Rhegmatogenous retinal detachment in uveitis

Abstract Background Retinal detachment is more common among uveitis patients than in the general population. Here, we aimed to assess the prevalence of rhegmatogenous retinal detachment (RRD) in a uveitis population. Methods We retrospectively studied 851 uveitis patients, recording characteristics such as uveitis duration, anatomical location, and cause; RRD occurrence; proliferative vitreoretinopathy (PVR) at presentation; surgical approach; reattachment rate; and initial and final visual acuity (VA). Results RRD occurred in 26 patients (3.1%; 29 affected eyes) and was significantly associated with posterior uveitis (p < 0.001), infectious uveitis (p < 0.001), and male gender (p = 0.012). Among cases of infectious uveitis, cytomegalovirus and varicella zoster virus were most commonly associated with RRD development. RRD in non-infectious uveitis was not found to be associated with any specific uveitis entity. The rate of single-operation reattachment was 48%, and the rate of final reattachment was 83%. Mean final VA was 20/125, with 41% of eyes ultimately having a VA of less than 20/200. Conclusion Uveitis is a risk factor for RRD development, which carries a poor prognosis

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons

Comparison among different diagnostic criteria for chronic ocular graft-versus-host disease applied with and without pre-transplant ophthalmological examination

none5noPurpose: To compare the proportion and the agreement rate in the diagnosis of chronic ocular graft-versus-host disease (GVHD) among three criteria applied with and without ophthalmological examination before hematopoietic stem cell transplantation (HSCT). Methods: National Institutes of Health (NIH), International Consensus Criteria on ocular GVHD (ICCGVHD) and TFOS Dry Eye Workshop (DEWS) II criteria were used for the diagnosis of ocular GVHD according to two protocols: ophthalmological examination after HSCT (Protocol A), or before and after HSCT (Protocol B). Proportion of GVHD diagnosis and inter-rate agreement coefficient Kappa (K) among the criteria were calculated. Results: One hundred nine patients undergone HSCT were included. NIH, ICCGVHD and DEWS II criteria diagnosed ocular GVHD in 14.7%, 17.4% and 59.6% of the patients (Protocol A), whereas in 11.9%, 15.6% and 33.0% of the HSCT patients (Protocol B). The coefficient K for the proportion of patients diagnosed with ocular GVHD by NIH and ICCGVHD criteria was K = 0.626 (Protocol A) and K = 0.615 (Protocol B). The K coefficient by NIH and DEWS II criteria was K = 0.144 (Protocol A), and K = 0.233 (Protocol B). The K coefficient by ICCGVHD and DEWS II criteria was K = 0.250 (Protocol A) and K = 0.499 (Protocol B). The K coefficient for ocular GVHD diagnosis applying Protocol A and B was K = 0.881 if NIH criteria were used, K = 0.933 if ICCGVHD criteria were used and K = 0.501 if DEWS II criteria were used. Conclusions: The diagnosis of ocular GVHD varied significantly in our cohort of hematological patients according to both the diagnostic criteria used and the visit protocols applied.mixedGiannaccare G, Versura P, Bonifazi F, Sessa M, Campos ECGiannaccare G, Versura P, Bonifazi F, Sessa M, Campos E

Prediction of personalised prognosis in patients with amyotrophic lateral sclerosis: development and validation of a prediction model

Background: Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive, fatal motor neuron disease with a variable natural history. There are no accurate models that predict the disease course and outcomes, which complicates risk assessment and counselling for individual patients, stratification of patients for trials, and timing of interventions. We therefore aimed to develop and validate a model for predicting a composite survival endpoint for individual patients with ALS. Methods: We obtained data for patients from 14 specialised ALS centres (each one designated as a cohort) in Belgium, France, the Netherlands, Germany, Ireland, Italy, Portugal, Switzerland, and the UK. All patients were diagnosed in the centres after excluding other diagnoses and classified according to revised El Escorial criteria. We assessed 16 patient characteristics as potential predictors of a composite survival outcome (time between onset of symptoms and noninvasive ventilation for more than 23 h per day, tracheostomy, or death) and applied backward elimination with bootstrapping in the largest population-based dataset for predictor selection. Data were gathered on the day of diagnosis or as soon as possible thereafter. Predictors that were selected in more than 70% of the bootstrap resamples were used to develop a multivariable Royston-Parmar model for predicting the composite survival outcome in individual patients. We assessed the generalisability of the model by estimating heterogeneity of predictive accuracy across external populations (ie, populations not used to develop the model) using internal–external cross-validation, and quantified the discrimination using the concordance (c) statistic (area under the receiver operator characteristic curve) and calibration using a calibration slope. Findings: Data were collected between Jan 1, 1992, and Sept 22, 2016 (the largest data-set included data from 1936 patients). The median follow-up time was 97·5 months (IQR 52·9–168·5). Eight candidate predictors entered the prediction model: bulbar versus non-bulbar onset (univariable hazard ratio [HR] 1·71, 95% CI 1·63–1·79), age at onset (1·03, 1·03–1·03), definite versus probable or possible ALS (1·47, 1·39–1·55), diagnostic delay (0·52, 0·51–0·53), forced vital capacity (HR 0·99, 0·99–0·99), progression rate (6·33, 5·92–6·76), frontotemporal dementia (1·34, 1·20–1·50), and presence of a C9orf72 repeat expansion (1·45, 1·31–1·61), all p&lt;0·0001. The c statistic for external predictive accuracy of the model was 0·78 (95% CI 0·77–0·80; 95% prediction interval [PI] 0·74–0·82) and the calibration slope was 1·01 (95% CI 0·95–1·07; 95% PI 0·83–1·18). The model was used to define five groups with distinct median predicted (SE) and observed (SE) times in months from symptom onset to the composite survival outcome: very short 17·7 (0·20), 16·5 (0·23); short 25·3 (0·06), 25·2 (0·35); intermediate 32·2 (0·09), 32·8 (0·46); long 43·7 (0·21), 44·6 (0·74); and very long 91·0 (1·84), 85·6 (1·96).Interpretation We have developed an externally validated model to predict survival without tracheostomy and non-invasive ventilation for more than 23 h per day in European patients with ALS. This model could be applied to individualised patient management, counselling, and future trial design, but to maximise the benefit and prevent harm it is intended to be used by medical doctors only.</p