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BackgroundImmunomodulatory 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.MethodsA 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.ResultsHighest 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.ConclusionConsensus 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.

Thi My Hanh Pham,1,2 Chien Thang Nguyen,1 Quoc Tung Mai,2 Thi Huong Giang Bui,2 Dung Hoa Do,2 Peter McCluskey,3 Trong Van Pham2 1Department of Ophthalmology, 103 Military Hospital, Hanoi, Vietnam; 2Department of Ophthalmology, Hanoi Medical University, Hanoi, Vietnam; 3Department of Ophthalmology, University of Sydney, Sydney, NSW, AustraliaCorrespondence: Quoc Tung MaiTung Department of Ophthalmology, Hanoi Medical University, 1 Ton That Tung Street, Hanoi, 100000, VietnamTel +84 915644181Email maiquoctung@hmu.edu.vnPurpose: To evaluate the efficacy and safety of endoscopic orbital decompression in patients with Graves’ orbitopathy.Patients and Methods: This is a prospective study in Hanoi Medical University and a Military Hospital from December 2017 to December 2018. Twenty-eight orbits of fifteen patients were undergoing endoscopic orbital decompression for Graves’ orbitopathy. Indications for surgery were proptosis in twenty-two orbits and compressive optic neuropathy in six orbits. The outcome measures were proptosis reduction, visual acuity, visual field test and diplopia. Post-operative complications including cerebrospinal fluid leakage, haemorrhage, lacrimal duct impairment, worsening diplopia, sinusitis and cellulitis were collected.Results: The mean proptosis reduction was 2.23 mm. Visual acuity and medium deviation in the Humphrey visual field were significantly improved in four of six eyes with compressive optic neuropathy. There was one patient with intra-operative excessive bleeding which resolved without affecting visual outcome. Post-operatively, two patients developed a new onset of diplopia and two others worsened diplopia; three have already undergone successful strabismus surgery and moderate proptosis reduction.Conclusion: Endoscopic orbital decompression surgery was effectively and safely to manage compressive optic neuropathy of Graves’ orbitopathy and moderately reduce proptosis in a group of Vietnamese patients.Keywords: endoscopy, Graves‘ orbitopathy, decompression, optic neuropathy

Additional file 1. Standards for Reporting Qualitative Research (SRQR).

TOPIC 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.

Additional file 2. Interview Questions Guide.

Purpose: To compare clinical features, complications, and outcomes of CMV retinitis in non-HIV immunocompromised patients with HIV infected patients. Methods: A retrospective study of patients diagnosed with CMV retinitis with or without HIV infection was performed. Results: Thirty-five eyes from 27 patients (median follow up 26 months) were included. Six patients had HIV infection, the others were immunocompromised from a range of causes. The baseline visual acuity (VA) was similar in the two groups. Prevalence of different types of retinitis (fulminant/indolent) was similar in the two groups. Presence of vitreous haze ≥1+ (p = .041), presence of arteritis, (p = .016) and widespread vascular occlusion (p = .003) were more common in the non-HIV group. Conclusion: CMV retinitis can present with different features depending on the cause of immunocompromise. Evidence of intraocular inflammation such as vitritis, retinal arteritis, and vascular occlusions was more common in HIV-negative subjects.

The delivery of platforms that can provide access to good quality analytical information on the chemical/biological status of water at an acceptable cost remains a formidable challenge, despite considerable efforts from the research community over many years. The relatively high cost of autonomous analytical platforms means that measurement frequency and density is much lower than desirable, and this in turn is a significant barrier to developing a clearer understanding of environmental status, processes and dynamics, and to the effective policing of environmental regulation. However, recent advances in satellite remote sensing and drone based measurements present opportunities to capture water status data with unprecedented spatial and temporal coverage. The availability of autonomous instruments that provide continuous in-situ data provides complementary information that in a sense completes the requirements for a more complete environmental informatics coverage in that these devices can provide molecular information on related to key determinants of water chemical and biological status. In this paper, I will outline the challenges that have up to now inhibited the emergence of these low-cost, reliable, autonomous biochemical analysers, and explain how developments in rapid prototyping, microfluidics and detection schemes will provide routes to surmounting these challenges. Furthermore, I will discuss how coupling in-situ sensing with satellite remote sensing will, in many instances, reduce the density requirement on in-situ sensors for tracking and modelling water chemistry dynamics.

