing number of vessels measured using the Parr-Hubbard formulas (p < 0.001), which in turn affected the relationship to mean arterial blood pressure. To the contrary, the revised formulas were not affected by the number of measured vessels (p > 0.50). Conclusions. We describe revised formulas for summarizing retinal vessel diameters measured from fundus photographs to be used in future studies and analyses. The revised formulas correlate highly with the previously used Parr-Hubbard formulas, but offer the advantages of being more robust against variability in the number of vessels observed, being independent of image scale, and being easier to implement.

Adult↗

PubMed2003

Relationships between age, blood pressure, and retinal vessel diameters in an older population.

PURPOSE: To describe the cross-sectional relationships between age, blood pressure (BP), and quantitative measures of retinal vessel diameters in an older Australian population. METHODS: Retinal photographs from right eyes of participants (n = 3654, aged 49+ years) in the Blue Mountains Eye study taken during baseline examinations (1992-1994) were digitized. The width of all retinal vessels located 0.5 to 1.0 disc diameters from the disc margin was measured by a computer-assisted method. Summarized estimates for central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) represent average retinal vessel diameters. The arteriole-to-venule ratio (AVR) was calculated. Associations between age and BP and CRAE, CRVE, and AVR were assessed with generalized linear models. RESULTS: Retinal vessel diameters decreased with increasing age in both men and women. CRAE and CRVE decreased by 4.8 microm and 4.1 microm, respectively, per decade increase in age, after adjusting for sex and mean arterial blood pressure. Mean AVR declined by 0.01 for each increasing decade of age, until 79 years. After adjustment for age, sex, smoking, and body mass index, CRAE, CRVE and AVR were all significantly and inversely associated with BP. For every 10-mm Hg increase in mean arterial blood pressure, AVR decreased by 0.012 and CRAE and CRVE decreased by 3.5 microm and 0.96 microm, respectively. CONCLUSIONS: Retinal arteriolar and venular diameters narrow with increasing age, and these parameters are inversely related to BP, independent of age, gender, and smoking. The findings are consistent with those from the Atherosclerosis Risk in Communities Study suggesting that decreased retinal vessel diameters may reflect microvascular damage from elevated blood pressure.

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PubMed2003

Retinal vessel diameters and their associations with age and blood pressure.

PURPOSE: To describe the cross-sectional relationship between retinal arteriolar and venular diameters with age and blood pressure. METHODS: A population-based study was conducted in Beaver Dam, Wisconsin (n=4926, age range, 43-84 years). Retinal photographs of right eyes taken at the baseline examination (1988-90) were digitized. All arterioles and venules located in the area between one-half and one disc diameter from the optic disc margin were measured with a computer-based program. These measurements were combined to provide the average diameters of retinal arterioles and venules of each eye, and the association with age and blood pressure (BP) was analyzed. RESULTS: After controlling for gender, hypertension, diabetes, serum glucose and lipids, cigarette smoking, and body mass index, retinal arteriolar diameters were found to be decreased by 2.1 microm (95% confidence interval [CI], 1.5-2.7) for each decade increase in age, and by 4.4 microm (95% CI, 3.8-5.0) for each 10-mm Hg increase in mean arterial BP. The association of narrowed retinal arterioles and higher BP was stronger in younger persons. For each 10-mm Hg increase in mean arterial BP, arteriolar diameters decreased by 7.0 microm in persons aged 43 to 54 years but by only 2.5 microm in persons aged 75 to 84 years. In contrast, retinal venular diameters narrowed with increasing age but not with increasing BP. CONCLUSIONS: Retinal arteriolar diameters are narrower in older persons and in persons with higher BP, independent of other factors. The weaker association of retinal arteriolar diameters and BP in older people may reflect greater sclerosis of the retinal arterioles, preventing a degree of narrowing with higher BP similar to that seen in younger persons.

Adult↗

PubMed2002

Cerebral white matter lesions, retinopathy, and incident clinical stroke.

