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To compare the efficacy and safety of ultrathin Descemet stripping (automated) endothelial keratoplasty (UT-DS(A)EK) versus Descemet membrane endothelial keratoplasty (DMEK) for the treatment of Fuchs endothelial dystrophy (FED) and bullous keratopathy (BK).Systematic review and meta-analysis.Literature containing DMEK and UT-DSAEK were searched in the Cochrane Database of Systematic Reviews, PubMed, EMBASE, LILACS, and through manual reference searching. Studies were included that measured the outcome of interventions-including best corrected visual acuity (BCVA), endothelial cell density (ECD), and postoperative complications, especially graft detachment with the need of re-bubbling, graft rejection, graft failure, and postoperative elevated intraocular pressure (IOP)-in patients with FED and BK. Included outcomes were pooled as standardized mean differences (SMD) or risk ratios (RR) using random effects models. Inter-study heterogeneity was assessed using the Q-test and ISeven (of 163) studies met all the inclusion and exclusion criteria. Meta-analysis showed a significantly better BCVA 12 months postoperatively, but an increased re-bubbling rate in eyes after DMEK compared with eyes after UT-DS(A)EK (BCVA: SMD = 0.50 [95% CI 0.27-0.74] and re-bubbling rate: RR = 0.33 [95% CI 0.16-0.67]). All other parameters did not differ significantly between both interventions, although estimates were imprecise (graft failure: RR = 0.65 [95% CI 0.18-2.30], graft rejection: RR = 1.40 [95% CI 0.27-7.30], and postoperative intraocular pressure elevation: RR = 1.14 [95% CI 0.60-2.18]). Postoperative SMDs of ECD could not be evaluated due to significant heterogeneity between studies.Although the improvement in BCVA was higher after UT-DS(A)EK than after conventional DS(A)EK, the BCVA after DMEK was still superior. The complication rates were comparable for both procedures, except for the higher rate of re-bubbling after DMEK.

Background. To report on the short-term outcome of intravitreal brolucizumab in patients with neovascular age-related macular degeneration (nAMD). Methods. This is a prospective, interventional, monocentric study on 10 eyes of 10 patients with a treatment-naïve neovascular AMD. Patients were treated according to the HAWK and HARRIER trials. After loading with 3 monthly injections, eyes received an injection 12 weeks after the upload (q12w) or were adjusted to an 8 week interval (q8w), if disease activity was present 8 weeks after the upload. Main outcome measures were the change in central retinal thickness (CRT) assessed by spectral domain optical coherence tomography (SD-OCT), the change in macular neovascularization (MNV) size on optical coherence tomography angiography (OCTA), and the change in best corrected visual acuity (BCVA) 8 and 12 weeks after the upload. We further assessed clinical parameters that predict the treatment response at baseline based on the need of q8w or q12w injections after the upload. Results. CRT decreased significantly from 461.7 ± 82.9 μm to 343.6 ± 74.3 μm ( p = 0.004 ) 12 weeks after the upload. The MNV size decreased significantly from 0.85 ± 1.1 to 0.75 ± 1.2 mm2 ( p = 0.022 ). BCVA improved from 0.67 ± 0.4 to 0.55 ± 0.4logMAR but without statistical significance. MNV size in eyes on q12w was considerably smaller compared to that in eyes on q8w (0.54 ± 0.7 mm2 vs. 1.98 ± 2.4 mm2). The percentage of eyes without any persistent fluid was 70% (7/10 eyes). Conclusions. Brolucizumab appears to be a valuable tool for the management of patients with nAMD. Furthermore, MNV size at baseline might serve as an early predictor of treatment response.

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Uveal melanoma is a rare intraocular tumour, for which there is currently no national evidence-based guideline in Germany. The aim of this project was to provide a common standard operating procedure (SOP) for the diagnosis, treatment and follow-up care of uveal melanoma, within the network of German leading oncology centres funded by German Cancer Aid. The SOP was created as part of a moderated consensus process.In a multistage process, a common SOP was developed for the diagnosis, therapy and follow-up of uveal melanoma, as based on current knowledge of the subject.Für das uveale Melanom fehlt als seltene onkologische Erkrankung derzeit in Deutschland eine nationale evidenzbasierte Leitlinie. Bis diese erstellt wird, bietet sich eine zentrumsübergreifende Standard Operating Procedure (SOP) an. Ziel des Projektes war die Erarbeitung einer konsentierten SOP zur Diagnostik, Therapie und Nachsorge des uvealen Melanoms im Rahmen des Netzwerkes Onkologischer Spitzenzentren, die von der Deutschen Krebshilfe gefördert werden.In einem auf dem aktuellen Wissensstand basierenden mehrstufigen Prozess eines moderierten Konsensusverfahrens konnte eine konsentierte SOP für die Diagnostik, Therapie und Nachsorge des uvealen Melanoms erarbeitet werden.

