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Abstract Macular edema is a known side effect of taxane-based anticancer drugs. We retrospectively investigated data from 11 centers between January 2016 and December 2021. Among 14,260 patients, 30 (0.21%) developed macular edema; from these, the number of cases associated with nab-paclitaxel was 16 (0.43%), significantly higher than the number of cases associated with paclitaxel or docetaxel (P

ABSTRACT Aims/Introduction To conduct a multicenter survey of visually impaired patients with diabetes mellitus (DM) and to identify the physical and ocular characteristics that lead to blindness in Japan. Materials and Methods Visually impaired patients with diabetes mellitus in Japan were divided into blind and low‐vision groups according to the World Health Organization classification. Data on parameters related to diabetes mellitus and ocular complications in the right and left eyes were collected from 19 highly advanced medical facilities and compared between the two groups. Results Among 408 visually impaired persons (blind group: 257, low‐vision group: 151), 72.1% were under 70 years of age. The rates of neovascular glaucoma (NVG) (right eye, P = 0.041; left eye, P = 0.0031) or proliferative diabetic retinopathy (PDR) (right eye: P = 0.014, left eye: P = 0.0047) and the rate of proliferative membrane beyond half of the retinal area (right eye: P = 0.0263, left eye: P = 0.037) were significantly higher in the blind group. The direct cause of visual impairment was retinal atrophy, common in both groups. Neovascular glaucoma and diabetic macular edema were equally prevalent in the blind and low‐vision groups, respectively. Conclusions In Japan, blind patients with diabetes mellitus are characterized by severe conditions such as neovascular glaucoma and progressive proliferative diabetic retinopathy upon their initial visit to an advanced care facility. These results highlight the importance of monitoring retinopathy through regular ophthalmological examinations, internal medicine, and appropriate therapeutic intervention.

Melatonin, a versatile hormone produced by the pineal gland, has garnered considerable scientific interest due to its diverse functions. In the eye, melatonin regulates a variety of key processes like inhibiting angiogenesis by reducing vascular endothelial growth factor levels and protecting the blood-retinal barrier (BRB) integrity by enhancing tight junction proteins and pericyte coverage. Melatonin also maintains cell health by modulating autophagy via the Sirt1/mTOR pathways, reduces inflammation, promotes antioxidant enzyme activity, and regulates intraocular pressure fluctuations. Additionally, melatonin protects retinal ganglion cells by modulating aging and inflammatory pathways. Understanding melatonin's multifaceted functions in ocular health could expand the knowledge of ocular pathogenesis, and shed new light on therapeutic approaches in ocular diseases. In this review, we summarize the current evidence of ocular functions and therapeutic potential of melatonin and describe its roles in angiogenesis, BRB integrity maintenance, and modulation of various eye diseases, which leads to a conclusion that melatonin holds promising treatment potential for a wide range of ocular health conditions.

Telecommunications technology has evolved rapidly, creating opportunities to diversify the communication culture through AI mediation. We anticipate that people will interchangeably use both user-controlled (controlled by transferring user movements) and AI-controlled avatars (controlled autonomously) in everyday communication. For example, users may temporarily use the AI-controlled mode during distractions. This paper argues the importance of investigating the auto-switching between user- and AI-controlled modes to improve the user experience in upcoming AI-mediated telecommunications. As a first step, we conducted a crowdsourced user experiment in a video chat context, focusing on the visual impressions of the displayed avatars. The result shows that impression improved when an appropriate switch setting is used, underscoring the value of this research direction. To identify the appropriate switch setting for our experiment, we developed a general-purpose adaptive experimental design tool based on Bayesian optimization, which we plan to release publicly.

