Genetic and epidemiologic studies have shown that lipid genes and High Density Lipoproteins (HDL) are implicated in age-related macular degeneration (AMD). We studied circulating lipid levels in relation to AMD in a large European dataset, and investigated whether this relationship is driven by certain sub fractions. Design: (Pooled) analysis of cross-sectional data. Participants: 30,953 individuals aged 50+ participating in the E3 consortium; and 1530 individuals from the Rotterdam Study with lipid sub fraction data. Methods: In E3, AMD features were graded per eye on fundus photographs using the Rotterdam Classification. Routine blood lipid measurements were available from each participant. Data on genetics, medication and confounders such as body mass index, were obtained from a common database. In a subgroup of the Rotterdam Study, lipid sub fractions were identified by the Nightingale biomarker platform. Random-intercepts mixed-effects models incorporating confounders and study site as a random-effect were used to estimate the associations. Main Outcome Measures: early, late or any AMD, phenotypic features of early AMD, lipid measurements. Results: HDL was associated with an increased risk of AMD, corrected for potential confounders (Odds Ratio (OR) 1.21 per 1mmol/L increase (95% confidence interval[CI] 1.14-1.29); while triglycerides were associated with a decreased risk (OR 0.94 per 1mmol/L increase [95%CI 0.91-0.97]). Both were associated with drusen size, higher HDL raises the odds of larger drusen while higher triglycerides decreases the odds. LDL-cholesterol only reached statistical significance in the association with early AMD (p=0.045). Regarding lipid sub fractions: the concentration of extra-large HDL particles showed the most prominent association with AMD (OR 1.24 [95%CI 1.10-1.40]). The CETP risk variant (rs17231506) for AMD was in line with increased-HDL levels (p=7.7x10-7); but LIPC risk variants (rs2043085, rs2070895) were associated in an opposite way (p=1.0x10-6 and 1.6x10-4). Conclusions: Our study suggests that HDL-cholesterol is associated with increased risk of AMD and triglycerides negatively associated. Both show the strongest association with early AMD and drusen. Extra-large HDL sub fractions seem to be drivers in the relation with AMD, variants in lipid genes play a more ambiguous role in this association. Whether systemic lipids directly influence AMD or represent lipid metabolism in the retina remains a question to be answered.

This cross-sectional study evaluated the relationship between ) functional and structural measurements of neurodegeneration in the initial stages of diabetic retinopathy (DR) and) the presence of neurodegeneration and early microvascular impairment. We analyzed baseline data of 449 patients with type 2 diabetes enrolled in the European Consortium for the Early Treatment of Diabetic Retinopathy (EUROCONDOR) study (NCT01726075). Functional studies by multifocal electroretinography (mfERG) evaluated neurodysfunction, and structural measurements using spectral domain optical coherence tomography (SD-OCT) evaluated neurodegeneration. The mfERG P1 amplitude was more sensitive than the P1 implicit time and was lower in patients with Early Treatment of Diabetic Retinopathy Study (ETDRS) level 20-35 than in patients with ETDRS level <20 ( = 0.005). In 58% of patients, mfERG abnormalities were present in the absence of visible retinopathy. Correspondence between SD-OCT thinning and mfERG abnormalities was shown in 67% of the eyes with ETDRS <20 and in 83% of the eyes with ETDRS level 20-35. Notably, 32% of patients with ETDRS 20-35 presented no abnormalities in mfERG or SD-OCT. We conclude that there is a link between mfERG and SD-OCT measurements that increases with the presence of microvascular impairment. However, a significant proportion of patients in our particular study population (ETDRS ≤35) had normal ganglion cell-inner plexiform layer thickness and normal mfERG findings. We raise the hypothesis that neurodegeneration may play a role in the pathogenesis of DR in many but not in all patients with type 2 diabetes.

Abstract. Web archiving has been gaining interest and recognized importance for modern societies around the world. However, for web archivists it is frequently difficult to demonstrate this fact, for instance, to funders. This study provides an updated and global overview of web archiving. The obtained results showed that the number of web archiving initiatives significantly grew after 2003 and they are concentrated on developed countries. We statistically analyzed metrics, such as, the volume of archived data, archive file formats or number of people engaged. Web archives all together must process more data than any web search engine. Considering the complexity and large amounts of data involved in web archiving, the results showed that the assigned resources are scarce. A Wikipedia page was created to complement the presented work and be collaboratively kept up-to-date by the community.

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Clinical trial reg. no. NCT01726075, clinicaltrials.gov This article contains Supplementary Data online at http://diabetes .diabetesjournals.org/lookup/suppl/

Purpose To analyse and compare the classification of eyes with diabetic retinopathy using fluorescein angiography (FA) and optical coherence tomography angiography (OCTA) performed either with AngioPlex or AngioVue. Methods This was an observational cross-sectional study of 50 eyes from 26 diabetic subjects. Two independent graders classified the FA angiograms, to assess the presence and severity of several characteristics according to the ETDRS Report 11, and a similar evaluation was performed for each 3×3 mm OCTA image from the superficial retinal layer and for the full retina slab. Results Percentages of non-gradable images for the outline of foveal avascular zone (FAZ) in the central subfield (CSF) were 29.0% for FA, 12.0% for AngioVue and 3.0% for AngioPlex. For capillary loss, percentages of non-gradable images in the CSF were 25.0% for FA, 11% for AngioVue and 0.0% for AngioPlex. For the inner ring (IR), percentages of non-gradable images were 12.5% for FA, 11.5% for AngioVue and 0.5% for AngioPlex. Agreement between graders was substantial for outline of FAZ. For capillary loss, the agreement was fair for the CSF, and moderate for the IR. Conclusions The OCTA allows better discrimination of the CSF and parafoveal macular microvasculature than FA, especially for FAZ disruption and capillary dropout, without the need of an intravenous injection of fluorescein. In addition, FA had also a higher number of non-gradable images. The OCTA can replace with advantage the FA, as a non-invasive and more sensitive procedure for detailed morphological evaluation of central macular vascular changes. Trial registration number NCT02391558, Pre-results.

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Purpose: To evaluate the age- and gender-specific prevalence of early and late age-related macular degeneration (AMD) in a Portuguese population-based sample. Methods: All patients aged ≥55 years of a Portuguese primary health-care unit were recruited for a cross-sectional population-based study. Responders underwent complete ophthalmological examination and digital fundus imaging. Early and late AMD was defined according to the International Age-Related Macular Epidemiological Study Group Classification, and the adopted staging for AMD was the same as that used in the Rotterdam study. The age- and gender-adjusted prevalence of early and late forms of AMD was calculated. Results: Of the 4,370 eligible subjects, 3,000 underwent study procedures (68.6% response rate) and 2,975 were included in the analysis; they had a mean age of 68.9 ± 8.6 years. The overall prevalence of early and late AMD was 15.53% (95% CI 14.25-16.88) and 0.67% (95% CI 0.41-1.04), respectively. Neovascular AMD (NV-AMD) and geographic atrophy (GA) accounted for 0.44% (95% CI 0.23-0.75) and 0.27% (95% CI 0.12-0.53) of individuals, respectively. The highest prevalence of advanced AMD was among those aged ≥75 years (1.13% for NV-AMD; 0.63% for GA). Conclusions: To our knowledge, this is the first AMD epidemiological study in a Portuguese population. The early forms of the disease had a similar prevalence to that of other large-scale population-based cohorts, but late AMD was less frequent than previously reported.