Background The cotton bollworm, Helicoverpa armigera (Hubner), is a damaging insect pest threatening agricultural crops worldwide as a result of its resistance to insecticides. Metabolic resistance to pyrethroid insecticides is conferred by the chimeric P450 enzyme CYP337B3, produced by unequal crossing-over between CYP337B1 and CYP337B2. CYP337B3 is 99.7% similar to CYP337B1 except for the 177 N-terminal amino acids (AAs) containing the substrate recognition site 1 from CYP337B2. Here, we studied the structure-function relationship of CYP337B3 and CYP337B1 to determine the AAs that enable CYP337B3 to efficiently hydroxylate the 4'-carbon position of fenvalerate, which neither CYP337B1 nor CYP337B2 can do. Results Site-directed mutagenesis showed that the L114F substitution in CYP337B3 reduced its 4'-hydroxylation activity by 89%, but the reciprocal F114L substitution in CYP337B1 increased its 4'-hydroxylation activity to only 49% of the level of CYP337B3. Docking models showed that AA 114 seems to have different functions in CYP337B1 and CYP337B3. Antibodies detected two- to three-fold more CYP337B1 than CYP337B3 in larval cuticle, which along with a 49% 4'-hydroxylation activity increase due to a F114L substitution in vivo might be expected to provide as much protection for the larva against exposure to fenvalerate as CYP337B3. However, CYP337B3 is present at much higher frequencies than CYP337B1-CYP337B2 in most populations, including those recently invading South America. Conclusion The metabolic resistance to pyrethroids in H. armigera has evolved by saltational evolution - by a single mutation, an unequal crossing-over, producing a larger selective advantage than could be attained gradually by stepwise improvement of the parental enzyme. © 2021 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

To investigate the oncological and functional outcomes of a large cohort of patients with a favorable stage of circumscribed and diffuse iris melanoma who underwent primary proton treatment and the risk factors related to initial tumor characteristics and the treatment field architecture.Retrospective, single-center, case study.We reviewed 225 patients with iris melanoma who were consecutively treated with proton beam therapy at our institution between 1998 and 2020.We performed Kaplan-Meier time-to-event analyses and multivariate Cox proportional hazard analyses to identify the impacts of tumor characteristics and target volumes on oncological and functional outcomes.We measured local tumor control, eye preservation rates, metastasis-free survival, cataract and glaucoma-directed surgery, intraocular pressure, and changes in visual acuity.Of the 192 patients with tumors confined to the iris (T1a-c) who underwent proton therapy as primary treatment, a total of 166 patients (mean age 58.4 years; 88 females) with a minimum follow-up of 6 months were included. Multifocal or diffuse tumor spread was present in 77 (46.4%) patients. The median follow-up time was 54.0 (IQR: 27.4-91.8) months. Local recurrence occurred in 2 patients (1.2%) with circumscribed iris melanoma. Enucleation was a rare event (n=5, 3%) and no patient developed metastatic disease. A large treatment field (full aperture, involving10 clock hours) was identified as a risk factor for the development of secondary glaucoma (HR: 6.3; p0.001) and subsequent surgical interventions (HR: 10.85; p0.001). The large treatment field group showed a significant decline in visual acuity (logMAR0.3; log-rank p0.0001), which was associated with secondary glaucoma (HR: 3.40; p=0.002).Proton therapy provides an effective, non-invasive treatment option for patients with a favorable stage of iris melanoma. Irradiation of the anterior segment up to 10 clock hours is associated with a low risk of the development of secondary glaucoma and vision loss.

Purpose The study aims to evaluate changes in contrast sensitivity (CS) during therapy with intravitreal vascular endothelial growth factor (VEGF) inhibitors in patients with neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). Methods Prospective, uncontrolled, multicenter study on patients with neovascular AMD or DME who underwent intravitreal injection therapy with Ranibizumab, Aflibercept, or Bevacizumab was conducted. Best corrected visual acuity (BCVA) and CS measured by Mars Letter Contrast Sensitivity Test (MLCS) and Freiburg Visual Acuity and Contrast Test (FrACT) in logCS were evaluated before 3 consecutive VEGF inhibitor injections, which followed the pro renata regimen in treatment-naïve and pretreated eyes with a maximum of 9 injections. Correlation of MLCS and FrACT was calculated by the Spearman’s rank correlation coefficient. Results Eighty eyes of 74 patients (mean age 72.7; SD ± 9.96) were included. BCVA improved significantly from 0.44 (SD ± 0.21) logMAR to 0.38 (SD ± 0.23) logMAR by 0.06 (SD ± 0.14) logMAR values (p p p = 0.035). A positive correlation between MLCS and FrACT was found (r = 0.389; p Conclusions Intravitreal injection therapy with VEGF inhibitors led to an improvement of BCVA and CS measured by MLCS and FrACT. MLCS was superior and more sensitive compared to FrACT and even BCVA to evaluate CS in elderly patients with macular pathology.

