Gene and cell therapy for age-related macular degeneration: A review.

Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss among the elderly in Western communities, with an estimated global prevalence of 10 - 20% in people older than 65 years. AMD leads to central vision loss due to degeneration of the photoreceptors, retinal pigment epithelium and the choriocapillaris. Beckman's classification for AMD, based upon color fundus photographs, divides the disease into early, intermediate, and late forms. The late, vision-threatening stage includes both neovascular AMD and geographic atrophy. Despite its high prevalence and impact on patients' quality of life, treatment options for AMD are limited. While neovascular AMD can be medically managed with anti-VEGF intravitreal injections, until very recently there has been no approved treatment options for atrophic AMD; however, in February 2023 the first treatment for geographic atrophy - pegcetacoplan - was approved by the US FDA. We describe the current landscape of potential gene and cell therapeutic strategies for late-stage AMD, with an emphasis on the therapeutic options that might become available in the next few years.

Development of a Smartphone-Based System for Intrinsically Photosensitive Retinal Ganglion Cells Targeted Chromatic Pupillometry.

Chromatic Pupillometry, used to assess Pupil Light Reflex (PLR) to a coloured light stimulus, has regained interest since the discovery of melanopsin in the intrinsically photosensitive Retinal Ganglion Cells (ipRGCs). This technique has shown the potential to be used as a screening tool for neuro-ophthalmological diseases; however, most of the pupillometers available are expensive and not portable, making it harder for them to be used as a widespread screening tool. In this study, we developed a smartphone-based system for chromatic pupillometry that allows targeted stimulation of the ipRGCs. Using a smartphone, this system is portable and accessible and takes advantage of the location of the ipRGCs in the perifovea. The system incorporates a 3D-printed support for the smartphone and an illumination system. Preliminary tests were carried out on a single individual and then validated on eleven healthy individuals with two different LED intensities. The average Post-Illumination Pupil Light Response 6 s after the stimuli offsets (PIPR-6s) showed a difference between the blue and the red stimuli of 9.5% for both intensities, which aligns with the studies using full-field stimulators. The results validated this system for a targeted stimulation of the ipRGCs for chromatic pupillometry, with the potential to be a portable and accessible screening tool for neuro-ophthalmological diseases.

Drosophila nasuta (Diptera, Drosophilidae) in Brazil: a decade of invasion and occupation of more than half of the country.

As a result of human activities and natural dispersal, exotic species can be brought to new areas, where they become established and spread, becoming invaders. These species are responsible for the loss of biodiversity and cause ecosystemic harm throughout the world. In this paper, we report the rapid, broad geographic expansion of the invasive fly Drosophila nasuta in Brazil. An 84% increase was found in its area of occupation in the country compared to previous studies. The present data reveal its arrival to the Pantanal wetlands in a location more than one thousand kilometers from the closest previous record in the Cerrado biome. We present the first record of D. nasuta in the Atlantic Forest in the states of Paraíba and Bahia. We report its introduction in the Amazon Forest in the state of Amazonas approximately 700 kilometers from previous records. The relative abundance of D. nasuta in this biome increased fivefold in comparison to a previous study. In the first decade of invasion in Brazil, D. nasuta has already colonized more than half of the country. The present data reveal its invasive potential and underscore the importance of following up the possible negative effects of this biological invasion.

Genetic Modulation of the Erythrocyte Phenotype Associated with Retinopathy of Prematurity-A Multicenter Portuguese Cohort Study.

