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Background: Eye injuries range from minor to severe and may lead to permanent visual impairment. There is still little in the way of epidemiological data on eye injuries in Germany., Aim: The aim of this study was to obtain an objective record of minor and severe eye injuries in Germany by evaluating hospital quality reports. We also investigated the relevance of injuries from fireworks in relation to the total number of eye injuries and the general population., Methods: This retrospective routine data study entailed analysing hospital quality reports from 2008 to 2022 in XML format. The R programming language was used for data processing and statistical analysis. The number of ICD-coded eye injuries was exported and analysed together with location data. We also included data from a prospective survey study on fireworks-related eye injuries from 2016 to 2023., Results: Eyeball and/or orbital contusions are the most common eye injuries treated in Germany at up to 2,500 cases per year. The most severe injuries comprise traumatic globe rupture with loss of intraocular tissue at up to 990 cases per year. Numbers of eye injuries of any type have been declining since 2020. As a percentage of population, Mecklenburg-Western Pomerania treats the most eye injuries at up to 0.017%; in absolute numbers, North Rhine-Westphalia leads the country at up to 1,600 injuries. Private firework displays are probably responsible for 1.4% of annual globe ruptures and 8.3% of eyeball contusions., Conclusion: Our analysis of hospital quality reports has provided the first comprehensive epidemiological record on eye injuries in Germany. Firework-related injuries account for a relevant proportion of total injuries. These results could serve as a basis for preventive measures and health policy decisions., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht./The authors declare that there is no conflict of interest., (Thieme. All rights reserved.)

Purpose: To describe optical coherence tomography angiography (OCTA)-guided navigated laser photocoagulation (LP) using the Navilas Laser System for treating retinal hemangioblastomas (RHs) associated with von Hippel-Lindau disease (VHLD)., Methods: Patients with VHLD were screened using ophthalmoscopy and widefield OCTA. Detected RHs were classified with regard to tumor morphology (endophytic, sessile, exophytic, recurrent) and size. Then, 6 × 6- or 3 × 3-mm2 en face OCTA scans of the RHs were uploaded to the Navilas system, generating a merged image combining the scan and Navilas fundus photography. LP was planned by placing laser spots in the OCTA scan and executed with the Navilas system. Treatment efficacy was assessed by conducting OCTA scans immediately after LP and at follow-up visits., Results: Fifteen RHs were detected in 10 patients (median, one RH; range, one to four). Twelve RHs were treatment naive (exophytic [3], sessile [3], and endophytic [6]), and there were three recurrent RHs in pretreated areas. Total applied energy per tumor correlated with tumor size (P < 0.001). After a mean first follow-up of 3.6 ± 1.5 months (range, 0.9-5.3), nine RHs exhibited complete regression (60%), five partial regression (33.3%), and one no regression (6.7%). No correlation between tumor morphology and treatment success was observed (P = 0.32). However, a correlation between treatment success and tumor size trended toward significance (P = 0.08), with a 100% success rate observed for small RHs., Conclusions: OCTA-guided LP via the Navilas Laser System is a promising technique, especially beneficial for targeting small RHs. Combining OCTA and ophthalmoscopy improves tumor detection, underscoring the utility of this approach., Translational Relevance: OCTA-guided LP enables highly precise and safe treatment of early-stage RHs, minimizing possible complications caused by LP or the tumor itself.

Purpose: The Supine Positioning for Descemet Membrane Endothelial Keratoplasty Attachment (SUPER-DMEK) trial assessed the efficacy of prolonged supine head positioning on graft attachment., Design: Randomized controlled trial., Methods: Participants with Fuchs' dystrophy were randomized to 5 days of supine head positioning (intervention) or to 1 day (control). Participants, surgeons, and investigators were masked until the day after surgery. Adherence to the allocated intervention was monitored using a head sensor. Main outcome measures were area and volume of graft detachment (coprimary end points) 2 weeks after surgery quantified using a validated neural network for image segmentation on anterior segment optical coherence tomography images, and repeat air injection (rebubbling), subjective visual function, and adverse events (secondary end points)., Results: A total of 86 participants received the allocated intervention (35 eyes intervention and 51 eyes control). In the intention-to-treat analysis, the mean area of graft detachment was 28.6% in the intervention arm and 27.5% in the control arm (adjusted between-arm difference, 1.3; 95% CI, -8.7 to 11.4; P = .80). Results for volume of detachment and as-treated analyses based on head position sensor data indicated no potentially clinically relevant effect of prolonged supine positioning on graft attachment. Results were not compatible with a relevant treatment effect on rebubbling or subjective visual function. Adverse events, most commonly back pain, were more common and more severe with the intervention., Conclusions: In this randomized controlled trial, graft attachment was not improved with prolonged supine head positioning. Prolonged supine positioning frequently caused back pain. Prolonged supine positioning after Descemet membrane endothelial keratoplasty for Fuchs' dystrophy may not be needed in routine practice., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Good vision highly depends on the transparency of the cornea, which is the "windscreen" of the eye. In fact, corneal blindness due to transparency loss is the second most common cause of blindness worldwide, and corneal transplantation is the main cure. Importantly, the cornea is normally avascular but can secondarily be invaded by pathological (blood and lymphatic) vessels due to severe inflammation, and the survival prognosis of a corneal graft mainly depends on the preoperative vascular condition of the recipient's cornea. Whereas transplants placed into avascular recipient beds enjoy long-term survival rates of > 90%, survival rates significantly decrease in pathologically pre-vascularized, so-called high-risk recipients, which account for around 10% of all performed transplants in Germany and > 75% in lower and middle-income countries worldwide., Methods: This parallel-grouped, open-randomized, multicenter, prospective controlled exploratory investigator-initiated trial (IIT) intends to improve graft survival by preconditioning pathologically vascularized recipient corneas by (lymph)angioregressive treatment before high-risk corneal transplantation. For this purpose, corneal crosslinking (CXL) will be used, which has been shown to potently regress corneal blood and lymphatic vessels. Prior to transplantation, patients will be randomized into 2 groups: (1) CXL (intervention) or (2) no pretreatment (control). CXL will be repeated once if insufficient reduction of corneal neovascularization should be observed. All patients (both groups) will then undergo corneal transplantation. In the intervention group, remaining blood vessels will be additionally regressed using fine needle diathermy (on the day of transplantation). Afterwards, the incidence of graft rejection episodes will be evaluated for 24 months (primary endpoint). Overall graft survival, as well as regression of corneal vessels and/or recurrence, among other factors, will be analyzed (secondary endpoints)., Discussion: Based on preclinical and early pilot clinical evidence, we want to test the novel concept of temporary (lymph)angioregressive pretreatment of high-risk eyes by CXL to promote subsequent corneal graft survival. So far, there is no evidence-based approach to reliably improve graft survival in the high-risk corneal transplantation setting available in clinical routine. If successful, this approach will be the first to promote graft survival in high-risk transplants. It will significantly improve vision and quality of life in patients suffering from corneal blindness., Trial Registration: ClinicalTrials.gov NCT05870566. Registered on 22 May 2023., (© 2024. The Author(s).)

