Research trends of worldwide ophthalmologic randomized controlled trials in the 21st century: A bibliometric study.

Background: Randomized controlled trials (RCTs) are often considered the gold standard and the cornerstone for clinical practice. However, bibliometric studies on worldwide RCTs of ophthalmology published in the 21st century have not been reported in detail yet. This study aims to perform a bibliometric study and visualization analysis of worldwide ophthalmologic RCTs in the 21st century. Methods: Global ophthalmologic RCTs from 2000 to 2022 were searched in the Web of Science Core Collection. The number of publications, country/region, institution, author, journal, and research hotspots of RCTs were analyzed using HistCite, VOSviewer, CiteSpace, and Excel software. Results: 2366 institutions and 90 journals from 83 countries/regions participated in the publication of 1769 global ophthalmologic RCTs, with the United States leading in the number of volumes and research field, and the Moorfields Eye Hospital contributing to the most publications. Ophthalmology received the greatest number of publications and co-citations. Jeffrey S. Heier owned the most publications and Jost B. Jonas owned the most co-citations. The knowledge foundations of global ophthalmologic RCTs were mainly retinopathy, glaucoma, dry eye disease (DED), and cataracts, and anti-vascular endothelial growth factor (VEGF) therapy (ranibizumab), topical ocular hypotensive medication, laser trabeculoplasty. Anti-VEGF therapy for age-related macular degeneration (AMD), DME (diabetic macular edema), and DED, the use of new diagnostic tools, and myopia were the hottest research highlights. Anti-VEGF therapy, prompt laser, triamcinolone, and verteporfin photodynamic therapy for AMD, DME, and CNV (choroidal neovascularization), DED, myopia, and open-angle glaucoma were the research hotspots with the longest duration. The future research hotspots might be DED and the prevention and control of myopia. Conclusions: Overall, the number of global ophthalmologic RCTs in the 21st century was keeping growing, there was an imbalance between the regions and institutions, and more efforts are required to raise the quantity, quality, and global impact of high-quality clinical evidence in developing countries/regions.

Metrology of a Focusing Capillary Using Optical Ptychography.

The focusing property of an ellipsoidal monocapillary has been characterized using the ptychography method with a 405 nm laser beam. The recovered wavefront gives a 12.5×10.4µm2 focus. The reconstructed phase profile of the focused beam can be used to estimate the height error of the capillary surface. The obtained height error shows a Gaussian distribution with a standard deviation of 1.3 µm. This approach can be used as a quantitative tool for evaluating the inner functional surfaces of reflective optics, complementary to conventional metrology methods.

Micromachined Silicon Platform for Precise Assembly of 2D Multilayer Laue Lenses for High-Resolution X-ray Microscopy.

We report on a developed micromachined silicon platform for the precise assembly of 2D multilayer Laue lenses (MLLs) for high-resolution X-ray microscopy. The platform is 10 × 10 mm2 and is fabricated on ~500 µm thick silicon wafers through multiple steps of photolithography and deep reactive-ion etching. The platform accommodates two linear MLLs in a pre-defined configuration with precise angular and lateral position control. In this work, we discuss the design and microfabrication of the platform, and characterization regarding MLLs assembly, position control, repeatability, and stability. The results demonstrate that a micromachined platform can be used for the assembly of a variety of MLLs with different dimensions and optical parameters. The angular misalignment of 2D MLLs is well controlled in the range of the designed accuracy, down to a few millidegrees. The separation distance between MLLs is adjustable from hundreds to more than one thousand micrometers. The use of the developed platform greatly simplifies the alignment procedure of the MLL optics and reduces the complexity of the X-ray microscope. It is a significant step forward for the development of monolithic 2D MLL nanofocusing optics for high-resolution X-ray microscopy.

2D MEMS-based multilayer Laue lens nanofocusing optics for high-resolution hard x-ray microscopy.

We report on the development of 2D integrated multilayer Laue lens (MLL) nanofocusing optics used for high-resolution x-ray microscopy. A Micro-Electro-Mechanical-Systems (MEMS) - based template has been designed and fabricated to accommodate two linear MLL optics in pre-aligned configuration. The orthogonality requirement between two MLLs has been satisfied to a better than 6 millidegrees level, and the separation along the x-ray beam direction was controlled on a micrometer scale. Developed planar 2D MLL structure has demonstrated astigmatism free point focus of ∼14 nm by ∼13 nm in horizontal and vertical directions, respectively, at 13.6 keV photon energy. Approaching 10 nm resolution with integrated 2D MLL optic is a significant step forward in applications of multilayer Laue lenses for high-resolution hard x-ray microscopy and their adoption by the general x-ray microscopy community.

Design, characterization, and performance of a hard x-ray transmission microscope at the National Synchrotron Light Source II 18-ID beamline.