Abstract We assessed the 10-year postoperative outcomes of pediatric cataract patients who underwent surgery at the age of 6 years or younger. A retrospective review of medical charts was conducted for 457 eyes of 277 patients, with the age at surgery averaging 1.3 ± 1.5 years (mean ± SD) and the follow-up duration averaging 12.8 ± 2.4 years (ranging from 10 to 17 years). The cohort included 250 eyes of 125 cases with bilateral aphakia (age at surgery 0.5 ± 0.8 years), 110 eyes of 55 cases with bilateral pseudophakia (1.9 ± 1.6 years), 42 cases with unilateral aphakia (1.1 ± 1.3 years), and 55 cases with unilateral pseudophakia (2.6 ± 1.7). A forward stepwise multiple regression analysis revealed that the best-corrected visual acuity at the final visit was significantly associated with laterality of cataract (with bilateral cases showing better results compared to unilateral cases), presence of systemic comorbidities, presence of ocular comorbidities, development of glaucoma, and phakic status (with better results in the pseudophakia group than the aphakia group). The age at surgery did not significantly affect visual acuity outcomes. A multiple logistic regression analysis demonstrated that the incidence of secondary glaucoma was significantly linked to younger age at surgery, phakic status (higher in aphakic than pseudophakic eyes), and presence of systemic comorbidities. In conclusion, after pediatric cataract surgery, final visual acuity was better in patients with bilateral cataracts, those treated with an intraocular lens, and cases without systemic or ocular comorbidities and secondary glaucoma. The development of secondary glaucoma was linked to younger age at surgery, aphakic status, and presence of systemic comorbidities.

Multi-rotor system (MRS) wind turbines can provide a competitive alternative to large-scale wind turbines due to their significant advantages in reducing capital, transportation, and operating costs. The main challenges of MRS wind turbines include the complexity of the supporting structure, mathematical modeling of the aerodynamic interaction between the rotors, and the yaw control mechanism. In this work, MATLAB 2018b/Simulink® software was used to model and simulate a twin-rotor wind turbine (TRWT), and an NREL 5 MW wind turbine was used to verify the model outputs. Different random signals of wind velocities and directions were used as inputs to each rotor to generate different thrust loads, inducing twisting moments on the main tower. A yaw controller system was adapted to ensure that the turbine constantly faced the wind to maximize the power output. A DC motor was used as the mechanism’s actuator. The goal was to achieve a compromise between aligning the rotors with the wind direction and reducing the torque induced on the main tower. A comparison between linear and nonlinear controllers was performed to test the yaw system actuator’s response at different wind speeds and directions. Sliding mode control (SMC) was chosen, as it was suitable for the nonlinearity of the system, and its performance showed a faster response compared with the PID controller, with a settling time of 0.17 sec and a very low overshoot. The controller used the transfer function of the motor to generate a sliding surface. The dynamic responses of the controlled angle are shown and discussed. The controller showed promising results, with a suitable response and low chattering signals.

Background: RNA methylation is involved in major life processes. Angiogenesis is a normal phenomenon that occurs constantly in the bodies of all mammals, once it is aberrant or something goes wrong, it may lead to pathological changes. The bibliometric analysis could produce a comprehensive overview of RNA methylation during angiogenesis. Methods: The Web of Science Core Collection (WoSCC) database was used to screen publications about RNA methylation during angiogenesis from Jan 1, 2000 to Nov 24, 2022. Bibliometric and visualization analyses were conducted to understand publication trends by CiteSpace and VOSviewer. Results: In total, 382 publications from 2000 to 2022 were included in the bibliometric and visualization analyses. On the whole, the number of publications had exponential growth. China was the country and Sun Yat-Sen University was the university associated with the largest number of publications, although publications from the United Kingdom and Soochow University were currently having the strongest impact. Cancer was the most studied topic in this field, and N6-methyladenosine is the most studied RNA methylation type. Conclusion: There is a continuously increasing trend in publications related to RNA methylation and angiogenesis, which has attracted much attention, particularly since 2011. RNA methylation might be a promising target in the investigation of pathological angiogenesis and related disorders, which deserves further investigation.

