AimsTo present current practice patterns in the diagnosis and management of Cytomegalovirus anterior uveitis (CMV AU) by uveitis experts worldwide.MethodsA two-round modified Delphi survey with... Show moreAimsTo present current practice patterns in the diagnosis and management of Cytomegalovirus anterior uveitis (CMV AU) by uveitis experts worldwide.MethodsA two-round modified Delphi survey with masking of the study team was performed. Based on experience and expertise, 100 international uveitis specialists from 21 countries were invited to participate in the survey. Variation in the diagnostic approaches and preferred management of CMV AU was captured using an online survey platform.ResultsSeventy-five experts completed both surveys. Fifty-five of the 75 experts (73.3%) would always perform diagnostic aqueous tap in suspected CMV AU cases. Consensus was achieved for starting topical antiviral treatment (85% of experts). About half of the experts (48%) would only commence systemic antiviral treatment for severe, prolonged, or atypical presentation. The preferred specific route was ganciclovir gel 0.15% for topical treatment (selected by 70% of experts) and oral valganciclovir for systemic treatment (78% of experts). The majority of experts (77%) would commence treatment with topical corticosteroid four times daily for one to two weeks along with antiviral coverage, with subsequent adjustment depending on the clinical response. Prednisolone acetate 1% was the drug of choice (opted by 70% of experts). Long-term maintenance treatment (up to 12 months) can be considered for chronic course of inflammation (88% of experts) and those with at least 2 episodes of CMV AU within a year (75-88% of experts).ConclusionsPreferred management practices for CMV AU vary widely. Further research is necessary to refine diagnosis and management and provide higher-level evidence. Show less
AimsTo present current expert practice patterns and to formulate a consensus for the management of HSV and VZV AU by uveitis specialists worldwide.MethodsA two-round online modified Delphi survey... Show moreAimsTo present current expert practice patterns and to formulate a consensus for the management of HSV and VZV AU by uveitis specialists worldwide.MethodsA two-round online modified Delphi survey with masking of the study team was conducted. Responses were collected from 76 international uveitis experts from 21 countries. Current practices in the diagnosis and treatment of HSV and VZV AU were identified. A working group (The Infectious Uveitis Treatment Algorithm Network [TITAN]) developed data into consensus guidelines. Consensus is defined as a particular response towards a specific question meeting & GE;75% of agreement or IQR & LE; 1 when a Likert scale is used.ResultsUnilaterality, increased intraocular pressure (IOP), decreased corneal sensation and diffuse or sectoral iris atrophy are quite specific for HSV or VZV AU from consensus opinion. Sectoral iris atrophy is characteristic of HSV AU. Treatment initiation is highly variable, but most experts preferred valacyclovir owing to simpler dosing. Topical corticosteroids and beta-blockers should be used if necessary. Resolution of inflammation and normalisation of IOP are clinical endpoints.ConclusionsConsensus was reached on several aspects of diagnosis, choice of initial treatment, and treatment endpoints for HSV and VZV AU. Treatment duration and management of recurrences varied between experts. Show less
The COVID-19 pandemic has galvanized the global response towards the development of new vaccines based on novel technologies at an unprecedented pace. Since the widespread implementation of... Show moreThe COVID-19 pandemic has galvanized the global response towards the development of new vaccines based on novel technologies at an unprecedented pace. Since the widespread implementation of vaccination campaigns, case reports on vaccines' systemic side effects, including ocular manifestations, have emerged. Since administered vaccines are generally not able to cause the disease in the recipient, or induce an immune response against the pathogen, we hypothesize that the development of ocular phenomena post-COVID-19 vaccination may occur via an immune response elicited by the vaccine. Of many, the most common ocular adverse events include facial nerve palsy, central venous sinus thrombosis and acute anterior uveitis. These COVID-19 vaccine-induced ocular (CVIO) adverse events could resemble the ocular findings in some of the COVID-19 patients. This review will provide a comprehensive overview of published ocular side effects potentially associated with COVID-19 vaccination and serve as a springboard for further research into CVIO adverse events. Show less
Ng, X. le; Betzler, B.K.; Testi, I.; Ho, S.L.; Tien, M.; Ngo, W.K.; ... ; Agrawal, R. 2021
