Gene network-based and ensemble modeling-based selection of tumor-associated antigens with a predicted low risk of tissue damage for targeted immunotherapy.

BACKGROUND: Tumor-associated antigens and their derived peptides constitute an opportunity to design off-the-shelf mainline or adjuvant anti-cancer immunotherapies for a broad array of patients. A performant and rational antigen selection pipeline would lay the foundation for immunotherapy trials with the potential to enhance treatment, tremendously benefiting patients suffering from rare, understudied cancers. METHODS: We present an experimentally validated, data-driven computational pipeline that selects and ranks antigens in a multipronged approach. In addition to minimizing the risk of immune-related adverse events by selecting antigens based on their expression profile in tumor biopsies and healthy tissues, we incorporated a network analysis-derived antigen indispensability index based on computational modeling results, and candidate immunogenicity predictions from a machine learning ensemble model relying on peptide physicochemical characteristics. RESULTS: In a model study of uveal melanoma, Human Leukocyte Antigen (HLA) docking simulations and experimental quantification of the peptide-major histocompatibility complex binding affinities confirmed that our approach discriminates between high-binding and low-binding affinity peptides with a performance similar to that of established methodologies. Blinded validation experiments with autologous T-cells yielded peptide stimulation-induced interferon-γ secretion and cytotoxic activity despite high interdonor variability. Dissecting the score contribution of the tested antigens revealed that peptides with the potential to induce cytotoxicity but unsuitable due to potential tissue damage or instability of expression were properly discarded by the computational pipeline. CONCLUSIONS: In this study, we demonstrate the feasibility of the de novo computational selection of antigens with the capacity to induce an anti-tumor immune response and a predicted low risk of tissue damage. On translation to the clinic, our pipeline supports fast turn-around validation, for example, for adoptive T-cell transfer preparations, in both generalized and personalized antigen-directed immunotherapy settings.

Glaucoma detection using non-perfused areas in OCTA.

Multiple ophthalmic diseases lead to decreased capillary perfusion that can be visualized using optical coherence tomography angiography images. To quantify the decrease in perfusion, past studies have often used the vessel density, which is the percentage of vessel pixels in the image. However, this method is often not sensitive enough to detect subtle changes in early pathology. More recent methods are based on quantifying non-perfused or intercapillary areas between the vessels. These methods rely upon the accuracy of vessel segmentation, which is a challenging task and therefore a limiting factor for reliability. Intercapillary areas computed from perfusion-distance measures are less sensitive to errors in the vessel segmentation since the distance to the next vessel is only slightly changing if gaps are present in the segmentation. We present a novel method for distinguishing between glaucoma patients and healthy controls based on features computed from the probability density function of these perfusion-distance areas. The proposed approach is evaluated on different capillary plexuses and outperforms previously proposed methods that use handcrafted features for classification. Moreover the results of the proposed method are in the same range as the ones of convolutional neural networks trained on the raw input images and is therefore a computationally efficient, simple to implement and explainable alternative to deep learning-based approaches.

Bilateral Acute Macular Neuroretinopathy (AMN) after COVID-19 and its Clinical Course. / Bilaterale akute makuläre Neuroretinopathie (AMN) nach COVID-19 und Verlauf.

Acute macular neuroretinopathy (AMN) is a rare disease entity. It is mainly observed in young women with a history of influenza-like infection or who have been taking oral contraceptives for several years. Patients typically describe subjective visual deterioration and mono- or bilateral paracentral relative scotomas. In some cases, funduscopic ophthalmic examination may reveal subtle sharply demarcated flat lesions of reddish-brown or orange colour in the macular region. Diagnosis is usually made by near-infrared fundus imaging which shows hyporeflective areas, and SD-OCT imaging which manifests changes in the outer retinal layers. In the following, three patient cases with bilateral AMN are described which occurred in direct temporal relationship to a recent SARS-CoV-2 infection.