Wind–solar towers are a relatively new method of capturing renewable energy from solar and wind power. Solar radiation is collected and heated air is forced to move through the tower. The thermal updraft propels a wind turbine to generate electricity. Furthermore, the top of the tower’s vortex generators produces a pressure differential, which intensifies the updraft. Data were gathered from a wind–solar tower system prototype developed and established at Kyushu University in Japan. Aiming to predict the power output of the system, while knowing a set of features, the data were evaluated and utilized to build a regression model. Sensitivity analysis guided the feature selection process. Several machine learning models were utilized in this study, and the most appropriate model was chosen based on prediction quality and temporal criteria. We started with a simple linear regression model but it was inaccurate. By adding some non-linearity through using polynomial regression of the second order, the accuracy increased considerably sufficiently. Moreover, deep neural networks were trained and tested to enhance the power prediction performance. These networks performed very well, having the most powerful prediction capabilities, with a coefficient of determination R2=0.99734 after hyper-parameter tuning. A 1-D convolutional neural network achieved less accuracy with R2=0.99647, but is still considered a competitive model. A reduced model was introduced trading off some accuracy (R2=0.9916) for significantly reduced data collection requirements and effort.

Spar is one of the promising floating platforms to support offshore wind turbines. Wind heeling moment is large in the case of floating offshore wind turbines and, therefore, it is important to reduce the pitch motion of the floating platform. To address this issue, a spar platform with damping plates is proposed and investigated in this study. (i) Type-A, (ii) Type-B, and (iii) Type-C models of 1/120 scale were fabricated with similar stability parameters. Type-A is a classic spar, Type-B and Type-C are spar with damping plates by replacing the ballast water part with horizontal plates and vertical plates, respectively. The rotor model consists of (i) no disk and (ii) with disk conditions. A series of model scale experiments were carried out in the water tank in regular waves, and motion response was measured. A calculation method based on classic frequency-domain was developed to incorporate damping plates and validated with the experiment results in no disk and with disk conditions. When pitch response of Type-B and Type-C were compared with respect to Type-A, it was found that the spar platform with damping plates reduced the pitch response in most wave frequencies.

PurposeIn patients with diabetic macular edema (DME) from YOSEMITE/RHINE, dual angiopoietin-2/vascular endothelial growth factor-A (VEGF-A) inhibition with faricimab resulted in visual/anatomic improvements with extended dosing. The SWAN trial (jRCTs031230213) will assess the efficacy, durability, and safety of faricimab during the treatment maintenance phase in patients with DME using a treat-and-extend (T&E)-based regimen adapted to clinical practice and the characteristics of patients achieving extended dosing intervals.MethodsSWAN is a 2-year, open-label, single-arm, interventional, multicenter trial enrolling adults with center-involving DME. All patients will receive three initial faricimab 6.0 mg doses every 4 weeks (Q4W). From week 12 onwards, in patients without active DME, dosing intervals will be extended in 8-week increments up to Q24W. In contrast, patients with active DME (central subfield thickness [CST] >325 μm and intraretinal fluid [IRF] or subretinal fluid [SRF] resulting in vision loss/disease aggravation) will receive a dose within a day and the dosing interval will be shortened by 4 weeks to a minimum of Q8W relative to the previous dosing interval. Recruitment commenced in August 2023 across a planned 16 sites in Japan.ResultsThe primary endpoint is change in best-corrected visual acuity (BCVA) from baseline at 1 year (averaged over weeks 52, 56, and 60). Key secondary endpoints include: change from baseline in BCVA, CST, and National Eye Institute Visual Function Questionnaire scores over time; proportion of patients with BCVA (decimal visual acuity) ≥0.5, ≥0.7, ≥1.0, or ≤0.1; proportion of patients with absence of DME, and IRF and/or SRF over time. Safety endpoints include incidence/severity of ocular/nonocular adverse events.ConclusionsThe SWAN trial is expected to provide evidence to support individualized faricimab dosing regimens, with the potential to reduce the burden of frequent treatments on patients, caregivers, and healthcare systems.

