Illness Self-Schema in Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a relatively rare autoimmune disease with no known aetiology or cure. In addition to numerous physical symptoms, those living with SLE have also been shown to experience significant emotional and psychosocial difficulties. There has been little psychological research into SLE despite the rapidly increasing interest in health psychology and quality of life issues over the last two decades. One such issue that has commanded particular attention is that of cognitive bias in individuals with chronic pain and/or chronic illness. Cognitive bias toward illness-related information is theorised to indicate the presence of an illness self-schema, and is a valuable tool of investigation as it permits access to a level of cognitive structure that is inaccessible via self-report instruments. The primary focus of the present study is to investigate recall bias for pain- and illness-related words in SLE patients. This bias is explored relative to the recall of neutral words and depression-related words, and also relative to the responses of rheumatoid arthritis (RA) patients and healthy controls. Two hypotheses are proposed: firstly, that bias is related to disease activity; and secondly, that bias is related to the combination of illness and depression. The findings provide support for the second hypothesis, with the additional caveat that the nature of the pain/illness stimuli used is important in determining the presence of cognitive bias. No recall bias for illness-related words as a whole was found in any of the groups, nor was there evidence of a recall bias in the SLE and RA patients when they were divided according to depression status. However, when the illness words were examined separately according to �sensory pain� and �disability-related� words, a clear bias for disability words was found in the depressed patient group. It is concluded that there is a relationship between depression in chronically ill individuals, and the way in which such individuals process disability-related words. In accordance with the schema-enmeshment model (Pincus & Morley, 2001), it is suggested that both a pain-schema and an illness-schema exist, and it is when these two schemas become enmeshed with the self-schema that depression occurs in chronic pain/chronically ill patients. The cognitive bias assessment paradigm adopted in this study-one that is typically used in similar investigations-is lengthy, requires sophisticated equipment and can be difficult to interpret on an individual level. The present study investigates the relationship between cognitive biases in SLE patients and a recently-developed task, PRISM, which appears to symbolise the enmeshment of illness-, pain- and self-schemas. Analyses confirmed that recall of negative illness words was the only independent predictor of PRISM scores. This suggests that PRISM, a quick and easy task to administer, may have considerable usefulness as a clinical tool to assess information relevant to the enmeshment of illness- and self-schema. A greater understanding of schema and the processing styles of chronically ill patients will allow for more effective psychological treatment such that quality of life can be improved

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

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

Automatic Drusen Quantification and Risk Assessment of Age-related Macular Degeneration on Color Fundus Images

Contains fulltext : 118034.pdf (Publisher’s version ) (Closed access)PURPOSE: To evaluate a machine learning algorithm that allows for computer aided diagnosis (CAD) of non-advanced age-related macular degeneration (AMD) by providing an accurate detection and quantification of drusen location, area and size. METHODS: Color fundus photographs of 407 eyes without AMD or with early to moderate AMD were randomly selected from a large European multicenter database. A machine learning system was developed to automatically detect and quantify drusen on each image. Based on detected drusen, the CAD software provided a risk assessment to develop advanced AMD. Evaluation of the CAD system was performed using annotations made by two blinded human graders. RESULTS: Free-response Receiver Operating Characteristics (FROC) analysis showed that the proposed system approaches the performance of human observers in detecting drusen. The estimated drusen area showed excellent agreement with both observers, with mean intra-class correlation coefficients (ICC) larger than 0.85. Maximum druse diameter agreement was lower with a maximum ICC of 0.69 but comparable to the interobserver agreement (ICC=0.79). For automatic AMD risk assessment, the system achieved areas under the Receiver Operating Characteristic (ROC) curve of 0.948 and 0.954, reaching similar performance as human observers. CONCLUSIONS: A machine learning system, capable of separating high risk from low risk patients with non-advanced AMD by providing accurate detection and quantification of drusen, was developed. The proposed method allows for quick and reliable diagnosis of AMD, opening the way for large dataset analysis within population studies and genotype-phenotype correlation analysis

Cuticular drusen: Stars in the sky

Item does not contain fulltextCuticular drusen is a specific clinical subtype of age-related macular degeneration (AMD). This subtype of AMD has an earlier age at onset, a stronger familial component, and genetic factors play a more prominent role in its development than in the general AMD population. In this review, we describe the clinical characteristics and differential diagnosis of cuticular drusen, as well as systemic associations including membranoproliferative glomerulonephritis type II. We discuss recent genetic and pathophysiological insights, and future therapeutic perspectives are highlighted

Association analysis of genetic and environmental risk factors in the cuticular drusen subtype of age-related macular degeneration.

