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Gabriella Tikellis

Publications and source records attributed to Gabriella Tikellis.

8 recordsLinked to original sources

Apolipoprotein e gene and age-related maculopathy in older individuals: the cardiovascular health study.

OBJECTIVE: To examine the association between the apolipoprotein E (APOE) gene and age-related maculopathy (ARM) in an older population. METHODS: Two thousand one hundred seventy persons 65 years and older sampled from 4 US communities had ARM signs assessed from retinal photographs using a modified Wisconsin Age-Related Maculopathy Grading System. DNA extracted from blood samples was analyzed for common APOE alleles. RESULTS: After controlling for age, sex, cigarette smoking, and other factors, white participants carrying the epsilon2 allele had an increased risk of late ARM (odds ratio, 2.53 [95% confidence interval, 1.08-5.90]) while carriers of the epsilon4 allele had a lower risk of late ARM (odds ratio, 0.69 [95% confidence interval, 0.19-2.50]). There were too few late ARM cases in African American individuals for analysis. CONCLUSION: APOE polymorphism is associated with late ARM in older white persons 65 years and older. Consistent with previous studies, the APOE epsilon2 allele is associated with a significant increased risk of late ARM development, whereas the epsilon4 allele may confer some protection.

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Age-related macular degeneration and risk of coronary heart disease: the Atherosclerosis Risk in Communities Study.

OBJECTIVE: To examine the association of age-related macular degeneration (AMD) with incident coronary heart disease (CHD) and all-cause mortality. DESIGN: Population-based prospective cohort study. PARTICIPANTS: From the Atherosclerosis Risk in Communities Study (n = 12 536; age range, 49-73 years). METHODS: Participants had retinal photographs of one eye taken between 1993 and 1995. Photographs were evaluated for the presence of early and late AMD signs according to the Wisconsin grading system. Incident CHD events (acute myocardial infarction, silent myocardial infarction, fatal CHD, and cardiac revascularization procedures) and all-cause mortality were identified prospectively using standardized methods. MAIN OUTCOME MEASURES: Incident CHD events and all-cause mortality. RESULTS: Of 11,414 persons at risk of CHD, there were 555 (4.9%) with AMD at baseline, of whom 540 were early AMD and 15 were late AMD cases. Over a 10-year follow-up, 922 persons developed an incident CHD event. After controlling for age, gender, race, systolic and diastolic blood pressure, pack-years of cigarette smoking, and other variables, early AMD was not associated with incident CHD (relative risk, 1.08; 95% confidence interval, 0.82-1.42). However, individuals with late AMD were significantly more likely to have an incident CHD event, with 4 CHD events among the 15 participants with late AMD at baseline (10-year cumulative incidence, 30.9%) as compared with 918 CHD events among the 11 399 participants without late AMD (incidence of 10.0%; P = 0.049, Fisher exact test). In the full cohort (n = 12 536), early AMD was not significantly associated with all-cause mortality. However, individuals with late AMD were more likely to die (10-year cumulative mortality rate, 23.5%) than those without late AMD (mortality rate, 8.9%; P = 0.088, Fisher exact test). CONCLUSIONS: These data provide no evidence of an association between early AMD signs with incident CHD and all-cause mortality in middle-aged persons. Individuals with late AMD appear to have a higher rate of CHD events than those without late AMD, but due to a small number of late AMD cases, this finding should be interpreted cautiously.

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Is early age-related macular degeneration associated with cerebral MRI changes? The Atherosclerosis Risk in Communities study.