N6-methyladenosine (m6A) modification, as the most common modification method in eukaryotes, is widely involved in numerous physiological and pathological processes, such as embryonic development, malignancy, immune regulation, and premature aging. Under pathological conditions of ocular diseases, changes in m6A modification and its metabolism can be detected in aqueous and vitreous humor. At the same time, an increasing number of studies showed that m6A modification is involved in the normal development of eye structures and the occurrence and progress of many ophthalmic diseases, especially ocular neovascular diseases, such as diabetic retinopathy, age-related macular degeneration, and melanoma. In this review, we summarized the latest progress regarding m6A modification in ophthalmic diseases, changes in m6A modification-related enzymes in various pathological states and their upstream and downstream regulatory networks, provided new prospects for m6A modification in ophthalmic diseases and new ideas for clinical diagnosis and treatment.

A coaxial counter-rotating rotor (CCRR), which has two rotors rotating in the opposite directions on the same axis, is seen as a promising technology for low-cost floating tidal current/ocean current power generation using single-point mooring, as the torques of the front and rear rotors are cancelled. In the evaluation and design of such turbines, there is a need for an accurate analysis method with a low computational load that considers the strong mutual induction between the two rotors placed close together. An individual rotor mutual induction (IRMI) method was developed in this study, aiming to significantly reduce the calculation time of conventional computational fluid dynamics (CFD), considering the mutual induction that are not considered in conventional modified blade element and momentum methods. In this method, the basic characteristics of the front and rear rotors are calculated in advance using full-model CFD. In calculations for the CCRR, in addition to these individual characteristics of each rotor, the interaction between the rotors is considered using the actuator disk model CFD calculated in advance. The condition where the torques of the front and rear rotors are cancelled is determined at the same time. This method was used to analyze models in which the front and rear rotors were approximately the same diameter and placed close together (10% of the rotor diameter). A comparison with the mixing plane model CFD revealed that they agree quite well when mutual induction is considered, although both the power and thrust are overcalculated when it is ignored. The simulation time of the IRMI would be almost counter-proportional to the numbers of TSR conditions to solve as compared with the CFD with the MP model.

Abstract Laser therapy is the most effective treatment considered for retinopathy of prematurity (ROP). We compared the foveal morphology of the retina in eyes with a history of ROP to that of full-term children. This cross-sectional comparative study included 74 patients with a history of ROP, aged 4–6 years. Among them, 41 underwent laser treatment for ROP. The clinical findings and retinal morphology in these patients were compared to that of 33 patients who had spontaneous ROP regression and 30 age-matched full-term controls. All the patients with ROP had 20/40 or better best-corrected visual acuity (BCVA). The foveal thickness was significantly thicker in laser-treated ROP eyes than in regressed ROP eyes and controls. The outer nuclear layer was significantly thicker, and the inner segment (IS) of the photoreceptors and the inner retinal layer were significantly thicker in the laser-treated ROP eyes than that in the control eyes. In the patients with ROP and controls, better BCVA was associated positively with deeper foveal depression, which was associated with a later gestational age. Our results suggest that prematurity and laser treatment affect the foveal morphology and BCVA.

Exosomes are extracellular vesicles that can be produced by most cells. Exosomes act as important intermediaries in intercellular communication, and participate in a variety of biological activities between cells. Non-coding RNAs (ncRNAs) usually refer to RNAs that do not encode proteins. Although ncRNAs have no protein-coding capacity, they are able to regulate gene expression at multiple levels. Angiogenesis is the formation of new blood vessels from pre-existing vessels, which is an important physiological process. However, abnormal angiogenesis could induce many diseases such as atherosclerosis, diabetic retinopathy and cancer. Many studies have shown that ncRNAs can stably exist in exosomes and play a wide range of physiological and pathological roles including regulation of angiogenesis. In brief, some specific ncRNAs can be enriched in exosomes secreted by cells and absorbed by recipient cells through the exosome pathway, thus activating relevant signaling pathways in target cells and playing a role in regulating angiogenesis. In this review, we describe the physiological and pathological functions of exosomal ncRNAs in angiogenesis, summarize their role in angiogenesis-related diseases, and illustrate potential clinical applications like novel drug therapy strategies and diagnostic markers in exosome research as inspiration for future investigations.