CONTEXT: White matter lesions (WMLs) detected on cerebral imaging scans have been hypothesized to have a microvascular etiology and to precede the development of clinical stroke. However, few clinical data are available to support these hypotheses. OBJECTIVE: To examine the relationship of WMLs, retinal microvascular abnormalities, and incident clinical stroke in healthy, middle-aged men and women. DESIGN AND SETTING: The Atherosclerosis Risk in Communities Study (ARIC), a prospective, population-based cohort study conducted in 4 US communities and initiated in 1987-1989. PARTICIPANTS: A total of 1684 persons aged 51 to 72 years who had cerebral magnetic resonance imaging (MRI) and retinal photography at the third examination (1993-1995). MAIN OUTCOME MEASURES: Odds of WMLs, defined by standardized methods from MRI, by presence or absence of specific retinal microvascular abnormality (eg, microaneurysm, retinal hemorrhage) on retinal photograph; incident clinical stroke, ascertained after a median follow-up of 4.7 years, according to presence or absence of WMLs and retinopathy. RESULTS: Persons with retinopathy were more likely to have WMLs than those without retinopathy (22.9% vs 9.9%; odds ratio, 2.5; 95% confidence interval [CI], 1.5-4.0, adjusted for age, sex, race, and vascular risk factors). The 5-year cumulative incidence of clinical stroke was higher in persons with vs without WMLs (6.8% vs 1.4%; adjusted relative risk [RR], 3.4; 95% CI, 1.5-7.7) and in persons with vs without retinopathy (8.0% vs 1.4%; adjusted RR, 4.9; 95% CI, 2.0-11.9). Persons with both WMLs and retinopathy had a significantly higher 5-year cumulative incidence of stroke than those without either WMLs or retinopathy (20.0% vs 1.4%; adjusted RR, 18.1; 95% CI, 5.9-55.4). CONCLUSIONS: In this cohort, middle-aged persons with cerebral WMLs detected on MRI were more likely to have retinal microvascular abnormalities and to have an increased risk of clinical stroke than people without WMLs. The risk of stroke was higher when retinopathy was simultaneously present in persons with WMLs.

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PubMed2002

Retinal arteriolar narrowing and risk of diabetes mellitus in middle-aged persons.

CONTEXT: Microvascular processes have been hypothesized to play a role in the pathogenesis of type 2 diabetes mellitus, but prospective clinical data regarding this hypothesis are unavailable. OBJECTIVE: To examine the relation of retinal arteriolar narrowing, a marker of microvascular damage from aging, hypertension, and inflammation, to incident diabetes in healthy middle-aged persons. DESIGN, SETTING, AND PARTICIPANTS: The Atherosclerosis Risk in Communities Study, an ongoing population-based, prospective cohort study in 4 US communities that began in 1987-1989. Included in this analysis were 7993 persons aged 49 to 73 years without diabetes, of whom retinal photographs were taken during the third examination (1993-1995). MAIN OUTCOME MEASURES: Incident diabetes (defined as fasting glucose levels of > or =126 mg/dL [7.0 mmol/L], casual levels of > or =200 mg/dL [11.1 mmol/L], diabetic medications use, or physician diagnosis of diabetes at the fourth examination) by quartile of retinal arteriole-to-venule ratio (AVR). RESULTS: After a median follow-up of 3.5 years, 291 persons (3.6%) had incident diabetes. The incidence of diabetes was higher in persons with lower AVR at baseline (2.4%, 3.1%, 4.0%, and 5.2%, from highest to lowest AVR quartile; P for trend < .001). After controlling for fasting glucose and insulin levels, family history of diabetes, adiposity, physical activity, blood pressure, and other factors, persons in the lowest quartile of AVR were 71% more likely to develop diabetes than those in the highest quartile (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.13-2.57; P for trend =.002). This association persisted with different diagnostic criteria (OR, 1.92; 95% CI, 1.10-3.36; P for trend =.01, using a fasting glucose level of > or =141 mg/dL [7.8 mmol/L] as a cutoff), and was seen even in people at lower risk of diabetes, including those without a family history of diabetes, without impaired fasting glucose, and with lower measures of adiposity. CONCLUSIONS: Retinal arteriolar narrowing is independently associated with risk of diabetes, supporting a microvascular role in the development of clinical diabetes.