"Multisystem Inflammatory Syndrome in Children"-Like Disease after COVID-19 Vaccination (MIS-V) with Potential Significance of Functional Active Autoantibodies Targeting G-Protein-Coupled Receptors (GPCR-fAAb) for Pathophysiology and Therapy.

BACKGROUND: An infection with SARS-CoV-2 can trigger a systemic disorder by pathological autoimmune processes. A certain type of this dysregulation is known as Multisystemic inflammatory syndrome in children (MIS-C). However, similar symptoms may occur and have been described as Multisystemic inflammatory syndrome after SARS-CoV-2 Vaccination (MIS-V) following vaccination against SARS-CoV-2. We report the case of a 12-year-old boy who was identified with MIS-C symptoms without previous SARS-CoV-2 infection after receiving two doses of the Pfizer-BioNTech COVID-19 vaccine approximately one month prior to the onset of symptoms. He showed polyserositis, severe gastrointestinal symptoms and, consequently, a manifestation of a multiorgan failure. IgG antibodies against spike proteins of SARS-CoV-2 were detected, indicating a successful vaccination, while SARS-CoV-2 Nucleocapsid protein antibodies and SARS-CoV-2 PCR were not detected. Several functional, active autoantibodies against G-protein-coupled receptors (GPCR-fAAb), previously associated with Long COVID disease, were detected in a cardiomyocyte bioassay. Immunosuppression with steroids was initiated. Due to side effects, treatment with steroids and later interleukin 1 receptor antagonists had to be terminated. Instead, immunoadsorption was performed and continued with tacrolimus and mycophenolic acid therapy, leading to improvement and discharge after 79 days. GPCR-fAAb decreased during therapy and remained negative after clinical curing and under continued immunosuppressive therapy with tacrolimus and mycophenolic acid. Follow-up of the patient showed him in good condition after one year. CONCLUSIONS: Infection with SARS-CoV-2 shows a broad and severe variety of symptoms, partly due to autoimmune dysregulation, which, in some instances, can lead to multiorgan failure. Despite its rarity, post-vaccine MIS-C-like disease may develop into a serious condition triggered by autoimmune dysregulation. The evidence of circulating GPCR-fAAb and their disappearance after therapy suggests a link of GPCR-fAAb to the clinical manifestations. Thus, we hypothesize a potential role of GPCR-fAAb in pathophysiology and their potential importance for the therapy of MIS-C or MIS-V. However, this observation needs further investigation to prove a causative correlation.

Correlation of retinal vascular characteristics with laboratory and ocular findings in Fabry disease: exploring ocular diagnostic biomarkers.

BACKGROUND: The goal of this study was to evaluate macular microvascular changes in patients with Fabry disease (FD) using optical coherence tomography angiography (OCTA) and to explore their correlation with laboratory and ocular findings. METHODS: A total of 76 eyes (38 patients) and 48 eyes of 24 healthy controls were enrolled in this prospective study. Vessel Area Density (VAD) and Foveal Avascular Zone (FAZ) area were calculated on 2.9 × 2.9 mm OCTA images scanned with the Heidelberg Spectralis II (Heidelberg, Germany). VAD was measured in three layers: Superficial Vascular Plexus (SVP), Intermediate Capillary Plexus (ICP), and Deep Capillary Plexus (DCP). All scans were analyzed with the EA-Tool (Version 1.0), which was coded in MATLAB (The MathWorks Inc, R2017b). FAZ area was manually measured in full-thickness, SVP, ICP and DCP scans. RESULTS: Average VAD in SVP, ICP and DCP was higher in Fabry disease patients than in controls (49.4 ± 11.0 vs. 26.5 ± 6.2, 29.6 ± 7.4 vs. 20.2 ± 4.4, 32.3 ± 8.8 vs. 21.7 ± 5.1 respectively, p < 0.001). Patients with cornea verticillata (CV) had a higher VAD in ICP and DCP compared to patients without CV (p < 0.01). Patients with increased lysoGb3 concentration had a higher VAD in DCP when compared to patients with normal lysoGb3 concentration (p < 0.04). There was no difference in VAD in patients with and without vascular tortuosity. However, a significantly higher VAD was observed in patients with vascular tortuosity compared to controls (p < 0.03). CONCLUSIONS: Increased lysoGb3 and VAD in DCP could be reliable biomarkers of disease activity. Cornea verticillata could be adopted as a predictive biomarker for VAD changes and disease progression. The combination of cornea verticillata and increased VAD may serve as a diagnostic biomarker for Fabry disease, however due to the discrepancies in VAD values in various studies, further research has to be done to address this claim.