Purpose: To evaluate early detection of retinal hemangioblastomas (RHs) in von Hippel-Lindau disease (VHLD) with widefield optical coherence tomography angiography (wOCTA) compared to the standard of care in ophthalmologic VHLD screening in a routine clinical setting., Methods: We conducted prospective comparisons of three screening methods: wOCTA, standard ophthalmoscopy, and fluorescein angiography (FA), which was performed only in uncertain cases. The numbers of detected RHs were compared among the three screening methods. The underlying causes for the lack of detection were investigated., Results: In 91 eyes (48 patients), 67 RHs were observed (mean, 0.74 ± 1.59 RH per eye). FA was performed in eight eyes. Ophthalmoscopy overlooked 25 of the 35 RHs detected by wOCTA (71.4%) due to the background color of the choroid (n = 5), small tumor size (n = 13), masking by a bright fundus reflex (n = 2), and masking by surrounding retinal scars (n = 5). However, wOCTA missed 29 RHs due to peripheral location (43.3%). The overall detection rates were up to 37% on the basis of ophthalmoscopy alone, up to 52% for wOCTA, and 89% for FA. Within the retinal area covered by wOCTA, the detection rates were up to 46.7% for ophthalmoscopy alone, up to 92.1% for wOCTA, and 73.3% for FA., Conclusions: The overall low detection rate of RHs using wOCTA is almost exclusively caused by its inability to visualize the entire peripheral retina. Therefore, in unclear cases, FA is necessary after ophthalmoscopy., Translational Relevance: Within the imageable retinal area, wOCTA shows a high detection rate of RHs and therefore may be suitable to improve screening for RHs in VHLD.

Purpose: To propose additional items for established dry eye disease (DED) instruments that cover blepharitis-specific signs and symptoms and to determine the association between the clinical findings and subjective complaints., Methods: Thirty-one patients with blepharitis and DED were prospectively included in the pretest period for selecting suitable questions. In the main phase of the study, the selected questions were then tested on 68 patients with blepharitis and DED and 20 controls without blepharitis or DED. Pearson's coefficient of correlation was calculated between the blepharitis-specific questions, tear break-up time (TBUT), the Schirmer test score, and the ocular surface disease index (OSDI) score; and the similarity between the blepharitis-specific questions, OSDI questions, and objective parameters for DED was assessed via hierarchical clustering. Furthermore, the discriminatory power of the blepharitis-specific questions was investigated with the receiver operating characteristic (ROC) curve., Results: The additional question about heavy eyelids revealed a significant correlation with the OSDI score (r = 0.45, p < 0.001) and Schirmer score (r =  - 0.32, p = 0.006). Cluster analysis demonstrated the similarity between the question about heavy eyelids and TBUT. In addition, the OSDI questionnaire had the highest discriminatory power in ROC analysis, and the OSDI score significantly correlated with the specific questions about eyelids sticking together (r = 0.47, p < 0.0001) and watery or teary eyes (r = 0.34, p = 0.003)., Conclusions: The blepharitis-specific additional questions were closely associated with objective parameters for DED. The question about heavy eyelids might be well suited for recording the symptoms of hyposecretory and hyperevaporative dry eye with blepharitis., (© 2023. The Author(s).)

Purpose: Keratoconus leads to visual deterioration due to irregular astigmatism and corneal thinning. Riboflavin-based corneal UV-A crosslinking (CXL) induces novel intramolecular and intermolecular links resulting in corneal tissue stiffening, thereby halting disease progression. The purpose of this study was to analyze the immediate and delayed biomechanical responses of human donor corneas to CXL., Methods: CXL was performed according to the Dresden protocol to corneas not suitable for transplantation. Biomechanical properties were subsequently monitored by measuring the Young modulus using nanoindentation. The immediate tissue response was determined after 0, 1, 15, and 30 minutes of irradiation. Delayed biomechanical effects were investigated with follow-up measurements immediately and 1, 3, and 7 days after CXL., Results: Young's modulus indicated a linear trend in direct response to increasing irradiation times (mean values: total 61.31 kPa [SD 25.53], 0 minutes 48.82 kPa [SD 19.73], 1 minute 53.44 kPa [SD 25.95], 15 minutes 63.56 kPa [SD 20.99], and 30 minutes 76.76 kPa [SD 24.92]). The linear mixed model for the elastic response of corneal tissue was 49.82 kPa + (0.91 kPa/min × time [minutes]); P < 0.001. The follow-up measurements showed no significant delayed changes in the Young modulus (mean values: total 55,28 kPa [SD 15.95], immediately after CXL 56,83 kPa [SD 18.74], day 1 50.28 kPa [SD 14.15], day 3 57.08 kPa [SD 14.98], and day 7 56.83 kPa [SD 15.07])., Conclusions: This study suggests a linear increase of corneal Young modulus as a function of CXL timing. No significant short-term delayed biomechanical changes posttreatment were observed., Competing Interests: The authors declare no conflict of interest. No funding was received for this study., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Tectonic keratoplasties (TK) are used to treat corneal and scleral perforations and to prevent the loss of the eye. In this study, we retrospectively analyzed indications, surgical procedures, and outcomes of eccentric mini and corneo-scleral tectonic keratoplasties with respect to anatomical survival and clear graft survival rates to identify risk factors for graft failure., Methods: This retrospective study includes 33 eccentric mini (graft diameter <6 mm) and/or corneo-scleral TK of 32 consecutive patients of a total of 41 TK carried out between 2005 and 2020 in the Eye Center, University of Freiburg, Germany, making up 0.7% of all keratoplasties performed during this period (n = 5557). Patient and graft specific data were extracted from medical files. Anatomical survival-defined as achieving integrity of the globe without further surgical interventions-and clear graft survival-defined as persisting graft clarity-were estimated using the Kaplan-Meier method. We also fitted Cox proportional hazard models to account for factors influencing anatomical and clear graft survival., Results: Median duration of anatomical success was 72.5 months (95% confidence interval (CI) 18.1-infinite (inf.)) and median duration of clear graft survival was 29.6 months (95% CI 12.5-Inf.). The 1-year survival rate for anatomical survival was 67.6% (95% CI 52.2% - 87.6%) and for clear graft survival 66.4% (95% CI 50.5%- 87.1%). No enucleation was necessary during this time-period. Non-inflammatory primary causes (n = 14) presented a trend towards better anatomical survival rates (median remained above 0.75 during follow-up) compared to inflammatory primary causes (n = 19, median 18.1 months (95% CI 2.8 - inf.)) and longer clear graft survival (median 29.6 months (95% CI 12.5 - inf.) versus 13.1 months (95% CI 3.2 - inf.)). Corneo-scleral grafts (n = 18) compared to corneal grafts (n = 15) showed a trend towards better anatomical survival (more than 50% of eyes did not fail during follow-up period (95% CI 21.9-Inf. months) versus 18.1 months (95% CI 2.4-Inf.)) and clear graft survival (median 29.6 months (95% CI 12.6-Inf.) versus 6.2 months (95% CI 2.8-Inf.)). Old age (n = 11, 75.2 - 90.1 years) compared to young age (n = 11, 6.2 - 60.2 years) was the only hazard ratio (hazard ratio 0.04 (95% CI 0.002-0.8)) that reached the level of significance (p = 0.03)., Conclusion: Eccentric TK is helpful in the successful treatment of a variety of severe eye diseases. Patients at young age, with pre-existing inflammatory conditions or corneal TK are at higher risk for anatomical failure as well as clear graft failure and therefore need to be monitored closely., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Wiedenmann et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Keratoconus is associated with an impairment in corneal biomechanics. Using nanoindentation, spatially resolved measurement of biomechanical properties can be performed on corneal tissue. The aim of this study is to assess the biomechanical properties of corneas with keratoconus in comparison to healthy controls., Methods: 17 corneas with keratoconus and 10 healthy corneas unsuitable for transplantation were included in the study. After explantation, corneas were kept in culture medium containing 15% dextran for at least 24 h. Nanoindentation was then performed to a depth of 25 µm at a force increase of 300 µN/min., Results: A total of 2328 individual indentations were performed for this study. In the keratoconus group; the mean modulus of elasticity was 23.2 kPa (± 15.0 kPa) for a total of 1802 indentations. In the control group, the mean modulus of elasticity was 48.7 kPa (± 20.5 kPa) with a total of 526 indentations. The Wilcoxon test showed that the differences were statistically significant., Conclusion: Using nanoindentation, a significantly lower elastic modulus was found in corneas with keratoconus compared to corneas without keratoconus. Further studies are needed to gain a better understanding of how keratoconus affects corneal biomechanics., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: Surgical procedures in ophthalmology are subject to fluctuations in their application and are dependent on new developments, availability, and success rates. In the field of glaucoma surgery in particular, numerous new procedures have been introduced over the last few years. So far, hardly any analyses have been done on the current application of these newer procedures. In this paper, we present the extent to which different glaucoma surgery procedures were used in German hospitals in 2019., Methods: The quality reports of German hospitals from 2019 were evaluated regarding all glaucoma-specific procedure codes. In particular, laser procedures, "classic" glaucoma procedures, and "modern" procedures such as MIGS (minimally invasive glaucoma surgery) are compared below., Results: In 2019, 49,031 glaucoma procedures were performed in German hospitals. Numerically, cyclodestructive procedures were used most frequently. MIGS accounted for approximately 10% of procedures according to the available data. Among filtering procedures, about 40% were implant-assisted., Discussion and Conclusion: On the one hand, the data analyzed show a mixed expansion of the spectrum with newer procedures such as the MIGS and implants; on the other hand, classic procedures such as cyclodestruction are still used. It can be assumed that further shifts in surgical methods will be seen in the coming years., Competing Interests: Lübke: Vortragstätigkeit für Allergan/Abbvie, MST./The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Favorable functional outcomes have been reported after excimer laser-assisted penetrating keratoplasty (EXL PKP). But this technique has not been widely adopted, and there are reports on EXL PKP from only a very limited number of institutions. Some of these results refer to operations carried out with laser systems that are not commercially available. In this retrospective case series, we report the long-term outcome of EXL PKP using the Schwind Amaris 500E laser system., Material and Methods: This retrospective consecutive case series included 30 eyes of 29 patients who had undergone EXL PKP between 2010 and 2013. Primary outcome measures were topographic astigmatism and visual acuity. Secondary outcome measures were the rates of graft rejection and graft failure, and the rate of grafts with an endothelial cell density below 500 cells/mm 2 . Survival analyses were carried out for the following endpoints: visual acuity, rate of graft rejection, and rate of grafts with endothelial cell densities higher than 500 cells/mm 2 ., Results: The median interquartile range (IQR) duration of follow-up was 45 (36) months. The indications for PKP were keratoconus (n = 21), corneal scarring (n = 6), Fuchs endothelial dystrophy (n = 1), and corneal dystrophy other than Fuchs endothelial dystrophy (n = 2). The median (IQR) topographic astigmatism at the end of the follow-up period was 5.3 (2.9) D. Forty-five months after surgery, 73% of all eyes had a visual acuity better than 0.3 LogMAR. The rate of graft rejection after 45 months of follow-up was 32%. All eyes maintained endothelial cell densities higher than 500 cells/mm 2 . There was no graft failure., Conclusions: EXL PKP is a safe and effective surgical procedure. No general conclusions can be drawn on the refractive outcome of EXL PKP. Potential advantages, such as a higher degree of graft-host congruity, that could possibly improve the refractive outcome should be weighed against the higher costs of EXL PKP., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Purpose: Limbo-keratoplasty enables visual improvement and limbal stem cell transplantation at the same. During follow-up, most grafts show vascularization of the limbus. However, it is unclear whether vascularization is harmful due to immunologic effects or helpful to nourish the limbal stem cells and is therefore necessary for a clear graft. The aim of our study is to analyze the influence of graft vascularization on graft survival following homologous limbo-keratoplasty., Methods: In this retrospective study, we assessed all consecutive limbo-keratoplasties performed in our hospital. All eyes with suitable photo-documentation were included and divided into two groups (limbal stem cell deficiency and corneal dystrophy). We categorized the grade of vascularization (0, 1, 2, 3, 3b) and analyzed clear graft survival, recurrence of the underlying disease and the endothelial cell density (ECD) with regard to the reason for the graft. Event rates were estimated with the Kaplan-Meier method., Results: A total of 79 eyes with limbal stem cell deficiency and 15 with corneal dystrophies were analyzed. A high degree of graft vascularization had a tendency for better graft survival in limbal stem cell deficiency, whereas in corneal dystrophies, grafts with no vascularization had preferable outcomes. Recurrence-free graft survival was only seen in grade 1 and 3 vascularization in corneal dystrophies., Conclusion: Vascularization of the limbus seems to have an impact on the long-term outcome of limbo-keratoplasty. The effect seems to be favorable in limbal stem cell deficiency and on recurrence rates in corneal dystrophies. However, the latter might be overshadowed by an unfavorable immunologic effect in corneal dystrophies where the baseline immunologic risk profile is commonly more favorable than in limbal stem cell deficiency., (© 2022. The Author(s).)

