Automatic identification of reticular pseudodrusen using multimodal retinal image analysis

Contains fulltext : 154610.pdf (Publisher’s version ) (Closed access)PURPOSE: To examine human performance and agreement on reticular pseudodrusen (RPD) detection and quantification by using single- and multimodality grading protocols and to describe and evaluate a machine learning system for the automatic detection and quantification of reticular pseudodrusen by using single- and multimodality information. METHODS: Color fundus, fundus autofluoresence, and near-infrared images of 278 eyes from 230 patients with or without presence of RPD were used in this study. All eyes were scored for presence of RPD during single- and multimodality setups by two experienced observers and a developed machine learning system. Furthermore, automatic quantification of RPD area was performed by the proposed system and compared with human delineations. RESULTS: Observers obtained a higher performance and better interobserver agreement for RPD detection with multimodality grading, achieving areas under the receiver operating characteristic (ROC) curve of 0.940 and 0.958, and a kappa agreement of 0.911. The proposed automatic system achieved an area under the ROC of 0.941 with a multimodality setup. Automatic RPD quantification resulted in an intraclass correlation (ICC) value of 0.704, which was comparable with ICC values obtained between single-modality manual delineations. CONCLUSIONS: Observer performance and agreement for RPD identification improved significantly by using a multimodality grading approach. The developed automatic system showed similar performance as observers, and automatic RPD area quantification was in concordance with manual delineations. The proposed automatic system allows for a fast and accurate identification and quantification of RPD, opening the way for efficient quantitative imaging biomarkers in large data set analysis

Antiplatelet and Anticoagulant Drugs Do Not Affect Visual Outcome in Neovascular Age-Related Macular Degeneration in the BRAMD Trial

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Epidemiology of Reticular Pseudodrusen in Age-Related Macular Degeneration: The Rotterdam Study

Contains fulltext : 167772.pdf (Publisher’s version ) (Open Access)Purpose: Reticular pseudodrusen (RPD) are considered to be a distinct feature in AMD. Population studies have studied the epidemiology of RPD using standard color fundus photographs (CFP). However, recent studies have shown that RPD are better imaged using near-infrared (NIR) imaging. We studied the epidemiology of RPD in a large population-based study using NIR and CFP. Methods: Participants aged 65+ years from the Rotterdam Study underwent ophthalmologic examination including NIR and CFP. Both images were graded for the presence of RPD and soft indistinct drusen (SID). Associations with demographic and environmental factors, 26 genetic variants, and total genetic risk score were analyzed using logistic regression analysis. Results: Reticular pseudodrusen were detected in 137 (4.9%) of 2774 study participants; of these, 92.7% were detected with NIR imaging and 38% on CFP. Most eyes with RPD showed presence of SID, whereas other drusen types coincided less frequently. Reticular pseudodrusen were significantly associated with age (odds ratio [OR] 1.21, 95% Confidence Interval [CI] 1.17-1.24) and female sex (OR 2.10, 95% CI 1.41-3.13). Environmental factors did not show a significant association with RPD. Major AMD risk variants were significantly associated with RPD and SID; however, ARMS2, C3, and VEGFA were more associated with RPD (RPD vs. SID P < 0.05). Total genetic risk score did not differ significantly (P = 0.88). Conclusion: Detection of RPD was better with NIR imaging than on CFP in a population-based setting. Presence of RPD often coincided with presence of SID; however, they showed quantitative differences in genetic risk profile

Prevalence of Age-Related Macular Degeneration in Europe

Contains fulltext : 179603.pdf (Publisher’s version ) (Open Access

Analysis of rare variants in the C3 gene in patients with age-related macular degeneration

Contains fulltext : 136382.pdf (publisher's version ) (Open Access)Age-related macular degeneration (AMD) is a progressive retinal disorder affecting over 33 million people worldwide. Genome-wide association studies (GWASs) for AMD identified common variants at 19 loci accounting for 15-65% of the heritability and it has been hypothesized that the missing heritability may be attributed to rare variants with large effect sizes. Common variants in the complement component 3 (C3) gene have been associated with AMD and recently a rare C3 variant (Lys155Gln) was identified which exerts a large effect on AMD susceptibility independent of the common variants. To explore whether additional rare variants in the C3 gene are associated with AMD, we sequenced all coding exons in 84 unrelated AMD cases. Subsequently, we genotyped all identified variants in 1474 AMD cases and 2258 controls. Additionally, because of the known genetic overlap between AMD and atypical hemolytic uremic syndrome (aHUS), we genotyped two recurrent aHUS-associated C3 mutations in the entire cohort. Overall, we identified three rare variants (Lys65Gln (P=0.04), Arg735Trp (OR=17.4, 95% CI=2.2-136; P=0.0003), and Ser1619Arg (OR=5.2, 95% CI=1.0-25; P=0.05) at the C3 locus that are associated with AMD in our EUGENDA cohort. However, the Arg735Trp and Ser1619Arg variants were not found to be associated with AMD in the Rotterdam Study. The Lys65Gln variant was only identified in patients from Nijmegen, the Netherlands, and thus may represent a region-specific AMD risk variant