Understanding, diagnosing, and treating Myalgic encephalomyelitis/chronic fatigue syndrome - State of the art: Report of the 2nd international meeting at the Charité Fatigue Center.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a devastating disease affecting millions of people worldwide. Due to the 2019 pandemic of coronavirus disease (COVID-19), we are facing a significant increase of ME/CFS prevalence. On May 11th to 12th, 2023, the second international ME/CFS conference of the Charité Fatigue Center was held in Berlin, Germany, focusing on pathomechanisms, diagnosis, and treatment. During the two-day conference, more than 100 researchers from various research fields met on-site and over 700 attendees participated online to discuss the state of the art and novel findings in this field. Key topics from the conference included: the role of the immune system, dysfunction of endothelial and autonomic nervous system, and viral reactivation. Furthermore, there were presentations on innovative diagnostic measures and assessments for this complex disease, cutting-edge treatment approaches, and clinical studies. Despite the increased public attention due to the COVID-19 pandemic, the subsequent rise of Long COVID-19 cases, and the rise of funding opportunities to unravel the pathomechanisms underlying ME/CFS, this severe disease remains highly underresearched. Future adequately funded research efforts are needed to further explore the disease etiology and to identify diagnostic markers and targeted therapies.

Investigation of OCTA Biomarkers in Fabry Disease: A Long Term Follow-Up of Macular Vessel Area Density and Foveal Avascular Zone Metrics.

INTRODUCTION: Retinal microvasculature is known to be altered in patients with Fabry disease (FD). We aimed to investigate the long-term changes in macular microvasculature and explore a reliable retinal biomarker for treatment monitoring in FD. METHODS: Prospective study of 26 eyes with FD followed up to 48 months (mean 24, range 8-48). OCT angiography (OCTA) images (2.9 × 2.9 mm) were obtained using Heidelberg Spectralis II at baseline and follow-up. Macular vessel area density (VAD, %) was measured in three layers: superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) in three peri-macular circular sectors (c1, c2, c3). Additionally, foveal avascular zone (FAZ) area (mm2) and horizontal and vertical diameters (µm) were assessed. RESULTS: VAD decreased over time in SVP, ICP (in sectors c2 and c3) and DCP (all sectors) (p < 0.04). VAD reduction was predominantly seen in treated FD patients. FAZ and horizontal diameters increased at follow-up in FD patients compared to baseline (p ≤ 0.025). Correlation analysis showed a moderate to strong negative correlation between VAD of SVP and DCP in the innermost circle and FAZ in treated patients (r = - 0.6; p < 0.0001). CONCLUSIONS: This is the first long-term follow-up OCTA study in FD to our knowledge. A decrease in VAD, pronounced in the peripheral circle and deeper layers, as well as an enlargement of the FAZ could be observed over time. These changes reflect the vascular remodelling during the course of the disease. Interestingly, the reduction of VAD was more pronounced in treated patients. This could be a result of enzyme replacement therapy and could be potentially used as a reliable biomarker for monitoring the treatment of the disease. A baseline examination of VAD and FAZ before treatment initiation is meaningful. Larger studies are needed to establish the use of VAD and FAZ as biomarkers for treatment monitoring.

[Leadership from the perspective of next generation ophthalmologists]. / Leadership aus Sicht des ophthalmologischen Nachwuchses.