Purpose The COVID-19 pandemic has galvanized the development of new vaccines at an unprecedented pace. Since the widespread implementation of vaccination campaigns, reports of ocular adverse... Show morePurpose The COVID-19 pandemic has galvanized the development of new vaccines at an unprecedented pace. Since the widespread implementation of vaccination campaigns, reports of ocular adverse effects after COVID-19 vaccinations have emerged. This review summarizes ocular adverse effects possibly associated with COVID-19 vaccination, and discusses their clinical characteristics and management. Methods Narrative Literature Review. Results Ocular adverse effects of COVID-19 vaccinations include facial nerve palsy, abducens nerve palsy, acute macular neuroretinopathy, central serous retinopathy, thrombosis, uveitis, multiple evanescent white dot syndrome, Vogt-Koyanagi-Harada disease reactivation, and new-onset Graves' Disease. Studies in current literature are primarily retrospective case series or isolated case reports - these are inherently weak in establishing association or causality. Nevertheless, the described presentations resemble the reported ocular manifestations of the COVID-19 disease itself. Hence, we hypothesize that the human body's immune response to COVID-19 vaccinations may be involved in the pathogenesis of the ocular adverse effects post-COVID-19 vaccination. Conclusion Ophthalmologists and generalists should be aware of the possible, albeit rare, ocular adverse effects after COVID-19 vaccination. Show less
Chronic obstructive pulmonary disease (COPD) is a destructive inflammatory disease and the genes expressed within the lung are crucial to its pathophysiology. We have determined the RNAseq... Show moreChronic obstructive pulmonary disease (COPD) is a destructive inflammatory disease and the genes expressed within the lung are crucial to its pathophysiology. We have determined the RNAseq transcriptome of bronchial brush cells from 312 stringently defined ex-smoker patients. Compared to healthy controls there were for males 40 differentially expressed genes (DEGs) and 73 DEGs for females with only 26 genes shared. The gene ontology (GO) term "response to bacterium" was shared, with several different DEGs contributing in males and females. Strongly upregulated genes TCN1 and CYP1B1 were unique to males and females, respectively. For male emphysema (E)-dominant and airway disease (A)-dominant COPD (defined by computed tomography) the term "response to stress" was found for both sub-phenotypes, but this included distinct up-regulated genes for the E-sub-phenotype (neutrophil-related CSF3R, CXCL1, MNDA) and for the A-sub-phenotype (macrophage-related KLF4, F3, CD36). In E-dominant disease, a cluster of mitochondria-encoded (MT) genes forms a signature, able to identify patients with emphysema features in a confirmation cohort. The MT-CO2 gene is upregulated transcriptionally in bronchial epithelial cells with the copy number essentially unchanged. Both MT-CO2 and the neutrophil chemoattractant CXCL1 are induced by reactive oxygen in bronchial epithelial cells. Of the female DEGs unique for E- and A-dominant COPD, 88% were detected in females only. In E-dominant disease we found a pronounced expression of mast cell-associated DEGs TPSB2, TPSAB1 and CPA3. The differential genes discovered in this study point towards involvement of different types of leukocytes in the E- and A-dominant COPD sub-phenotypes in males and females. Show less
Agrawal, R.; Testi, I.; Lee, C.S.; Tsui, E.; Blazes, M.; Thorne, J.E.; ... ; COVID-19 Imt Study Grp 2021
Background Immunomodulatory therapy (IMT) is often considered for systemic treatment of non-infectious uveitis (NIU). During the evolving coronavirus disease-2019 (COVID-19) pandemic, given the... Show moreBackground Immunomodulatory therapy (IMT) is often considered for systemic treatment of non-infectious uveitis (NIU). During the evolving coronavirus disease-2019 (COVID-19) pandemic, given the concerns related to IMT and the increased risk of infections, an urgent need for guidance on the management of IMT in patients with uveitis has emerged. Methods A cross-sectional survey of international uveitis experts was conducted. An expert steering committee identified clinical questions on the use of IMT in patients with NIU during the COVID-19 pandemic. Using an interactive online questionnaire, guided by background experience and knowledge, 139 global uveitis experts generated consensus statements for IMT. In total, 216 statements were developed around when to initiate, continue, decrease and stop systemic and local corticosteroids, conventional immunosuppressive agents and biologics in patients with NIU. Thirty-one additional questions were added, related to general recommendations, including the use of non-steroidal anti-inflammatory drugs (NSAIDs) and hydroxychloroquine. Results Highest consensus was achieved for not initiating IMT in patients who have suspected or confirmed COVID-19, and for using local over systemic corticosteroid therapy in patients who are at high-risk and very high-risk for severe or fatal COVID-19. While there was a consensus in starting or initiating NSAIDs for the treatment of scleritis in healthy patients, there was no consensus in starting hydroxychloroquine in any risk groups. Conclusion Consensus guidelines were proposed based on global expert opinion and practical experience to bridge the gap between clinical needs and the absence of medical evidence, to guide the treatment of patients with NIU during the COVID-19 pandemic. Show less