Background: Gene therapy is a treatment approach at the genetic level, which brings great advances in many diseases and develops rapidly in recent years. Currently, its mechanism of action is mainly through the replacement of missing or defective genes, or the reduction of harmful gene products. However, the application of gene therapy in ophthalmology remains limited. Methods: A total of 1143 articles and reviews published in the field of ocular gene therapies were found in the Web of Science Core Collection database and used for the bibliometric analysis. CiteSpace was mainly applied to the network analysis of countries, institutions, keywords, and dual-map overlay of journals. The visual analysis of authors, journals, and references was used by VOSviewer. The geographical distribution of publications was conducted by R language. Results: The annual publications are increasing in general. Currently, the USA and the UK are two main sources of publications in this field. Switzerland, Denmark, and Finland are the top 3 countries that establish the most cooperation and exchanges with other countries or regions. The most cited and co-cited journal in this field is Investigative Ophthalmology & Visual Science. Gene therapy studies for eye diseases are mainly focused on retinal dysfunctions by the analysis of references, keywords, and counting of original research, including Leber's congenital amaurosis and retinitis pigmentosa. Conclusion: This study used bibliometrics to analyze overall characteristics and put forward prospects for the future in the field of gene therapy in ophthalmology. Ocular diseases, especially hereditary retinal diseases, will be the major focus of gene therapy in the future.

In this paper, we present the findings of a study investigating the impact of shape on the taste perception of chocolate. Previous research has explored the influence of various sensory information on taste perception, but there has been little focus on the effect of food shape being eaten on taste perception. To explore this, we focused on the Bouba-Kiki effect, illustrating an interaction between shape and several modalities, and investigated the effect of Bouba- and Kiki-shaped (rounded and angular) foods eaten on taste perception. We utilized a 3D food printer to produce four different shapes of chocolate pieces based on the Bouba-Kiki. Participants tasted each piece and completed a chocolate flavor questionnaire. With Bayesian analysis, we determined that the Bouba-shaped chocolate pieces were perceived as sweeter than the Kiki-shaped ones, supporting earlier studies on crossmodal correspondences between shape and taste perception. However, there were no significant differences in ratings of other tastes, such as sourness and bitterness. Our research indicates that shape can affect taste perception during consumption and suggests that 3D food printers offer an opportunity to design specific shapes that influence taste experiences.

Typical large scale pitch-controlled wind turbines idle their rotors during storm conditions. The design loads of wind turbines are calculated by aeroelastic simulations under various conditions. These include grid loss and failures, which can increase rotor speed and excite the first-mode of the tower bending. In this study, the influences of self-excitation by the idling rotor on the ultimate loads in storm conditions were investigated. Aeroelastic simulations were conducted for a three-bladed 5 MW upwind turbine as an example, under steady and extreme turbulent wind conditions according to the international design standard IEC61400-1 ed.4. As a result, we confirmed that yaw misalignment increases the idling rotor speed and 6P, second order harmonics of blade passing frequency, excites the first-mode tower bending, which can generate a large load on the tower. Pitch stick can increase the rotor speed but not as noticeably as yaw error. Although no clear provisions exist in wind turbine design standards or guidelines for the self-excited vibration during wind turbine idling, these results indicate that conditions must be set that consider self-excited vibration.

A color extraction interface reflecting human color perception helps pick colors from natural images as users see. Apparent color in photos differs from pixel color due to complex factors, including color constancy and adjacent color. However, methodologies for estimating the apparent color in photos have yet to be proposed. In this paper, the authors investigate suitable model structures and features for constructing an apparent color picker, which extracts the apparent color from natural photos. Regression models were constructed based on the psychophysical dataset for given images to predict the apparent color from image features. The linear regression model incorporates features that reflect multi-scale adjacent colors. The evaluation experiments confirm that the estimated color was closer to the apparent color than the pixel color for an average of 70%–80% of the images. However, the accuracy decreased for several conditions, including low and high saturation at low luminance. The authors believe that the proposed methodology could be applied to develop user interfaces to compensate for the discrepancy between human perception and computer predictions.