Managers in the healthcare system play a critical role in ensuring high quality patient care, optimization of resources, management of complex situations, creation of a positive work environment and promotion of continuous progress. They set clear goals, support interdisciplinary collaboration, ensure patient safety and quality care, and assist in the development of future leaders. To accomplish these multiple tasks, important qualities such as integrity, communication skills, self-awareness, ability to learn, influence, empathy, courage, respect, ability to delegate and gratitude are essential. We conducted a survey among the followers and members of the Young-DOG to find out their desired characteristics of leaders. In this survey modern aspects of leadership styles such as communication, loyalty, support, reliability and trust were particularly important to young medical professionals. Classical attributes such as expertise and assertiveness were rated as somewhat less significant. This finding underlines the importance of leadership programs such as the Leadership Academy of the German Society of Ophthalmology (DOG) or the European Leadership Development Program of the European Society of Ophthalmology (SOE). The latter is briefly presented in an excursus.

"Multisystem Inflammatory Syndrome in Children" (MIS-C) after COVID-19 Infection in the Metropolitan Area of Nuremberg-Erlangen, Germany-Expectations and Results of a Two-Year Period.

BACKGROUND: Multisystemic Inflammatory Syndrome in children (MIS-C) is a rare autoimmune disorder occurring after a latency period following acute SARS-CoV-2 infection. The therapeutic regime of MIS-C is adapted to the therapy of the Kawasaki disease, as clinical symptoms are similar. Since the Kawasaki disease can potentially result in severe symptoms, which may even affect long-term health, it is essential to gain further knowledge about MIS-C. Thus, we aimed to investigate the incidence, symptoms, therapeutical procedure and outcome of MIS-C patients in the metropolitan area of Nuremberg-Erlangen during the SARS-CoV2 pandemic. MATERIAL AND METHODS: Retrospective analysis of clinical charts of MIS-C patients was carried out at three children's hospitals covering the medical care of the metropolitan area of Nuremberg-Erlangen in Germany. Demographic characteristics and symptoms at first visit, their clinical course, therapeutic regime and outcome were recorded within the time period January 2021-December 2022. RESULTS: Analysis of 10 patients (5 male, 5 female) with MIS-C resulting in an incidence of 2.14/100.000 children. The median time between COVID-19 infection and admission to hospital was 5 weeks. The median age was 7 years. Symptoms comprised fever (100%), rash (70%), bilateral non-purulent conjunctivitis (70%) and urticaria (20%). At the time of presentation, diagnosis-defining inflammation parameters were increased and the range for C-reactive protein was 4.13 mg/dL to 28 mg/dL, with a median of 24.7 mg/dL. Procalcitonin was initially determined in six patients (1.92 ng/mL to 21.5 ng/mL) with a median value of 5.5 pg/mL. Two patients displayed leukocytosis and two displayed leukopenia. None of the patients presented coronary pathologies. Nine of the ten patients received intravenous immunoglobulin (IVIG) therapy. In addition, patients received intravenous steroids (80%) and acetylsalicylic acid (80%). CONCLUSION: SARS-CoV virus may rarely exert multiorgan manifestations due to hyperinflammatory immunological processes. Within two years of the COVID-19 pandemic, we identified ten patients with COVID-induced MIS-C in the metropolitan area Nuremberg-Erlangen. In the description of the patient collective, we can confirm that MIS-C is distinguished from the Kawasaki disease by the lack of coronary manifestations. Interestingly, although having monitored all pediatric facilities in the investigated area, we find lower incidences of MIS-C compared to findings in the literature. In conclusion, an overestimation of incidences in the upcoming MIS-C during the pandemic needs to be considered.

Virtual reality for assessing stereopsis performance and eye characteristics in Post-COVID.