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 in Wuhan city, Hubei province, China. This is the third and largest coronavirus outbreak since the new... Show moreThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 in Wuhan city, Hubei province, China. This is the third and largest coronavirus outbreak since the new millennium after SARS in 2002 and Middle East respiratory syndrome (MERS) in 2012. Over 3 million people have been infected and the COVID-19 has caused more than 217 000 deaths. A concern exists regarding the vulnerability of patients who have been treated with immunosuppressive drugs prior or during this pandemic. Would they be more susceptible to infection by the SARS-CoV-2 and how would their clinical course be altered by their immunosuppressed state? This is a question the wider medical fraternity-including ophthalmologists, rheumatologists, gastroenterologist and transplant physicians among others-must answer. The evidence from the SARS and MERS outbreak offer some degree of confidence that immunosuppression is largely safe in the current COVID-19 pandemic. Preliminary clinical experiences based on case reports, small series and observational studies show the morbidity and mortality rates in immunosuppressed patients may not differ largely from the general population. Overwhelmingly, current best practice guidelines worldwide recommended the continuation of immunosuppression treatment in patients who require them except for perhaps high-dose corticosteroid therapy and in patients with associated risk factors for severe COVID-19 disease. Show less
Topic: The Collaborative Ocular Tuberculosis Study (COTS), supported by the International Ocular Inflammation Society, International Uveitis Study Group, and Foster Ocular Immunological Society,... Show moreTopic: The Collaborative Ocular Tuberculosis Study (COTS), supported by the International Ocular Inflammation Society, International Uveitis Study Group, and Foster Ocular Immunological Society, set up an international, expert-led consensus project to develop evidence- and experience-based guidelines for the management of tubercular uveitis (TBU).Clinical Relevance: The absence of international agreement on the use of antitubercular therapy (ATT) in patients with TBU contributes to a significant heterogeneity in the approach to the management of this condition.Methods: Consensus statements for the initiation of ATT in TBU were generated using a 2-step modified Delphi technique. In Delphi step 1, a smart web-based survey based on background evidence from published literature was prepared to collect the opinion of 81 international experts on the use of ATT in different clinical scenarios. The survey included 324 questions related to tubercular anterior uveitis (TAU), tubercular intermediate uveitis (TIU), tubercular panuveitis (TPU), and tubercular retinal vasculitis (TRV) administered by the experts, after which the COTS group met in November 2019 for a systematic and critical discussion of the statements in accordance with the second round of the modified Delphi process.Results: Forty-four consensus statements on the initiation of ATT in TAU, TIU, TPU, and TRV were obtained, based on ocular phenotypes suggestive of TBU and corroborative evidence of tuberculosis, provided by several combinations of immunologic and radiologic test results. Experts agreed on initiating ATT in recurrent TAU, TIU, TPU, and active TRV depending on the TB endemicity. In the presence of positive results for any 1 of the immunologic tests along with radiologic features suggestive of past evidence of tuberculosis infection. In patients with a first episode of TAU, consensus to initiate ATT was reached only if both immunologic and radiologic test results were positive.Discussion: The COTS consensus guidelines were generated based on the evidence from published literature, specialists' opinions, and logic construction to address the initiation of ATT in TBU. The guidelines also should inform public policy by adding specific types of TBU to the list of conditions that should be treated as tuberculosis. (C) 2020 by the American Academy of Ophthalmology Show less
This document summarizes the experience of the International Uveitis Study Group (IUSG), the Intraocular Inflammation Society (IOIS) and the Foster Ocular Inflammation Society (FOIS) and can aid as... Show moreThis document summarizes the experience of the International Uveitis Study Group (IUSG), the Intraocular Inflammation Society (IOIS) and the Foster Ocular Inflammation Society (FOIS) and can aid as a guide for the treatment of uveitis patients in the era of COVID-19 pandemic. Show less
Zierhut, M.; Smet, M.D. de; Gupta, V.; Pavesio, C.; Nguyen, Q.D.; Chee, S.P.; ... ; Agrawal, R. 2020
This document summarizes the experience of the International Uveitis Study Group (IUSG), the Intraocular Inflammation Society (IOIS), and the Foster Ocular Inflammation Society (FOIS) and can aid... Show moreThis document summarizes the experience of the International Uveitis Study Group (IUSG), the Intraocular Inflammation Society (IOIS), and the Foster Ocular Inflammation Society (FOIS) and can aid as a guide for the treatment of uveitis patients in the era of COVID-19 pandemic. Show less