Breast cancer is the most common cancer and the leading cause of cancer-related mortality among females worldwide. From the leaves of Callistemon citrinus, we have isolated a novel phloroglucinol dimer, calcitrinone A, and analyzed its potential anticancer activity using the triple-negative breast cancer cell line MDA-MB-231. Calcitrinone A decreased the total intracellular ATP levels, inhibited proliferation, and induced apoptosis in MDA-MB-231 cells, but was less toxic to peripheral blood mononuclear cells. The antiproliferative and apoptosis-inducing effects of calcitrinone A were confirmed in vivo using breast cancer xenografts grown on chick chorioallantoic membranes. Mechanistic analysis showed mitochondrial membrane-potential dissipation and interference with energy-yielding processes resulting in cell accumulation in the S phase of the cell cycle. Seahorse assay analysis revealed an early inhibition of mitochondrial oxidative phosphorylation (OXPHOS). At the molecular level, calcitrinone A inhibited activity of the succinate-coenzyme Q reductase (SQR) (mitochondrial complex II). In silico docking identified the coenzyme Q binding pocket as a possible high affinity binding site for calcitrinone A in SQR. Inhibition of complex II was accompanied by strong elevation of mitochondrial superoxide and cytoplasmic ROS. Calcitrinone A might be a promising anticancer lead compound acting through the interference with the mitochondrial complex II activity., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Readmission after coronary artery bypass grafting (CABG) is associated with adverse outcomes and increased cost. We evaluated the impact of a high-value care discharge protocol on readmission, length of stay (LOS), and discharge destination in patients undergoing isolated CABG., Methods: In 2016, a comprehensive, patient-centered discharge protocol was implemented. A nurse practitioner was the fulcrum of this program, which focused on improving health literacy, disease management, and rigorous follow-up. All patients undergoing isolated CABG between 2012 and 2019 were retrospectively analyzed with regard to 30-day readmission, LOS, and discharge disposition. Differences were analyzed by Mann-Whitney, chi-square, and t tests. Analyses were repeated using propensity matching., Results: A total of 910 consecutive patients undergoing isolated CABG were included in the analyses: 353 preprotocol and 557 postprotocol. Preprotocol patients had a readmission rate of 14.4% (n = 51), compared with 6.8% (n = 38) in the postprotocol patients (P < .001). Median postoperative LOS before implementation was 6 (interquartile range, 5-8) days compared with 5 (interquartile range, 4-6) days postimplementation (P < .001). Postimplementation, a higher proportion of patients were discharged to home compared with a skilled nursing facility (82.7% [n = 461] vs 73.9% [n = 261]; P = .002). After propensity matching, 298 well-balanced patients were included for analysis and these significant reductions in LOS, readmission, and discharge destination persisted., Conclusions: Implementation of a new discharge protocol was significantly associated with reduced readmission and LOS, along with higher rates of discharge to home in isolated CABG patients. Importantly, the results were sustainable and did not require additional resources, delivering high-value care., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Blunt traumatic innominate artery injuries occur in polytrauma victims who have suffered high-speed motor vehicle collisions. Their associated injuries may preclude the use of heparin and affect surgical management and perioperative neurological risk. The uniqueness of this case is combining the arterial injury repair with a severe progressive neurological injury that prohibited standard perioperative antiplatelet or anticoagulent use., Competing Interests: The authors declare no conflict of interest related to this article., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Keratoconus is morphologically associated with increasing deformation, thinning and scarring of the cornea. This functionally leads to refractive changes and visual deterioration. In the early stages there are often no clear clinical signs in the slit-lamp examination; however, confirming the diagnosis as early as possible is important in order to provide patients with an appropriate treatment. For the early diagnosis of keratoconus, various diagnostic devices have been introduced in recent years and decades. These include keratometry with reflection-based or elevation-based systems and optical coherence tomography. High-frequency ultrasound microscopy and corneal biomechanics can also be used to establish the diagnosis of keratoconus by the measurement of other parameters. The necessity and the available possibilities for early diagnosis of keratoconus are presented in more detail in this article., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background/aims: Retinal haemangioblastomas (RH) remain a major cause of visual impairment in patients with von Hippel-Lindau (VHL) disease. Identification of genotype-phenotype correlation is an important prerequisite for better management, treatment and prognosis., Methods: Retrospective, single-centre cohort study of 200 VHL patients. Genetic data and date of onset of RH, central nervous system haemangioblastomas (CNSH), pheochromocytoma/paraganglioma (PPGL), clear cell renal cell carcinoma (ccRCC) and pancreatic neuroendocrine neoplasm (PNEN) were collected. The number and locations of RH were recorded., Results: The first clinical finding occurred at an age of 26 ± 14 years (y) [mean ± SD]. In 91 ± 3% (95% CI 88-94) of the patients, at least one RH occur until the age of 60y. A total of 42 different rare VHL gene variants in 166 patients were detected. A higher age-related incidence of RH, CNSH, ccRCC and PNEN was detected in patients with a truncating variant (TV) compared to patients with a single amino-acid substitution/deletion (AASD) (all p < 0.01), while it is reverse for PPGL (p < 0.01). Patients with a TV showed 0.10 ± 0.15 RH per y during their lifetime compared to 0.05 ± 0.07 in patients with AASD (p < 0.02). The median enucleation/phthisis-free survival time in patients with a TV was 56y (95% CI 50-62) compared to 78y (95% CI 75-81) in patients with AASD (p < 0.02)., Conclusion: Compared to patients with AASD, patients with a TV develop RH, CNSH, ccRCC and PNEN earlier. They experience a higher number of RH and bear a higher risk of enucleation/phthisis. Thus, patients with a TV might be considered for a more intensive ophthalmological monitoring., (© 2021 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: The posterior cornea is rotationally asymmetric, and Descemet membrane endothelial keratoplasty (DMEK) grafts preferentially scroll vertically. This prospective study assessed whether graft attachment after DMEK differed depending on the rotational alignment of the donor graft in the recipient eye., Methods: Pseudo-randomization and blinding of the graft orientation in the recipient's eye were possible by procedural separation: (1) The eye bank recorded the position of an orientation marker in the donor cornea; (2) the surgeon preparing the DMEK graft recorded an upside-down marker relative to the eye bank marker; and (3) the surgeon assessed the position of the upside-down marker in the recipient after DMEK. Surgeons were masked towards the eye bank marker. Using mixed-effects models, we assessed graft attachment relative to the rotational alignment of the donor graft., Results: Postoperatively, the graft was not fully attached in 59 of 179 eyes (33%). A second air fill (rebubbling) was performed in 11%. The graft axis was in line with the recipient cornea axis in 40%, oblique in 28% and orthogonal in 32%. We did not detect an elevated risk of incomplete attachment (odds ratio [OR], 1.16; 95% CI, 0.61-2.20), risk of rebubbling (OR, 1.25; 95% CI, 0.47-3.31) or larger areas of graft detachment in non-aligned grafts compared to aligned grafts., Conclusion: Rotational alignment was not strongly associated with the risk of incomplete graft attachment, although modestly elevated risks cannot be ruled out. Efforts are needed to reduce the need for rebubbling after DMEK and to identify modifiable risk factors for graft detachment., (© 2021 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