In 2019, we faced a pandemic due to the coronavirus disease (COVID-19), with millions of confirmed cases and reported deaths. Even in recovered patients, symptoms can be persistent over weeks, termed Post-COVID. In addition to common symptoms of fatigue, muscle weakness, and cognitive impairments, visual impairments have been reported. Automatic classification of COVID and Post-COVID is researched based on blood samples and radiation-based procedures, among others. However, a symptom-oriented assessment for visual impairments is still missing. Thus, we propose a Virtual Reality environment in which stereoscopic stimuli are displayed to test the patient's stereopsis performance. While performing the visual tasks, the eyes' gaze and pupil diameter are recorded. We collected data from 15 controls and 20 Post-COVID patients in a study. Therefrom, we extracted features of three main data groups, stereopsis performance, pupil diameter, and gaze behavior, and trained various classifiers. The Random Forest classifier achieved the best result with 71% accuracy. The recorded data support the classification result showing worse stereopsis performance and eye movement alterations in Post-COVID. There are limitations in the study design, comprising a small sample size and the use of an eye tracking system.

SSN2V: unsupervised OCT denoising using speckle split.

Denoising in optical coherence tomography (OCT) is important to compensate the low signal-to-noise ratio originating from laser speckle. In recent years learning algorithms have been established as the most powerful denoising approach. Especially unsupervised denoising is an interesting topic since it is not possible to acquire noise free scans with OCT. However, speckle in in-vivo OCT images contains not only noise but also information about blood flow. Existing OCT denoising algorithms treat all speckle equally and do not distinguish between the noise component and the flow information component of speckle. Consequently they either tend to either remove all speckle or denoise insufficiently. Unsupervised denoising methods tend to remove all speckle but create results that have a blurry impression which is not desired in a clinical application. To this end we propose the concept, that an OCT denoising method should, besides reducing uninformative noise, additionally preserve the flow-related speckle information. In this work, we present a fully unsupervised algorithm for single-frame OCT denoising (SSN2V) that fulfills these goals by incorporating known operators into our network. This additional constraint greatly improves the denoising capability compared to a network without. Quantitative and qualitative results show that the proposed method can effectively reduce the speckle noise in OCT B-scans of the human retina while maintaining a sharp impression outperforming the compared methods.

The influence of trace elements on the therapeutic success of suprachoroidal draining devices.

PURPOSE: The therapeutic success of minimal invasive glaucoma surgery (MIGS) is challenging due to many factors including fibrotic or occlusive events. Recent clinical data show sudden peaks of intraocular pressure (IOP) in the postoperative care of glaucoma patients after suprachoroidal draining stents. Yet, the reasons for the IOP peaks are speculative. As a link between trace elements and fibrosis had been previously observed in systemic disorders, the present study aimed to investigate the impact of trace elements on the therapeutic success of the suprachoroidal draining stents in patients with open-angle glaucoma (OAG). MATERIAL AND METHODS: An analysis of a prospective single-center study was done: fifty-five eyes of patients with OAG (29 female, 26 male) underwent Cypass Micro-Stent implantation either as a stand-alone procedure or combined with cataract surgery. All patients underwent pre-operatively an ophthalmological examination which included slit lamp biomicroscopy and fundoscopy. IOP was measured by Goldmann applanation tonometry. Functional and morphometric data were assessed by Octopus G1-perimetry, which included measurement of retinal nerve fiber layer thickness (Spectralis OCT). Data of the patients' follow-ups were recorded during 18 months post-operatively. The therapeutic success of CyPass Micro-Stent was classified as 'success' (IOP reduction ≥20% compared to a pre-operative baseline without any medication), 'qualified success' (IOP reduction ≥20 % with same or lower additional eye medication), and 'failure' (IOP reduction ≤20 % or additional surgical treatment necessary). Aqueous humour was extracted once during surgery for analysis of the level of 14 trace elements: Copper (Cu), Cadmium (Cd), Cobalt (Co), Chromium (Cr), Iron (Fe), Lithium (Li), Magnesium (Mg), Manganese (Mn), Phosphorus (P), Lead (Pb), Titanium (Ti), Uranium (U), Vanadium (V), and Zinc (Zn). Analysis of the trace elements was done using an ELEMENT 2, ICP-sf-MS instrument (Thermo-Fisher Scientific, Bremen, Germany). Analysis of levels of trace elements was done across the patients' groups of the three subclasses of therapeutic success. Statistical investigations for substantial differences were conducted using the method of least squares to fit general linear models and mixed models. The last one for the repeated measurements of IOP. RESULTS: Levels of Mg were significantly lower one month postoperatively in the success group (LS-Mean 1.30 mg/L) compared to the qualified success group (LS-Mean 1.22 mg/L; p-value = 0.04). Fe was significantly increased in the failure group (LS-Mean 2.07 µg/L) compared to the qualified success group (LS-Mean 1.64 µg/L; p-value = 0.019) after 3 months of follow-up. Additionally, Fe levels were significantly lower in the success group (LS-Mean 1.47 µg/L) compared to the failure cohort (LS-Mean 2.07 µg/L; p-value = 0.009). After a period of 18 months, significantly higher levels of Mn were observed in the success group (LS-Mean 1.24 µg/L) than in the failure group (LS Mean 0.30 µg/L, p-value = 0.019). CONCLUSION: The present data might suggest that trace elements can influence therapeutic success of suprachoroidal draining devices postoperatively and thus offer first hints for potential novel therapeutic options.