Contains fulltext : 109959.pdf (publisher's version ) (Open Access)PURPOSE: To assess the association of gender, cigarette smoking, body-mass index, and nine genetic risk variants with cuticular drusen (CD), a well recognized subtype of age-related macular degeneration (AMD). METHODS: A total of 757 patients with AMD, including 217 patients with CD, and 553 control individuals were interviewed with a questionnaire and underwent an ophthalmic examination. Venous blood samples were obtained for genomic DNA extraction, and genotyping was performed of single nucleotide polymorphisms previously associated with AMD. Odds ratios were calculated for patients with CD, using unaffected control individuals as a reference. Furthermore, odds ratios in patients with CD were compared to those in patients with "non-CD" AMD. RESULTS: The CD subtype of AMD was significantly associated with current smoking as well as variants in the complement factor H (CFH), age-related maculopathy susceptibility 2 (ARMS2), complement factor B/complement component 2 (CFB/C2), complement component 3 (C3), and apolipoprotein E (APOE) genes. In patients with CD, the association with the CFH Y402H risk allele was significantly higher (p=0.022), whereas the association with current smoking was significantly lower (p<0.001) than in the heterogeneous group of patients with "non-CD" AMD. CONCLUSIONS: The AMD subtype of CD was associated with previously identified genetic AMD risk factors. However, the association with the CFH Y402H risk allele appeared to be stronger, whereas the association with smoking was less pronounced when compared to AMD as a whole. This study suggests a more important role for genetic factors than environmental factors in the development of this well defined subtype of AMD. These findings stress the importance of detailed phenotyping in AMD to identify homogeneous AMD subtypes, which may be associated with different risk factors and disease mechanisms. Such studies will improve the accuracy of predictive models and the effectiveness of preventive and therapeutic options in AMD

Carbonic Anhydrase Inhibitors for the Treatment of Cystic Macular Lesions in Children With X-Linked Juvenile Retinoschisis

Purpose: Little is known regarding the therapeutic effect of carbonic anhydrase inhibitors (CAIs) in the management of cystic macular lesions in children with X-linked juvenile retinoschisis (XLRS) despite the fact that this disease often manifests during childhood. Therefore, our goal was to determine the efficacy of CAIs in the treatment of cystic macular lesions in children with XLRS. Methods: We used CAIs to treat cystic macular lesions in 18 eyes of nine children with XLRS. We evaluated the therapeutic effect of CAI treatment with the best-corrected visual acuity and foveal zone thickness (FZT) with spectral-domain optical coherence tomography. A reduction of at least 22.4% in FZT was defined as objective evidence of response. Results: Five of nine (55.6%) XLRS patients showed a significant reduction of FZT in both eyes over a median treatment interval of 6.8 months (range, 1-23). In four of five (80.0%) patients, this reduction was already apparent after 1 month of treatment. An improvement of visual acuity was observed in five eyes (27.8%) of three patients (33.3%). Six patients (66.6%) reported minor side effects. Conclusions: Treatment with CAIs decreased FZT in more than half of the children with XLRS. This effect was observed within 1 month in the majority of patients. Carbonic anhydrase inhibitor treatment restores retinal anatomy and may contribute to creating optimal circumstances for gene therapy

Automatic differentiation of color fundus images containing drusen or exudates using a contextual spatial pyramid approach

We developed an automatic system to identify and differentiate color fundus images containing no lesions, drusen or exudates. Drusen and exudates are lesions with a bright appearance, associated with age-related macular degeneration and diabetic retinopathy, respectively. The system consists of three lesion detectors operating at pixel-level, combining their outputs using spatial pooling and classification with a random forest classifier. System performance was compared with ratings of two independent human observers using human-expert annotations as reference. Kappa agreements of 0.89, 0.97 and 0.92 and accuracies of 0.93, 0.98 and 0.95 were obtained for the system and observers, respectively

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

Whole Exome Sequencing in Patients with the Cuticular Drusen Subtype of Age-Related Macular Degeneration

Contains fulltext : 162154.PDF (publisher's version ) (Open Access)Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in elderly people worldwide. Cuticular drusen (CD) is a clinical subtype of AMD, which typically displays an earlier age at onset, and has a strong genetic component. Genetic studies support a role for rare sequence variants in CD susceptibility, and rare sequence variants in the CFH gene have been identified in 8.8% of CD cases. To further explore the role of rare variants in CD, we performed whole exome sequencing (WES) in 14 affected members of six families and 12 sporadic cases with CD. We detected rare sequence variants in CFH and FBLN5, which previously were shown to harbor rare variants in patients with CD. In addition, we detected heterozygous rare sequence variants in several genes encoding components of the extracellular matrix (ECM), including FBLN1, FBLN3/EFEMP1, FBLN5, FBLN6/HMCN1, FBN2, and COL15A1. Two rare pathogenic variants were identified in the COL15A1 gene: one in a sporadic case and another was found to segregate in a family with six affected individuals with CD. In addition, two rare pathogenic variants were identified in the FGL1 gene in three unrelated CD cases. These findings suggest that alterations in the ECM and in the coagulation pathway may play a role in the pathogenesis of CD. The identified candidate genes require further analyses in larger cohorts to confirm their role in the CD subtype of AMD. No evidence was found of rare sequence variants in a single gene that segregate with CD in the six families, suggesting that the disease is genetically heterogeneous