PURPOSE Recent studies indicate that FLASH irradiation, which involves ultra-high dose rates in a short time window (usually >40 Gy/s in

PURPOSE To study the change in contrast sensitivities in eyes with Fuchs endothelial dystrophy and bullous keratopathy after Descemet membrane endothelial keratoplasty (DMEK). METHODS In this prospective study, 50 pseudophakic eyes of 50 patients who received DMEK surgery at the Charite-Universitatsmedizin Berlin were included. Visual acuity; contrast sensitivity using OPTEC 6500 at spatial frequencies of 1.5, 3, 6, 12, and 18 cycles/degree in photopic and mesopic light with and without glare; central corneal thickness (CCT); and anterior and posterior corneal aberrations were measured preoperatively and at 3 and 12 months postoperatively. RESULTS Best-corrected visual acuity (preoperative 0.67 ± 0.46 and after 12 months 0.19 ± 0.16 LogMAR, P < 0.001) and photopic and mesopic contrast sensitivities with and without glare improved significantly, whereas CCT decreased significantly (preoperative 677 ± 114 μm, after 12 months 527 ± 29 μm, P < 0.001). Preoperative CCT correlates significantly with preoperative photopic contrast sensitivity (correlation coefficient -0.462, P = 0.002), and postoperative total anterior aberrations correlates with postoperative photopic contrast sensitivity (correlation coefficient -0.361, P = 0.006). CONCLUSIONS Photopic and mesopic contrast sensitivities, especially with glare, are impaired in patients with Fuchs endothelial dystrophy and bullous keratopathy. The extent of the corneal thickening seems to mainly influence the contrast sensitivity preoperatively. DMEK surgery improves the contrast sensitivity significantly. However, higher postoperative anterior corneal aberrations limit the postoperative contrast sensitivities.

The angopoietin/tyrosine kinase with immunoglobulin and epidermal growth factor homology domains (Ang/Tie) pathway is an emerging key regulator in vascular development and maintenance. Its relevance to clinicians and basic scientists as a potential therapeutic target in retinal and choroidal vascular diseases is highlighted by recent preclinical and clinical evidence. The Ang/Tie pathway plays an important role in the regulation of vascular stability, in angiogenesis under physiological and pathological conditions, as well as in inflammation. Under physiological conditions, angiopoietin-1 (Ang-1) binds to and phosphorylates the Tie2 receptor, leading to downstream signalling that promotes cell survival and vascular stability. Angiopoietin-2 (Ang-2) is upregulated under pathological conditions and acts as a context-dependent agonist/antagonist of the Ang-1/Tie2 axis, causing vascular destabilisation and sensitising blood vessels to the effects of vascular endothelial growth factor-A (VEGF-A). Ang-2 and VEGF-A synergistically drive vascular leakage, neovascularisation and inflammation, key components of retinal vascular diseases. Preclinical evidence suggests that modulating the Ang/Tie pathway restores vascular stabilisation and reduces inflammation. This review discusses how targeting the Ang/Tie pathway or applying Ang-2/VEGF-A combination therapy may be a valuable therapeutic strategy for restoring vascular stability and reducing inflammation in the treatment of retinal and choroidal vascular diseases.摘要: 本篇文章是关于不同照明条件对原发性开角型青光眼 (POAG) 患者视力和生活质量影响的研究的系统回顾。研究对CINAHL, MEDLINE, PsycARTICLES, PsycINFO, Embase and Ovid Nursing Database六个数据库进行系统文献检索, 截止发表日期为2019年4月。检索内容包括诊断为POAG的患者, 在变换照明设备/光照水平或炫光的情况下评估人群的视功能和生活质量。两名研究者独立筛选符合标准的受试者。从实验设计, 入选者标准, 结果与结论中挑选合格的研究并提取数据。入选研究的质量经过了严格的评估。在8437项研究中, 共有56项研究符合入选标准。在POAG患者中调查光照对以下因素的影响: 生活质量 (18/56),心理物理学干预 (16/56), 功能性视力 (10/56), 日常活动 (10/56) 和定性发现 (2/56)。POAG会影响患者的低亮度对比敏感度, 炫光症状, 暗适应的时间和程度。在视觉生活质量调查问卷中, 根据POAG患者反馈, 照明设备, 炫光和暗适应的问题较其它问题更多见。这些问题随着进行性视野的缺失而严重, 与同年龄对照组相比(AMC), POAG患者在发病的早期在低亮度和不同亮度切换的环境中会面临更多的困难, 这对之前POAG患者早期阶段没有症状的认知进行了挑战。但是, 基于性能方面的研究很少显示POAG参与者和AMC在模拟非最佳照明条件下日常活动方面有显着差异。 需要对较大的样本进行进一步研究, 以优化环境照明和面向任务的照明, 以支持患者适应POAG。未来亟待大样本的研究为POAG患者提供优化环境和适合工作的照明。.

