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RATIONALE & OBJECTIVE: Biomarkers that enable better identification of persons with chronic kidney disease (CKD) who are at higher risk for disease progression and adverse events are needed. This study sought to identify urine and plasma metabolites associated with progression of kidney disease. STUDY DESIGN: Prospective metabolome-wide association study. SETTING & PARTICIPANTS: Persons with CKD enrolled in the GCKD (German CKD) study with metabolite measurements, with external validation within the ARIC (Atherosclerosis Risk in Communities) Study. EXPOSURES: 1,513 urine and 1,416 plasma metabolites (Metabolon Inc) measured at study entry using untargeted mass spectrometry. OUTCOMES: Main end points were kidney failure (KF) and a composite kidney end point (CKE) of KF, estimated glomerular filtration rate<15mL/min/1.73m2, or a 40% decrease in estimated glomerular filtration rate. Death from any cause was a secondary end point. After a median of 6.5 years of follow-up, 500 persons had experienced KF, 1,083 had experienced the CKE, and 680 had died. ANALYTICAL APPROACH: Time-to-event analyses using multivariable proportional hazard regression models in a discovery-replication design with external validation. RESULTS: 5,088 GCKD study participants were included in analyses of urine metabolites, and 5,144 were included in analyses of plasma metabolites. Among 182 unique metabolites, 30 were significantly associated with KF, 49 with the CKE, and 163 with death. The strongest association with KF was observed for plasma hydroxyasparagine (HR, 1.95; 95% CI, 1.68-2.25). An unnamed metabolite measured in plasma and urine was significantly associated with KF, the CKE, and death. External validation of the identified associations of metabolites with KF or the CKE revealed directional consistency for 88% of observed associations. Selected associations of 18 metabolites with study outcomes have not been previously reported. LIMITATIONS: Use of observational data and semiquantitative metabolite measurements at a single time point. CONCLUSIONS: The observed associations between metabolites and KF, the CKE, or death in persons with CKD confirmed previously reported findings and also revealed several associations not previously described. These findings warrant confirmatory research in other study cohorts. PLAIN-LANGUAGE SUMMARY: Incomplete understanding of the variability of chronic kidney disease (CKD) progression motivated the search for new biomarkers that would help identify people at increased risk. We explored metabolites in plasma and urine for their association with unfavorable kidney outcomes or death in persons with CKD. Metabolomic analyses revealed 182 metabolites significantly associated with CKD progression or death. Many of these associations confirmed previously reported findings or were validated by analysis in an external study population. Our comprehensive screen of the metabolome serves as a valuable foundation for future investigations into biomarkers associated with CKD progression.
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OBJECTIVES: Ultrasound is a standard tool to diagnose giant cell arteritis (GCA). Until now, only few studies investigated the role of ultrasound in the follow-up of GCA. The aim of this study was to assess the changes in the intima media thickness (IMT), total number of affected arteries and provisional OMERACT GCA ultrasonography score (OGUS) in a 12-months follow-up period. METHODS: Patients with newly diagnosed GCA were prospectively enrolled. Ultrasound examinations of facial, temporal, carotid, vertebral and axillary arteries were performed at baseline, after three, six, nine and 12 months. Changes of IMT, total number of affected arteries, and OGUS values were evaluated. In a subgroup of patients, exams were conducted weekly in the first 100 days. RESULTS: Fifty patients were enrolled, 36 completed the follow-up. Significant reductions in IMT, total number of affected arteries and OGUS were observed. Eighteen patients presented to weekly exams. The mean IMT of the axillary artery normalized after seven days, while IMT of the common temporal artery normalized after 50 days. The mean OGUS values were below one after six months. There were no differences in IMT changes between GCA patients with or without PMR or between those with and without additional tocilizumab treatment. A relapse occurred in 4 patients. At relapse, mean IMT and OGUS were higher as compared with the preceding assessment. No predictive values indicating a relapse were identified. CONCLUSION: Vascular ultrasound is sensitive to change in GCA. The presence of PMR or treatment with tocilizumab did not affect IMT decrease.