Through developments in 3D fabrication technologies in recent years, we can now build and characterize much more sophisticated 3D platforms than was previously possible. We can create regions of differing polarity and hydrophobicity, mix passive and binding behaviours, and regions of differing flexibility/rigidity, hardness/softness. In addition, we can integrate materials that can switch between these characteristics, enabling the creation of biomimetic microfluidic building blocks that exhibit switchable characteristics such as programmed microvehicle movement (chemotaxis), switchable binding and release, switchable soft polymer actuation (e.g. valving), and detection. These building blocks can be in turn integrated into microfluidic systems with hitherto unsurpassed functionalities that can contribute to bridging the gap between what is required for many applications, and what we can currently deliver [1]. The emerging transition from existing engineering-inspired 2D to bioinspired 3D fluidic concepts represents a major turning point in the evolution of microfluidics. Implementation of these disruptive concepts may open the way to realise biochemical sensing systems with performance characteristics far beyond those of current devices. A key development will be the integration of biomimetic functions like self-awareness/self-diagnosis of condition and self-repair capabilities to extend their useful lifetime [2]. In this contribution, I will present ideas and demonstrations of practical ways to begin building a biomimetic function toolbox that could form the basis of futuristic microfluidic systems. Examples will include chemotactic microvehicles that can collaborate to perform sophisticated functions at specific locations [3] and precision control of flow behaviour in channels using light [4]. Strategies for creating high resolution (sub-200 nm) 3D soft-polymer responsive structures will be discussed. References [1] F. Benito-Lopez, R. Byrne, A.M. Răduţă, N.E. Vrana, G. McGuinness, D. Diamond, Ionogel-based light-actuated valves for controlling liquid flow in micro-fluidic manifolds, Lab Chip. 10 (2010) 195–201. doi:10.1039/B914709H. [2] L. Florea, K. Wagner, P. Wagner, G.G. Wallace, F. Benito-Lopez, D.L. Officer, D. Diamond, Photo-Chemopropulsion - Light-Stimulated Movement of Microdroplets, Advanced Materials. 26 (2014) 7339–7345. doi:10.1002/adma.201403007. [3] W. Francis, C. Fay, L. Florea, D. Diamond, Self-propelled chemotactic ionic liquid droplets, Chem. Commun. 51 (2015) 2342–2344. doi:10.1039/C4CC09214G. [4] C. Delaney, P. McCluskey, S. Coleman, J. Whyte, N. Kent, D. Diamond, Precision control of flow rate in microfluidic channels using photoresponsive soft polymer actuators, Lab Chip. 17 (2017) 2013–2021. doi:10.1039/C7LC00368D.

Nutrients such as Phosphate, Ammonia, Nitrite and Nitrate are central in any environmental processes, including several microbial, plant and animal metabolic processes. The nutrient platform is based on a combination of microfluidic analytical systems, colorimetric reagent chemistries, low cost LED based optical detection and wireless communications. Each component was developed, assessed and optimised to evaluate the suitability before being integrated to form a working pre-competitive prototype