This publication provides an overview of current evidence for the development of retinal pigment epithelium tears during anti-vascular endothelial growth factor therapy, and summarizes the recommendations of the Vision Academy Steering Committee on appropriate imaging techniques for documenting retinal pigment epithelium tears, the identification of high-risk patients, and the management of patients who develop retinal pigment epithelium tear., Purpose: This article aims to review current evidence on the development, diagnosis, and management of retinal pigment epithelium (RPE) tear during anti–vascular endothelial growth factor (VEGF) therapy. Methods: Literature searches were performed using MEDLINE/PubMed databases (cut-off date: August 2019). Results: Three key recommendations were made based on existing literature and clinical experience: 1) Multimodal imaging with color fundus photography, optical coherence tomography, near-infrared reflectance imaging, fundus autofluorescence imaging, optical coherence tomography-angiography, and/or fluorescein angiography are recommended to diagnose RPE tear and assess risk factors. Retinal pigment epithelium tears can be graded by size and foveal involvement. 2) Patients at high risk of developing RPE tear should be monitored after each anti-VEGF injection. If risk factors worsen, it is not yet definitively known whether anti-VEGF administration should be more frequent, or alternatively stopped in such patients. Prospective research into high-risk characteristics is needed. 3) After RPE tear develops, anti-VEGF treatment should be continued in patients with active disease (as indicated by presence of intraretinal or subretinal fluid), although cessation of therapy should be considered in eyes with multilobular tears. Conclusion: Although evidence to support the assumption that anti-VEGF treatment contributes to development of RPE tear is not definitive, some data suggest this link.

Purpose/Aim of the study: Graft detachment after DMEK can be treated easily with an additional air injection – re-bubbling. The aim of our study was to investigate the effect of a re-bubbling on th...

AimsTo investigate the retinal vascular structure and capillary anomalies of affected and fellow eyes of patients with unilateral Coats’ disease using multimodal imaging.MethodsClinical investigation of both eyes of each patient with diagnosed Coats’ disease using ultra-widefield (UWF) fundus imaging, including UWF fluorescein angiography (UWFFA), spectral domain optical coherence tomography (OCT) and optical coherence tomography angiography (OCT-A).ResultsWe analysed 38 eyes of 19 patients with unilateral Coats’ disease and found that all fellow eyes (19/19; 100%) revealed vascular alterations, detected by UWFFA, predominantly located in the temporal periphery. Thereby, 89% of the fellow eyes (17/19) presented capillary bed abnormalities, that did not exceed the capillary level; 58% (11/19) presented tortuous abnormalities and 26% (5/19) presented microaneurysmatic abnormalities, exceeding the capillary level. If primarily affected eyes presented central Coats’ specific vascular abnormalities, fellow eyes revealed tortuous vascular abnormalities twice as often (78% (7/9) vs 40% (4/10); P=0.096). In primarily affected eyes, a tendency towards larger foveal avascular zones was revealed, compared to fellow eyes (0.28±0.16 mm2 vs 0.20±0.10 mm2; P=0.123).ConclusionThe use of modern multimodal imaging allows the detection of even subtle vascular changes in fellow eyes of patients with Coats’ disease. Coats’ disease appears to be a bilateral ocular disease with a predominant manifestation in one eye of the affected patients.