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OBJECTIVES: The objective of this study was to prospectively evaluate the diagnostic efficacy of transorbital ultrasound (TOS) in patients newly diagnosed with giant cell arteritis (GCA), presenting with visual symptoms. METHODS: Patients with newly diagnosed, untreated GCA were examined using TOS, assessing central retinal artery flow velocity [peak systolic velocity (PSV), end-diastolic velocity (EDV), resistance index (RI)], and optic nerve diameter (OND). Vascular ultrasound was conducted to evaluate the superficial temporal arteries, their branches, facial, axillary, carotid, and vertebral arteries. RESULTS: We enrolled 54 GCA patients, 27 with visual symptoms, and 27 healthy controls. Eyes of GCA patients with visual symptoms demonstrated significantly lower PSV and EDV (PSV: ß=-1.91; p=0.029; EDV: ß=-0.57; p=0.032) and significantly elevated OND (ß = 0.79; p=0.003) compared with controls. RI did not significantly differ from controls (ß=-0.06, p=0.129). Vascular ultrasound identified an average of 8.7 (SD ± 2.8) pathological vessels per GCA patient. A significant negative association was observed between the number of affected vessels and both PSV (p=0.048) and EDV (p=0.040). No association was found with RI (p=0.249), while a positive significant association was noted with OND (p<0.001). CONCLUSIONS: This study pioneers the application of TOS to assess structural eye changes in newly diagnosed, untreated GCA patients with visual symptoms. Our findings suggest reduced central retinal artery flow and increased optic nerve diameter as potential biomarkers for serious ocular involvement in GCA. The detected association between internal and external carotid artery involvement indicates a common pathophysiological mechanism underlying systemic and ocular manifestations of GCA.
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INTRODUCTION: The emergence of handheld ultrasound devices capable of connecting to cell phones or tablets heralds a significant advancement in medical technology, particularly within the field of obstetrics. These devices offer the promise of immediate bedside ultrasound examinations, potentially revolutionizing patient care by enabling fetal assessments in diverse settings. MATERIAL AND METHODS: This prospective study aimed to validate the reliability of non-piezo, chip-based handheld ultrasound devices in clinical obstetric practice. Conducted in a university hospital obstetric ward, the study included 100 pregnant women between 17 and 41 weeks of gestation. Participants underwent ultrasound examinations using both conventional and portable point-of-care ultrasound (POCUS) devices to compare the accuracy in estimating fetal weight and other parameters, such as cardiac activity, fetal presentation, placental location, and amniotic fluid volume. The reliability and agreement between the devices were assessed using intraclass correlation coefficients, Bland-Altman plots, and Pearson correlation coefficients. RESULTS: The results show a near-perfect agreement (0.98) and correlation (r = 0.98, p < 0.001) for estimated fetal weight and most biometry measurements between the two types of ultrasound devices, with slight deviations in head circumference and amniotic fluid index measurements. Subgroup analysis revealed variations in agreement and correlation rates with higher BMI and advanced gestational age, indicating areas for further refinement. CONCLUSIONS: These findings affirm the high reliability of handheld ultrasound devices for basic obstetric ultrasound evaluations, supporting their integration into daily clinical practice. This technology improves the flexibility and immediacy of prenatal care, although further research is needed to optimize its application across patient populations and treatment settings.