Through developments in 3D fabrication technologies in recent years, it is now possible to build and characterize much more sophisticated 3D platforms than was formerly the case. Regions of differing polarity, binding behaviour, flexibility/rigidity, can be incorporated into these fluidic systems. Furthermore, materials that can switch these characteristics can be incorporated, enabling the creation of microfluidic building blocks that exhibit switchable characteristics such as programmed microvehicle movement (chemotaxis), switchable binding and release, switchable soft polymer actuation (e.g. valving), and selective uptake and release of molecular targets. These building blocks can be in turn integrated into microfluidic systems with hitherto unsurpassed functionalities that can contribute to bridging the gap between what is required and what science can currently deliver for many challenging applications. The emerging transition from existing engineering-inspired 2D to bioinspired 3D fluidic concepts appears to represent a major turning point in the evolution of microfluidics. Implementation of these disruptive concepts may open the way to realising biochemical sensing systems with performance characteristics far beyond those of current devices. A key development will be the integration of biomimetic functions like self-awareness of condition and self-repair capabilities to extend their useful lifetime. In this contribution I will present ideas and demonstrations of practical ways to begin building a biomimetic function toolbox that could form the basis of these futuristic biomimetic systems.

Through developments in 3D fabrication technologies in recent years, it is now possible to build and characterize much more sophisticated 3D platforms than was formerly the case. Regions of differing polarity, binding behaviour, flexibility/rigidity, can be incorporated into these fluidic systems. Furthermore, materials that can switch these characteristics can be incorporated, enabling the creation of microfluidic building blocks that exhibit switchable characteristics such as programmed microvehicle movement (chemotaxis), switchable binding and release, switchable soft polymer actuation (e.g. valving), and selective uptake and release of molecular targets. These building blocks can be in turn integrated into microfluidic systems with hitherto unsurpassed functionalities that can contribute to bridging the gap between what is required for many applications, and what we can currently deliver. The emerging transition from existing engineering-inspired 2D to bioinspired 3D fluidic concepts represents a major turning point in the evolution of microfluidics. Implementation of these disruptive concepts may open the way to realising biochemical sensing systems with performance characteristics far beyond those of current devices. A key development will be the integration of biomimetic functions like self-awareness of condition and self-repair capabilities to extend their useful lifetime. In this contribution I will present ideas and demonstrations of practical ways to begin building a biomimetic function toolbox that could form the basis of these futuristic microfluidic systems. Examples will include chemotactic microvehicles that can collaborate to perform sophisticated functions at specific locations, and precision remote control of flow behaviour in channels using light

Since the initial breakthroughs in the 1960’s and 70’s that led to the development of the glucose biosensor, the oxygen electrode, ion-selective electrodes, and electrochemical/optochemical diagnostic devices, the vision of very reliable, affordable chemical sensors and bio-sensors capable of functioning autonomously for long periods of time (years) remains unrealized. This is despite massive investment in research and the publication of many thousands of papers in the literature. It is over 40 years since the first papers proposing the concept of the artificial pancreas, by combining glucose monitoring with an insulin pump. Yet even now, there is no chemical sensor/biosensor that can function reliably inside the body for more than a few days, and such is the gap in what can be delivered (days), and what is required (years) for implantable devices, it is not surprising that in health diagnostics, the overwhelmingly dominant paradigm for reliable measurements is still single use disposable sensors. Realising disruptive improvements in chem/bio-sensing platforms capable of long-term independent operation requires a step-back and rethinking of strategies, and considering solutions suggested by nature and materials science, rather than incremental improvements in existing approaches. Through developments in 3D fabrication technologies in recent years, we can now build and characterize much more sophisticated 3D platforms than was previously possible. We can create regions of differing polarity and hydrophobicity, mix passive and binding behaviours, and regions of differing flexibility/rigidity, hardness/softness. In addition, we can integrate materials that can switch between these characteristics, enabling the creation of biomimetic microfluidic building blocks that exhibit switchable characteristics such as programmed microvehicle movement (chemotaxis), switchable binding and release, switchable soft polymer actuation (e.g. valving), and detection. These building blocks can be in turn integrated into microfluidic systems with hitherto unsurpassed functionalities that can contribute to bridging the gap between what is required for many applications, and what we can currently deliver. The emerging transition from existing engineering-inspired 2D to bioinspired 3D fluidic concepts represents a major turning point in the evolution of microfluidics. Implementation of these disruptive concepts may open the way to realise biochemical sensing systems with performance characteristics far beyond those of current devices. A key development will be the integration of biomimetic functions like self-diagnosis of condition and self-repair capabilities to extend their useful lifetime.