Due to their complexity, globe ruptures are highly compromising traumas for the patient. This is due on the one hand to the eye injury itself with the accompanying loss of vision and on the other hand due to the need for extended treatment with uncertain prognosis and the resulting psychological stress. Globe ruptures are among the prognostically most unfavorable injuries due to the force and peak pressure impacting the eye. Furthermore, contusional retinal necrosis may be of significance prognostically. In the present review, we discuss treatment of globe ruptures involving retinal surgery. We discuss the primary sugery, its chronological planning and extent as well as the necessity for follow-up interventions. We also discuss the origin of traumatic retinal detachment with differential diagnosis of giant retinal tear versus oradialysis as well as secondary sequelae of traumas such as formation of macular holes and their treatment. On this basis, the use of buckling surgery versus pars-plana vitrectomy is discussed. Further focus is set on the role of the iris lens diaphragm in surgery of globe ruptures.Bulbusberstungen sind aufgrund der Komplexität sehr beeinträchtigende Traumata für den Patienten, zum einen wegen der Augenverletzung selbst und des damit einhergehenden Visusverlustes, zum anderen wegen der langwierigen Behandlung mit ungewisser Prognose und der damit einhergehenden psychologischen Belastung. Bulbusberstungen gehören zu den prognostisch ungünstigsten Verletzungen wegen der auf das Auge einwirkenden Gewalt und Druckspitze. Zusätzlich können schwere kontusionelle Netzhautnekrosen prognostisch bedeutsam sein. In der vorliegenden Übersicht diskutieren wir die netzhautchirurgische Versorgung von Bulbusberstungen. Hierbei wird die Primär-OP, ihre zeitliche Planung und ihr Umfang wie auch die Notwendigkeit von Folgeeingriffen diskutiert. Die Genese einer traumatischen Ablatio mit der Differenzialdiagnose Riesenriss vs. Oradialyse werden ebenso diskutiert wie die Sekundärfolgen von Traumata wie die Entstehung von Makulaforamina und deren Versorgung. Vor diesem Hintergrund wird der Einsatz der Buckelchirurgie und/oder der Pars-plana-Vitrektomie erläutert. Einen weiteren Schwerpunkt haben wir auf die Rolle des Iris-Linsen-Diaphragmas in der Chirurgie von Bulbusberstungen gelegt.

Unfolding and attachment of the posterior donor lamella may be the most challenging part in Descemet membrane endothelial keratoplasty (DMEK) procedure. We investigated the correlation of the difficulty degrees of this step to the postoperative clinical outcome 6 years after surgery. One hundred sixty-nine consecutive DMEKs between September 2012 and August 2013 at the Charite–University Medicine Berlin were graded prospectively into 4 groups according to their grade of difficulty in unfolding and attachment of the graft lamella. Postoperative visual acuity, endothelial cell density, and rate of graft failure were measured after 1 year, after 2 years, and after 6 years and analyzed according to their grading group. Visual acuity improved significantly in all groups and did not differ significantly between the grading groups at any time point postoperatively. There was a significant decrease of endothelial cell density in all groups with a significantly higher endothelial cell loss in group IV compared with the other groups within the first 24 months after surgery. The graft failure rate was significantly higher in eyes graded III and IV than in groups I and II (p = 0.012). Although the endothelial cell loss and the graft failure rate increase significantly with a more difficult graft unfolding and attachment, DMEK surgery is a promising procedure with a good long-term postoperative outcome. A direct manipulation of the graft lamella for unfolding and centering by cannula or forceps should be avoided if possible to reduce the risk of an increased endothelial cell loss and a higher graft failure rate. NCT02020044

ZusammenfassungAnalysebasierte Dienstleistungen stellen einen neuartigen Servicetyp dar. Sie stützen ihre Wertschöpfung im Schwerpunkt auf die Anwendung statistischer Analyseverfahren auf Daten, um es ihren Kunden zu ermöglichen bessere Entscheidungen zu treffen oder komplexere Probleme lösen zu können. Während jedoch ihr Potenzial für neue Wertschöpfungsmöglichkeiten viel diskutiert ist, bleibt das Service Design als Instrument zur Erarbeitung neuer Dienstleistungen in Bezug auf diesen Servicetyp bisher unspezifisch. Als Folge haben Service Design Teams nach wie vor Schwierigkeiten, analysebasierte Dienstleistungen systematisch zu entwickeln. In diesem Beitrag entwickeln wir ein neues methodisches Werkzeug, das Service Designer dabei unterstützt Servicekonzepte analysebasierter Dienstleistungen zu entwickeln. Hierfür stellen wir allgemeingültige Gestaltungsrichtlinien auf und nutzen diese anschließend, um ein neues methodisches Werkzeug – das Analysebasierte-Dienstleistungs-Canvas – vorzuschlagen.

To analyze the impact of the dose to the optic disc and the irradiated length of the optic nerve on radiation-induced optic neuropathy, radiation-induced retinopathy, iris neovascularization, secondary glaucoma, enucleation, and local tumor control after proton beam therapy (PBT) of choroidal melanoma. Retrospective analysis of 1129 patients, who received primary PBT for the treatment of choroidal melanoma with a dose of 60 cobalt gray equivalents (CGE) between 1998 and 2013 at the Helmholtz-Zentrum Berlin, Germany. Kaplan-Meier curves and logrank test have been used for time-to-event analyses. Adjustment for potential confounders was done using multiple Cox regression models with forward and backward selection. We found a significant correlation between the irradiated length of the optic nerve and the dose to the optic disc (correlation coefficient, 0.93). Multivariate Cox regression revealed the dose to the optic disc as an independent predictive risk factor for the development of radiation-induced optic neuropathy (p < 0.001, HR 1.023, 95 CI 1.016–1.029), iris neovascularization (p < 0.001, HR 1.013, 95% CI 1.008–1.019), secondary glaucoma (p < 0.001, HR 1.017, 95% CI: 1.011-1.023) and enucleation (p < 0.001, HR 1.037, 95% CI 1.020-1.053). The irradiated length of the optic nerve was not a statistically independent predictive risk factor in multivariate analysis. Our data implicate the predominance of the dose to the optic disc over the irradiated length of the optic nerve regarding radiation-induced optic neuropathy, iris neovascularization, secondary glaucoma, and enucleation.