During the coronavirus disease 2019 (COVID-19) pandmic, more patients are presenting with complications late after acute myocardial infarction. We report the case of a 71-year-old man who delayed seeking medical care for 2 weeks, despite progressive shortness of breath, cough, and tactile fever, for fear of contracting COVID-19 in the hospital. Clinical and echocardiographic evaluation revealed a ventricular septal rupture secondary to acute myocardial infarction. The patient underwent urgent cardiac catheterization, followed by successful saphenous vein grafting to the left anterior descending coronary artery and open surgical repair of the ventricular septal rupture with a bovine pericardial patch. This case highlights a potential long-lasting negative effect that the COVID-19 pandemic will have on the care-seeking behavior and health of patients with acute cardiovascular disease., (© 2021 by the Texas Heart® Institute, Houston.)

Keratoconus leads to a progressive protrusion and thinning of the cornea. In order to stop this, corneal crosslinking can be performed if the progression of the disease is proven. Crosslinking according to the "Dresden protocol" includes abrasion of the corneal epithelium, application of riboflavin eye drops and irradiation with UV-A light of an intensity of 3 mW/cm² for 30 minutes. The efficacy has been shown in several prospective randomized studies. One of the more recent developments is accelerated crosslinking, which allows a shorter irradiation time. On the other hand, the possibility of transepithelial crosslinking was presented, which does not require an abrasion of the cornea. This should reduce the occurrence of postoperative pain. The range of indications has also been expanded. Corneal crosslinking is used for post-LASIK keratectasia as well. It is also being considered for use in infectious keratitis. Topographically controlled crosslinking can likewise be used to try to positively influence the refractive power of the cornea. The risks of crosslinking include the occurrence of pain, haze or scarring, endothelial cell damage and, rarely, the occurrence of keratitis., Competing Interests: Erklärung zu finanziellen Interessen Forschungsförderung erhalten: ja, von einer anderen Institution (Pharma- oder Medizintechnikfirma usw.); Honorar/geldwerten Vorteil für Referententätigkeit erhalten: nein; Bezahlter Berater/interner Schulungsreferent/Gehaltsempfänger: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an im Bereich der Medizin aktiven Firma: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an zu Sponsoren dieser Fortbildung bzw. durch die Fortbildung in ihren Geschäftsinteressen berührten Firma: nein. Erklärung zu nichtfinanziellen Interessen Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Cardenolide glycosides are natural compounds known to inhibit the ion pumping function of the Na + /K + -ATPase in cellular systems. Interestingly, various cancer cell types are highly susceptible to cardenolide glycosides. Herein, we explore the cardenolide glycoside Acovenoside A (AcoA) with respect to its influences on human A549 non-small cell lung cancer (NSCLC) cells. We found that exposure to AcoA, digoxin and ouabain increases intracellular sodium and ATP levels indicating that the ion pumping function of the transmembrane Na + /K + -ATPase is effectively inhibited. Like digoxin and ouabain, AcoA inhibits transcription factor NF-κB activation and induces apoptotic cell death in NSCLC cells. This was confirmed by a preclinical in vivo model in which AcoA treatment of NSCLC xenografts grown on chick chorioallantoic membranes inhibited the expression of proliferation antigen Ki-67 and induced apoptotic DNA strand breaks. We aimed to elucidate the underlying mechanisms. The Na + /K + -ATPase transmembrane complex contains Src kinase and epidermal growth factor receptor (EGFR). Indeed, we found that AcoA activates Src kinase in A549 cells, but not in a cell-free assay using recombinant Src kinase. Src kinase is a downstream target of EGFR, and correlation analysis using the NCI60 database pointed to a role of EGFR in cardenolide glycoside-induced cancer cell death. Accordingly, NSCLC cells expressing hyperphosphorylated EGFR mut exhibited resistance to AcoA. To investigate the interaction between cardenolide glycosides and EGFR in detail, we performed immunoblotting studies: Whereas ligand binding and EGFR phosphorylation were not significantly affected, ubiquitinated EGFR accumulated after prolonged incubation with AcoA. To visualize EGFR trafficking we used A549 cells transfected with a fluorescent biosensor which binds to activated EGFR. Pretreatment with AcoA and digoxin induced accumulation of EGFR in endosomal compartments thus inhibiting EGF-induced EGFR degradation comparable to the Na + ionophore monensin, a known inducer of EGFR endosomal arrest. Intracellular Na + concentrations regulate EGFR trafficking and signaling. Na + homeostasis is maintained by the Na + /K + -ATPase, which might account for its close interaction with the EGFR. Cardenolide glycosides inhibit the ATP-dependent Na + /K + exchange through the Na + /K + -ATPase resulting in higher intracellular Na + levels. Our data provide first evidence that this impedes efficient EGFR trafficking at the endosomal compartment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hafner, Schmiech and Lang.)