Association of Smoking and CFH and ARMS2 Risk Variants With Younger Age at Onset of Neovascular Age-Related Macular Degeneration

Contains fulltext : 154591.pdf (publisher's version ) (Closed access)IMPORTANCE: The age at which the first signs of age-related macular degeneration (AMD) manifest is variable. Better insight into factors that influence disease onset has direct implications for preventive measures and patient counseling. OBJECTIVE: To identify risk factors for an earlier age at onset of neovascular AMD. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study, including patient data from the European Genetic Database collected between April 2006 and July 2010. All patients had at least 1 documented visit to the outpatient AMD clinic of the Radboud University Medical Center, Nijmegen, the Netherlands, a tertiary referral center for retinal disorders. In total, 275 patients with a known age at onset of neovascular AMD and a genetic risk analysis were included. MAIN OUTCOMES AND MEASURES: Effects of several genetic, sociodemographic, behavioral, and ocular factors on the age at onset of neovascular AMD. The mean differences in the age at onset were determined using general linear models with the age at onset as the dependent variable. RESULTS: Past smokers and current smokers developed neovascular AMD on average 4.9 (95% CI, 3.0-6.8) and 7.7 (95% CI, 5.3-10.0) years earlier, respectively, than never smokers (P < .001 for both). Compared with the reference group, the age at onset was 5.2 (95% CI, 2.8-7.7) years earlier for homozygous carriers of the A69S risk allele in the age-related maculopathy susceptibility 2 (ARMS2) gene (P < .001). Homozygous carriers of the Y402H risk variant in the complement factor H (CFH) gene developed neovascular AMD 2.8 (95% CI, 0.5-5.0) years earlier (P = .02). Patients carrying 4 risk alleles in CFH and ARMS2 developed neovascular AMD 12.2 (95% CI, 6.2-18.3) years earlier than patients with zero risk alleles (P < .001). CONCLUSIONS AND RELEVANCE: Genetic and environmental risk factors influence the age at onset of neovascular AMD. Individuals at risk could be identified at an early age if and when preventive or therapeutic options become available. Insight into individual risk profiles might influence patients' consideration of interventions to increase their chance of avoiding vision loss from AMD

Five-year progression of unilateral age-related macular degeneration to bilateral involvement: the Three Continent AMD Consortium report

Item does not contain fulltextPURPOSE: To assess the 5-year progression from unilateral to bilateral age-related macular degeneration (AMD) and associated risk factors. DESIGN: Pooled data analyses of three prospective population-based cohorts, the Blue Mountains Eye Study, Beaver Dam Eye Study and Rotterdam Study. METHODS: Retinal photography and interview with comprehensive questionnaires were conducted at each visit of three studies. AMD was assessed following the modified Wisconsin AMD grading protocol. Progression to bilateral any (early and late) or late AMD was assessed among participants with unilateral involvement only. Factors associated with the progression were assessed using logistic regression models while simultaneously adjusting for other significant risk factors. RESULTS: In any 5-year duration, 19-28% of unilateral any AMD cases became bilateral and 27-68% of unilateral late AMD became bilateral. Factors associated with the progression to bilateral involvement of any AMD were age (per year increase, adjusted OR 1.07), carrying risk alleles of the complement factor H and age-related maculopathy susceptibility 2 genes (compared with none, OR 1.76 for 1 risk allele and OR 3.34 for 2+ risk alleles), smoking (compared with non-smokers, OR 1.64 for past and OR 1.67 for current smokers), and the presence of large drusen area or retinal pigmentary abnormalities in the first eye. CONCLUSION: One in four to one in five unilateral any AMD cases, and up to one in two unilateral late AMD cases, progressed to bilateral in 5 years. Known AMD risk factors, including smoking, are significantly associated with the progression to bilateral involvement

Distribution geografica de Mycosphaerella fijiensis y Mycosphaerella musicola en Costa Rica

Recherche effectuée dans 5 localités de la province de Cartago, au Costa Rica, d'octobre 1990 à février 1991, à 1350, 1000, 900 et 600 mètres d'altitud