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PURPOSE: The main objective of this study is to assess the test-retest and inter-administration mode reliability of the Impact of Vision Impairment profile (IVI), a common patient-reported outcome measure (PROM) for people with chronic eye diseases. METHODS: The IVI was administered to adult patients with stable, chronic eye diseases two to four times per participant (average intervals between administrations 12 to 20 days; maximum two phone interviews, paper administration, electronic administration) by two trained interviewers. Rasch models were fit to the data. Intra-class correlation coefficients (ICCs), mean differences and Cronbach's alpha between test-retest administrations (two phone interviews) and inter-mode comparisons were calculated. RESULTS: Two hundred-sixteen patients (mean age 67 ± 12 years, 40% male) were included in the study. The IVI met all psychometric requirements of the Rasch model, and the division into the domains of functional items (IVI_F) and emotional items (IVI_E) corresponded to the German validation study. ICCs (all for IVI_F and IVI_E, respectively) for the retest administrations were 0.938 and 0.912, and 0.853 and 0.893 for inter-mode comparisons phone/paper, 0.939 and 0.930 for phone/electronic, and 0.937 and 0.920 for paper/electronic (all p < 0.01). Mean differences (all for IVI_F and IVI_E, respectively) for the retest administrations were 2.8% and 0.7% and ranged from 2.0% to 6.2% and from 0.4 % to 4.9% between administration modes. Cronbach's alpha ranged from 0.886 to 0.944 for retest and inter-mode comparisons. CONCLUSION: Due to the high test-retest reliability and the almost equally high comparability of different modes of administration of the IVI, the study endorses its use as a robust PROM to capture vision-related quality of life. Our results further support the use of the IVI as an endpoint in clinical trials and may simplify implementing it in both clinical trials or real-world evidence generation by offering multiple administration modes with high reliability.
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Psicometría , Calidad de Vida , Perfil de Impacto de Enfermedad , Humanos , Masculino , Femenino , Reproducibilidad de los Resultados , Anciano , Enfermedad Crónica , Psicometría/métodos , Encuestas y Cuestionarios , Medición de Resultados Informados por el Paciente , Oftalmopatías/diagnóstico , Trastornos de la Visión/diagnóstico , Trastornos de la Visión/fisiopatología , Trastornos de la Visión/psicología , Agudeza Visual , Persona de Mediana Edad , Personas con Daño Visual/psicologíaRESUMEN
OBJECTIVES: This cross-sectional study aimed to determine the prevalence, manifestation, and risk factors of pulmonary involvement in newly diagnosed, untreated rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients, and to evaluate the efficacy of various diagnostic tools in screening for pulmonary involvement. METHODS: Untreated, newly diagnosed patients with RA and PsA underwent an extensive multimodal diagnostic approach including clinical and laboratory assessment, pulmonary function tests, and chest radiography. RESULTS: We recruited 50 arthritis patients (26 RA, 24 PsA) and 26 control subjects. Respiratory symptoms were found in 36.0 % of arthritis patients and 11.5 % of controls (p = 0.031). Pathologically reduced breathing width (< 3.0 cm) was significantly more common in arthritis patients (64.0 %) than in controls (23.1 %) (p < 0.001). Pulmonary function test results did not differ significantly between groups. Chest radiography revealed pulmonary involvement in 37.0 % of arthritis patients, higher in RA (50.0 %) than in PsA (22.7 %). Notably, only 35.3 % of arthritis patients with radiographic pulmonary involvement were symptomatic, with 64.7 % being asymptomatic. Radiographic pulmonary involvement was associated with advanced age (p = 0.002) and increased rheumatoid factor levels (p = 0.024). CONCLUSION: Our research underscores the significant prevalence of largely asymptomatic pulmonary involvement in newly diagnosed RA and PsA patients. These findings highlight the importance of an early, multidisciplinary screening approach, particularly for high-risk individuals. Further large-scale studies are needed to develop comprehensive screening protocols to improve early detection and treatment of pulmonary involvement in arthritis.