Background: Keratoplasty is considered the most frequently performed type of transplantation in humans. Traditionally, penetrating keratoplasty has been the most common procedure. However, over the last 15 years, the importance of posterior lamellar keratoplasty has increased for the treatment of Fuchs endothelial dystrophy and bullous keratopathy. In Germany, based on national surveys, it was suggested that there was a trend towards lamellar keratoplasty., Objective: The main objective of this study was to determine whether the proportion of lamellar keratoplasties carried out in Germany between 2006 and 2017 had increased. Furthermore, the number of keratoplasties carried out as HLA-matched (HLA: human leukocyte antigen) keratoplasties should be calculated., Materials and Methods: The numbers of all keratoplasties carried out as lamellar/penetrating and HLA-matched keratoplasties was extracted from the hospital quality reports published between 2006 and 2017. Descriptive statistical analysis was carried out in R (www.r-project.org)., Results: Between 2006 and 2017, 43,021 keratoplasties were carried out in Germany. The number of keratoplasties increased from 2,849 (2006) to 8,231 (2017). The number of penetrating keratoplasties remained stable. The proportion of lamellar keratoplasties increased from 6.5% (2006) to 61.4% (2017). The proportion of HLA-matched keratoplasties was below 20% and declined between 2010 and 2017 (2010: 19.7%; 2017: 9.8%)., Discussion: In Germany, posterior lamellar keratoplasty has become increasingly important. Since 2014, the number of lamellar keratoplasties has exceeded the number of penetrating keratoplasties. However, the number of penetrating keratoplasties remained stable between 2006 and 2017 and still plays an important role in the management of patients with predominantly stromal or corneal defects affecting all layers. The decreasing number of HLA-matched keratoplasties is most likely due to the lack of clear evidence of a significant reduction in the rejection rates in cases of normal risk keratoplasty., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Allogenic transplants of the cornea are prone to rejection, especially in repetitive transplantation and in scarred or highly vascularized recipient sites. Patients with these ailments would particularly benefit from the possibility to use non-immunogenic decellularized tissue scaffolds for transplantation, which may be repopulated by host cells in situ or in vitro. So, the aim of this study was to develop a fast and efficient decellularization method for creating a human corneal extracellular matrix scaffold suitable for repopulation with human cells from the corneal limbus. To decellularize human donor corneas, sodium deoxycholate, deoxyribonuclease I, and dextran were assessed to remove cells and nuclei and to control tissue swelling, respectively. We evaluated the decellularization effects on the ultrastructure, optical, mechanical, and biological properties of the human cornea. Scaffold recellularization was studied using primary human limbal epithelial cells, stromal cells, and melanocytes in vitro and a lamellar transplantation approach ex vivo. Our data strongly suggest that this approach allowed the effective removal of cellular and nuclear material in a very short period of time while preserving extracellular matrix proteins, glycosaminoglycans, tissue structure, and optical transmission properties. In vitro recellularization demonstrated good biocompatibility of the decellularized human cornea and ex vivo transplantation revealed complete epithelialization and stromal repopulation from the host tissue. Thus, the generated decellularized human corneal scaffold could be a promising biological material for anterior corneal reconstruction in the treatment of corneal defects.

Blocking the terminal complement pathway with the C5 inhibitor eculizumab has revolutionized the clinical management of several complement-mediated diseases and has boosted the clinical development of new inhibitors. Data on the C3 inhibitor Compstatin and the C5 inhibitors eculizumab and Coversin reported here demonstrate that C3/C5 convertases function differently from prevailing concepts. Stoichiometric C3 inhibition failed to inhibit C5 activation and lytic activity during strong classical pathway activation, demonstrating a "C3 bypass" activation of C5. We show that, instead of C3b, surface-deposited C4b alone can also recruit and prime C5 for consecutive proteolytic activation. Surface-bound C3b and C4b possess similar affinities for C5. By demonstrating that the fluid phase convertase C3bBb is sufficient to cleave C5 as long as C5 is bound on C3b/C4b-decorated surfaces, we show that surface fixation is necessary only for the C3b/C4b opsonins that prime C5 but not for the catalytic convertase unit C3bBb. Of note, at very high C3b densities, we observed membrane attack complex formation in absence of C5-activating enzymes. This is explained by a conformational activation in which C5 adopts a C5b-like conformation when bound to densely C3b-opsonized surfaces. Stoichiometric C5 inhibitors failed to prevent conformational C5 activation, which explains the clinical phenomenon of residual C5 activity documented for different inhibitors of C5. The new insights into the mechanism of C3/C5 convertases provided here have important implications for the development and therapeutic use of complement inhibitors as well as the interpretation of former clinical and preclinical data., (© 2021 by The American Society of Hematology.)

Boswellic acids, and particularly 11-keto-boswellic acids, triterpenoids derived from the genus Boswellia ( Burseraceae ), are known for their anti-inflammatory and potential antitumor efficacy. Although boswellic acids generally occur as α-isomers (oleanane type) and β-isomers (ursane type), 11-keto-boswellic acid (KBA) was found only as the β-isomer, β-KBA. Here, the existence and natural occurrence of the respective α-isomer, 11-keto-α-boswellic acid (α-KBA), is demonstrated for the first time. Initially, α-KBA was synthesized and characterized by high-resolution mass spectrometry (HR-MS) and nuclear magnetic resonance (NMR) spectroscopy, and a highly selective, sensitive, and accurate high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) method was developed by Design of Experiments (DoE) using a pentafluorophenyl stationary phase. This method allowed the selective quantification of individual 11-keto-boswellic acids and provided evidence for α-KBA in Boswellia spp. oleogum resins. The contents of α-KBA as well as further boswellic acids and the composition of essential oils were used to chemotaxonomically classify 41 Boswellia oleogum resins from 9 different species. Moreover, α-KBA exhibited cytotoxicity against three treatment-resistant triple-negative breast cancer (TNBC) cell lines in vitro and also induced apoptosis in MDA-MB-231 xenografts in vivo. The respective β-isomer and the acetylated form demonstrate higher cytotoxic efficacies against TNBC cells. This provides further insights into the structure-activity relationship of boswellic acids and could support future developments of potential anti-inflammatory and antitumor drugs.