Pressure-Dependent Elevation of Vasoactive Intestinal Peptide Level in Chicken Choroid.

PURPOSE: Autonomic control is important in maintaining ocular integrity. As recent data suggested that intrinsic choroidal neurons (ICN), an intrinsic choroidal autonomic control, may regulate choroidal thickening via release of the vasodilative vasoactive intestinal peptide (VIP), it was the aim of the study to investigate the level of choroidal VIP (VIPchor) in the presence of an increased atmospheric pressure in a chicken model. METHODS: Chicken choroidal whole mounts were exposed to ambient pressure (n = 20) and 40 mm Hg (n = 20) in a PC-controlled, open chamber system for 24 and 72 h, respectively. The VIP concentration was analyzed by ELISA, and the total protein concentration was measured by the BCA assay. Statistical analysis was done using an unpaired two-tailed t-test. RESULTS: The pressurization systems enabled choroidal whole mount pressurization (40 mm Hg) with humidifying, pressure, temperature, and gas exchange. Overall, the VIPchor level concentration was significantly increased at 40 mmHg compared to the ambient pressure (30.09 ± 7.18 pg vs. 20.69 ± 3.24 pg; p < 0.0001). Subgroup analysis yielded a significantly increased VIPchor level at 40 mmHg compared to the ambient pressure after 24 h (28.42 ± 6.03 pg vs. 20.76 ± 4.06 pg; p = 0.005) and 72 h (31.77 ± 7.82 pg vs. 20.61 ± 2.12 pg; p = 0.002), respectively. The VIPchor elevation at 40 mm Hg ranged between 1.37- (24 h) and 1.54-fold (72 h) compared to the ambient pressure. No difference was observed between the VIPchor level at 24 h and 72 h (p > 0.05). CONCLUSIONS: The increase of the total choroidal VIP level, representing the intracellular VIP content, in the presence of an increased ambient pressure argues for a retention of VIP within the neurons, decreasing both vasodilatation and, consequently, choroid thickness. This finding might be a passive or even active function of ICN in the regulation of choroidal thickness, ocular integrity and IOP.

APSified OCT-angiography analysis: Macula vessel density in healthy eyes during office hours.

