Behandlung der Meibomdrüsen-Dysfunktion durch klassische Lidhygiene-Maßnahmen mit und ohne zusätzliche Lipidsubstitution zur Stabilisierung des Tränenfilms

Einführung: Das Ziel dieser Studie war es, den Behandlungserfolg von Lidhygienemaßnahmen mit BlephaCura® zu dokumentieren und mithilfe neuer Diagnosemöglichkeiten festzustellen, ob eine zusätzliche Lipidsubstitution einen messbaren Nutzen für den Tränenfilm bei der Behandlung der Meibomdrüsendysfunktion bietet. Methoden: Zwischen Mai 2017 und Mai 2018 wurde eine monozentrische, kontrollierte, teilweise einfach verblindete Studie durchgeführt. Insgesamt wurden 82 Patienten eingeschlossen, welche in 2 Gruppen randomisiert wurden. Patienten der Gruppe A wurden ausschließlich mit Lidhygienemaßnahmen therapiert, während Patienten der Gruppe B zusätzlich das liposomale Augenspray Tears Again® Sensitive 3- bis 4-mal täglich zur Stabilisierung des Tränenfilms applizierten. Es wurden das subjektive Empfinden mittels Ocular Surface Disease Index (OSDI) Fragebogen, die Messung der Osmolarität des Tränenfilms mittels Tear Lab®, die Messung der nicht-invasiven Tränenfilmaufrisszeit, die Beurteilung der Lipidschicht, die Meibographie und die Inspektion der Lidränder mit Hilfe des Keratograph 5M, die Beurteilung der Meibomdrüsen mittels Korb Meibomian Gland Evaluator (MGE) sowie die Messung des Entzündungsmarkers MMP-9 (Matrix-Metalloproteinase-9) mit Inflamma Dry Schnelltests zu Beginn der Studie sowie nach 12 Wochen erhoben. Ergebnisse: Vor Behandlungsbeginn zeigten die Gruppen A und B keine Unterschiede in Bezug auf alle Messparameter. Hinsichtlich des Behandlungseffekts zeigte sich sowohl in Gruppe A als auch in Gruppe B ein Absinken des OSDI-Scores (p<0,001). Bei der Messung der Osmolarität konnte weder eine Veränderung über die Zeit (p=0,69) noch ein Unterschied zwischen den beiden Gruppen (p=0,43) festgestellt werden. Die durchschnittliche Tränenfilmaufrisszeit (NIBUT) betrug 8,6 Sekunden vor Behandlungsbeginn und veränderte sich in beiden Gruppen nach 12 Wochen nicht signifikant (p=0,58). Im Hinblick auf die Lipidschichtdicke kam es in beiden Gruppen zu einem Zuwachs von 3,5 auf 4,2 Punkte mit einer Verbesserung in gleicher Weise (p<0,001) ohne Unterschied zwischen den beiden Behandlungsgruppen (p=0,88). Der Verlustgrad der Meibomdrüsen des Ober- und Unterlids zeigte in beiden Gruppen eine signifikante Verbesserung nach 12 Wochen (p<0,001) mit parallelem zeitlichem Verlauf der beiden Gruppen. Auch im Hinblick auf das Schädigungsbild der Lidkanten erfuhren beide Gruppen im zeitlichen Verlauf eine Besserung (p<0,001) ohne signifikanten Unterschied zwischen den beiden Gruppen. Die Veränderung der Qualität des Meibomdrüsensekrets zeigte in beiden Gruppen eine Verbesserung mit ähnlichem Verlauf. Der Entzündungsparameter MMP-9 wurde bei 59 Probanden vor Behandlungsbeginn (72%) positiv getestet, wobei bei 42,3% nach 12 Wochen eine Verbesserung eintrat. Auch hier ergab sich kein signifikanter Unterschied zwischen den Gruppen (p=0,83). Schlussfolgerungen: Unsere Studie bestätigt den messbaren Behandlungserfolg von Lidhygienemaßnahmen mit BlephaCura®. Ein zusätzlicher Nutzen einer ergänzenden Lipidsubstitution konnte zum Zeitpunkt der Messung nach 12 Wochen Behandlung in unserer Studie nicht nachgewiesen werden. Weitere Studien sollten durchgeführt werden, um frühere Messintervalle zu untersuchen, die auf eine größere Wirksamkeit der zusätzlichen Behandlung hindeuten könnten.Purpose: The purpose of this study was to document the treatment success of eyelid hygiene measures with BlephaCura® using new diagnostic tools and to determine whether additional lipid substitution provides measurable tear film benefit in the treatment of meibomian gland dysfunction. Methods: A monocentric, controlled, partially single-blinded study was conducted between May 2017 and May 2018. A total of 82 patients were included and randomized into 2 groups. Patients in group A were treated with eyelid hygiene measures only, while patients in group B additionally applied the liposomal ophthalmic spray Tears Again® Sensitive 3 to 4 times a day to stabilize the tear film. Subjective perception using the Ocular Surface Disease Index (OSDI) questionnaire, measurement of tear film osmolarity using Tear Lab®, measurement of non-invasive tear film break-up time, assessment of the lipid layer, meibography as well as inspection of the lid margins using Keratograph 5M, assessment of the meibomian glands using Korb-MGE and measurement of the inflammatory marker MMP-9 using Inflamma Dry rapid tests were collected at baseline and after 12 weeks. Results: Before the start of treatment, groups A and B showed no differences with respect to all measurement parameters. Regarding the treatment effect, both group A and B showed a significant decrease in the OSDI score (p<0.001). There was no significant change in osmolarity over time (p=0.69) or between the two groups (p=0.43). The mean tear film breakup time (NIBUT) was 8.6 seconds at baseline and did not change significantly in either group after 12 weeks (p=0.58). In terms of lipid layer thickness, there was an increase from 3.5 to 4.2 points in both groups with an improvement in the same manner (p<0.001) with no difference between the two treatment groups (p=0.88). The area of loss of the meibomian glands of the upper and lower eyelid showed significant improvement in both groups after 12 weeks (p<0.001) with a corresponding time course between the two groups. Both groups showed a significant reduction in damage pattern of the eyelid margins over time (p<0.001) without variation between the two treatment groups. The change in the quality of the meibomian gland secretion showed significant improvement in both groups with a similar pattern of improvement. The inflammatory parameter MMP-9 tested positive in 72% (n=59) of subjects before treatment, with 42.3% showing improvement after 12 weeks. Again, there was no significant difference between the groups (p=0.83). Conclusion: Our study confirms the successful treatment of eyelid hygiene measures with BlephaCura®. An additional benefit of lipid substitution could not be significantly demonstrated after 12 weeks of treatment in our study. Further studies should be conducted to investigate earlier intervals of measurement which may suggest a greater efficacy of the additional treatment