Nodular scleritis and necrotizing scleritis are rare complications of acanthamoeba keratitis. This article presents the case of a 61-year-old female patient who had suffered from persistent keratitis in the right eye for more than 4 months. The patient was initially treated with propamidine isethionate and polyhexamethylene biguanide eye drops. A penetrating limbo-keratoplasty was performed. Examination of the corneal explant showed acanthamoeba cysts. In the following 5 months the sclera showed recurrent abscesses. A total of two thermal cauterizations and three amniotic membrane grafts were carried out. To our knowledge, this is the first case of sclerokeratitis after acanthamoeba keratitis which was treated with a combination of thermal cauterization and amniotic membrane transplantation. Further studies are necessary to investigate this procedure as an alternative to the established cryotherapy.

Background: All hospitals in Germany have a legal obligation to carry out internal quality management (QM). This means enormous costs as well as a burden for the employees through QM-specific tasks. The benefits can be advertising through certification, higher quality and safety for the treated patients and thus greater patient and employee satisfaction. The aim of this work is to compare effort and benefit of a QM system in ophthalmology., Material and Methods: The surgical quality parameters already published in the annual reports, the available data of the QM handbook via the digital QM portal and patient feedbacks from 2004 to 2018/2019 were evaluated., Results: In 2004, a quality management system was established for the first time in the Eye Centre at the Freiburg University Hospital. From 2005 to 2017, the entire hospital was KTQ-certified. In order to analyse the quality of surgery and patient safety, different surgical quality parameters were collected over the years with a constantly increasing number of operations. The majority of the quality parameters have remained stable or even decreased over the years. A peak in the postoperative endophthalmitis rate of 0.14% in 2015 and the decreasing percentage of cataract operations under topical anaesthesia in recent years were striking. The QM handbook was slimmed down. The analysis of clicks shows that the documents are increasingly used by the employees. The statistics of patient feedbacks show that this is a tool that is used quite frequently by patients to provide feedback on their stay and that the feedback is often positive., Conclusion: To operate quality management over many years, i.e. in our case to collect data of surgical quality parameters, to maintain the QM manual and to process patient feedbacks, means considerable effort. However, only the analysis of these parameters provides an insight into the current state of our clinic, from which conclusions can be drawn as to where processes or treatments can be optimised, which in turn can increase employee and patient satisfaction. Overall, transparency is increased and creates confidence for future treatments at the Eye Centre at the Freiburg University Hospital., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Purpose: Recently, intraoperative optical coherence tomography (iOCT) has evolved in the field of ophthalmic surgery. So far, the use of iOCT was mainly focused to lamellar keratoplasty, especially deep anterior lamellar keratoplasty (DALK) and Descemet membrane endothelial keratoplasty (DMEK). The aim of this study was to report our experiences with iOCT to introduce new possibilities of this application., Methods: We used iOCT in 18 patients who underwent the following surgeries: DALK, DMEK, penetrating keratoplasty, autologous limbal transplantation, transscleral suture fixation of a posterior chamber lens, pannus removal on corneal surface and newborn investigation in Peters' anomaly. We obtained qualitative video data for all procedures., Results: With the iOCT, the cannula placement during DALK preparation of the recipient cornea and bubble formation could be visualized to improve the success rate of the big bubble injection. In DMEK, the iOCT enables the visualization of Descemet's membrane removal in the recipient and graft orientation as well as better control of graft attachment. The iOCT enables intraoperative visualization of the graft-host interface during penetrating keratoplasty. During autologous limbal transplantation, transscleral suture fixation of a posterior chamber lens and removal of corneal surface pannus the iOCT is capable of showing the thickness of lamellar preparations to avoid penetrations and to save healthy recipient's tissue., Conclusion: The iOCT is a helpful device for intraoperative anterior segment imaging not only for DALK and DMEK. It is also beneficial in penetrating keratoplasty and every other form of lamellar preparation during corneoscleral surgery.

Background: The treatment of tumors increasingly takes place in specialised interdisciplinary centres. Therapeutic decisions are usually made at case conferences. Ophthalmologists, oromaximillofacial surgeons, ENT physicians, neurosurgeons, as well as pediatricians, radiotherapists and radiologists are all involved in the treatment of orbital diseases. The aim of this article is to present the concept of a multidisciplinary case conference for orbital diseases and to analyse case numbers, indications, and the influence on the patient's therapy., Methods: We analysed an anonymized data set of patients who presented in the case conference of the University Hospital Freiburg from 2008 to 2018 with regard to clinical diagnosis, histological diagnoses, number of surgical interventions, and number of interdisciplinary therapy decisions., Results: From 2008 to 2018, 545 patients were presented in a weekly conference. Of these, 453 were available for anonymous evaluation. The median age was 56 years (quartiles 41; 69). The most frequent indication was an orbital tumour of unclear malignancy (n = 52; 11%). Further indications included Grave's orbitopathy (n = 39; 9%), orbital pseudotumour (n = 36; 8%), cranial nerve palsy (n = 22; 5%), and orbital lymphoma (n = 22; 5%). The most frequent histological diagnoses were B-cell lymphoma (n = 10; 2%), venous malformation (cavernoma, n = 8; 2%), marginal zone lymphoma (n = 8; 2%), and squamous cell carcinoma (n = 6; 1%). An interdisciplinary therapeutic approach was defined for 174 patients., Conclusion: A high demand for the interdisciplinary case conference was demonstrated. The high rate of primary or secondary interdisciplinary decisions indicates the value of such a conference. Hence, the patient is spared multiple examinations in the individual specialist areas and quick and effective therapy decisions can be achieved., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Purpose: To characterize the choriocapillaris (CC) structure in relation to subretinal fluid (SRF) as a possible systematic error source using spectral domain (SD-OCTA) compared to swept-source optical coherence tomography angiography (SS-OCTA)., Methods: This is a prospective case-control study of 23 eyes. Ten patients with acute central serous chorioretinopathy (CSC), three patients with partial macular-off retinal detachment (RD) and ten healthy, age-matched controls were included. Abnormal CC decorrelation signals were quantitatively compared in CSC and controls by means of custom image processing. To investigate the influence of SRF on CC OCTA signal, the extent of SRF was quantified with a macular heatmap and compared with the corresponding OCTA signal of the CC., Results: SS-OCTA yielded a more homogeneous OCTA signal from the CC than SD-OCTA, offering less signal dispersion and variability in healthy and diseased eyes. Both devices demonstrated CC signal voids in CSC and RD, respectively. In CCS, the voids were predominantly located in the area with SRF. Compared to SD-OCTA, SS-OCTA delivered a more homogenous OCTA signal and reduced signal voids in the CC underneath SRF in both RD and CSC (CSC, 7.6% ± 6.3% vs, 19.7% ± 9.6%, p < 0.01). Despite this significant attenuation of signal voids, SS-OCTA continued to reveal signal voids below SRF and more pixels with reduced OCTA signals in CSC patients compared to controls (7.6% ± 6.3%, 0.1% ± 0.1%, p < 0.0001)., Conclusion: Understanding OCTA artifacts is critical to ensure accurate clinical evaluations. In this study, we describe the presence of SRF as an important shadow-causing artifact source for CC OCTA analysis which can be mitigated but not completely eliminated by employing SS-OCTA.

Medical information websites are usually targeted toward patients, physicians, and medical students. Most of the latest studies researched the usability of such websites. However, reports on user numbers and behavior are rare.The goal of our study is to analyze the utility of a website of a large tertiary referral center in ophthalmology in terms of various target audiences (patients, applicants, medical students, referring ophthalmologists).The web access data from our institutional website was assessed with Google Analytics. Data collection started in 2016.From 2016 to 2018, we counted a total of 763,942 page views. The overall number of users dropped from 81,572 to 67,740. This drop's onset correlates with a change in the website structure. All target audience pages received constant traffic from 2016 to 2019, with the patients' and doctors' sites attracting the most traffic. The pages for medical students and job applicants, although not viewed often, revealed a long session duration.Our website is used by all our target audiences. The behavior and the user numbers of each target group differ. Changes to a website's structure can influence the number of users and their behavior. It is not possible to make a direct comparison to other institutions' websites as there are so few similar reports available. By adding more parameters to the analytics profile in a prospective setting, more detailed analyses of user behavior may be possible in the future.