PURPOSE: Optical coherence tomography angiography (OCT-A) can visualize retinal capillary microcirculation non-invasively. In order to investigate potential factors influencing OCT-A diagnostics, the aim of the present study was to determine circadian changes in macular vessel density (VD) in healthy adults during office hours, considering axial length (AL) and subfoveal choroidal thickness (CT). METHODS: In the prospective study 30 eyes of 30 healthy subjects (mean age 28.7 ± 11.8, range 19-60 years) were recruited who underwent repeated measurements of AL, subfoveal CT and three-layer macula VD (superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP)) on a single day at three predetermined timepoints (9 AM, 3 PM, and 9 PM). For better intra- and interindividual scan comparability, the new Anatomic Positioning System function (APS, part of Glaucoma Module Premium Edition [GMPE], Heidelberg Engineering, Germany) allowing analysis of identical retinal areas, was used for quantitative OCT-A analysis. RESULTS: Overall mean macula VD was unchanged during office hours in SVP, ICP and DCP, respectively (p>0.05). In addition, AL and CT showed no statistically significant changes over time (p>0.05). Rather, a large interindividual variance of VD with different peak time was observed. Contrary to the overall data, sectorial VD changed in dependency of office hours in all layers with an increase of VD in SVP between 9 AM and 9 PM (p = 0.003), in ICP between 3 PM and 9 PM (p = 0.000), in DCP between 9 AM and 9 PM (p = 0.048), and 3 PM and 9 PM (p = 0.000), respectively. CONCLUSION: Overall mean macula VD, subfoveal CT and AL tended not to show statistically significant changes over time in this cohort, whereas a regional analysis of VD did. Therefore, a circadian influence on capillary microcirculation should be kept in mind. Moreover, the results highlight the importance of a more detailed analysis of VD in different sectors and different vascular layers. In addition, the pattern of diurnal variation could vary inter-individually, thus a patient-specific fluctuation pattern would need to be considered when evaluating these parameters in clinical practice.

Autoantibodies targeting G protein-coupled receptors: An evolving history in autoimmunity. Report of the 4th international symposium.

G protein-coupled receptors (GPCR) are involved in various physiological and pathophysiological processes. Functional autoantibodies targeting GPCRs have been associated with multiple disease manifestations in this context. Here we summarize and discuss the relevant findings and concepts presented in the biennial International Meeting on autoantibodies targeting GPCRs (the 4th Symposium), held in Lübeck, Germany, 15-16 September 2022. The symposium focused on the current knowledge of these autoantibodies' role in various diseases, such as cardiovascular, renal, infectious (COVID-19), and autoimmune diseases (e.g., systemic sclerosis and systemic lupus erythematosus). Beyond their association with disease phenotypes, intense research related to the mechanistic action of these autoantibodies on immune regulation and pathogenesis has been developed, underscoring the role of autoantibodies targeting GPCRs on disease outcomes and etiopathogenesis. The observation repeatedly highlighted that autoantibodies targeting GPCRs could also be present in healthy individuals, suggesting that anti-GPCR autoantibodies play a physiologic role in modeling the course of diseases. Since numerous therapies targeting GPCRs have been developed, including small molecules and monoclonal antibodies designed for treating cancer, infections, metabolic disorders, or inflammatory conditions, anti-GPCR autoantibodies themselves can serve as therapeutic targets to reduce patients' morbidity and mortality, representing a new area for the development of novel therapeutic interventions.

Moonlighting chromatin: when DNA escapes nuclear control.

Extracellular chromatin, for example in the form of neutrophil extracellular traps (NETs), is an important element that propels the pathological progression of a plethora of diseases. DNA drives the interferon system, serves as autoantigen, and forms the extracellular scaffold for proteins of the innate immune system. An insufficient clearance of extruded chromatin after the release of DNA from the nucleus into the extracellular milieu can perform a secret task of moonlighting in immune-inflammatory and occlusive disorders. Here, we discuss (I) the cellular events involved in the extracellular release of chromatin and NET formation, (II) the devastating consequence of a dysregulated NET formation, and (III) the imbalance between NET formation and clearance. We include the role of NET formation in the occlusion of vessels and ducts, in lung disease, in autoimmune diseases, in chronic oral disorders, in cancer, in the formation of adhesions, and in traumatic spinal cord injury. To develop effective therapies, it is of utmost importance to target pathways that cause decondensation of chromatin during exaggerated NET formation and aggregation. Alternatively, therapies that support the clearance of extracellular chromatin are conceivable.

Teleglaucoma Using a New Smartphone-Based Tool for Visual Field Assessment.