The development of retinopathy of prematurity (ROP) may be influenced by anemia or a low fetal/adult hemoglobin ratio. We aimed to analyze the association between DNA methyltransferase 3 ß (DNMT3B) (rs2424913), methylenetetrahydrofolate reductase (MTHFR) (rs1801133), and lysine-specific histone demethylase 1A (KDM1A) (rs7548692) polymorphisms, erythrocyte parameters during the first week of life, and ROP. In total, 396 infants (gestational age < 32 weeks or birth weight < 1500 g) were evaluated clinically and hematologically. Genotyping was performed using a MicroChip DNA on a platform employing iPlex MassARRAY®. Multivariate regression was performed after determining risk factors for ROP using univariate regression. In the group of infants who developed ROP red blood cell distribution width (RDW), erythroblasts, and mean corpuscular volume (MCV) were higher, while mean hemoglobin and mean corpuscular hemoglobin concentration (MCHC) were lower; higher RDW was associated with KDM1A (AA), MTHFR (CC and CC + TT), KDM1A (AA) + MTHFR (CC), and KDM1A (AA) + DNMT3B (allele C); KDM1A (AA) + MTHFR (CC) were associated with higher RDW, erythroblasts, MCV, and mean corpuscular hemoglobin (MCH); higher MCV and MCH were also associated with KDM1A (AA) + MTHFR (CC) + DNMT3B (allele C). We concluded that the polymorphisms studied may influence susceptibility to ROP by modulating erythropoiesis and gene expression of the fetal/adult hemoglobin ratio.

Asymptomatic chronic red eye: A surgical technique case report.

Introduction and importance: Ocular Surface Squamous-cell Neoplasia (OSSN) is an infrequent diagnosis whose clinical suspicion assumes great importance and should not be overlooked. The following case-report aims to describe the diagnosis and treatment of a patient with OSSN whose complaints were mild in comparison to the severity of the disease. The chosen surgical technique was paramount for a disease-free outcome while minimizing the scarring effects of surgical removal. CASE PRESENTATION: Patient presented mild discomfort right eye and painless persistent hyperaemia. Slit-lamp observation showed a clear diagnosis and lesion's extent evaluated through multimodal imaging. After surgical excision the patient underwent topical ocular treatment with mitomycin-C for a higher margin of safety even before the pathology results were available. DISCUSSION: Ancillary exam technology improvement has allowed a higher margin of safety while determining the extent of OSSN lesions. In the absence of clear diagnostic criteria and guidelines, clinical reasoning and OSSN awareness are critical for timely diagnosis and treatment, as several treatment options are available, allowing an increasing number of patients to be treated non-invasively. In this case-report, we highlight the importance of early-recognition and the reasoning for choosing a combined treatment option with a higher margin of safety. CONCLUSION: Early recognition and prompt treatment of OSSN lesions is of paramount importance to avoid ocular invasiveness and potentially preclude both ocular and systemic complication. The choice of a combined surgical and medical approach may provide a higher margin of safety for suitable cases. This patient is currently disease-free at 6-month follow-up.

Complete blood count parameters as biomarkers of retinopathy of prematurity: a Portuguese multicenter study.

PURPOSE: To evaluate complete blood count (CBC) parameters in the first week of life as predictive biomarkers for the development of retinopathy of prematurity (ROP). METHODS: Multicenter, prospective, observational study of a cohort of preterm infants born with gestational age (GA) < 32 weeks or birth weight < 1500 g in eight Portuguese neonatal intensive care units. All demographic, clinical, and laboratory data from the first week of life were collected. Univariate logistic regression was used to assess risk factors for ROP and then multivariate regression was performed. RESULTS: A total of 455 infants were included in the study. The median GA was 29.6 weeks, and the median birth weight was 1295 g. One hundred and seventy-two infants (37.8%) developed ROP. Median values of erythrocytes (p < 0.001), hemoglobin (p < 0.001), hematocrit (p < 0.001), mean corpuscular hemoglobin concentration (p < 0.001), lymphocytes (p = 0.035), and platelets (p = 0.003) of the group of infants diagnosed with ROP any stage were lower than those without ROP. Mean corpuscular volume (MCV) (p = 0.044), red blood cell distribution width (RDW) (p < 0.001), erythroblasts (p < 0.001), neutrophils (p = 0.030), neutrophils-lymphocytes ratio (p = 0.028), and basophils (p = 0.003) were higher in the ROP group. Higher values of MCV, erythroblasts, and basophils remained significantly associated with ROP after multivariate regression. CONCLUSION: In our cohort, the increase in erythroblasts, MCV, and basophils in the first week of life was significantly and independently associated with the development of ROP. These CBC parameters may be early predictive biomarkers for ROP.

