Test-Retest Variability and Discriminatory Power of Measurements From Microperimetry and Dark Adaptation Assessment in People With Intermediate Age-Related Macular Degeneration – A MACUSTAR Study Report

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

Use of composite endpoints in early and intermediate age-related macular degeneration clinical trials - state-of-the-art and future directions

The slow progression of early AMD stages to advanced AMD requires the use of surrogate endpoints in clinical trials. The use of combined endpoints may allow for shorter and smaller trials due to increased precision. We performed a literature search for the use of composite endpoints as primary outcome measures in clinical studies of early AMD stages. PubMed was searched for composite endpoints 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 endpoint categories were: Combined structural and functional endpoints, combined structural endpoints, combined functional endpoints and combined multi-categorical endpoints. The majority of the studies included binary composite endpoints. There was a lack of sensitivity analyses of different endpoints 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 endpoints in clinical studies of early stages of AMD exists and no surrogate endpoints have been accepted for AMD progression

Modeling of atrophy size trajectories: variable transformation, prediction and age-of-onset estimation

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 \textgreekl. Model evaluation is performed on data collected for two longitudinal, prospective multi-center cohort studies on GA size progression. RESULTS A transformation parameter of \textgreekl=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

Complete hemispheric exposure vs. superior sagittal sinus sparing craniectomy: incidence of shear-bleeding and shunt-dependency

Purpose!#!Decompressive hemicraniectomy (DC) has been established as a standard therapeutical procedure for raised intracranial pressure. However, the size of the DC remains unspecified. The aim of this study was to analyze size related complications following DC.!##!Methods!#!Between 2013 and 2019, 306 patients underwent DC for elevated intracranial pressure at author´s institution. Anteroposterior and craniocaudal DC size was measured according to the postoperative CT scans. Patients were divided into two groups with (1) exposed superior sagittal sinus (SE) and (2) without superior sagittal sinus exposure (SC). DC related complications e.g. shear-bleeding at the margins of craniectomy and secondary hydrocephalus were evaluated and compared.!##!Results!#!Craniectomy size according to anteroposterior diameter and surface was larger in the SE group; 14.1 ± 1 cm vs. 13.7 ± 1.2 cm, p = 0.003, resp. 222.5 ± 40 cm!##!Conclusions!#!Complete hemispheric exposure in terms of DC with SE was associated with significantly lower levels of iatrogenic shear-bleedings compared to a SC-surgical regime. Although we did not find significant outcome difference, our findings suggest aggressive craniectomy regimes including SE to constitute the surgical treatment strategy of choice for malignant intracranial pressure

Specialized dermatological-rheumatological patient management improves diagnostic outcome and patient journey in psoriasis and psoriatic arthritis: a four-year analysis

Background!#!Management of psoriasis patients with arthralgia suffering from suspected psoriatic arthritis (PsA) requires an interdisciplinary approach involving dermatologists and rheumatologists. The aim of the study was to analyze the specialized dermatological-rheumatological management of these patients before and after foundation of a PsA center.!##!Methods!#!A retrospective cohort study of all dermatological-rheumatological consultations during two periods was conducted. Period one, from April 1st, 2016 to February 28th, 2018 versus period two, from March 1st, 2018 to January 31st, 2020, after foundation of a PsA center. Clinical data on patient characteristics including psoriasis subtypes, clinical symptoms and signs, disease activity scores, classification criteria and comorbidities as well as patient journey were extracted and analyzed.!##!Results!#!Four hundred four consultations were studied. Close collaboration in a PsA center lead to a relevantly shortened patient journey concerning rheumatological complaints: period 1: median (IQR): 36.0 (10.0-126.0) months, period 2: median (IQR): 24.0 (6.0-60.0) months. Established scores and classification criteria such as GEPARD or CASPAR did not assist in diagnosis of PsA. Arthralgia (p = 0.0407), swollen joints (p = 0.0151), morning stiffness (p = 0.0451) and dactylitis (p = 0.0086) helped to distinguish between osteoarthritis and PsA.!##!Conclusions!#!Clinical signs and symptoms, scores and classification criteria usually assessed were less helpful than expected in diagnosis of PsA. Close collaboration in a specialized PsA center yielded the fastest way of diagnosis

The role of dual energy computed tomography in the differentiation of acute gout flares and acute calcium pyrophosphate crystal arthritis

