The impact of diabetes mellitus and hyperglycaemia on the refractive status of the eye

Purpose. Diabetes mellitus is a condition of considerable concern globally, which can affect the visual system in various ways, including changes to visual function, the integrity of the ocular surface and the retinal microcirculation. The aim of this article is to provide an overview on the perspectives around the relationship between diabetes and refractive status. Material and Methods. Narrative literature review. Results. The relationship between diabetes, hyperglycaemia and refractive error has been of interest to clinicians and researchers for more than a century. This review shows that research studies investigating the relationship have varied considerably in their design, methodology, their outcome measures used as well as their reported results. While some uncertainty remains, there is evidence that short-term, drastic changes in blood glucose levels affect the refractive status of human eyes leading to fluctuating and blurred vision. Conclusion. Patients starting glycaemic treatment or under- going adaptation to a new treatment regime may present with considerable refractive changes and visual complaints. Before considering the prescription of spectacle lenses, clinicians should ideally monitor patients in whom glycaemic control has been initiated or is being adjusted until a stabilisation of blood glucose levels has been confirmed. Keywords Diabetes, refraction, refractive error, variability</jats:p

Die PARP-Inhibitoren Niraparib und Talazoparib sensibilisieren Zellen des Malignen Melanoms für ionisierende Strahlung