Retinopathy of prematurity: A review of pathophysiology and signaling pathways.

Retinopathy of prematurity (ROP) is a vasoproliferative disorder of the retina and a leading cause of visual impairment and childhood blindness worldwide. The disease is characterized by an early stage of retinal microvascular degeneration, followed by neovascularization that can lead to subsequent retinal detachment and permanent visual loss. Several factors play a key role during the different pathological stages of the disease. Oxidative and nitrosative stress and inflammatory processes are important contributors to the early stage of ROP. Nitric oxide synthase and arginase play important roles in ischemia/reperfusion-induced neurovascular degeneration. Destructive neovascularization is driven by mediators of the hypoxia-inducible factor pathway, such as vascular endothelial growth factor and metabolic factors (succinate). The extracellular matrix is involved in hypoxia-induced retinal neovascularization. Vasorepulsive molecules (semaphorin 3A) intervene preventing the revascularization of the avascular zone. This review focuses on current concepts about signaling pathways and their mediators, involved in the pathogenesis of ROP, highlighting new potentially preventive and therapeutic modalities. A better understanding of the intricate molecular mechanisms underlying the pathogenesis of ROP should allow the development of more effective and targeted therapeutic agents to reduce aberrant vasoproliferation and facilitate physiological retinal vascular development.

Pandemic origins and a One Health approach to preparedness and prevention: Solutions based on SARS-CoV-2 and other RNA viruses.

COVID-19 is the latest zoonotic RNA virus epidemic of concern. Learning how it began and spread will help to determine how to reduce the risk of future events. We review major RNA virus outbreaks since 1967 to identify common features and opportunities to prevent emergence, including ancestral viral origins in birds, bats, and other mammals; animal reservoirs and intermediate hosts; and pathways for zoonotic spillover and community spread, leading to local, regional, or international outbreaks. The increasing scientific evidence concerning the origins of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is most consistent with a zoonotic origin and a spillover pathway from wildlife to people via wildlife farming and the wildlife trade. We apply what we know about these outbreaks to identify relevant, feasible, and implementable interventions. We identify three primary targets for pandemic prevention and preparedness: first, smart surveillance coupled with epidemiological risk assessment across wildlife-livestock-human (One Health) spillover interfaces; second, research to enhance pandemic preparedness and expedite development of vaccines and therapeutics; and third, strategies to reduce underlying drivers of spillover risk and spread and reduce the influence of misinformation. For all three, continued efforts to improve and integrate biosafety and biosecurity with the implementation of a One Health approach are essential. We discuss new models to address the challenges of creating an inclusive and effective governance structure, with the necessary stable funding for cross-disciplinary collaborative research. Finally, we offer recommendations for feasible actions to close the knowledge gaps across the One Health continuum and improve preparedness and response in the future.

Long-Term Effect of Anti-Vascular Endothelial Growth Factor (Anti-VEGF) Injections in Choroidal Neovascularization Secondary to Angioid Streaks.