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OBJECTIVES: This cross-sectional study aimed to determine the prevalence and risk factors for sleep-related breathing disorders (SRBD) in newly diagnosed, untreated rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients, and to develop a screening algorithm for early detection. METHODS: We evaluated newly diagnosed RA or PsA patients using the Epworth Sleepiness Scale (ESS) questionnaire, cardiorespiratory polygraphy (RPG), and clinical and laboratory assessments. Sleep apnea syndrome (SAS) was diagnosed based on pathological RPG findings excessive daytime sleepiness, defined as ESS score above 10. RESULTS: The study included 39 patients (22 RA, 17 PsA) and 23 controls. In RPG, SRBD was identified in 38.5% of arthritis patients compared to 39.1% of controls (p = 1.00), with male gender (p = .004) and age (p < .001) identified as risk factors. Excessive daytime sleepiness was noted in 36.4% of RA patients, 17.6% of PsA patients, and 21.7% of controls. Of the 24 patients diagnosed with SRBD, 41.6% met the criteria for SAS. SAS prevalence was 31.8% among RA patients, 0% in PsA patients, and 13% in controls. A significant association was observed between excessive daytime sleepiness and SRBD (p = .036). CONCLUSION: Our findings reveal a high prevalence of SRBD in newly diagnosed, untreated RA and PsA patients in ESS and RPG, with excessive daytime sleepiness being a reliable predictor of SRBD. Patients with RA exhibited a higher predisposition to SAS. We therefore suggest incorporating ESS and RPG as screening tools in RA or PsA for early detection and management of SRBD.
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Artritis Psoriásica , Artritis Reumatoide , Síndromes de la Apnea del Sueño , Humanos , Masculino , Estudios Transversales , Artritis Psoriásica/diagnóstico , Artritis Psoriásica/epidemiología , Femenino , Persona de Mediana Edad , Síndromes de la Apnea del Sueño/diagnóstico , Síndromes de la Apnea del Sueño/epidemiología , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/epidemiología , Artritis Reumatoide/complicaciones , Adulto , Prevalencia , Factores de Riesgo , Anciano , Polisomnografía , Estudios de Casos y Controles , Encuestas y CuestionariosRESUMEN
Random survival forests (RSF) can be applied to many time-to-event research questions and are particularly useful in situations where the relationship between the independent variables and the event of interest is rather complex. However, in many clinical settings, the occurrence of the event of interest is affected by competing events, which means that a patient can experience an outcome other than the event of interest. Neglecting the competing event (i.e., regarding competing events as censoring) will typically result in biased estimates of the cumulative incidence function (CIF). A popular approach for competing events is Fine and Gray's subdistribution hazard model, which directly estimates the CIF by fitting a single-event model defined on a subdistribution timescale. Here, we integrate concepts from the subdistribution hazard modeling approach into the RSF. We develop several imputation strategies that use weights as in a discrete-time subdistribution hazard model to impute censoring times in cases where a competing event is observed. Our simulations show that the CIF is well estimated if the imputation already takes place outside the forest on the overall dataset. Especially in settings with a low rate of the event of interest or a high censoring rate, competing events must not be neglected, that is, treated as censoring. When applied to a real-world epidemiological dataset on chronic kidney disease, the imputation approach resulted in highly plausible predictor-response relationships and CIF estimates of renal events.
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Biometría , Humanos , Biometría/métodos , Análisis de Supervivencia , Modelos Estadísticos , Modelos de Riesgos ProporcionalesRESUMEN
OBJECTIVES: This study evaluated musculoskeletal ultrasound (MSUS) use by dermatologists previously trained on a novel handheld, chip-based ultrasound device (HHUD) to screen for early PsA. METHODS: Twelve dermatologists were recruited to screen psoriasis patients for PsA using the novel HHUD in one major hospital in Bonn (Germany) and six private practices in surrounding regions. Patient screening was based on medical history, clinical examination, and the GEPARD questionnaire paired with an MSUS examination of up to three painful joints. All screened patients were then referred to rheumatologists, who determined the final diagnosis. The screening effect of MSUS was assessed according to its sensitivity and specificity before and after its application. RESULTS: Between 1 October 2020 and 26 May 2021, a total of 140 psoriasis patients with arthralgia participated in this study. PsA was diagnosed in 19 (13.6%) cases. Before applying MSUS, dermatologists' screening sensitivity and specificity were recorded as 88.2% and 54.4%, respectively, while after applying MSUS the sensitivity and specificity changed to 70.6% and 90.4%, respectively. MSUS led to a change of PsA suspicion in 46 cases, with PsA no longer being suspected in 45 of them. CONCLUSION: This study was able to demonstrate that PsA screening using MSUS by previously trained dermatologists can lead to more precise PsA detection and potentially decreased rheumatologist referral rates.