Purpose: To compare spectral-domain (SD) and swept-source (SS) optical coherence tomography angiography (OCTA) for imaging retinal capillary hemangioblastomas (RCHs) in von Hippel-Lindau disease (VHLD)., Methods: Prospective single-center cross-sectional study. Tumor size (TS) of perfused RCHs was assessed clinically in relation to the optic disc size. For both technologies, SD-OCTA and SS-OCTA, corresponding images with a scan size of 3 × 3 mm 2 and 6 × 6 mm 2 , respectively, were overlaid according to the set of marker positions to determine the TS., Results: From 200 patients with VHLD, 48 patients showed 84 RCHs. SD-OCTA images of 39 RCHs (46.4%) and SS-OCTA images of 48 RCHs (57.2%) were suitable for analysis. The average in OCTA-measured TS of 1.60 ± 2.58 mm 2 (range, 0.01-10.43) was congruent to the clinically assessed TS in 81.3% of cases ( r = 0.86, P < 0.0001). TS measured in SD-OCTA compared to SS-OCTA showed similar values and a high correlation (all P < 0.0001). Nevertheless, despite the similarities, a slight trend in SS-OCTA was observed whereby with increasing TS, an elevated TS was detected compared to SD-OCTA (3 × 3-mm 2 scans: mean difference of 0.03 ± 0.04  mm 2 , 6 × 6-mm 2 scans: 0.08 ± 0.19 mm 2 ). However, within the same imaging technology method, TS values almost did not differ (SD-OCTA: mean difference of 0.01 ± 0.02 mm 2 , SS-OCTA: 0.001 ± 0.01 mm 2 )., Conclusions: OCTA may serve as an additional tool for diagnosis and monitoring of RCHs. Nevertheless, due to the differences between the technologies, the values cannot be used interchangeably., Translational Relevance: SD-OCTA and SS-OCTA are suitable to detect and monitor RCHs and provide a more detailed assessment about the TS than this is clinically possible., Competing Interests: Disclosure: M. Reich, None; A. Glatz, None; D. Boehringer, None; C. Evers, None; M. Daniel, None; F. Bucher, None; F. Ludwig, None; S. Nuessle, None; W.A. Lagrèze, None; P.M. Maloca, None; C. Lange, None; T. Reinhard, None; H. Agostini, None; S.J. Lang, None, (Copyright 2020 The Authors.)

Introduction: Deep learning has received increasing attention in recent years and is used in many different areas. Since image analysis is a strength of deep learning, it would be obvious to use it for histopathological questions too. Our goal is to identify possible deep learning approaches from general pathology which could be used in ophthalmic pathology. In addition, the data of the past year will be used to estimate the proportion of potentially interesting cases and the necessary technical effort., Methods: Firstly, a literature search for deep learning models and their possible applications in the field of pathology was carried out. In order to estimate the potential benefit, technical challenges and feasibility, the number of suitable ophthalmopathology cases in our lab in 2019 for the identified models was determined and put in relation to the resulting amount of data and the scanning time., Results: We identified 7 areas of particular interest: determination of regions of interest (ROI), classification of histological images in scoring systems, mapping of tumor fractions, differentiation of different types of inflammation, differentiation of various cutaneous tumors, classification of lymphomas and prediction of patient outcome-based on tumor histology. Within one year, a total of 831 cases (43%) would have been suitable for the above models. The creation of whole slide images (WSI) for all histological cases would have required a storage capacity of 630 GB with a scanning time of 35 h., Conclusion: There are several deep learning approaches which are also interesting for ophthalmic pathology. Most of them would have to be specially trained for the ophthalmopathological aspects. To be able to apply deep learning approaches, it is necessary to have a good IT infrastructure with the possibility to create and permanently store WSI, and this seems to be technically feasible. Future studies should focus on the specific practical implementation of current deep learning possibilities for ophthalmic pathology., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Georg Thieme Verlag KG Stuttgart · New York.)

Telepathology has experienced enormous growth over the last two decades due to significant advances in IT and has led to the introduction of innovative solutions for digital imaging in ophthalmology. Whole Slide Imaging (WSI), where conventional glass slides are fully scanned, offers a wide range of applications, including remote (conciliary) diagnostics, second opinions, (remote) teaching and research and presentation. In addition to qualified and experienced personnel, a comparatively expensive basic equipment has so far also been an essential requirement. The focus ophthalmology at the Eye Centre in Freiburg is able to involve a de facto unlimited number of users and consulting partners (also overseas) in the digital microscopy of identical sections independent of location, device and time. This is done simply by using the internet. This procedure has proven to be very successful and opens up completely new avenues, not only for correct diagnosis (clinical-pathological correlation), but also for education and training. Preparation and distribution of further histological slides in addition to the scanned slide is not required for small specimens with scant material, for example, nor is it necessary to purchase microscopes for the participants if funds are lacking or the infrastructure is unsuitable. When dealing with transferring data, it is essential to comply with data protection regulations., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Georg Thieme Verlag KG Stuttgart · New York.)

Triple negative human breast cancer (TNBC) is an aggressive cancer subtype with poor prognosis. Besides the better-known artemisinin, Artemisia annua L. contains numerous active compounds not well-studied yet. High-performance liquid chromatography coupled with diode-array and mass spectrometric detection (HPLC-DAD-MS) was used for the analysis of the most abundant compounds of an Artemisia annua extract exhibiting toxicity to MDA-MB-231 TNBC cells. Artemisinin, 6,7-dimethoxycoumarin, arteannuic acid were not toxic to any of the cancer cell lines tested. The flavonols chrysosplenol d and casticin selectively inhibited the viability of the TNBC cell lines, MDA-MB-231, CAL-51, CAL-148, as well as MCF7, A549, MIA PaCa-2, and PC-3. PC-3 prostate cancer cells exhibiting high basal protein kinase B (AKT) and no ERK1/2 activation were relatively resistant, whereas MDA-MB-231 cells with high basal ERK1/2 and low AKT activity were more sensitive to chrysosplenol d treatment. In vivo, chrysosplenol d and casticin inhibited MDA-MB-231 tumor growth on chick chorioallantoic membranes. Both compounds induced mitochondrial membrane potential loss and apoptosis. Chrysosplenol d activated ERK1/2, but not other kinases tested, increased cytosolic reactive oxygen species (ROS) and induced autophagy in MDA-MB-231 cells. Lysosomal aberrations and toxicity could be antagonized by ERK1/2 inhibition. The Artemisia annua flavonols chrysosplenol d and casticin merit exploration as potential anticancer therapeutics.

Background and Objectives: Scleral buckling and pars-plana vitrectomy are therapeutic options for the treatment of rhegmatogenous retinal detachment. Comparative studies still support the value of scleral buckling in phakic eyes. Nevertheless, the number of sceral buckling procedures may be continuously decreasing over time. The study aims to analyse the incidence of scleral buckling procedures for the treatment of patients with retinal detachment in Germany over time., Material and Methods: The numbers of scleral buckling procedures (OPS 5-152) and rhegmatogenous retinal detachment (ICD H33.0) in Germany are analysed on the basis of data from the quality reports published by the Federal Joint Committee and secondary analyses of the DRG-based billing system (DRG-Statistik) of the Federal Statistical Office between 2006 and 2017., Results: Based on the quality reports, numbers of scleral buckling procedures performed between 2006 and 2017 dropped by 49% from 8841 to 4510. During this period of time, the number of rhegmatogenous retinal detachments, identified by the ICD code H33.0, rose by 102% from 11 507 to 23 314. A decrease in scleral buckling procedures of 42% between 2006 and 2017 was also observed in the DRG Statistics. Regional and age-dependent subgroup analyses suggests that there are both regional and age-dependent differences in the practice of scleral buckling., Conclusions: Our analysis clearly illustrates that scleral buckling procedures are now less commonly performed in Germany than in 2006. However, the total of ~ 4500 billed procedures in 2017 in Germany shows that scleral buckling is still an important and current therapeutic option in the treatment of retinal detachment., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Georg Thieme Verlag KG Stuttgart · New York.)