(1) Background: Niraparib and Talazoparib are poly (ADP-ribose) polymerase (PARP) 1/2 inhibitors. It is assumed that combining PARP inhibitors with radiotherapy could be beneficial for cancer treatment. In this study, melanoma cells were treated with Niraparib and Talazoparib in combination with ionizing radiation (IR). (2) Methods: The effects of Talazoparib and Niraparib in combination with IR on cell death, clonogenicity and cell cycle arrest were studied in healthy primary fibroblasts and primary melanoma cells. (3) Results: The melanoma cells had a higher PARP1 and PARP2 content than the healthy fibroblasts, and further increased their PARP2 content after the combination therapy. PARP inhibitors both sensitized fibroblasts and melanoma cells to IR. A clear supra-additive effect of KI+IR treatment was detected in two melanoma cell lines analyzing the surviving fraction. The cell death rate increased in the healthy fibroblasts, but to a larger extent in melanoma cells after combined treatment. Finally, a lower percentage of cells in the radiosensitive G2/M phase is present in the healthy fibroblasts compared to the melanoma cells. (4) Conclusions: Both PARP inhibitors sensitize melanoma cells to IR. Healthy tissue seems to be less affected than melanoma cells. However, the great heterogeneity of the results suggests prior testing of the tumor cells in order to personalize the treatment.Hintergrund und Ziele: Aufgrund ihrer Eigenschaft, die DNA-Reparaturfähigkeit einer Zelle reduzieren zu können, findet die Gruppe der Poly(ADP-Ribose)-Polymerase-Inhibitoren (PARP- Inhibitoren) bereits Anwendung in der Krebstherapie. Eine Kombination mit einer DNA-schädigenden Therapiemethode, wie beispielsweise der Radiotherapie, gilt als vielversprechend, um weitere Fortschritte in der zukünftigen Tumorbehandlung erzielen zu können. Man vermutet dabei, dass gesunde Zellen den schädigenden Einfluss einer solchen Kombinationsbehandlung besser kompensieren können als Krebszellen. Ziel der vorliegenden Arbeit „Die PARP-Inhibitoren Niraparib und Talazoparib sensibilisieren Zellen des Malignen Melanoms für ionisierende Strahlung“ war es, die Auswirkungen der beiden PARP-Inhibitoren Niraparib und Talazoparib bei der Bestrahlung von Melanomzellen im Hinblick auf verschiedene zelluläre Prozesse zu untersuchen. Methoden: In dieser Arbeit wurden zunächst die relativen PARP1- und PARP2-Expressionen von Melanomzellen im Vergleich zu gesunden Hautfibroblasten analysiert. Im Anschluss wurden die Veränderungen dieser Proteinlevel nach einer Kombinationsbehandlung mit ionisierender Strahlung und Niraparib beziehungsweise Talazoparib gemessen. Nachfolgend wurde der Einfluss der Bestrahlung mit und ohne simultane Inhibitor- Behandlung auf das klonogene Zellüberleben, auf den Zelltod und auf die Verteilung in die verschiedenen Phasen des Zellzyklus untersucht. Darüber hinaus wurde der Status der Homologen Rekombination (HR) der Zellen ermittelt. Ergebnisse und Beobachtungen: In den Melamomzellen zeigten sich höhere relative PARP1- und PARP2-Level als in den gesunden Hautfibroblasten. Dies könnte als Hinweis auf eine größere Empfindlichkeit der Krebszellen gegenüber einer PARP-Inhibierung gedeutet werden. Nach einer Kombination aus Bestrahlung und Inhibitor-Behandlung stieg der Gehalt an PARP2 in den Melanomzellen noch weiter an. Sowohl Niraparib als auch Talazoparib sensibilisierten die untersuchten Zellen für ionisierende Strahlung. Bei den meisten Zelllinien zeigte sich ein superadditiver Effekt der Kombinationstherapie in Bezug auf 1 das klonogene Überleben. Der Anstieg der Zelltodrate nach Kombinationsbehandlung war bei den Melanomzellen meist höher als bei den gesunden Fibroblasten. Darüber hinaus war der prozentuale Anteil der Zellen in der G2/M-Phase, welche als strahlensensibelste Phase des Zellzyklus gilt, bei den Melanomzellen signifikant höher als bei den gesunden Fibroblasten. Die Kombinationstherapie steigerte diesen G2/M- Arrest nochmals deutlich. Das verwendete Zelllinienpanel repräsentiert ein breites Spektrum von Melanom-Patienten. Die beobachteten Effekte unterschieden sich zwischen den verschiedenen Zelllinien bisweilen erheblich. Die Untersuchung des HR- Status lieferte einzelne Hinweise für mögliche Erklärungen dieser Effekte. Dennoch konnten nicht alle Beobachtungen mit Hilfe der bisher durchgeführten Analysen vollständig gedeutet werden. Weitere genetische Charakterisierungen scheinen notwendig zu sein, um die beobachteten Effekte schlüssig zu erklären und zukünftig zuverlässige Empfehlungen für die Kombinationstherapie zu geben. Schlussfolgerungen: Zusammengefasst deuten unsere Studien darauf hin, dass die beiden PARP-Inhibitoren Niraparib und Talazoparib die untersuchten Melanomzellen für ionisierende Strahlung sensibilisieren, während Zellen gesunden Gewebes weniger sensibilisiert werden. Diese Ergebnisse könnten als Potential dafür interpretiert werden, dass eine Kombinationsbehandlung dieser PARP-Inhibitoren mit ionisierender Strahlung erfolgreich auf das Krebsgewebe von Melanom-Patienten wirken könnte und gleichzeitig das umliegende gesunde Gewebe weniger schädigen würde. Es wird jedoch darauf hingewiesen, dass die Zelllinien teilweise sehr unterschiedlich auf die Behandlung ansprachen und dass einzelne Zelllinien gegen die Kombinationsbehandlung resistent zu sein schienen. Um ein bestmögliches Therapie- Ergebnis zu erzielen, ist daher dringend anzuraten, die individuelle Therapie-Strategie nur nach vorheriger Untersuchung und Analyse des Tumorgewebes zu erstellen. Es wird empfohlen, eine weiterführende Verifizierung dieser Ergebnisse, insbesondere in klinischer Hinsicht, durchzuführen

SelfPaint-A self-programming paint booth

In this paper we present a unique Fraunhofer approach that aims towards a vision to automate the product preparation in paint shops by automatically generating robot paths and process conditions that guarantee a certain wanted paint coverage. This will be accomplished through a combination of state-of-the-art simulation technology, inline quality control by novel terahertz thickness measurement technology, and surface treatment technology. The benefits of the approach are a shortened product preparation time, increased quality and reduced material and energy consumption. The painting of a tractor fender is used to demonstrate the approach

Exploring eye care pathways, patient priorities and economics in Pakistan: a scoping review and expert consultation study with thematic analysis