Herein we demonstrate remarkable control of flow within fluidic channels using photo-actuated hydrogel valves. By polymerizing the valves in situ it has been possible to create highly- reproducible valves. Through the use of an LED platform and a PID algorithm we have generated extremely accurate flow control and created prototype devices to document their potential application within the microfluidics field.

The move towards services based on so-called ‘big data’ is already (and will increasingly) having a profound impact on almost every aspect of modern society. The environmental sector will be a major contributor to these changes, based on multi-modal information obtained from numerous sources. Critical to the creation of new services and related industries that will emerge from these trends will be access to high quality data that is essential for informed and accurate decision-making across agriculture and land use, optimised food production, management of water bodies, prediction of major climatic events (e.g. flooding, droughts) and organisation of their subsequent management. Two major sources of environmental information will be via remote sensing using satellite and flyovers (including drones), and in-situ distributed monitoring using sensor networks. In this paper, I will discuss the strengths and weaknesses of remote and in-situ sensing, and show how many of the weaknesses of each can be overcome by pooling the information from both sources, as this will enable the creation of a much more complete and robust picture of environmental status over time. Issues related to long-term in-situ chemical and biosensing will be discussed, along with the potential use of surrogate measurements (e.g. temperature) to track changes in the status of local chemistry/biology. *Corresponding Author: dermot.diamond@dcu.ie

Globally, the move towards services based on so-called ‘big data’ is, and will increasingly, profoundly affect the way in which every aspect of society functions. The the environmental sector will be a major contributor to these changes, based on multi-modal information obtained from numerous sources. Critical to the creation of new services and related industries that will emerge from these trends will be access to high quality data that is essential for informed and accurate decision-making across agriculture and land use, optimised food production, management of water bodies, prediction of climatic events (e.g. flooding, droughts) and organisation of their subsequent management. Two major sources of environmental information will be via remote sensing using satellite and flyovers (including drones), and in-situ distributed monitoring using sensor networks. In this paper, I will discuss the strengths and weaknesses of remote and in-situ sensing, and show how many of the weaknesses of each can be overcome by pooling the information from both sources, as this will enable the creation of a much more complete and robust picture of environmental status over time. Issues related to long-term in-situ chemical and biosensing will be discussed, along with the potential use of surrogate measurements to indicate the status of local chemistry/biology.

This work details the development of two distinct prototype point-of-care diagnostic systems to be used to determine the ecacy of anti-platelet ther- apies. Novel micro uidic chips were designed for each system, to enable the on-chip testing of multiple anti-platelet therapies. The prototypes work with whole blood and integrate with a new detection method used to de- termine the percentage of platelets adhered to an array of brinogen spots. The system uses customised image analysis software to objectively quantify single platelet binding events from a single blood sample, without the need to add any form of labelling to the blood. The system was validated by comparing the percentage of platelets adhered from `normal' blood samples compared to samples treated with an established platelet therapy. These treatments inhibit a specic receptor on the platelet surface, thus inter- fering with stable adhesion to brinogen, rendering platelets \less sticky". This prototype point-of-care device could allow for the automated testing of large numbers of patient samples, potentially diagnosing individuals at risk of suering a cardiovascular event or undiagnosed bleeding disorder.