Uveal Melanoma (UM) is the most common primary intra-ocular tumor in adults. New diagnostic procedures and basic science discoveries continue to change our patient management paradigms. A recent meeting of the European Vision Institute (EVI) special interest focus group was held on “Outcome Measures of New Technologies in Uveal Melanoma”, addressing the latest advances in UM, starting with genetic developments, then moving on to imaging and treatment of the primary tumor, as well as to investigating the most recent developments in treating metastases, and eventually taking care of the patient’s wellbeing. This review highlights the meeting’s presentations in the context of the published literature.

Retinal manifestations have been described in COVID-19 patients, but it is unknown whether SARS-CoV-2, the causal agent in COVID-19, can directly infect posterior ocular tissues. Here, we investigate SARS-CoV-2 host factor gene expression levels and their distribution across retinal and choroidal cell types.Query of single-cell RNA sequencing data from human retina and choroid.We find no relevant expression of two key genes involved in SARS-CoV-2 entry, ACE2 and TMPRSS2, in retinal cell types. By contrast, scarce expression levels could be detected in choroidal vascular cells.Given the current understanding of viral host cell entry, these findings suggest a low vulnerability of the posterior eye segment to SARS-CoV-2 with a potential weak spot in the vasculature, which could play a putative causative role in ocular lesions in COVID-19 patients. This may qualify the vasculature of the human posterior eye segment as an in vivo biomarker for life-threatening vascular occlusions in COVID-19 patients.

Targeted therapies for metastatic uveal melanoma have shown limited benefit in biomarker-unselected populations. The Treat20 Plus study prospectively evaluated the feasibility of a precision oncology strategy in routine clinical practice.Fresh biopsies were analyzed by high-throughput genomics (whole-genome, whole-exome, and RNA sequencing). A multidisciplinary molecular and immunologic tumor board (MiTB) made individualized treatment recommendations based on identified molecular aberrations, patient situation, drug, and clinical trial availability. Therapy selection was at the discretion of the treating physician. The primary endpoint was the feasibility of the precision oncology clinical program.Molecular analyses were available for 39/45 patients (87%). The MiTB provided treatment recommendations for 40/45 patients (89%), of whom 27/45 (60%) received ≥1 matched therapy. First-line matched therapies included MEK inhibitors (n = 15), MET inhibitors (n = 10), sorafenib (n = 1), and nivolumab (n = 1). The best response to first-line matched therapy was partial response in one patient (nivolumab based on tumor mutational burden), mixed response in two patients, and stable disease in 12 patients for a clinical benefit of 56%. The matched therapy population had a median progression-free survival and overall survival of 3.3 and 13.9 months, respectively. The growth modulation index with matched therapy was1.33 in 6/17 patients (35%) with prior systemic therapy, suggesting clinical benefit.A precision oncology approach was feasible for patients with metastatic uveal melanoma, with 60% receiving a therapy matched to identify molecular aberrations. The clinical benefit after checkpoint inhibitors highlights the value of tumor mutational burden testing.

Background Cytogenetic testing (CGT) in uveal melanoma patients reveals prognostic information about the individual risk of developing distant metastasis with dismal prognosis. There is currently no medical intervention strategy with proven effect on the prognosis, rendering the result of the cytogenetic testing purely informative. We explored patients’ socio-demographic backgrounds, psychological preconditions, coping strategies, external influences, and concerns about “knowing their fate” to study their possible interactions with decision-making for CGT. Methods Uveal melanoma patients were asked to complete questionnaires on their interest in undergoing CGT for prognostication and the factors influencing their decision. Data were collected on socio-demographics, baseline anxiety (GAD-7), depression (PHQ-9), coping strategies (Brief COPE), and assumed future concerns regarding the CGT result. Data were analyzed by using multiple ordinal logistic regression and exploring estimated marginal effects. Results Questionnaires were returned by 121 of 131 (92.4%) patients. Fifty-two patients (43%) had no interest in CGT, 34 (28.1%) were undecided, and 35 (28.9%) were interested. We observed no significant differences regarding age, sex, partnership, education, occupation, baseline anxiety, or depression. Decision-making favoring CGT was influenced by the treating physicians, internet resources, and level of baseline anxiety. Patients were likely to reject CGT when they worried that “knowing the result will have an unintended influence” on their life. Conclusion Decision-making about CGT for prognostication in uveal melanoma is burdensome to many patients and in general not guided by medical advice regarding further treatment and screening procedures. The psychological impact of the decision is therefore unique and requires careful support by psycho-oncologists considering the patient’s fears and expectations.