Purpose: This study aimed to evaluate the long-term effectiveness of intravitreal anti-vascular endothelial growth factor (VEGF) injections in the treatment of choroidal neovascularization (CNV) associated with angioid streaks. Methods: Multicenter retrospective cohort study, including eyes with CNV secondary to angioid streaks treated with anti-VEGF injections, were performed. Best-corrected visual acuity (BCVA) in ETDRS letters; qualitative and quantitative (foveal thickness) OCT parameters; anti-VEGF type; and number of injections were collected at baseline and at 3, 6, 12, 24, 36, 48, 60, and 72 months. Results: Thirty-nine eyes from 29 patients, 17 (58.6%) females, were included. The mean follow-up time was 69.4 ± 34.5 months. BCVA was 59.3 ± 23.3 letters at baseline and 63.7 ± 21.9 letters at 48 months. At 3 months, BCVA improved 6.9 ± 11.7 letters (P=0.003). Then, BCVA remained stable. The mean foveal thickness decreased from 343.3 ± 120.2 µm at baseline to 268.3 ± 65.4 at 48 months (P=0.021). The mean number of injections was 4.6 ± 2.1 at 12 months, decreasing to 1.7 ± 2.4 injections between 36 and 48 months (P=0.093). Conclusion: This real-world study suggests that the functional and morphologic response to anti-VEGF therapy for CNV related to angioid streaks is generally satisfactory and maintained in the long term.

Retinopathy of prematurity: contribution of inflammatory and genetic factors.

Retinopathy of prematurity (ROP) is a retinal vasoproliferative disorder that represents an important cause of childhood visual impairment and blindness. Although oxidative stress has long been implicated in ROP etiology, other prenatal and perinatal factors are also involved. This review focuses on current research involving inflammation and genetic factors in the pathogenesis of ROP. Increasing evidence suggests that perinatal inflammation or infection contributes to ROP pathogenesis. Cytokines and chemokines with a fundamental role in inflammatory responses and that significantly contributing to angiogenesis are analyzed. Microglia cells, the retinal-resident macrophages, are crucial for retinal homeostasis, however, under sustained pathological stimuli release exaggerated amounts of inflammatory mediators and can promote pathological neovascularization. Current modulation of angiogenic cytokines, such as treatment with antibodies to vascular endothelial growth factor (anti-VEGF), has shown efficacy in the treatment of ocular neovascularization; however, some patients are refractory to anti-VEGF agents, suggesting that other angiogenic or anti-angiogenic cytokines need to be identified. Much evidence suggests that genetic factors contribute to the phenotypic variability of ROP. Several studies have implicated the involvement of candidate genes from different signaling pathways in the development of ROP. However, a genetic component with a major impact on ROP has not yet been discovered. Most studies have limitations and did not replicate results. Future research involving bioinformatics, genomics, and proteomics may contribute to finding more genes associated with ROP and may allow discovering better solutions in the management and treatment of ROP.

A Delphi study on the clinical management of age-related macular degeneration.

PURPOSE: Age-related macular degeneration (AMD) is one of the main causes of blindness and visual impairment worldwide. As achieving a dry macula is one of the main objectives in AMD management, the purpose of this work was to reach a consensus on the relevance of retinal fluid in function, disease activity control and treatment patterns. METHODS: Forty-seven Portuguese ophthalmologists specialized in AMD participated in a DELPHI panel. Two rounds of presential meetings were conducted and a cut-off of 80% or more of votes was defined to consider answers consensual. RESULTS: Consensus was reached for 11 out of 18 questions. These questions focused on the impact of anatomical results on visual acuity, standards exams and parameters to assess disease activity, frequency and factors which influence disease activity assessment, criteria to use non-fixed treatment regimens, usefulness of individualized regimens and conditions for treatment interruption. No consensus was obtained for relevance of the different fluid types in AMD prognosis, frequency of fluid presence assessment, factors commonly associated with progression to geographic atrophy, ideal conditions for a fixed treatment regimen, date of first disease activity assessment and parameters to monitor disease activity. CONCLUSIONS: Consensus was achieved for over half of the questions assessed through this Delphi study. The questions for which no consensus was reached concerned either subjects that need further investigation or monitoring times which are influenced by resource availability. Raising awareness for these issues will allow the improvement of AMD management and treatment.

Trabeculectomy with mitomycin C alone or coupled with intracamerular bevacizumab? A 2-year comparative study.