PURPOSE: To examine the relation of early age-related macular degeneration (AMD) with cerebral magnetic resonance imaging (MRI) changes. DESIGN: Population-based, cross-sectional study. METHODS: A sample of 1,684 persons ages 51 to 72 years with no history of stroke had cerebral MRI and retinal photography. MRI scans were graded for severity of white matter lesions (WML), sulcal widening (SW), and ventricular enlargement (VE). AMD was graded from retinal photographs. RESULTS: After adjustment for age, gender, race, or center, early AMD (5.0% of participants) was not significantly associated with WML (odds ratio [OR] 1.0, 95% confidence intervals [CI], 0.6 to 1.6), SW (OR 0.6, 95% CI, 0.4 to 1.2), or VE (OR 1.0, 95% CI, 0.6 to 1.8). CONCLUSIONS: These data showed no statistically significant association of early AMD with cerebral MRI changes, but the study was limited by a small number of cases with wide CIs. Further studies may clarify these associations.

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Apolipoprotein (APOE) gene is associated with progression of age-related macular degeneration (AMD).

Progression of age-related macular degeneration (AMD), the leading cause of blindness in the elderly, was followed in a cohort of 238 individuals from a single center. Individuals with an epsilon (epsilon)2 genotype (c.526C>T of reference sequence NM_000041.2) of the apolipoprotein (APOE) gene were found to be strongly associated with disease with a significant 4.8-fold increased relative risk compared to individuals with an epsilon4 genotype (c.388T>C of reference sequence NM_000041.2) (odds ratio [OR], 4.8; 95% confidence interval [CI], 1.19-19.09) and a nearly significant three-fold increased relative risk compared to individuals with an epsilon3 genotype (reference sequence NM_000041.2) (OR, 2.8; 95% CI, 0.96-19.09). This finding was present only in females who progressed with AMD, which suggests that there may be a gender-specific role in progression of AMD in individuals with an epsilon2 allele. A gender-related factor is therefore implicated either directly or indirectly in the AMD disease process.

Age Distribution↗

Exposure to Chlamydia pneumoniae infection and progression of age-related macular degeneration.

Recent studies have found an association between exposure to Chlamydia pneumoniae infection and risk of age-related macular degeneration (AMD). To assess a potential risk of AMD progression posed by exposure to C. pneumoniae, the authors reexamined Australian residents in 2001-2002 who were aged 51-89 years with early AMD at baseline (1992-1995). Examination included macular photography and an enzyme-linked immunosorbent assay to determine antibody titers to the elementary bodies from C. pneumoniae AR39. AMD progression was assessed quantitatively, using both coarse and fine progression steps following an international classification for AMD grading, and also qualitatively, by side-by-side comparison of baseline and follow-up macular photographs. Serologic data were available for 246 of 254 (97%) subjects. AMD progression was associated with a higher antibody titer. After adjustment for age, smoking, family history of AMD, history of cardiovascular diseases, and source study, the subjects in the upper tertiles of antibody titers were 2.1 (95% confidence interval: 0.92, 4.69), 2.6 (95% confidence interval: 1.24, 5.41), and 3.0 (95% confidence interval: 1.46, 6.37) times more at risk of progression than those in the lowest tertile, using three definitions of progression, respectively. The fact that seroreactivity to C. pneumoniae was independently associated with the risk of AMD progression suggests that C. pneumoniae infection may be an additional risk factor for AMD progression.

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Vitamin E supplementation and cataract: randomized controlled trial.