Objectives!#!To analyse the diagnostic impact of dual energy computed tomography (DECT) in acute gout flares and acute calcium pyrophosphate (CPP) crystal arthritis when compared to the gold standard of arthrocentesis with compensated polarised light microscopy. Microscopy results were also compared to musculoskeletal ultrasound (MUS), conventional radiographs, and the suspected clinical diagnosis (SCD).!##!Methods!#!Thirty-six patients with a suspected gout flare (n = 24) or acute CPP crystal arthritis (n = 11, n = 1 suffered from neither) who received a DECT and underwent arthrocentesis were included. Two independent readers assessed DECT images for signs of monosodium urate crystals or calcium pyrophosphate deposition.!##!Results!#!Sensitivity of DECT for gout was 63% (95% CI 0.41-0.81) with a specificity of 92% (0.41-0.81) while sensitivity and specificity for acute CPP arthritis were 55% (0.23-0.83) and 92% (0.74-0.99), respectively. MUS had the highest sensitivity of all imaging modalities with 92% (0.73-0.99) and a specificity of 83% (0.52-0.98) for gout, while sensitivity and specificity for acute CPP crystal arthritis were 91% (0.59-1.00) and 92% (0.74-0.99), respectively.!##!Conclusion!#!DECT is an adequate non-invasive diagnostic tool for acute gout flares but might have a lower sensitivity than described by previous studies. Both MUS and SCD had higher sensitivities than DECT for acute gout flares and acute CPP crystal arthritis

Changes in ultrasound imaging of joints, entheses, bursae and tendons 24 and 48 h after adjusted weight training

Background: Joint effusion and enthesitis are common ultrasound findings in rheumatic diseases such as rheumatoid arthritis or spondyloarthritis. However, changes of joints and entheses were not only observed in patients but also in physically active individuals and athletes. Objectives: The purpose of this study was to evaluate joint, entheseal, bursal and tendon musculoskeletal ultrasound (MSUS) findings in large and medium joints of young healthy individuals after completing a standardised weight training. Design: This is a prospective cohort study. Methods: MSUS examinations of large- and medium-sized joints, and related entheseal sites, bursae and tendons were performed on young healthy individuals (ages 18–30 years). Before, 24 and 48 h after completing 1 h of standardised weight exercise, the subjects were evaluated by MSUS. The development of the MSUS findings and associated effects were examined using generalised linear mixed effects models. Results: In total, 51 healthy individuals (52.9% female) with a mean age of 23.7 (±2.5) years were enrolled. The results showed an increase in the number of individuals with at least one joint effusion from 37 (72.5%) before the weight training to 48 (94.1%) after 48 h. Entheses with pathologies were observed in 14 participants (27.5%) at baseline, increasing to 29 participants (56.9%) 48 h after the weight training. Biceps tendon sheath effusion was detected in 9 individuals (17.6%) prior to training, rising to 22 individuals (43.1%) after 48 h. A significant increase in the number of joints with effusion and abnormal entheses within 48 h after the weight training was indicated by the generalised linear mixed effects models. Conclusion: Within 48 h after the weight training session, a significant increase in the prevalence of joint effusion in large and medium joints and the prevalence of abnormal entheses was observed. As a result, when performing and interpreting an MSUS examination, the patient’s physical activities should be taken into account

Structural retinal changes in cerebral small vessel disease

Cerebral small vessel disease (CSVD) is an important contributor to cognitive impairment and stroke. Previous research has suggested associations with alterations in single retinal layers. We have assessed changes of all individual retinal layers in CSVD using high-resolution optical coherence tomography (OCT) for the first time. Subjects with recent magnetic resonance imaging (MRI) underwent macular and peripapillary retinal imaging using OCT for this case-control study. Number and volume ratio index (WMRI) of white matter lesions (WML) were determined on MRI. Data were analyzed using multiple linear regression models. 27 CSVD patients and 9 control participants were included. Ganglion cell layer (GCL) volume was significantly reduced in patients with CSVD compared to age-matched controls (p = 0.008). In patients with CSVD, larger foveal outer plexiform layer (OPL) volume and decreased temporal peripapillary retinal nerve fiber layer (RNFL) thickness were significantly associated with a higher WMRI in linear regression when controlling for age (p ≤ 0.033). Decreased foveal GCL volume and temporal-inferior RNFL thickness at Bruch's membrane opening (MRW), and increased temporal MRW were associated with a higher WML burden (p ≤ 0.037). Thus, we identified alterations in several OCT layers in individuals with CSVD (GCL, OPL, MRW and RNFL). Their potential diagnostic value merits further study