PURPOSE: To compare outcomes of primary trabeculectomy using either mitomycin C (MMC) alone versus MMC augmented with intracamerular bevacizumab in patients with open-angle glaucoma. METHODS: Retrospective, cohort, two-centre, comparative study. Patients' data were screened between October 2015 and March 2019, with inclusion requiring a minimum follow-up of 24 months. Primary outcome was intraocular pressure (IOP) lowering at 24 months, with surgical success defined with different maximum IOP targets (≤18, ≤16 and ≤14 mm Hg) and at least 30% reduction and higher than 5 mm Hg. Absolute success was achieved if no IOP-lowering medication was needed and a qualified success if otherwise. Safety outcomes were analysed. RESULTS: A total of 110 eyes underwent trabeculectomy with MMC, 51 of these combined with intracamerular bevacizumab. Both strategies were effective in terms of IOP lowering (baseline vs 2 years postoperatively: 24.4 (8.0) mm Hg vs 12.1 (5.3) mm Hg in the MMC group; 25.1 (8.7) vs 10.8 (3.8) mm Hg in the MMC+bevacizumab group; p<0.001 in both comparisons). The MMC+bevacizumab group had a significant difference towards higher efficacy on absolute success rates at all targets (IOP≤14 or ≤16 or ≤18 mm Hg; p=0.010, p=0.039 and p=0.007, respectively). The large majority (93%) of the MMC+bevacizumab group was drop-free at 24 months, and 41% had IOP below 10 mm Hg. Complication rates were low and similar between groups, with no systemic adverse events. CONCLUSIONS: Intracamerular bevacizumab in MMC-augmented primary trabeculectomy increases the chances of obtaining low IOP outcomes. This strategy may be useful when planning for surgeries aiming at target pressures in the low teens. TRIAL REGISTRATION NUMBER: ISRCTN93098069.

Firmicutes Dysbiosis After Chlorhexidine Prophylaxis in Healthy Patients Submitted to Impacted Lower Third Molar Extraction.

Prophylaxis with antiseptic and antibiotic therapy is common in impacted lower third molar surgeries, despite the lack of consensus among professionals and researchers in the indication for healthy patients. The aim of the present preliminary study was to verify the impact of prophylaxis therapy with antiseptic and antibiotic in healthy patients submitted to impacted lower third molar extraction, according to oral microorganism quantification. Eleven patients submitted to impacted lower third molar extraction, under prophylactic therapy with 0.12% chlorhexidine and amoxicillin in four experimental phases, were evaluated. Our results showed no significant reduction in total bacteria load, as well as in Bacteroidetes and C. albicans loads in the oral cavity, after prophylactic therapy with antiseptic and antibiotic. On the other hand, there was a significant difference between the Firmicutes levels across the follow-up, and this effect seems to be large (ηp²=0.94). Post-hoc test demonstrated that the levels of Firmicutes in T1 were higher than T0, T2, and T3, suggesting a microbiota dysbiosis, when 0.12% chlorhexidine use, which may be responsible for selection of antibiotic-resistant microorganisms. Our results alert for an overuse of antiseptic and antibiotics by dentists and for a better evaluation of the available protocols.

Digital Rehabilitation for Acute Ankle Sprains: Prospective Longitudinal Cohort Study.