OBJECTIVE: To determine whether treatment with vitamin E (500 IU daily) reduces either the incidence or rate of progression of age-related cataracts. DESIGN: A prospective, randomized, double-masked, placebo-controlled clinical trial entitled the Vitamin E, Cataract and Age-Related Maculopathy Trial. PARTICIPANTS: Of 1906 screened volunteers, 1193 eligible subjects with early or no cataract, aged 55 to 80 years, were enrolled and followed up for 4 years. INTERVENTION: Subjects were assigned randomly to receive either 500 IU of natural vitamin E in soybean oil encapsulated in gelatin or a placebo with an identical appearance. MAIN OUTCOME MEASURES: The incidence and progression rates of age-related cataract were assessed annually with both clinical lens opacity gradings and computerized analysis of Scheimpflug and retroillumination digital lens images obtained with a Nidek EAS-1000 lens camera. The analysis was undertaken using data from the eye with the more advanced opacity for each type of cataract separately and for any cataract changes in each individual. RESULTS: Overall, 87% of the study population completed the 4 years of follow-up, with 74% of the vitamin E group and 76% of the placebo group continuing on their randomized treatment allocation throughout this time. For cortical cataract, the 4-year cumulative incidence rate was 4.5% among those randomized to vitamin E and 4.8% among those randomized to placebo (P = 0.87). For nuclear cataract, the corresponding rates were 12.9% and 12.1% (P = 0.77). For posterior subcapsular cataract, the rates were 1.7% and 3.5% (P = 0.08), whereas for any of these forms of cataract, they were 17.1% and 16.7%, respectively. Progression of cortical cataract was seen in 16.7% of the vitamin E group and 18.4% of the placebo group (P = 0.76). Corresponding rates for nuclear cataract were 11.4% and 11.9% (P = 0.84), whereas those of any cataract were 16.5% and 16.7%, respectively. There was no difference in the rate of cataract extraction between the 2 groups (P = 0.87). Lens characteristics of the participants withdrawn from the randomized medications were not different from those who continued. CONCLUSIONS: Vitamin E given for 4 years at a dose of 500 IU daily did not reduce the incidence of or progression of nuclear, cortical, or posterior subcapsular cataracts. These findings do not support the use of vitamin E to prevent the development or to slow the progression of age-related cataracts.

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Iris colour, ethnic origin and progression of age-related macular degeneration.

AIM: To investigate the relationship between iris colour, ethnic origin and the progression of age-related macular degeneration (AMD). METHODS: Participants were recruited from the population-based Melbourne Visual Impairment Project or the prospective, randomized, double-masked Vitamin E, Cataract and Age-Related Macular Degeneration study. From these two cohorts, 171 participants aged between 52 and 93 years who were identified as having early AMD features at their baseline examination (1992-1995) were followed for an average of 6.8 years (until 2001) to determine the progression rate of early AMD. The participants' iris colour was categorized as light, intermediate or dark. Ethnic origin was categorized as Anglo-Saxon or non-Anglo-Saxon, according to the participants' grandparents' country of birth. RESULTS: In total, 53 (31%) of the 171 participants showed signs of AMD progression. Participants with light iris colour had twofold the risk of AMD progression of those with dark or intermediate iris colours, although the age-adjusted and multivariate-adjusted associations were not significant (both P = 0.13). Age-adjusted and multivariate comparisons of Anglo-Saxon ethnic origin to non-Anglo-Saxon ethnic origin showed a noticeable but non-significant association with progression of AMD (P= 0.22 and P= 0.14, respectively). CONCLUSION: Individuals with light iris colour or of Anglo-Saxon ethnic origin had a strong tendency to greater progression of AMD. A larger sample is required to confirm these clinically important, but statistically non-significant, associations.

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Vitamin E supplementation and macular degeneration: randomised controlled trial.

OBJECTIVE: To determine whether vitamin E supplementation influences the incidence or rate of progression of age related maculopathy (AMD). DESIGN: Prospective randomised placebo controlled clinical trial. SETTING: An urban study centre in a residential area supervised by university research staff. PARTICIPANTS: 1193 healthy volunteers aged between 55 and 80 years; 73% completed the trial on full protocol. INTERVENTIONS: Vitamin E 500 IU or placebo daily for four years. MAIN OUTCOME MEASURES PRIMARY OUTCOME: development of early age related macular degeneration in retinal photographs. Other measures included alternative definitions of age related macular degeneration, progression, changes in component features, visual acuity, and visual function RESULTS: The incidence of early age related macular degeneration (early AMD 3) was 8.6% in those receiving vitamin E versus 8.1% in those on placebo (relative risk 1.05, 95% confidence interval 0.69 to 1.61). For late disease the incidence was 0.8% versus 0.6% (1.36, 0.67 to 2.77). Further analysis showed no consistent differences in secondary outcomes. CONCLUSION: Daily supplement with vitamin E supplement does not prevent the development or progression of early or later stages of age related macular degeneration.

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