PRCIS: COVID-19 underlines the importance of telemedical diagnostics. The smartphone-based campimetry (Sb-C) is a newly developed digital application allowing visual field testing using a head-mounted device and a smartphone. It enables visual field screening remotely from a clinic. BACKGROUND: Sb-C is a newly developed tool for functional ophthalmic diagnosis. This study aimed to examine the comparability of the Sb-C and Octopus 900 to ensure ophthalmological care in times of social distancing. METHODS: Total 93 eyes were included in the study. After an ophthalmological examination, the visual field was tested by the Octopus program G1 and by the smartphone-based campimeter. The Sb-C was performed using VR glasses and an iPhone 6. The software Sb-C was downloaded and installed as SmartCampiTracker app and is examining the 30-degree visual field with 59 test positions corresponding to the G pattern of Octopus G1. Sensitivities were recorded and saved on the app. In addition, test-retest reliability was tested on 6 ophthalmologically healthy participants. RESULTS: The group comprised 48 women and 45 men (mean age: 62.52±12.2 y) including 19 controls, 17 patients with ocular hypertension, 11 preperimetric glaucomas, and 46 perimetric glaucomas. The mean sensitivity (MS) of all points of G1 perimetry was 23.13 dB (95% CI, 22.08-24.18). The MS of the Sb-C was 21.23 dB (95% CI, 20.37-22.08). The correlation between the mean MS measured by G1 perimetry and the Sb-C was strong ( r =0.815, P <0.05). The test-retest reliability showed a correlation of r =0.591 ( P <0.05) . CONCLUSIONS: With some technical adjustments, the Sb-C shows promise for screening glaucoma and monitoring disease progression remotely from an ophthalmologic clinic.

Endophthalmitis: Epidemiology, Causing Agents, Therapy and Visual Outcome with Special Focus on Glaucoma Patients. / Endophthalmitis: Ursachen, Erreger, Therapie und Visusverlauf mit Fokus auf Glaukompatienten.

BACKGROUND: Endophthalmitis is one of the most serious emergencies in ophthalmology. In order to reduce its prevalence, it is important to have a proper understanding of potential risk. Surgical therapy with targeted, pathogen-specific medication and an intact immune system are fundamental for preserving visual acuity. As it is unclear whether an unfavourable course is more likely in the presence of underlying ocular disease, a comparison was made between glaucoma patients (G) and non-glaucoma patients (NG) in terms of causative factors, pathogens, treatment and visual acuity. Since a potential alteration of the local immune system in glaucoma has been described, it is of interest to determine whether the clinical course of endophthalmitis in glaucoma patients differ from that of non-glaucoma patients. PATIENTS AND METHODS: A retrospective analysis of 75 eyes (13 G, 62 NG) who underwent treatment and surgery following a diagnosis of endophthalmitis in the Department of Ophthalmology, University of Erlangen-Nuremberg has been evaluated over a period of 5 years. Clinical characteristics, surgical treatment, microbial spectrum and visual acuity in glaucoma and non-glaucoma eyes were investigated. RESULTS: Severe visual impairment (44%) with inflammation of the anterior chamber (62.7%), hypopyon (52%) and reduced (40%) or absent view (26.7%) of the fundus were predominantly present at first diagnosis in all patients. Previous eye surgery was observed in a total of 53%, primarily cataract surgery. Gram-positive cocci were seen as the most common causative agent in both groups, (G: 23.1%; NG: 38.7%), whereas other rare pathogens were present only in glaucomatous eyes. Pars plana vitrectomy was performed in 76% and enucleations in 20% of all patients, with the latter significantly more common in glaucomatous eyes (p = 0.01). A significant postoperative improvement in visual acuity was achieved in non-glaucoma patients (p < 0.001); visual acuity was worse in glaucomatous eyes. CONCLUSION: Although rare, early diagnosis and treatment of endophthalmitis is crucial in terms of prognosis. In the present cohort, worse visual acuity outcomes were obtained in glaucoma patients in comparison to non-glaucoma patients.