BACKGROUND: Ankle sprains are one of the most prevalent soft-tissue injuries worldwide. Physical therapy, especially progressive exercise, has proven effective in improving function, while preventing recurrence. OBJECTIVE: We aim to present the results of a fully remote and digitally guided rehabilitation program for acute ankle sprains. METHODS: We performed a prospective longitudinal cohort study of individuals eligible for workers' compensation, who were referred for digital rehabilitation therapy for a sprained ankle. Therapeutic exercise sessions were to be performed independently by the patient at home using the biofeedback device provided by SWORD Health. Primary endpoints were the change in self-reported Numerical Pain Rating Scale (NPRS) and Foot and Ankle Ability Measure-activities of daily living (FAAM-ADL) and FAAM-Sports scores. Participants were assessed at baseline, end of the program, and 6 months after program completion. Secondary outcomes included digital therapy dosage, pain and fatigue during sessions, and satisfaction. RESULTS: In total, 93 (89.4%) patients completed the program and 79 (76.0%) were available for follow-up. Changes in the primary outcomes between baseline and the 6-month follow-up were both significant (P<.001) and clinically meaningful: mean difference of -2.72 points (95% CI -3.31 to -2.13) on the NPRS (49.8% reduction), 21.7 points (95% CI 17.13-26.27) on the FAAM-ADL (41.1% increase), and 37.8 points (95% CI 30.45-45.15) on the FAAM-Sports (151.8% increase). Longer waiting periods between the accident date and treatment initiation were found to negatively impact functional status at baseline and at the end of the program, triggering an extension in the program duration. The total training volume (12.5 hours, SD 10.5 hours) was similar to that of other interventions for ankle sprains, but the dosage per week was much higher (2.4 hours per week, SD 0.87 hours per week). The mean patient satisfaction score was 8.8 (SD 1.57) out of 10. Among program completers, 83.9% attained full recovery and were discharged with no residual disability. CONCLUSIONS: Being far less demanding in terms of human resources, the digital program presented constituted a viable, clinically effective, and convenient solution for ankle sprain rehabilitation, particularly during the pandemic. This is the first study presenting a fully remote home-based rehabilitation program for acute ankle sprains, with patients achieving sustained long-term results. This was a prospective cohort study and, as such, did not include a control group, but the results appear comparable to those published for face-to-face interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT04819022; https://clinicaltrials.gov/ct2/show/NCT04819022.

Guidelines for the Management of Center-Involving Diabetic Macular Edema: Treatment Options and Patient Monitorization.

Diabetic macular edema (DME) is the main cause of visual impairment associated with diabetic retinopathy (DR) and macular laser, during approximately three decades, and was the single treatment option. More recently, intravitreous injections of anti-angiogenics and corticosteroids modified the treatment paradigm associated with significant vision improvements. Nevertheless, not all patients respond satisfactorily to anti-VEGF or corticosteroid injections, so an adequate treatment choice and a prompt switch in therapeutic class is recommended. Several algorithms and guidelines have been proposed for treating center involving DME to improve patients' vision and quality of life. However, in Portugal, such guidelines are lacking. The present review aimed to provide guidelines for the treatment options and patient monitorization in the management of center-involving DME. We recommend anti-vascular endothelial growth factor (VEGF) as first-line therapy after a clinical evaluation accompanied by a rigorous metabolic control. Depending on the response obtained after 3-6 monthly intravitreal injections we suggest switching outside the class in case of a non-responder, maintaining the anti-VEGF-therapy in responders to anti-angiogenics. The treatment regimen for Dexamethasone intravitreal implant (DEXii) should be pro-re-nata with bi-monthly or quarterly monitoring visits (with a scheduled visit at 6-8 weeks after DEXii for intraocular pressure control). If a patient does not respond to DEXii, switch again to anti-VEGF therapy, combine therapies, or re-evaluate patients diagnose. There is a resilient need to understand the disease, its treatments, regimens available, and convenience for all involved to propose an adequate algorithm for the treatment of diabetic retinopathy (DR) and DME in an individualized regimen. Further understanding of the contributing factors to the development and progression of DR should bring new drug discoveries for more effective and better-tolerated treatments.

Plasmid-associated antimicrobial resistance and virulence genes in Escherichia coli in a high arctic reindeer subspecies.