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PubMed2002

Retinal arteriolar narrowing and risk of coronary heart disease in men and women. The Atherosclerosis Risk in Communities Study.

CONTEXT: Microvascular processes have been hypothesized to play a greater role in the development of coronary heart disease (CHD) in women than in men; however, prospective clinical data are limited. OBJECTIVE: To examine the association between retinal arteriolar narrowing, a marker of microvascular damage from hypertension and inflammation, and incident CHD in healthy middle-aged women and men. DESIGN, SETTING, AND PARTICIPANTS: The Atherosclerosis Risk in Communities Study, an ongoing prospective, population-based cohort study in 4 US communities initiated in 1987-1989. Retinal photographs were taken in 9648 women and men aged 51 to 72 years without CHD at the third examination (1993-1995). To quantify retinal arteriolar narrowing, the photographs were digitized, individual arteriolar and venular diameters were measured, and a summary arteriole-to-venule ratio (AVR) was calculated. MAIN OUTCOME MEASURE: Risk of CHD associated with retinal arteriolar narrowing. RESULTS: During an average 3.5 years of follow-up, 84 women and 187 men experienced incident CHD events. In women, after controlling for mean arterial blood pressure averaged over the previous 6 years, diabetes, cigarette smoking, plasma lipid levels, and other risk factors, each SD decrease in the AVR was associated with an increased risk of any incident CHD (relative risk [RR], 1.37; 95% confidence interval [CI], 1.08-1.72) and of acute myocardial infarction (RR, 1.50; 95% CI, 1.10-2.04). In contrast, AVR was unrelated to any incident CHD in men (RR, 1.00; 95% CI, 0.84-1.18) or to acute myocardial infarction (RR, 1.08; 95% CI, 0.85-1.38). CONCLUSION: Retinal arteriolar narrowing is related to risk of CHD in women but not in men, supporting a more prominent microvascular role in the development of CHD in women than in men. Future work is needed to confirm these findings.

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PubMed2002

Reliability of retinal photography in the assessment of retinal microvascular characteristics: the Atherosclerosis Risk in Communities Study.

PURPOSE: Retinal microvascular characteristics, as graded from retinal photography, have been shown to predict stroke. We evaluated the reliability of retinal photographic grading in the Atherosclerosis Risk in Communities Study. DESIGN: Cohort study. METHODS: Retinal photographs were taken of all subjects who attended the third Atherosclerosis Risk in Communities Study examination (1993 to 1995). These were graded using standardized protocols. Focal retinal characteristics were graded using a "light box" system. Generalized retinal arteriolar narrowing was quantified from computer-assisted measurements of digitized photographs. Two sub-studies were conducted to investigate the reliability of these grading methods. In the Individual Variability Study, selected subjects (n = 206) had two retinal photographs taken on one day, and a further one or two photographs taken 3 weeks later. In the Grader Variability Study, a stratified random sample of photographs had repeat retinal grading (n = 495 photographs for light box grading; n = 276 photographs for computer-assisted grading). RESULTS: Reliability of the computer-assisted quantification of generalized retinal arteriolar narrowing was high in both studies (reliability coefficients 0.64 to 0.69 for Individual Variability Study, and 0.79 to 0.83 for the Grader Variability Study). There was more variability for focal abnormalities graded using the light box system. Variability for Individual Variability Study (same individuals, repeat photographs) tended to be greater than for the Grader Variability Study (same photographs, repeat gradings). CONCLUSION: Retinal microvascular characteristics, especially computer-assisted quantification of generalized retinal arteriolar narrowing, can be ascertained reliably by standardized photographic grading methods, supporting the validity of their associations with cardiovascular disease. However, these characteristics appear to vary somewhat between eyes and over time in a single individual.

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PubMed2002

Characteristics of patients with cytomegalovirus retinitis in the era of highly active antiretroviral therapy.

