Associations of inner retinal layers with risk of incident dementia: An individual participant data analysis of four prospective cohort studies

INTRODUCTION - Our main objective was to investigate whether retinal neurodegeneration, estimated from lower thickness of inner retinal layers, was associated with incident all-cause dementia and Alzheimer's disease (AD). METHODS - We performed an individual participant data meta-analysis using unpublished data from four prospective cohort studies with a total of 69,955 participants (n = 1087 cases of incident all-cause dementia; n = 520 cases incident AD; follow-up time median [interquartile range] 11.3 [8.8–11.5] years). RESULTS - General baseline characteristics of the study population were mean (standard deviation) age, 58.1 (8.8) years; 47% women. After adjustment, lower baseline macular retinal nerve fiber layer thickness was significantly associated with a 10% and 11% higher incidence of all-cause dementia and AD, respectively. Lower baseline macular ganglion cell-inner plexiform layer thickness was not significantly associated with these outcomes. DISCUSSION - These findings suggest that retinal neurodegeneration precedes the onset of clinical dementia. Retinal imaging tools may be informative biomarkers for the study of the early pathophysiology of dementia

Associations of inner retinal layers with risk of incident dementia: An individual participant data analysis of four prospective cohort studies

INTRODUCTION: Our main objective was to investigate whether retinal neurodegeneration, estimated from lower thickness of inner retinal layers, was associated with incident all-cause dementia and Alzheimer's disease (AD). METHODS: We performed an individual participant data meta-analysis using unpublished data from four prospective cohort studies with a total of 69,955 participants (n = 1087 cases of incident all-cause dementia; n = 520 cases incident AD; follow-up time median [interquartile range] 11.3 [8.8-11.5] years). RESULTS: General baseline characteristics of the study population were mean (standard deviation) age, 58.1 (8.8) years; 47% women. After adjustment, lower baseline macular retinal nerve fiber layer thickness was significantly associated with a 10% and 11% higher incidence of all-cause dementia and AD, respectively. Lower baseline macular ganglion cell-inner plexiform layer thickness was not significantly associated with these outcomes. DISCUSSION: These findings suggest that retinal neurodegeneration precedes the onset of clinical dementia. Retinal imaging tools may be informative biomarkers for the study of the early pathophysiology of dementia

Increasing Prevalence of Myopia in Europe and the Impact of Education

Purpose To investigate whether myopia is becoming more common across Europe and explore whether increasing education levels, an important environmental risk factor for myopia, might explain any temporal trend. Design Meta-analysis of population-based, cross-sectional studies from the European Eye Epidemiology (E3) Consortium. Participants The E3 Consortium is a collaborative network of epidemiological studies of common eye diseases in adults across Europe. Refractive data were available for 61 946 participants from 15 population-based studies performed between 1990 and 2013; participants had a range of median ages from 44 to 78 years. Methods Noncycloplegic refraction, year of birth, and highest educational level achieved were obtained for all participants. Myopia was defined as a mean spherical equivalent ≤-0.75 diopters. A random-effects meta-analysis of age-specific myopia prevalence was performed, with sequential analyses stratified by year of birth and highest level of educational attainment. Main Outcome Measures Variation in age-specific myopia prevalence for differing years of birth and educational level. Results There was a significant cohort effect for increasing myopia prevalence across more recent birth decades; age-standardized myopia prevalence increased from 17.8% (95% confidence interval [CI], 17.6-18.1) to 23.5% (95% CI, 23.2-23.7) in those born between 1910 and 1939 compared with 1940 and 1979 (P = 0.03). Education was significantly associated with myopia; for those completing primary, secondary, and higher education, the age-standardized prevalences were 25.4% (CI, 25.0-25.8), 29.1% (CI, 28.8-29.5), and 36.6% (CI, 36.1-37.2), respectively. Although more recent birth cohorts were more educated, this did not fully explain the cohort effect. Compared with the reference risk of participants born in the 1920s with only primary education, higher education or being born in the 1960s doubled the myopia prevalence ratio-2.43 (CI, 1.26-4.17) and 2.62 (CI, 1.31-5.00), respectively - whereas individuals born in the 1960s and completing higher education had approximately 4 times the reference risk: a prevalence ratio of 3.76 (CI, 2.21-6.57). Conclusions Myopia is becoming more common in Europe; although education levels have increased and are associated with myopia, higher education seems to be an additive rather than explanatory factor. Increasing levels of myopia carry significant clinical and economic implications, with more people at risk of the sight-threatening complications associated with high myopia

Prevalence of refractive error in Europe: the European Eye Epidemiology (E3) Consortium