Gossypol is a toxic sesquiterpene dimer produced by cotton plants which deters herbivory by insects and vertebrates. Two highly reactive aldehyde groups contribute to gossypol toxicity by cross-linking herbivore proteins. We identified another consequence of consuming gossypol in two insect pests of cotton: increased amounts of fatty acid-amino acid conjugates (FACs). Eight different FACs in the feces of larval Helicoverpa armigera and Heliothis virescens increased when larvae consumed artificial diet containing gossypol, but not a gossypol derivative lacking free aldehyde groups (SB-gossypol). FACs are produced by joining plant-derived fatty acids with amino acids of insect origin in the larval midgut tissue by an unknown conjugase, and translocated into the gut lumen by an unknown transporter. FACs are hydrolyzed back into fatty acids and amino acids by an aminoacylase (L-ACY-1) in the gut lumen. The equilibrium level of FACs in the lumen is determined by a balance between conjugation and hydrolysis, which may differ among species. When heterologously expressed, L-ACY-1 of H. armigera but not H. virescens was inhibited by gossypol; consistent with the excretion of more FACs in the feces by H. armigera. FACs are known to benefit the plant host by inducing anti-herbivore defensive responses, and have been hypothesized to benefit the herbivore by acting as a surfactant and increasing nitrogen uptake efficiency. Thus in addition to its direct toxic effects, gossypol may negatively impact insect nitrogen uptake efficiency and amplify the signal used by the plant to elicit release of volatile compounds that attract parasitoids.

Purpose To compare intravitreal therapy with the natural course of radiation optic neuropathy after primary proton beam therapy for choroidal melanoma with respect to long-term visual acuity and development of optic atrophy. Design Retrospective comparative case series. Methods Inclusion criteria: patients treated with primary proton beam therapy for choroidal melanoma with a minimum follow-up of 24 months after the occurrence of radiation optic neuropathy and optic disc imaging during follow-up. Exclusion criteria: pathologic condition of the optic disc before irradiation and intravitreal therapy to treat cystoid macular edema not originating from the optic disc. Results Of 93 patients, 48 were observed only after radiation optic neuropathy, and 45 were treated with intravitreal therapy (triamcinolone, bevacizumab, and/or dexamethasone). Median follow-up was 55 months (29-187 months); median interval between onset of radiation optic neuropathy and the last patient visit was 34 months (24-125 months). Of 48 observed patients, 41 (85.4%) developed an optic atrophy after a median of 14 months (3-86 months) after radiation optic neuropathy; and of 45 intravitreally treated patients, 34 (75.5%) presented with an optic atrophy after a median of 12.5 months (1-55 months) following optic neuropathy, indicating no statistically significant differences between the groups. Comparing the change in visual acuity from occurrence of optic neuropathy to final visual acuity, no statistically significant differences were found between either group (P = 0.579). Conclusions Patients treated with intravitreal therapy for radiation optic neuropathy showed no statistically significant differences related to visual acuity or optic atrophy development from patients who underwent only observation.

Netrin-4 (NTN4) is a protein that plays an important role in the regulation of angiogenesis in the pathological retina. Some evidences show that it can also have a role in inflammation and vascular stability. We will explore these questions in vivo in the mature mouse retina. We created a NTN4 knockout that expresses EGFP in mononuclear phagocytes (CSFR1-positive cells) to track inflammation in vivo in the retina by scanning laser ophthalmoscopy (SLO). Fundus angiography permitted to study blood vessels. Retinal function was assessed with electroretinography (ERG). Lack of NTN4 leads to an increased amount of amoeboid mononuclear phagocytes in the adult retina, and blood vessels displayed increased tortuosity when compared with the wildtype. Inner retina function also seemed affected in NTN4 null. Lack of NTN4 resulted in a higher persistence of hyaloid artery and spontaneous leakage in the adult retina. No differences were found regarding vessel bifurcation, vessel width, or vein/artery ratio. These in vivo data show for the first time that lack of NTN4 induces changes in the retinal vascular phenotype in a non-pathological scenario. This evidence widens the role of NTN4 as a guidance cue in vascular remodeling.