PURPOSE: To describe the characteristics of patients with AIDS and cytomegalovirus retinitis in the era of highly active antiretroviral therapy (HAART). METHODS: Prospective cohort study. Baseline (enrollment) data were compared between patients with newly diagnosed cytomegalovirus retinitis (incident cases) and those with previously diagnosed cytomegalovirus retinitis (prevalent cases). RESULTS: As of December 31, 2000, 45 incident and 200 prevalent cases had been enrolled. Among prevalent cases, the median time from cytomegalovirus retinitis diagnosis was 2.9 years. Incident cases were more likely than prevalent cases to be women (35.4% vs 15.3%, P =.001), African American (45.4% vs 20.4%, P =.002), and uninsured (29.6% vs 7.6%, P <.001). Incident cases were less likely than prevalent cases to be on HAART (51.2% vs 77.6%, P =.001) and to have had an immunologic response to HAART (increase in CD4(+) T-cell count to > 100 cells/microl) (12.2% vs 57.5%, P <.001). The median CD4(+) T-cell count at enrollment among incident cases was 17 cells/microl and among prevalent cases was 159 cells/microl (P <.001). Immune recovery uveitis had been diagnosed in 15.5% of the prevalent cases. Sixty-three percent of prevalent cases were not on anticytomegalovirus therapy. CONCLUSIONS: There is a population of patients with previously diagnosed and longstanding cytomegalovirus retinitis who have experienced immune recovery as a consequence of HAART and are no longer receiving anticytomegalovirus therapy. There are demographic differences between incident and prevalent cases that may reflect the evolution of the AIDS epidemic and differences in utilization of health care services.

AIDS-Related Opportunistic Infections↗

PubMed2002

Is early age-related maculopathy related to cognitive function? The Atherosclerosis Risk in Communities Study.

PURPOSE: Age-related maculopathy (ARM) and cognitive impairment are both neurodegenerative disorders associated with aging and have been hypothesized to share common pathogenic pathways. We describe the association between cognitive function and ARM in middle-aged persons. DESIGN: Population-based, cross-sectional study involving participants of the Atherosclerosis Risk in Communities Study, an ongoing cardiovascular investigation of persons 51 to 70 years of age, examined every 3 years between 1987 to 1998. METHODS: At visit three (1993-1995), retinal photographs were obtained and evaluated for ARM using a modification of the Wisconsin ARM Grading System. Cognitive function was assessed using standardized tests (Delayed Word Recall, Digit Symbol, and Word Fluency) at visits two (1990-1992) and four (1996-1998) and averaged for analysis. Severe cognitive impairment was defined as scores falling in the lowest 10th percentile of the population. RESULTS: Data were available in 9286 persons after exclusion of persons with stroke or using antipsychotic medication. After adjusting for age, gender, race, education, diabetes, hypertension, cigarette smoking, and alcohol consumption, persons with severe cognitive impairment based on Word Fluency Test scores were more likely to have early ARM (odds ratio [OR]: 1.6, 95% confidence interval [CI]: 1.1-2.2) and its components, soft drusen (OR: 1.6; 95% CI: 1.1-2.3) and pigmentary abnormality (OR: 1.5; 95% CI: 0.9-2.5) than those without severe impairment. However, severe cognitive impairment in scores of the other two cognitive function tests was not associated with ARM. CONCLUSION: These population-based data suggest a weak association between cognitive function and early ARM in middle-aged persons.

Arteriosclerosis↗

PubMed2002

The association of atherosclerosis, vascular risk factors, and retinopathy in adults with diabetes : the atherosclerosis risk in communities study.