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Artritis Psoriásica , Psoriasis , Humanos , Artritis Psoriásica/diagnóstico por imagen , Dermatólogos , Método Doble Ciego , Estudios Prospectivos , Psoriasis/diagnósticoRESUMEN
BACKGROUND: To model the progression of geographic atrophy (GA) in patients with age-related macular degeneration (AMD) by building a suitable statistical regression model for GA size measurements obtained from fundus autofluorescence imaging. METHODS: Based on theoretical considerations, we develop a linear mixed-effects model for GA size progression that incorporates covariable-dependent enlargement rates as well as correlations between longitudinally collected GA size measurements. To capture nonlinear progression in a flexible way, we systematically assess Box-Cox transformations with different transformation parameters λ. Model evaluation is performed on data collected for two longitudinal, prospective multi-center cohort studies on GA size progression. RESULTS: A transformation parameter of λ=0.45 yielded the best model fit regarding the Akaike information criterion (AIC). When hypertension and hypercholesterolemia were included as risk factors in the model, they showed an association with progression of GA size. The mean estimated age-of-onset in this model was 67.21±6.49 years. CONCLUSIONS: We provide a comprehensive framework for modeling the course of uni- or bilateral GA size progression in longitudinal observational studies. Specifically, the model allows for age-of-onset estimation, identification of risk factors and prediction of future GA size. A square-root transformation of atrophy size is recommended before model fitting.
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Atrofia Geográfica , Degeneración Macular , Anciano , Atrofia , Progresión de la Enfermedad , Humanos , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
BACKGROUND: Recruiting asymptomatic participants with early disease stages into studies is challenging and only little is known about facilitators and barriers to screening and recruitment of study participants. Thus we assessed factors associated with screening rates in the MACUSTAR study, a multi-centre, low-interventional cohort study of early stages of age-related macular degeneration (AMD). METHODS: Screening rates per clinical site and per week were compiled and applicable recruitment factors were assigned to respective time periods. A generalized linear mixed-effects model including the most relevant recruitment factors identified via in-depth interviews with study personnel was fitted to the screening data. Only participants with intermediate AMD were considered. RESULTS: A total of 766 individual screenings within 87 weeks were available for analysis. The mean screening rate was 0.6 ± 0.9 screenings per week among all sites. The participation at investigator teleconferences (relative risk increase 1.466, 95% CI [1.018-2.112]), public holidays (relative risk decrease 0.466, 95% CI [0.367-0.591]) and reaching 80% of the site's recruitment target (relative risk decrease 0.699, 95% CI [0.367-0.591]) were associated with the number of screenings at an individual site level. CONCLUSIONS: Careful planning of screening activities is necessary when recruiting early disease stages in multi-centre observational or low-interventional studies. Conducting teleconferences with local investigators can increase screening rates. When planning recruitment, seasonal and saturation effects at clinical site level need to be taken into account. TRIAL REGISTRATION: ClinicalTrials.gov NCT03349801 . Registered on 22 November 2017.
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Degeneración Macular , Estudios de Cohortes , Humanos , InvestigadoresRESUMEN
The slow progression of early age-related macular degeneration (AMD) stages to advanced AMD requires the use of surrogate end points in clinical trials. The use of combined end points may allow for shorter and smaller trials due to increased precision. We performed a literature search for the use of composite end points as primary outcome measures in clinical studies of early AMD stages. PubMed was searched for composite end points used in early/intermediate AMD studies published during the last 10 years. A total of 673 articles of interest were identified. After reviewing abstracts and applicable full-text articles, 33 articles were eligible and thus included in the qualitative synthesis. The main composite end point categories were: combined structural and functional end points, combined structural end points, combined functional end points and combined multicategorical end points. The majority of the studies included binary composite end points. There was a lack of sensitivity analyses of different end points against accepted outcomes (i.e., progression) in the literature. Various composite outcome measures have been used but there is a lack of standardization. To date no agreement on the optimal approach to implement combined end points in clinical studies of early stages of AMD exists, and no surrogate end points have been accepted for AMD progression.