Zusammenfassung Hintergrund Die nicht neovaskuläre (trockene) altersbedingte Makuladegeneration (AMD) ist bis heute nicht behandelbar. Dieser Artikel fasst die klinischen Forschungsansätze für eine medikamentöse Therapie zusammen und analysiert, warum diese nicht zum Erfolg geführt haben. Material und Methoden Literatur und Datenbankrecherche. Ergebnisse Insgesamt ist die Zahl der verfolgten Therapieansätze begrenzt. Nur die Reduktion von Lipofuscinablagerungen und Drusen ist spezifisch für die AMD. Weitere Ansätze sind die Modulation der Entzündung und Neuroprotektion. Derzeit konnte mit keinem der Verfahren in einer konfirmatorischen Studie das Voranschreiten der AMD gestoppt oder verlangsamt werden. Diskussion Um die Chancen für Entwicklungserfolge zu erhöhen, muss der aktuell begrenzte pharmakologische Target Space durch die Anwendung molekularer Netzwerkanalysen erweitert werden. Da bei der trockenen AMD der Visus oft nicht der primär betroffene Parameter ist, muss flankierend die Perspektive Betroffener näher untersucht werden, um sinnvolle Therapieziele jenseits des Visus zu definieren.

Extracellular adenosine triphosphate (ATP) regulates a broad variety of physiological functions in a number of tissues partly via ionotropic P2X receptors. Therefore, P2X receptors are promising targets for the development of therapeutically active molecules. Bile acids are cholesterol-derived amphiphilic molecules; their primary function is the facilitation of efficient nutrient fat digestion. However, bile acids have also been shown to serve as signaling molecules and as modulators of different membrane proteins and receptors including ion channels. In addition, some P2X receptors are sensitive to structurally related steroid hormones. In this study, we systematically analyzed whether rat P2X receptors are affected by micromolar concentrations of different bile acids. The taurine-conjugated bile acids TLCA, THDCA, and TCDCA potently inhibited P2X2, whereas other P2X receptors were only mildly affected. Furthermore, stoichiometry and species origin of the P2X receptors affected the modulation by bile acids: in comparison to rat P2X2, the heteromeric P2X2/3 receptor was less potently modulated and the human P2X2 receptor was potentiated by TLCA. In summary, bile acids are a new class of P2X receptor modulators, which might be of physiological relevance.

Background: Knowledge about artifacts in optical coherence tomography angiography (OCTA) is important to avoid misinterpretations. An overview of possible artifacts in posterior uveitis provides important information for interpretations. Methods: In this monocentric prospective study, OCTA images from a total of 102 eyes of 54 patients with posterior uveitis, and an age-matched control group including 34 healthy subjects (67 eyes), were evaluated (day 0, month 3, month 6). We assigned different artifacts to distinct layers. Various types of artifacts were examined in different retinal layers. The χ2 test for the comparison between the control and uveitis group and Cochran’s Q test for the longitudinal comparison within the uveitis group were used. Results: A total of 2238 images were evaluated; 1836 from uveitis patients and 402 from healthy subjects. A total of 2193 artifacts were revealed. Projection (812 [36.3%]), segmentation (579 [25.9%]), shadowing (404 [18.1%]), and blink artifacts (297 [13.3%]) were the most common artifact types. The uveitis group displayed significantly more segmentation artifacts and projection artifacts (p < 0.001). No segmentation artifacts were documented in healthy subjects. The consecutive examinations within the uveitis group revealed the same artifact types without significance (p > 0.1). Conclusions: The uveitis patients showed more segmentation and projection artifacts than the control group. Within the uveitis group, artifacts remained longitudinally constant in terms of artifact type and pattern. The artifacts therefore appear to be reproducible on an individual level.

Diabetic retinopathy is characterized by dysfunction of the retinal vascular network, combined with a persistent low-grade inflammation that leads to vision-threatening complications. Netrin-4 (NTN4) is a laminin-related secreted protein and guidance cue molecule present in the vascular basal membrane and highly expressed in the retina. A number of studies inferred that the angiogenic abilities of NTN4 could contribute to stabilize vascular networks and modulate inflammation. Analyzing human specimens, we show that NTN4 and netrin receptors are upregulated in the diabetic retina. We further evaluated a knock-out model for NTN4 undergoing experimental diabetes induced by streptozotocin. We investigated retina function and immune cells in vivo and demonstrated that NTN4 provides a protective milieu against inflammation in the diabetic retina and prevents cytokine production.

Additional file 12. Heatmap showing spearman’s rank correlation coefficients between all variables regrading a given subscale for timepoints T0-T3.

Additional file 5. Heatmap showing spearman’s rank correlation coefficients between all variables regrading a given subscale for timepoints T0-T3.

Additional file 6. Heatmap showing spearman’s rank correlation coefficients between all variables regrading a given subscale for timepoints T0-T3.

Additional file 19. Visualization of marginal estimates of outcome values with 95% confidence interval at different time points (T0-T3) by sex and GAD-7 subcategory.