PURPOSE: As the prevalence of eye diseases increases, demand for effective, accessible and equitable eye care grows worldwide. This is especially true in lower and middle‐income countries, which have variable levels of infrastructure and economic resources to meet this increased demand. In the present study we aimed to review the literature on eye care in Pakistan comprehensively, with a particular focus on eye care pathways, patient priorities and economics. METHODS: A systematic scoping review was performed to identify literature relating to eye care in Pakistan. Searches of relevant electronic databases and grey literature were carried out. The results were analysed through a mixed methods approach encompassing descriptive numerical summary and thematic analysis. To consolidate results and define priority areas for future study, expert consultation exercises with key stakeholders were conducted using qualitative semi‐structured interviews. RESULTS: One hundred and thirty‐two papers (published and unpublished) were included in the final review. The majority (n = 93) of studies utilised a quantitative design. Seven interlinked themes were identified: eye care pathways, burden of eye disease, public views on eye‐related issues, workforce, barriers to uptake of eye care services, quality of eye care services and economic impact of blindness. Research priorities included investigating the eye care workforce, the quality and efficiency of current eye care services, eye care services available in rural Pakistan and the costs and benefits related to eye care provision and sustaining eye care programmes. CONCLUSIONS: To the best of our knowledge, this is the first review to synthesise evidence from papers across the field relating to eye care in Pakistan. As such, this work provides new insights into the achievements of the national eye health programme, challenges in eye care in Pakistan and priority areas for future research

The role of peripheral ocular length and peripheral corneal radius of curvature in determining refractive error

PURPOSE: The purpose of this study was to extend the knowledge of peripheral biometric component and its relationship to refractive status in healthy individuals by determining the correlation between peripheral ocular length to peripheral corneal radius ratio and the refractive error. METHODS: This prospective study was conducted on thirty-three healthy adult participants. Refractive error was assessed objectively and subjectively and recorded as the mean spherical equivalent. Central and peripheral ocular lengths at 30° were assessed using partial coherence interferometry under dilation with 1% tropicamide. Central and peripheral corneal radius of curvature was assessed using Scheimpflug topography. Peripheral ocular lengths at 30° were paired with peripheral corneal curvatures at the incident points of the IOLMaster beam (3.8 mm away from corneal apex) superiorly, inferiorly, temporally and nasally to calculate the peripheral ocular length-peripheral corneal radius ratio. Descriptive statistics were used to describe the distribution and spread of the data. Pearson’s correlation analysis was used to present the association between biometric and refractive variables. RESULTS: Refractive error was negatively correlated with the axial length-central corneal radius ratio (r = −0.91; p < 0.001) and with 30° peripheral ocular length-peripheral corneal radius ratio in all four meridians (r ≤ −0.76; p < 0.001). The strength of the correlation was considerably lower when only axial length or peripheral ocular lengths were used. CONCLUSION: Using the ratios of peripheral ocular length-peripheral corneal radius to predict refractive error is more effective than using peripheral corneal radius or peripheral ocular length alone

Barriers to accessing eye care in Pakistan: a mixed methods study

Aims: To support policymakers in enhancing access to eye care for the population aged 45 years andolder in Pakistan, this study aims to identify and quantify the barriers that hinder effective eye caredelivery to this group. Additionally, it seeks to explore patients' experiences with the Sehat Sahulat(health insurance) program in the context of eye care services.Background: Accessible eye care services can reduce avoidable blindness by delivering timely, highquality interventions. In Pakistan, the lack of primary eye care burdens overcrowded hospitals andcombined with economic challenges, limits access for underprivileged populations. To address this, anationwide health insurance scheme (SSP) was introduced to reduce out-of-pocket expenses andimprove healthcare access for economically disadvantaged groups.Methods: Using an exploratory sequential mixed methods design, an initial qualitative phaseexplored participant experiences and identified specific barriers. The qualitative study provided thebasis for the development of a customised survey tool. The survey tool was then used in a secondphase to obtain quantitative data to capture the magnitude of barriers and costs associated withaccessing eye care in Pakistan.Findings: Numerous considerable barriers were identified including illiteracy, long travel times,female gender, old age, mobility issues, and costs, all of which limited access to eye care in Pakistan.Awareness surrounding use of the SSP was poor, with the programme seldom used towards eye carecosts. This study highlights patient experiences with eye care in urban and rural Pakistan, includingenablers and barriers to accessing eye care. Improvements should focus on educating the public oneye health, increasing availability of eye care services in rural areas, improving accessibility withineye care facilities, addressing gender disparities, and reducing costs associated with eye caretreatments, potentially through advancement of the SSP