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Degeneración Macular , Progresión de la Enfermedad , Humanos , Degeneración Macular/diagnósticoRESUMEN
Background: It is known that giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) often occur together. So far, the prevalence of GCA in newly diagnosed PMR patients has not been evaluated in a prospective ultrasound study. Objective: The aim of this study was to assess the prevalence of GCA using vascular ultrasound in patients with newly diagnosed PMR. Design: A consecutive cohort of newly diagnosed PMR patients was prospectively evaluated for the presence of GCA with the use of systematic musculoskeletal and vascular ultrasound examination. Methods: Overall, 60 patients with newly diagnosed PMR were prospectively enrolled. Symptoms and laboratory findings were collected. All patients underwent ultrasound of shoulder and hip joints, and vascular ultrasound evaluating the facial, temporal, carotid, vertebral and axillary arteries. Patients were diagnosed with GCA if they had ultrasound imaging findings of GCA. Patients with PMR (PMR-group) and patients with PMR and GCA (PMR-GCA-group) were compared, and a C-reactive protein (CRP) cut-off value was evaluated. Results: GCA was diagnosed in 28 of 60 PMR patients (46%). The PMR-group consisted of 20 (62.5%) females with a mean age of 69 (±9.9) years, while the PMR-GCA-group consisted of 11 (39.3%) females with a mean age of 74 (±8.4) years. In 13 of 28 patients (46%) in the PMR-GCA-group, GCA was subclinical and only diagnosed by ultrasound. The PMR-GCA-group showed higher values of joint effusion and significantly higher CRP values. A CRP cut-off value of 26.5 mg/litre (reference range 0-5 mg/litre) yielded a sensitivity of 66% with a specificity of 73% for GCA. Conclusion: GCA was found in 46% of newly diagnosed PMR patients; 22% of the patients with PMR had asymptomatic GCA. Joint effusions were higher in the PMR-GCA-group, with significant results for the hip joint. A CRP cut-off value of ⩾26.5 mg/litre in PMR can help in the identification of subclinical GCA.
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Objective: Elevated double-stranded DNA (dsDNA) antibody levels in blood serum are considered a disease-specific marker in systemic lupus erythematosus (SLE), correlate with disease activity and the incidence of lupus nephritis, and can be detected in up to 86% of all SLE cases. Despite the high clinical relevance, the variety of dsDNA antibody testing methods with heterogenous performance in clinical use remains challenging. This study is the first to prospectively investigate the performance of two of today's most commonly applied anti-dsDNA testing methods head-to-head under real-world conditions, as well as their correlation with other clinical and serological disease parameters in SLE patients. Methods: In this prospective study, all SLE patients undergoing treatment at the Department of Rheumatology at the University Hospital Bonn within a 13-months period (n=41) and control patients without connective-tissue disease (n=51) were consecutively enrolled and examined. For all study participants' serum samples both anti-dsDNA-NcX enzyme-linked immunoassay testing EUROIMMUN, Luebeck, Germany) and the fluorescence immunoassay ELiA dsDNA (Thermo Fisher Scientific, Waltham, USA) were performed. In addition, demographic data, further laboratory values and disease activity parameters were recorded. Clinical disease activity was assessed by SLEDAI-2K. Results: Both assays showed high specificity (anti-dsDNA-NcX ELISA: 0.9, ELiA dsDNA: 0.959), but there were notable differences in sensitivity (anti-dsDNA-NcX ELISA: 0.51, ELiA dsDNA: 0.38). Pearsons's correlation yielded a positive correlation between anti-dsDNA concentrations and CRP concentrations for the anti-dsDNA-NcX ELISA (R=0.22; p=0.038) and a mild-to-moderate inverse correlation between concentrations of anti-dsDNA and complement C4 for the ELiA dsDNA test (R=-0.22; p=0.045) when SLE and control patients were considered together. Other than, no significant correlation between anti-dsDNA concentrations and clinical or laboratory findings was found for either test procedure. Conclusion: Both anti-dsDNA antibody assays represent reliable examination methods with high specificity for the diagnosis of SLE that fulfill EULAR/ACR requirements. However, the anti-dsDNA-NcX ELISA showed superior sensitivity and significant correlation with disease activity (as measured by CRP concentrations).