Reliability and efficiency of corneal thickness measurements using sterile donor tomography in the eye bank

To evaluate the reliability and efficiency of sterile pachymetric measurements of donor corneas based on tomographic data using two different methods: a “manual” and a “(semi-)automated” method. Twenty-five (25) donor corneas (50%) stored in MI and 25 (50%) in MII were imaged 5 times consecutively using an anterior segment OCT (AS-OCT). The central corneal thickness (CCT) was measured both with the manual measurement tool of the AS-OCT (= CCTm) and with a MATLAB self-programmed software allowing (semi-)automated analysis (= CCTa). We analyzed the reliability of CCTm and CCTa using Cronbach´s alpha (α) and Wilcoxon signed-Rank Test. Concerning CCTm, 68 measurements (54.4%) in MI and 46 (36.8%) in MII presented distortions in the imaged 3D-volumes and were discarded. Concerning CCTa, 5 (4%) in MI and 1 (0.8%) in MII were not analyzable. The mean (± SD) CCTm was 1129 ± 6.8 in MI and 820 ± 5.1 µm in MII. The mean CCTa was 1149 ± 2.7 and 811 ± 2.4 µm, respectively. Both methods showed a high reliability with a Cronbach´s α for CCTm of 1.0 (MI/MII) and for CCTa of 0.99 (MI) and 1.0 (MII). Nevertheless, the mean SD of the 5 measurements was significantly higher for CCTm compared to CCTa in MI (p = 0.03), but not in MII (p = 0.92). Sterile donor tomography proves to be highly reliable for assessment of CCT with both methods. However, due to frequent distortions regarding the manual method, the (semi-)automated method is more efficient and should be preferred

Approval rates for corneal donation and the origin of donor tissue for transplantation at a university-based tertiary referral center with corneal subspecialization hosting a LIONS Eye Bank