Penetrating keratoplasty in children is associated with very specific difficulties for the surgeon as well as for the patient and the parents. Special features are specific pediatric indications, which do not occur in adults, a more difficult examination and treatment adherence depending on the parents. Diseases with a favorable prognosis include keratoconus and herpetic keratitis. Especially sclerocornea and the Peters' anomaly often have a limited prognosis regarding vision and graft survival due to secondary malformations of the eye. In addition, younger age represents a risk factor. This is most likely due to the impaired examination during follow-up and reduced compliance. For successful penetrating keratoplasty in children the timing for the operation, in which the risk for the graft is weighed up against the risk for amblyopia, is crucial.

Background and Objective: Since 2006, at the Eye Center, University of Freiburg, an advanced-training curriculum has been used for medical specialists in ophthalmology. This training curriculum was evaluated for the years 2006 until 2017., Methods: Internal quality management documents were worked through on the subject of training curriculum. Moreover, we analyzed the internet presence of the Eye Center Freiburg as well as its presentation of the training curriculum and the generally accessible annual reports. Furthermore, administrative personnel data were provided. Quantitative analyses were made with Microsoft Excel., Results: A medical specialist's career is organized as follows: 1) Structured application procedure with evaluation through the Head of the Department, the section heads and the resident's representative. 2) Initial training through medical colleagues and a mentor. 3) Rotation through all sections and areas. 4a) Annual appraisal interviews. 4b) Definition of a career pathway after 3 years. 5) Regular participation in internal/external training sessions. 6) Research after 3 months. 7) Possibility of work shadowing in practices in the 5th year. For reconciling of work and family life, parental leave and part-time employment are possible. In the years between 2006 and 2017, the analyzed data show an increasing number of job interviews and employees. All interns reached the specialist qualification in ophthalmology during the investigation period, 48% additionally got the Fellow of the European Board of Ophthalmology (FEBO)., Conclusions: Since 2006, a structured curriculum has existed for the training of medical specialists in ophthalmology at the Eye Center Freiburg. This is well documented on the homepage as well as in the internal quality management manual. The transparency, paired with the quality of the training program, leads to an increasing number of employees as well as the number of employees with specialist medical qualifications. This can be seen as an indicator for a successful curriculum which secures medical care and research., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Numerous surgeries in the field of ophthalmology take place on an outpatient basis or only as part of a short inpatient stay. The quality requirements are very high. Postoperative quality controls often can't be done by surgeons themselves because the postoperative aftercare is usually no longer carried out at the surgical centre but by the referring ophthalmologists., Methods: To optimize our operative quality assurance, the eye center of the University Hospital Freiburg has developed an internet-based quality assurance procedure in cooperation with the Augennetz Südbaden (ANSB), in which numerous established ophthalmologists from the region network. There is comprehensive reporting on cataract surgeries. The results of the follow-up examinations are reported in a structured manner via secure internet masks from the doctors' practices, taking into account data protection regulations. Feedback always takes place after 3 months and, thus, at a point in time at which the final surgical result can usually be assessed., Results: Since the establishment of the quality register in November 2009, a total of 8043 records of cataract operations have been reported until the end of 2018. This sample comprises 20.2% of all cataract operations performed at the eye center of the University Hospital Freiburg during the same period. Mean follow-up was 76 days. During cataract surgery, the target refraction was missed by less than 1 dioptre in 90% of all operated eyes. Keratoplasty was identified as a risk factor for missing the target refraction., Conclusion: The internet-based quality assurance of the eye center of the University Hospital Freiburg enables continuous monitoring of the operation quality over a longer period of time. In patients that underwent keratoplasty, the biometry should be critically questioned preoperatively., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Transformation into a standardised code system such as ICD-10 or Alpha-ID is required before medical reports can be scientifically analysed. This is due to the use of different terminologies and the frequent use of synonyms. The so-called "word vector embedding" seems to be suitable for the generation of the required thesaurus, because synonymous diagnoses can be identified independently of the spelling - after suitable training of the underlying neural network., Methods: All letters from a total of 50,000 patients were extracted anonymously. Diagnoses consisting of several words were merged into single words by means of phrase recognition and the "word2vec" model was trained on the text corpus of 352 megabytes. A total of 3742 diagnoses and ophthalmological interventions were extracted semi-automatically. The ophthalmological ICD and Alpha-ID codes were downloaded together with the official descriptions from the DIMDI website and the ophthalmological diagnoses/interventions were automatically linked with the nearest ICD- and Alpha-ID codes in the "word2vec" model., Results: The "word2vec" model assigned 90% of the doctor's letter diagnoses correctly to appropriate ICD-10 codes. At the finer level of Alpha-ID, the rate of correct assignments was only 76%. The interventions were assigned to the correct indication in 92% of cases. Rare diseases, unusual designations and code degeneration in the official DIMDI file were identified as sources of error for incorrect or missing allocations., Discussion: A diagnostic thesaurus can be generated with the "word2vec" method from a corpus of anonymised medical reports and the official Alpha-ID file from the DIMDI website. This thesaurus could be used for automatic extraction of diagnoses from doctor's letters in the future, given appropriate manual revision., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Georg Thieme Verlag KG Stuttgart · New York.)

Positive behavioral support (PBS) employs applied behavioral analysis to enhance the quality of life of people who behave in challenging ways. PBS builds on the straightforward and intuitively appealing notion that if people know how to control their environments, they will have less need to behave in challenging ways. Accordingly, PBS focuses on the perspective of those who have behavioral issues, and assesses success via reduction in incidences of challenging behaviors. The qualitative research presented in this report approaches PBS from a different viewpoint and, using thematic analysis, considers the impact of PBS training on the lived experience of staff who deliver services. Thirteen support staff who work for a company supplying social care and supported living services for people with learning disabilities and complex needs in the northwest of England took part. Analysis of interviews identified five major themes. These were: (1) training: enjoyable and useful; (2) widening of perspective: different ways of thinking; (3) increased competence: better outcomes; (4) spill over into private lives: increased tolerance in relationships; and (5) reflecting on practice and moving to a holistic view: "I am aware that people…are not just being naughty." These themes evidenced personal growth on the part of service providers receiving training. Explicitly, they demonstrated that greater awareness of PBS equipped recipients with an appropriate set of values, and the technical knowledge required to realize them., (Copyright © 2019 Walsh, McClean, Doyle, Ryan, Scarborough-Lang, Rishton and Dagnall.)

The data in this article contain supporting information for the research manuscript entitled "Antitumor activity of an Artemisia annua herbal preparation and identification of active ingredients" by Lang et al. [1]. Momundo Artemisia annua extract and an acetonitrile fraction thereof induce apoptosis in MDA-MB-231 triple negative breast cancer cells as shown by XTT viability assay and induction of the subG 0 /G 1 cell population by flow cytometric analysis. Furthermore, the HPLC-DAD method used to characterize the Artemisia annua herbal preparation as well as UHPLC-MS/MS method used to quantify the most abundant compounds in the extract and its validation are presented., (© 2019 The Author(s).)