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Anticuerpos Antinucleares , Lupus Eritematoso Sistémico , Humanos , Estudios Prospectivos , ADNRESUMEN
PURPOSE: To report the prevalence and topographic distribution of structural characteristics in study participants with age-related macular degeneration (AMD) and controls in the cross-sectional study part of the MACUSTAR study (ClinicalTrials.gov Identifier: NCT03349801). DESIGN: European, multicenter cohort study. SUBJECTS: Overall, 301 eyes of 301 subjects with early (n = 34), intermediate (n = 168), and late AMD (n = 43), as well as eyes without any AMD features (n = 56). METHODS: In study eyes with intermediate AMD (iAMD), the presence of structural AMD biomarkers, including pigmentary abnormalities (PAs), pigment epithelium detachment (PED), refractile deposits, reticular pseudodrusen (RPD), hyperreflective foci (HRF), incomplete/complete retinal pigment epithelium (RPE), and outer retinal atrophy (i/cRORA), and quiescent choroidal neovascularization (qCNV) was systematically determined in the prospectively acquired multimodal retinal imaging cross-sectional data set of MACUSTAR. Retinal layer thicknesses and the RPE drusen complex (RPEDC) volume were determined for the total study cohort in spectral-domain (SD) OCT imaging using a deep-learning-based algorithm. MAIN OUTCOME MEASURES: Prevalence and topographic distribution of structural iAMD features. RESULTS: A total of 301 study eyes of 301 subjects with a mean (± standard deviation) age of 71.2 ± 7.20 years (63.1% women) were included. Besides large drusen, the most prevalent structural feature in iAMD study eyes were PA (57.1%), followed by HRF (51.8%) and RPD (22.0%). Pigment epithelium detachment lesions were observed in 4.8%, vitelliform lesions in 4.2%, refractile deposits in 3.0%, and qCNV in 2.4%. Direct precursor lesions for manifest retinal atrophy were detected in 10.7% (iRORA) and 4.2% (cRORA) in iAMD eyes. Overall, the highest RPEDC volume with a median of 98.92 × 10-4 mm³ was found in iAMD study eyes. Spatial analysis demonstrated a predominant distribution of RPD in the superior and temporal subfields at a foveal eccentricity of 1.5 to 2 mm, whereas HRF and large drusen had a distinct topographic distribution involving the foveal center. CONCLUSIONS: Detailed knowledge of the prevalence and distribution of structural iAMD biomarkers is vital to identify reliable outcome measure for disease progression. Longitudinal analyses are needed to evaluate their prognostic value for conversion to advanced disease stages. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
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Neovascularización Coroidal , Degeneración Macular , Desprendimiento de Retina , Drusas Retinianas , Humanos , Femenino , Persona de Mediana Edad , Anciano , Masculino , Estudios Transversales , Estudios de Cohortes , Tomografía de Coherencia Óptica/métodos , Degeneración Macular/diagnóstico , Degeneración Macular/epidemiología , Degeneración Macular/patología , Drusas Retinianas/diagnóstico , Drusas Retinianas/epidemiología , Neovascularización Coroidal/diagnóstico , Neovascularización Coroidal/epidemiología , AtrofiaRESUMEN