Background: With the increasing demand for corneas, eye banks must optimize the tissue donation, collection, and selection process. This retrospective monocentric study analyzed the approval rates for corneal donation and the origin of and reasons for discarding donor corneas from 2010 to 2019. Methods: Data included the number of deceased, approval or rejection by the family for corneal donation and contraindications. Corneal grafts were included from all deceased persons who were full-body and multi-organ donors at the Saarland University Medical Center (UKS) and from external institutions. Additional analyzed parameters included endothelial cell count (ECC), blood sample serology for infections, and conjunctival swab testing . Results: A total of 1748 corneoscleral buttons were harvested from 10,265 deceased persons (17% with no contraindication) at the UKS between 2010 and 2019, with a consent rate of 23.3%. The number of explants increased from 136 in 2010 (15% of the deceased, total = 925) to 251 in 2019 (21%, total = 1214). Both the general and departmentspecifc data showed similar percentages for corneal donation over the years, with intensive care and palliative units recently providing the most corneas. The increase in the number of corneas processed by the cornea bank over the years (368 in 2010 compared with 857 in 2019) was linked both to a better internal supply in 2010 (262, 71.2% of the total) compared with 2019 (519, 60.6%) and to an external supply by reinforcement of cooperation with external hospitals, including Luxembourg in 2010 (106, 28.8% of the total) compared with 2019 (338, 39.4%). A total of 195 of 377 corneas (52%) were discarded in 2009 compared with 260 out of 715 (36%) in 2019. The main reasons for discarding were low ECC (36% of discarded corneas in 2009; 11% in 2019), positive conjunctival swab (11% in 2009; 13% in 2019), and blood sample serology (6% in 2009 and in 2019). Conclusion: Despite an increasing number of donors, the demand for corneas is still rising. Improved cooperation with internal departments and with external clinics has led to an increasing number of explanted corneas. The main reason for discarding corneas was low ECC, followed by a positive conjunctival swab for fungal or bacterial contamination and serology. Increased donation rates and continued improvements in collection and selection processes are necessary to cover the high demand for cornea

Intravitreal aflibercept following treat and extend protocol versus fixed protocol for treatment of neovascular age-related macular degeneration

Background To assess the morphological and functional outcome of intravitreal aflibercept following the treat and extend protocol compared to the fixed protocol for treatment of eyes with neovascular age-related macular degeneration. Methods This retrospective study included 126 eyes of 113 patients with primary onset neovascular age-related macular degeneration who were followed for 12 months. All eyes were treated with 2 mg/0.05 mL aflibercept. All eyes received an upload with three monthly aflibercept injections. We subsequently studied two groups of eyes. For group 1, 54 eyes were treated following the treat and extend protocol. For group 2, 72 eyes were treated following the fixed protocol (fixed 2-monthly interval). Main outcome measures included: best corrected visual acuity (BCVA), central macular thickness (CMT) and number of injections. Results BCVA (logMAR) in group 1 vs group 2 was (0.61 ± 0.3 vs 0.72 ± 0.3, p = 0.09) before treatment and (0.48 ± 0.3 vs 0.51 ± 0.3, p = 0.6) after one year of treatment. CMT in group 1 vs group 2 was (371 ± 101 μm vs 393 ± 116 μm, p = 0.5) before treatment and (284 ± 60 μm vs 290 ± 67 μm, p = 0.1) after one year of treatment. Number of injections/eye in group 1 vs group 2 was (8.5 ± 2.2 vs 7.0 ± 0, p < 0.001). Conclusions Significant differences regarding BCVA and central macular thickness were not found between both treatment protocols during the first year of treatment using aflibercept. However, a significantly higher number of injections was needed for eyes in the treat and extend group during the first year of treatment. This might suggest that aflibercept should better not be extended past an 8 weeks interval during the first year of treatment. Study registration This study was approved by the Ethics Committee of the Medical Association of Saarland, Germany (Nr. 123/20, Date: 16.06.2020). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors

Distinctive Wessely immune ring in keratitis-a chameleon

Ein Wessely-Immunring kann bei verschiedenen kornealen Infektionen sowie bei nichtinfektiöser Ätiologie auftreten und differenzialdiagnostisch wegweisend, aber auch irreführend sein. Eine definitive Diagnosestellung kann nur in Gesamtschau der klinischen und mikrobiologischen Befunde erfolgen. Differenzialdiagnostische Überlegungen und Therapiestrategien werden im Kontext der Kasuistik eines 31 Jahre alten Kontaktlinsenträgers mit diffuser Endotheldekompensation bei fokalem mittelperipherem Infiltrat mit Wessely-Immunring exemplarisch erörtert und kritisch reflektiert.A Wessely immune ring can be found in various corneal infections as well as in non-infectious processes. Its appearance can aid in the differential diagnosis but can also be misleading. A definitive diagnosis can only be reached when all clinical and microbiological findings are taken into consideration. This article discusses and critically reflects on the differential diagnostic considerations and treatment strategies in the context of a case report on a 31-year-old patient with contact lenses and diffuse endothelial decompensation with a focal, mid-peripheral infiltrate and a Wessely immune ring

Hydra: A mixture modeling framework for subtyping pediatric cancer cohorts using multimodal gene expression signatures.

Precision oncology has primarily relied on coding mutations as biomarkers of response to therapies. While transcriptome analysis can provide valuable information, incorporation into workflows has been difficult. For example, the relative rather than absolute gene expression level needs to be considered, requiring differential expression analysis across samples. However, expression programs related to the cell-of-origin and tumor microenvironment effects confound the search for cancer-specific expression changes. To address these challenges, we developed an unsupervised clustering approach for discovering differential pathway expression within cancer cohorts using gene expression measurements. The hydra approach uses a Dirichlet process mixture model to automatically detect multimodally distributed genes and expression signatures without the need for matched normal tissue. We demonstrate that the hydra approach is more sensitive than widely-used gene set enrichment approaches for detecting multimodal expression signatures. Application of the hydra analysis framework to small blue round cell tumors (including rhabdomyosarcoma, synovial sarcoma, neuroblastoma, Ewing sarcoma, and osteosarcoma) identified expression signatures associated with changes in the tumor microenvironment. The hydra approach also identified an association between ATRX deletions and elevated immune marker expression in high-risk neuroblastoma. Notably, hydra analysis of all small blue round cell tumors revealed similar subtypes, characterized by changes to infiltrating immune and stromal expression signatures

Use of Sensors in the Treatment and Follow-up of Patients with Diabetes Mellitus

Glucose control is the cornerstone of Diabetes Mellitus (DM) treatment. Although self-regulation using capillary glycemia (SRCG) still remains the best procedure in clinical practice, continuous glucose monitoring systems (CGM) offer the possibility of continuous and dynamic assessment of interstitial glucose concentration. CGM systems have the potential to improve glycemic control while decreasing the incidence of hypoglycemia but the efficiency, compared with SRCG, is still debated. CGM systems have the greatest potential value in patients with hypoglycemic unawareness and in controlling daily fluctuations in blood glucose. The implementation of continuous monitoring in the standard clinical setting has not yet been established but a new generation of open and close loop subcutaneous insulin infusion devices are emerging making insulin treatment and glycemic control more reliable

Supporting Spartina: Interdisciplinary perspective shows Spartina as a distinct solid genus

In 2014 a DNA-based phylogenetic study confirming the paraphyly of the grass subtribe Sporobolinae proposed the creation of a large monophyletic genus Sporobolus, including (among others) species previously included in the genera Spartina, Calamovilfa, and Sporobolus. Spartina species have contributed substantially (and continue contributing) to our knowledge in multiple disciplines, including ecology, evolutionary biology, molecular biology, biogeography, experimental ecology, environmental management, restoration ecology, history, economics, and sociology. There is no rationale so compelling to subsume the name Spartina as a subgenus that could rival the striking, global iconic history and use of the name Spartina for over 200 years. We do not agree with the arguments underlying the proposal to change Spartina to Sporobolus. We understand the importance of taxonomy and of formalized nomenclature and hope that by opening this debate we will encourage positive feedback that will strengthen taxonomic decisions with an interdisciplinary perspective. We consider the strongly distinct, monophyletic clade Spartina should simply and efficiently be treated as the genus Spartina

Energy Resolution Performance of the CMS Electromagnetic Calorimeter

The energy resolution performance of the CMS lead tungstate crystal electromagnetic calorimeter is presented. Measurements were made with an electron beam using a fully equipped supermodule of the calorimeter barrel. Results are given both for electrons incident on the centre of crystals and for electrons distributed uniformly over the calorimeter surface. The electron energy is reconstructed in matrices of 3 times 3 or 5 times 5 crystals centred on the crystal containing the maximum energy. Corrections for variations in the shower containment are applied in the case of uniform incidence. The resolution measured is consistent with the design goals