ObjectiveTo use high-density genotyping to investigate the genetic associations of acute anterior uveitis (AAU) in patients with and those without ankylosing spondylitis (AS).MethodsWe genotyped samples from 1,711 patients with AAU (either primary or combined with AS), 2,339 AS patients without AAU, and 10,000 control subjects on an Illumina Immunochip Infinium microarray. We also used data for AS patients from previous genome-wide association studies to investigate the AS risk locus ANTXR2 for its putative effect in AAU. ANTXR2 expression in mouse eyes was investigated by real-time quantitative reverse transcription-polymerase chain reaction.ResultsA comparison between all patients with AAU and healthy control subjects showed strong association over HLA-B, corresponding to the HLA-B27 tag single-nucleotide polymorphism rs116488202. The association of 3 non-major histocompatibility complex loci, IL23R, the intergenic region 2p15, and ERAP1, reached genome-wide significance (P < 5 × 10(-8)). Five loci harboring the immune-related genes IL10-IL19, IL18R1-IL1R1, IL6R, the chromosome 1q32 locus harboring KIF21B, as well as the eye-related gene EYS, were also associated, reaching a suggestive level of significance (P < 5 × 10(-6)). Several previously confirmed AS associations demonstrated significant differences in effect size between AS patients with AAU and AS patients without AAU. ANTXR2 expression varied across eye compartments.ConclusionThese findings of both novel AAU-specific associations and associations shared with AS demonstrate overlapping but also distinct genetic susceptibility loci for AAU and AS. The associations in IL10 and IL18R1 are shared with inflammatory bowel disease, suggesting common etiologic pathways.

BackgroundInvasive fungal sinusitis is a rare condition that usually occurs in immunocompromised patients and often presents as an orbital apex syndrome. It is frequently misdiagnosed on presentation and is almost always lethal without early treatment.

Lumican is keratan sulfate proteoglycan of the small leucine rich proteoglycan family. Through studies in animal models lumican has been found to be critical in maintaining corneal clarity. It maintains ordered collagen fibrils which are vital in keeping the cornea transparent. It may also be important in primary open angle glaucoma influencing aqueous outflow. Lumican deficiency in mice results in increased axial length with fibromodulin deficiency and thinner sclerae. There is evidence suggesting that this characteristic may be pertinent in humans and lumican gene polymorphisms could be related to high myopia. Lumican plays a fundamental role in inflammation and wound healing. It localises macrophages to the site of corneal injury and recruits neutrophils in lipopolysaccharide-induced keratitis in mice. It has also been shown to bind lipopolysaccharide which may be critical in inflammatory diseases such as uveitis. Lumican is also important in wound healing revealing decreased synthesis in scar tissue and mediating Fas-Fas ligand interactions. It is present in human placenta and amniotic membrane suggesting that it may ensure viable amniotic membrane grafts. Lumican may also be involved in the formation of posterior capsular opacification following cataract surgery. Research into the pivotal role of lumican in the pathogenesis of ocular disease has resulted in greater understanding of the key role which proteoglycans play in human disease.

Background: It is critical to consult patients to develop patient-centred cataract surgery care. We aimed to identify attributes patients consider when making decisions about cataract surgery in an Australian context, where both publicly and privately funded surgery are available. This is the first step in investigating how decisions are made about cataract surgery services.Methods: This observational qualitative study was undertaken in two public hospitals and one private practice in Sydney, Australia. The study involved 19 women and men with age-related cataracts and no previous cataract surgery, aged > 18 years, able to speak conversational English or Mandarin. A multi-stage attribute development process was followed, including: literature review, semi-structured interviews with surgery candidates in three eye clinics, and review by an expert panel. The main outcome measures were primary attributes for making choices about cataract surgery.Results: Wait time, cost, institutional reputation, surgeon experience and travel time were identified as principal attributes; lower value was placed on consultation length and accessibility. Non-English speaking participants indicated greater interest in pre-operative information than English speakers, but expressed trust in the Australian healthcare system.Conclusions: Findings suggest individuals prioritise attributes which consume time or incur costs when accessing care (wait time, cost and travel time). They also consider factors associated with the outcome of their cataract surgery (surgeon experience and institutional reputation). Similar to other decision-making processes, patients are likely to trade between these different attributes depending on their personal preferences and circumstances. Refereed/Peer-reviewed