BACKGROUND/AIMS: To further validate the Vision Impairment in Low Luminance (VILL) questionnaire, which captures visual functioning and vision-related quality of life (VRQoL) under low luminance, low-contrast conditions relevant to age-related macular degeneration (AMD). METHODS: The VILL was translated from German into English (UK), Danish, Dutch, French, Italian and Portuguese. Rasch analysis was used to assess psychometric characteristics of 716 participants (65% female, mean age 72±7 years, 82% intermediate AMD) from the baseline visit of the MACUSTAR study. In a subset of participants (n=301), test-retest reliability (intraclass correlation coefficient (ICC) and coefficient of repeatability (CoR)) and construct validity were assessed. RESULTS: Four items were removed from the VILL with 37 items due to misfit. The resulting Vision Impairment in Low Luminance with 33 items (VILL-33) has three subscales with no disordered thresholds and no misfitting items. No differential item functioning and no multidimensionality were observed. Person reliability and person separation index were 0.91 and 3.27 for the Vision Impairment in Low Luminance Reading Subscale (VILL-R), 0.87 and 2.58 for the Vision Impairment in Low Luminance Mobility Subscale (VILL-M), and 0.78 and 1.90 for the Vision Impairment in Low Luminance Emotional Subscale (VILL-E). ICC and CoR were 0.92 and 1.9 for VILL-R, 0.93 and 1.8 for VILL-M and 0.82 and 5.0 for VILL-E. Reported VRQoL decreased with advanced AMD stage (p<0.0001) and was lower in the intermediate AMD group than in the no AMD group (p≤0.0053). CONCLUSION: The VILL is a psychometrically sound patient-reported outcome instrument, and the results further support its reliability and validity across all AMD stages. We recommend the shortened version of the questionnaire with three subscales (VILL-33) for future use. TRIAL REGISTRATION NUMBER: NCT03349801.
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Degeneración Macular , Baja Visión , Anciano , Femenino , Humanos , Masculino , Degeneración Macular/complicaciones , Degeneración Macular/diagnóstico , Psicometría/métodos , Calidad de Vida/psicología , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Visión OcularRESUMEN
Purpose: The purpose of this study was to assess test-retest variability and discriminatory power of measures from macular integrity assessment (S-MAIA) and AdaptDx. Methods: This is a cross-sectional study of 167 people with intermediate age-related macular degeneration (iAMD), no AMD (controls; n = 54), early AMD (n = 28), and late AMD (n = 41), recruited across 18 European ophthalmology centers. Repeat measures of mesopic and scotopic S-MAIA average (mean) threshold (MMAT decibels [dB] and SMAT [dB]) and rod intercept time (RIT [mins]) at 2 visits 14 (±7) days apart were recorded. Repeat measures were assessed by Bland-Altman analysis, intra-class correlation coefficients (ICCs) and variability ratios. Secondary analysis assessed the area under the receiver operating characteristic curves (AUC) to determine the ability to distinguish people as having no AMD, early AMD, or iAMD. Results: Data were available for 128, 131, and 103 iAMD participants for the mesopic and scotopic S-MAIA and AdaptDx, respectively. MMAT and SMAT demonstrate similar test-retest variability in iAMD (95% confidence interval [CI] ICC of 0.79-0.89 and 0.78-0.89, respectively). ICCs were worse in RIT (95% CI ICC = 0.55-0.77). All tests had equivalent AUCs (approximately 70%) distinguishing between subjects with iAMD and controls, whereas early AMD was indistinguishable from iAMD on all measures (AUC = <55%). A learning effect was not seen in these assessments under the operating procedures used. Conclusions: MMAT, SMAT, and RIT have adequate test-retest variability and are all moderately good at separating people with iAMD from controls. Translational Relevance: Expected levels of test-retest variability and discriminatory power of the AdaptDx and MAIA devices in a clinical study setting must be considered when designing future trials for people with AMD.