Coronary artery disease(CAD) is one of the leading causes of mortality and morbidity worldwide. Clinically, it refers to atherosclerotic changes in the coronary arteries and is usually assessed... Show moreCoronary artery disease(CAD) is one of the leading causes of mortality and morbidity worldwide. Clinically, it refers to atherosclerotic changes in the coronary arteries and is usually assessed with a stress electrocardiogram and conventional coronary angiography(CCA). CCA, however, is an invasive technique and carries a small risk of complications. Non-invasive techniques such as coronary angiography with CT(CTCA), and myocardial perfusion imaging (MPI) with SPECT and MR are therefore used as gatekeeper tests before CCA. These techniques provide valuable information on both the coronary stenoses and their hemodynamic impact on the myocardial function. However, each of these techniques presents only one aspect of CAD. To achieve a higher level of accuracy and precision in CAD assessment, integration of information from different cardiac imaging modalities is essential. The goal of this thesis was therefore to develop techniques to realize this multimodal diagnostic image integration to enhance CAD diagnosis. To this end, we developed novel algorithms for near automated analysis of magnetic resonance based myocardial perfusion images. In addition, we developed and evaluated a new integration framework that allows comprehensive visualization of physiologic information from myocardial perfusion imaging -either with MR or SPECT and anatomical information from CTCA Show less
First-pass cardiac MR perfusion (CMRP) imaging has undergone rapid technical advancements in recent years. Although the efficacy of CMRP imaging in the assessment of coronary artery diseases (CAD)... Show moreFirst-pass cardiac MR perfusion (CMRP) imaging has undergone rapid technical advancements in recent years. Although the efficacy of CMRP imaging in the assessment of coronary artery diseases (CAD) has been proven, its clinical use is still limited. This limitation stems, in part, from manual interaction required to quantitatively analyze the large amount of data. This process is tedious, time-consuming, and prone to operator bias. Furthermore, acquisition and patient related image artifacts reduce the accuracy of quantitative perfusion assessment. With the advent of semi- and fully automatic image processing methods, not only the challenges posed by these artifacts have been overcome to a large extent, but a significant reduction has also been achieved in analysis time and operator bias. Despite an extensive literature on such image processing methods, to date, no survey has been performed to discuss this dynamic field. The purpose of this article is to provide an overview of the current state of the field with a categorical study, along with a future perspective on the clinical acceptance of image processing methods in the diagnosis of CAD. Show less
Gupta, V.; Hendriks, E.A.; Milles, J.; Geest, R.J. van der; Jerosch-Herold, M.; Reiber, J.H.C.; Lelieveldt, B.P.F. 2010
Rationale and Objectives: Derivation of diagnostically relevant parameters from first-pass myocardial perfusion magnetic resonance images involves the tedious and time-consuming manual segmentation... Show moreRationale and Objectives: Derivation of diagnostically relevant parameters from first-pass myocardial perfusion magnetic resonance images involves the tedious and time-consuming manual segmentation of the myocardium in a large number of images. To reduce the manual interaction and expedite the perfusion analysis, we propose an automatic registration and segmentation method for the derivation of perfusion linked parameters. Materials and Methods: A complete automation was accomplished by first registering misaligned images using a method based on independent component analysis, and then using the registered data to automatically segment the myocardium with active appearance models. We used 18 perfusion studies (100 images per study) for validation in which the automatically obtained (AO) contours were compared with expert drawn contours on the basis of point-to-curve error, Dice index, and relative perfusion upslope in the myocardium. Results: Visual inspection revealed successful segmentation in 15 out of 18 studies. Comparison of the AO contours with expert drawn contours yielded 2.23 0.53 mm and 0.91 +/- 0.02 as point-to-curve error and Dice index, respectively. The average difference between manually and automatically obtained relative upslope parameters was found to be statistically insignificant (P = .37). Moreover, the analysis time per slice was reduced from 20 minutes (manual) to 1.5 minutes (automatic), Conclusion: We proposed an automatic method that significantly reduced the time required for analysis of first-pass cardiac magnetic resonance perfusion images. The robustness and accuracy of the proposed method were demonstrated by the high spatial correspondence and statistically insignificant difference in perfusion parameters, when AO contours were compared with expert drawn contours. Show less