A transmission X-ray microscope has been designed and commissioned at the 18-ID Full-field X-ray Imaging beamline at the National Synchrotron Light Source II. This instrument operates in the 5-11 keV range, and, with the current set of optics, is capable of 30 nm spatial resolution imaging, with a field of view of about 40 µm. For absorption contrast, the minimum exposure time for a single projection image is about 20 ms and an entire 3D tomography data set can be acquired in under 1 min. The system enables tomographic reconstructions with sub-50 nm spatial resolution without the use of markers on the sample or corrections for rotation run-outs.

High-speed raster-scanning synchrotron serial microcrystallography with a high-precision piezo-scanner.

The Frontier Microfocus Macromolecular Crystallography (FMX) beamline at the National Synchrotron Light Source II with its 1 µm beam size and photon flux of 3 × 1012 photons s-1 at a photon energy of 12.66 keV has reached unprecedented dose rates for a structural biology beamline. The high dose rate presents a great advantage for serial microcrystallography in cutting measurement time from hours to minutes. To provide the instrumentation basis for such measurements at the full flux of the FMX beamline, a high-speed, high-precision goniometer based on a unique XYZ piezo positioner has been designed and constructed. The piezo-based goniometer is able to achieve sub-100 nm raster-scanning precision at over 10 grid-linepairs s-1 frequency for fly scans of a 200 µm-wide raster. The performance of the scanner in both laboratory and serial crystallography measurements up to the maximum frame rate of 750 Hz of the Eiger 16M's 4M region-of-interest mode has been verified in this work. This unprecedented experimental speed significantly reduces serial-crystallography data collection time at synchrotrons, allowing utilization of the full brightness of the emerging synchrotron radiation facilities.

Hard x-ray scanning imaging achieved with bonded multilayer Laue lenses.

We report scanning hard x-ray imaging with a monolithic focusing optic consisting of two multilayer Laue lenses (MLLs) bonded together. With optics pre-characterization and accurate control of the bonding process, we show that a common focal plane for both MLLs can be realized at 9.317 keV. Using bonded MLLs, we obtained a scanning transmission image of a star test pattern with a resolution of 50 × 50 nm2. By applying a ptychography algorithm, we obtained a probe size of 17 × 38 nm2 and an object image with a resolution of 13 × 13 nm2. The significant reduction in alignment complexity for bonded MLLs will greatly extend the application range in both scanning and full-field x-ray microscopies.

Fly-scan ptychography.

We report an experimental ptychography measurement performed in fly-scan mode. With a visible-light laser source, we demonstrate a 5-fold reduction of data acquisition time. By including multiple mutually incoherent modes into the incident illumination, high quality images were successfully reconstructed from blurry diffraction patterns. This approach significantly increases the throughput of ptychography, especially for three-dimensional applications and the visualization of dynamic systems.

A high-precision instrument for mapping of rotational errors in rotary stages.

A rotational stage is a key component of every X-ray instrument capable of providing tomographic or diffraction measurements. To perform accurate three-dimensional reconstructions, runout errors due to imperfect rotation (e.g. circle of confusion) must be quantified and corrected. A dedicated instrument capable of full characterization and circle of confusion mapping in rotary stages down to the sub-10 nm level has been developed. A high-stability design, with an array of five capacitive sensors, allows simultaneous measurements of wobble, radial and axial displacements. The developed instrument has been used for characterization of two mechanical stages which are part of an X-ray microscope.

Design and characterization of a compact nano-positioning system for a portable transmission x-ray microscope.

We have designed and constructed a compact nano-positioning system for a Portable Transmission X-ray Microscope (PTXM). We introduce a concept of PTXM and adopt modular approach which implements identical nano-motion platforms to perform manipulation of PTXM components. Modular design provides higher stiffness of the system and allows for reduction of relative thermal drifts between individual constituents of the PTXM apparatus, ensuring a high degree of stability for nanoscale x-ray imaging. We have measured relative thermal drifts between two identical modules to be as low as 15 nm/h, sufficient to perform nanoscale imaging by TXM. Spatial resolution achieved by developed linear piezo stages was measured to be 3 nm with repeatability of 20 nm over 1 mm travel range.

The fabrication of thermoelectric La0.95Sr0.05CoO3 nanofibers and Seebeck coefficient measurement.

The P-type perovskite oxides La(1-x)Sr(x)CoO(3) are a promising group of complex oxide thermoelectric (TE) materials. The thermoelectric properties of these oxides are expected to be significantly improved when their critical dimensions are reduced to the nanoscale. In this paper, the La(0.95)Sr(0.05)CoO(3) nanofibers, with diameters in the range of approximately 35 nm, were successfully prepared by the electrospinning process. X-ray diffraction (XRD) and scanning electron microscopy (SEM) were used to characterize these thermoelectric nanofibers. A micro-electromechanical (MEMS) tester was designed and fabricated to measure the Seebeck coefficient of the nanofibers. The measured voltage output was as large as 1.7 mV and the obtained Seebeck coefficient of the nanofibers reached 650 microV K(-1).