A Validation Study for SHE Score for Acute Subdural Hematoma in the Elderly

Objective: The aim of this study was the verification of the Subdural Hematoma in the Elderly (SHE) score proposed by Alford et al. as a mortality predictor in patients older than 65 years with nontraumatic/minor trauma acute subdural hematoma (aSDH). Additionally, we evaluated further predictors associated with poor outcome. Methods: Patients were scored according to age (1 point is given if patients were older than 80 years), GCS by admission (1 point for GCS 5&ndash;12, 2 points for GCS 3&ndash;4), and SDH volume (1 point for volume 50 mL). The sum of points determines the SHE score. Multivariate logistic regression analysis was performed to identify additional independent risk factors associated with 30-day mortality. Results: We evaluated 131 patients with aSDH who were treated at our institution between 2008 and 2020. We observed the same 30-day mortality rates published by Alford et al.: SHE 0: 4.3% vs. 3.2%, p = 1.0; SHE 1: 12.2% vs. 13.1%, p = 1.0; SHE 2: 36.6% vs. 32.7%, p = 0.8; SHE 3: 97.1% vs. 95.7%, p = 1.0 and SHE 4: 100% vs. 100%, p = 1.0. Additionally, 18 patients who developed status epilepticus (SE) had a mortality of 100 percent regardless of the SHE score. The distribution of SE among the groups was: 1 for SHE 1, 6 for SHE 2, 9 for SHE 3, and 2 for SHE 4. The logistic regression showed the surgical evacuation to be the only significant risk factor for developing the seizure. All patients who developed SE underwent surgery (p = 0.0065). Furthermore, SHE 3 and 4 showed no difference regarding the outcome between surgical and conservative treatment. Conclusions: SHE score is a reliable mortality predictor for minor trauma acute subdural hematoma in elderly patients. In addition, we identified status epilepticus as a strong life-expectancy-limiting factor in patients undergoing surgical evacuation

Characteristics and Spatial Distribution of Structural Features in Age-Related Macular Degeneration: A MACUSTAR Study Report

&lt;h3&gt;Purpose&lt;/h3&gt;&lt;p&gt;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 (&lt;a href="https://clinicaltrials.gov/"&gt;ClinicalTrials.gov&lt;/a&gt; Identifier: NCT03349801).&lt;/p&gt;&lt;h3&gt;Design&lt;/h3&gt;&lt;p&gt;European, multicenter &lt;a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/cohort-analysis"&gt;cohort study&lt;/a&gt;.&lt;/p&gt;&lt;h3&gt;Subjects&lt;/h3&gt;&lt;p&gt;Overall, 301 eyes of 301 subjects with early (n&nbsp;= 34), intermediate (n&nbsp;= 168), and late AMD (n&nbsp;= 43), as well as eyes without any AMD features (n&nbsp;= 56).&lt;/p&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;In study eyes with intermediate AMD (iAMD), the presence of structural AMD biomarkers, including pigmentary abnormalities (PAs), &lt;a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/retinal-detachment"&gt;pigment epithelium detachment&lt;/a&gt; (PED), refractile deposits, reticular pseudodrusen (RPD), hyperreflective foci (HRF), incomplete/complete &lt;a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/retinal-pigment-epithelium"&gt;retinal pigment epithelium&lt;/a&gt; (RPE), and outer retinal atrophy (i/cRORA), and quiescent &lt;a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/choroidal-neovascularization"&gt;choroidal neovascularization&lt;/a&gt; (qCNV) was systematically determined in the prospectively acquired multimodal &lt;a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/retinal-imaging"&gt;retinal imaging&lt;/a&gt; cross-sectional data set of MACUSTAR. Retinal layer thicknesses and the RPE &lt;a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/drusen"&gt;drusen&lt;/a&gt; complex (RPEDC) volume were determined for the total study cohort in spectral-domain (SD) OCT imaging using a deep-learning–based algorithm.&lt;/p&gt;&lt;h3&gt;Main Outcome Measures&lt;/h3&gt;&lt;p&gt;Prevalence and topographic distribution of structural iAMD features.&lt;/p&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;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&nbsp;× 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.&lt;/p&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;p&gt;Detailed knowledge of the prevalence and distribution of structural iAMD biomarkers is vital to identify reliable outcome measure for &lt;a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/disease-exacerbation"&gt;disease progression&lt;/a&gt;. Longitudinal analyses are needed to evaluate their prognostic value for conversion to advanced disease stages.&lt;/p&gt