CONCLUSIONS The opposite patterns of TIGIT expression in the CNS between MS and glioblastoma reflects the divergent features of the immune response in these 2 CNS diseases. These data raise the possibility that anti-TIGIT therapy may be beneficial for patients with glioblastoma. Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.As the COVID-19 pandemic took hold in North America, rheumatology clinics across the continent were inundated with phone calls from lupus patients understandably fearful of COVID-19. One of the most common questions from patients was whether they should stop taking their lupus medications.One month into the COVID-19 crisis in the US, rheumatologists have begun to feel the effects of our hastily constructed temporary response plans. While we may not be staffing the front lines with our colleagues in emergency medicine and critical care, our patients are uniquely vulnerable to infection and continue to require care.BACKGROUND/AIMS To investigate the time-dependent change of corneal endothelial cell (CEC) morphology and density (CECD) in patients with glaucoma post instillation of rho-associated protein kinase inhibitor ripasudil (Rip) 0.4% eye drops. METHODS This observational study involved 163 eyes of 163 patients with glaucoma in whom CEC morphological change was evaluated by CECD calculated via non-contact specular microscopy (NCSM) before and at 1 or 3 months post-Rip instillation. The change of CECD was plotted along with elapsed time from last instillation of Rip. The patients were divided into the following three groups based on the elapsed time post-Rip instillation Early Group ( less then 2 hours), Middle Group (≥2 hours, yet less then 6 hours) and Late Group (≥6 hours). The rate of CECD change was then analysed and compared among the three groups. An additional eight eyes of four patients with glaucoma were enrolled for a time-dependent study, with NCSM images evaluated before and at 1, 2, 3, 4 and 6 hours post-Rip instillation. RESULTS Morphological changes in the CECs appeared within 1 hour and recovered to normal within 6 hours post instillation. In the Early, Middle and Late Group, the median rate of CECD change as calculated by the NCSM automated software was -5.68%, -4.95% and -0.07%, respectively. The CEC images showed the same morphological changes with observational study in all four cases. CONCLUSION Due to transient morphological changes, the NCSM software produced misleading data for determining CECD within 1 hour post-Rip instillation, yet revealed that CEC morphology gradually recovered to normal within 6 hours. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.BACKGROUND To characterise early stages of geographic atrophy (GA) development in age-related macular degeneration (AMD) and to determine the prognostic value of structural precursor lesions in eyes with intermediate (i) AMD on the subsequent GA progression. METHODS Structural precursor lesions for atrophic areas (lesion size at least 0.5 mm² in fundus autofluorescence images) were retrospectively identified based on multimodal imaging and evaluated for association with the subsequent GA enlargement rates (square-root transformed, sqrt). A linear mixed-effects model was used to account for the hierarchical nature of the data with a Tukey post hoc test to assess the impact of the local precursor on the subsequent GA progression rate. RESULTS A total of 39 eyes with GA of 34 patients with a mean age of 74.4±6.7 (±SD) years were included in this study. Five precursor lesions (phenotypes 1-5) preceding GA development were identified large, sub-retinal pigment epithelial drusen (n=19), reticular pseudodrusen (RPD, n=10), refractile deposits (n=4), pigment epithelial detachment (n=4) and vitelliform lesions (n=2). Precursor lesions exhibited a significant association with the subsequent (sqrt) GA progression rates (p=0.0018) with RPD (phenotype 2) being associated with the fastest GA enlargement (2.29±0.52 (±SE) mm/year. CONCLUSIONS The results indicate the prognostic relevance of iAMD phenotyping for subsequent GA progression highlighting the role of structural AMD features across different AMD stages. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.Age-related macular degeneration (AMD) is one of the leading causes of irreversible blindness in the developed world. Antivascular endothelial growth factor therapy has transformed the management and outcome of neovascular AMD (nAMD), although the need for repeated intravitreal injections-even lifelong-and the related complications, high drug costs, frequent clinic visits and repeated imaging have resulted in an enormous burden both to healthcare systems and patients.  https://www.selleckchem.com/products/PD-98059.html  The application of gene therapy approaches for sustained delivery of a range of antiangiogenic proteins has the promise of helping to address these aforementioned challenges. A number of early phase clinical trials of gene therapy in nAMD have provided encouraging results, with many more ongoing or anticipated. There remain significant areas of controversy, including regarding the optimal treatment targets, routes of administration and potential safety concerns. In this review we aim to provide an update of the current status of gene therapy for nAMD and briefly discuss future prospects. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.OBJECTIVES Obesity is a well-recognised risk factor for osteoarthritis (OA). Our aim is to characterise body mass index (BMI)-associated pathological changes in the osteochondral unit and determine if obesity is the major causal antecedent of early joint replacement in patients with OA. METHODS We analysed the correlation between BMI and the age at which patients undergo total knee replacement (TKR) in 41 023 patients from the Australian Orthopaedic Association National Joint Replacement Registry. We then investigated the effect of BMI on pathological changes of the tibia plateau of knee joint in a representative subset of the registry. RESULTS 57.58% of patients in Australia who had TKR were obese. Patients with overweight, obese class I & II or obese class III received a TKR 1.89, 4.48 and 8.08 years earlier than patients with normal weight, respectively. Microscopic examination revealed that horizontal fissuring at the osteochondral interface was the major pathological feature of obesity-related OA. The frequency of horizontal fissure was strongly associated with increased BMI in the predominant compartment.