To estimate the prevalence of refractive error in adults across Europe. Refractive data (mean spherical equivalent) collected between 1990 and 2013 from fifteen population-based cohort and cross-sectional studies of the European Eye Epidemiology (E3) Consortium were combined in a random effects meta-analysis stratified by 5-year age intervals and gender. Participants were excluded if they were identified as having had cataract surgery, retinal detachment, refractive surgery or other factors that might influence refraction. Estimates of refractive error prevalence were obtained including the following classifications: myopia ≤−0.75 diopters (D), high myopia ≤−6D, hyperopia ≥1D and astigmatism ≥1D. Meta-analysis of refractive error was performed for 61,946 individuals from fifteen studies with median age ranging from 44 to 81 and minimal ethnic variation (98 % European ancestry). The age-standardised prevalences (using the 2010 European Standard Population, limited to those ≥25 and <90 years old) were: myopia 30.6 % [95 % confidence interval (CI) 30.4–30.9], high myopia 2.7 % (95 % CI 2.69–2.73), hyperopia 25.2 % (95 % CI 25.0–25.4) and astigmatism 23.9 % (95 % CI 23.7–24.1). Age-specific estimates revealed a high prevalence of myopia in younger participants [47.2 % (CI 41.8–52.5) in 25–29 years-olds]. Refractive error affects just over a half of European adults. The greatest burden of refractive error is due to myopia, with high prevalence rates in young adults. Using the 2010 European population estimates, we estimate there are 227.2 million people with myopia across Europe

Prevalence of Age-Related Macular Degeneration in Europe: The Past and the Future

Purpose Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD in Europe from 1990 to 2013 using the European Eye Epidemiology (E3) consortium, and made projections for the future. Design Meta-analysis of prevalence data. Participants A total of 42 080 individuals 40 years of age and older participating in 14 population-based cohorts from 10 countries in Europe. Methods AMD was diagnosed based on fundus photographs using the Rotterdam Classification. Prevalence of early and late AMD was calculated using random-effects meta-analysis stratified for age, birth cohort, gender, geographic region, and time period of the study. Best-corrected visual acuity (BCVA) was compared between late AMD subtypes; geographic atrophy (GA) and choroidal neovascularization (CNV). Main Outcome Measures Prevalence of early and late AMD, BCVA, and number of AMD cases. Results Prevalence of early AMD increased from 3.5% (95% confidence interval [CI] 2.1%–5.0%) in those aged 55–59 years to 17.6% (95%

Retinal vascular calibres: Risk factors and methodological aspects of retinal vascular imaging. The Tromsø Eye Study – a part of the Tromsø Study.

The papers of this thesis are not available in Munin: 1. von Hanno T, Bertelsen G, Sjølie AK, Mathiesen EB.: 'Retinal vascular calibres are significantly associated with cardiovascular risk factors: the Tromsø Eye Study', Acta Ophthalmologica (2013), Online ahead of print. Available at http://dx.doi.org/10.1111/aos.121022. von Hanno T, Bertelsen G, Broderstad AR, Wilsgaard T, Mathiesen EB.: 'Serum ferritin and hemoglobin are independently associated with wider retinal venular caliber. The Tromsø Study 2001-2008', Investigative Ophthalmology & Visual Science (2013), vol. 54(10):7053-7060. Available at http://dx.doi.org/10.1167/iovs.13-12204 3. von Hanno T, Sjølie AK, Mathiesen EB.: 'Retinal vascular calibre and response to light exposure and serial imaging', Acta Ophthalmologica (2013), Online before print. Available at http://dx.doi.org/10.1111/aos.12213Cardiovascular disease is a major cause of death and morbidity in developed countries. The eye offers a unique window to the study of the microvasculature in vivo, which has been less investigated than the macrovasculature. We wanted to investigate the relationship between the traditional cardiovascular risk factors and retinal vascular calibres. Further, iron is a proposed cardiovascular risk factor and we wanted to investigate whether measures of iron stores and hemoglobin are related to retinal vascular calibre. The two first papers in this thesis are based on data from the Tromsø Study. We have measured the diameter of the retinal arterioles and venules on retinal images from 6353 participants of the sixth survey of the Tromsø Study (Tromsø 6, 2007-2008). We found that blood pressure and smoking were the factors with the most pronounced effect on the retinal vascular calibre. Blood pressure and age were associated with narrower retinal vessels and mainly affecting arteriolar calibre. Smoking, overweight (body mass index) and unfavourable lipid-profile were associated with wider retinal vessels, mainly affecting venular calibre. The effect of low HDL cholesterol and high BMI with venular widening was significantly stronger in men than in women. Further, 2993 participants with retinal vascular calibre measurements in Tromsø 6 also participated in the fifth survey (Tromsø 5, 2001-2002) when measurements of iron stores (serum ferritin and transferring saturation) and hemoglobin were performed. Men have higher levels of both iron stores and hemoglobin. We found that serum ferritin was associated with wider retinal venules in men. Hemoglobin was associated with wider retinal venules in both men and women. Cameras used for retinal photography commonly use light in the visual spectrum for the imaging technique and include several exposures with flash illumination to capture different fields of the retina. We examined 32 healthy volunteers and found that retinal venular calibre increased during an image sequence of 6 images and that the venular calibre was wider after light exposure compared to dark exposure before imaging