PURPOSE: The aim of this report is to describe the prevalence of retinopathy and its associations with atherosclerosis and vascular risk factors in people with diabetes. DESIGN: Cross-sectional study. PARTICIPANTS: Persons with diabetes, having gradable fundus photographs, from a biracial population-based cohort of adults (ages 51-72 years), and living in four United States communities (Forsyth County, North Carolina; the city of Jackson, Mississippi; suburbs of Minneapolis, Minnesota; and Washington County, Maryland) were studied from 1993 to 1995. METHODS: Lesions typical of diabetic retinopathy were detected by grading a 45 degrees color fundus photograph of one eye of each participant, using a modification of the Airlie House classification system. MAIN OUTCOME MEASURE: Severity of diabetic retinopathy (none, minimal nonproliferative, moderate nonproliferative, severe nonproliferative, and proliferative) and macular edema. RESULTS: Retinopathy was detected in 328/1600 (20.5%) of those with diabetes; 114/1724 (6.6%) had hard exudate, 28/1600 (1.8%) had proliferative diabetic retinopathy, and 27/1662 (1.6%) had macular edema. The prevalence of diabetic retinopathy was higher in blacks (27.7%) compared with whites (16.7%). Controlling for duration of diabetes, serum glucose, systolic blood pressure, and type of diabetes medications taken, severity of retinopathy was associated with carotid artery intima-media wall thickness (odds ratio [OR]/0.1-mm thickness 1.09; 95% confidence interval [CI], 1.01, 1.17; P = 0.01), serum albumin (OR/0.1 g/dl 0.94; 95% CI, 0.88, 0.99; P = 0.02), but not race (OR blacks versus whites,1.24; 95% CI, 0.88, 1.75; P = 0.21). Severity of diabetic retinopathy was not associated with coronary artery disease or stroke history or any of the plasma lipids studied. Controlling for age, gender, duration of diabetes, serum glucose, and type of diabetes medications taken, the presence of retinal hard exudates was associated with plasma low-density lipoprotein cholesterol (OR/10 mg/dl 1.18; 95% CI, 1.09, 1.29; P < 0.001), and plasma Lp(a) (OR/10 mg/dl 1.02; 95% CI, 1.00, 1.05; P = 0.04) but not race or blood pressure. CONCLUSIONS: These data suggest that plasma lipids are associated with the presence of hard exudate and that carotid artery intima-media wall thickness is associated with retinopathy, but other manifestations of atherosclerosis and most of its risk factors are not associated with severity of diabetic retinopathy.

Aged↗

PubMed2002

High dose oral ganciclovir treatment for cytomegalovirus retinitis.

BACKGROUND: The oral formulation of ganciclovir is approved at a dose of 3.0 g/day for maintenance treatment of cytomegalovirus (CMV) retinitis following an initial induction course of intravenous (IV) anti-CMV therapy. Median time to progression of CMV retinitis is 12-20 days shorter with oral compared to IV ganciclovir maintenance, likely due to the limited oral bioavailability of ganciclovir. OBJECTIVES: We hypothesized that higher systemic drug exposures associated with increased doses of oral ganciclovir would be associated with increased efficacy. STUDY DESIGN: Maintenance treatment of CMV retinitis with higher than standard doses of oral ganciclovir (>3.0 g/day) was studied in 281 AIDS patients with previously treated, stable retinitis randomized to 3.0, 4.5 or 6.0 g/day oral, or 5 m/kg/day IV ganciclovir. Graders unaware of treatment assignments determined retinitis progression using fundus photographs. Vision, other ophthalmic measures and safety were assessed open-label. RESULTS: Median days to photographic progression were 41, 50, 57 and 70, respectively (P=0.052; 3.0 g vs. IV). Hazard ratios for progression relative to IV were 1.66, 1.28 and 1.19 (P=0.016 for 3.0 g). NONMEM-modeled estimates of average serum ganciclovir concentration area under the curve (AUC(0-24)) correlated best with time to progression (P=0.0019). Six grams per day oral ganciclovir was most similar in efficacy to IV, although broad confidence intervals prevented a conclusive comparison. Patients receiving oral ganciclovir had a lower frequency of sepsis and IV catheter events. CONCLUSIONS: This study suggests that the efficacy of ganciclovir for the maintenance treatment of CMV retinitis improves with increasing total drug exposure (measured as average serum concentration AUC(0-24)). All four regimens of ganciclovir were reasonably well tolerated, with safety profiles similar to what has been reported in prior work.

AIDS-Related Opportunistic Infections↗