OBJECTIVES: In extreme environments, such as the Arctic region, the anthropogenic influence is low and the presence of antimicrobial-resistant bacteria is unexpected. In this study, we screened wild reindeer (Rangifer tarandus platyrhynchus) from the Svalbard High Arctic Archipelago for antimicrobial-resistant Escherichia coli and performed in-depth strain characterisation. METHODS: Using selective culturing of faecal samples from 55 animals, resistant E. coli were isolated and subjected to minimum inhibitory concentration (MIC) determination, conjugation experiments and whole-genome sequencing. RESULTS: Twelve animals carried antimicrobial-resistant E. coli. Genomic analysis showed IncF plasmids as vectors both for resistance and virulence genes in most strains. Plasmid-associated genes encoding resistance to ampicillin, sulfonamides, streptomycin and trimethoprim were found in addition to virulence genes typical for colicin V (ColV)-producing plasmids. Comparison with previously reported IncF ColV plasmids from human and animal hosts showed high genetic similarity. The plasmids were detected in E. coli sequence types (STs) previously described as hosts for such plasmids, such as ST58, ST88 and ST131. CONCLUSION: Antimicrobial-resistant E. coli were detected from Svalbard reindeer. Our findings show that successful hybrid antimicrobial resistance-ColV plasmids and their host strains are widely distributed also occurring in extreme environmental niches such as arctic ecosystems. Possible introduction routes of resistant bacterial strains and plasmids into Svalbard ecosystems may be through migrating birds, marine fish or mammals, arctic fox (Vulpes lagopus) or via human anthropogenic activities such as tourism.

First detection of highly pathogenic avian influenza virus in Norway.

BACKGROUND: Several outbreaks of highly pathogenic avian influenza (HPAI) caused by influenza A virus of subtype H5N8 have been reported in wild birds and poultry in Europe during autumn 2020. Norway is one of the few countries in Europe that had not previously detected HPAI virus, despite widespread active monitoring of both domestic and wild birds since 2005. RESULTS: We report detection of HPAI virus subtype H5N8 in a wild pink-footed goose (Anser brachyrhynchus), and several other geese, ducks and a gull, from south-western Norway in November and December 2020. Despite previous reports of low pathogenic avian influenza (LPAI), this constitutes the first detections of HPAI in Norway. CONCLUSIONS: The mode of introduction is unclear, but a northward migration of infected geese or gulls from Denmark or the Netherlands during the autumn of 2020 is currently our main hypothesis for the introduction of HPAI to Norway. The presence of HPAI in wild birds constitutes a new, and ongoing, threat to the Norwegian poultry industry, and compliance with the improved biosecurity measures on poultry farms should therefore be ensured. [MK1]Finally, although HPAI of subtype H5N8 has been reported to have very low zoonotic potential, this is a reminder that HPAI with greater zoonotic potential in wild birds may pose a threat in the future. [MK1]Updated with a sentence emphasizing the risk HPAI pose to poultry farms, both in the Abstract and in the Conclusion-section in main text, as suggested by Reviewer 1 (#7).

A Non-Infectious Uveitis Multidisciplinary Clinic in a Tertiary Referral Center: Clinical Impact and Added Value.

Non-infectious uveitis (NIU) is a group of sight-threatening diseases that generates significant burden for the healthcare systems due to its adverse outcomes, irreversible structural complications in the eye with loss of visual function, limited clinical expertise and low-grade evidence for best practice. The usefulness of multidisciplinary care, specifically close collaboration between Rheumatologists and Ophthalmologists in NIU, has been emphasized in the literature. In this paper, the assessment tools and protocols used in our clinic are depicted and an overview of our activity with a brief description of the patients included in our registry, between 2018 and 2020 is provided. The cohort of 290 patients assessed in our NIU clinic, their demographics, sources of referral, details about immunosuppression treatment, and internal and external collaborations is described. This experience-based manuscript aims to describe the general functioning of our multidisciplinary NIU clinic, highlighting the benefits and drawbacks of multidisciplinary team management in patients with NIU, ultimately initiating a dialogue on what an NIU clinic should be and providing information for newly NIU clinics start-up. In conclusion, establishing a standardized and multidisciplinary clinic in NIU allows to systematically observe and follow-up this infrequent disease at a tertiary hospital level, thus improving quality of care delivery and research avenues.