Exposure therapy is a mainstream of treatment for social anxiety disorder (SAD). However, effort and time are required to recreate interpersonal situations that produce moderate anxiety. On the other hand, virtual reality exposure therapy can easily control anxiety-inducing conditions and allow for graduated exposure. However, artificial intelligence and animations that speak as naturally as actual humans are not yet practical, adding to the limitations of these treatments. The authors propose the use of a virtual reality technology that can transform facial expressions into smiling or sad faces in real time and display them on a monitor, potentially solving the above-mentioned problems associated with virtual reality animations. This feasibility study was conducted to determine whether this system can be safely applied to the treatment of SAD patients. A total of four SAD patients received 16 exposure therapy sessions led by an experienced therapist over a monitor; throughout the sessions, the facial expressions of the therapist were modified using software to display expressions ranging from smiling to sad on the monitor that was being viewed by the patient. Client satisfaction, treatment alliance, and symptom assessments were then conducted. Although one patient dropped out of the study, treatment satisfaction and treatment alliance were scored high in all the cases. In two of the four cases, the improvement in symptoms was sustained over time. Exposure therapy in which the interviewer’s facial expressions are modified to induce appropriate levels of anxiety in the patient can be safely used for the treatment of SAD patients and may be effective for some patients.

Many vertical-axis wind turbines (VAWTs) require arms, which generally provide aerodynamic resistance, to connect the main blades to the rotating shaft. Three–dimensional numerical simulations were conducted to clarify the effects of a gap placed at the blade–arm connection portion on VAWT performance. A VAWT with two straight blades (diameter: 0.75 m, height: 0.5 m) was used as the calculation model. Two horizontal arms were assumed to be connected to the blade of the model with or without a gap. A cylindrical rod with a diameter of 1 or 5 mm was installed in the gap, and its length varied from 10 to 30 mm. The arm cross section has the same airfoil shape (NACA 0018) as the main blade; however, the chord length is half (0.04 m) that of the blade. The simulation shows that the power of the VAWT with gaps is higher than that of the gapless VAWT. The longer gap length tends to decrease the power, and increasing the diameter of the connecting rod amplifies this decreasing tendency. Providing a short gap at the blade–arm connection and decreasing the cross–sectional area of the connecting member is effective in increasing VAWT power.

In recent years, the increasing environmental problems, especially the issue of global warming, have motivated demand for a cleaner, more sustainable, and economically viable energy source. In this context, wind energy plays a significant role due to the small negative impact it has on the environment, which makes it among the most widespread potential sustainable renewable fuel nowadays. However, wind turbine control systems are important factors in determining the efficiency and cost-effectiveness of a wind turbine (WT) system for wind applications. As wind turbines become more flexible and larger, it is difficult to develop a control algorithm that guarantees both efficiency and reliability as these are conflicting objectives. This paper reviews various control strategies for the three main control systems of WT, which are pitch, torque, and yaw control, in different operational regions considering multi-objective control techniques. The different control algorithms are generally categorized as classical, modern (soft computing) and artificial intelligence (AI) for each WT control system. Modern and soft computing techniques have been showing remarkable improvement in system performance with minimal cost and faster response. For pitch and yaw systems, soft computing control algorithms like fuzzy logic control (FLC), sliding mode control (SMC), and maximum power point tracking (MPPT) showed superior performance and enhanced the WT power performance by up to 5% for small-scale WTs and up to 2% for multi-megawatt WTs. For torque control systems, direct torque control (DTC) and MPPT AI-based techniques were suitable for reducing generator torque fluctuations and estimating the torque coefficient for different wind speed regions. Classical control techniques such as PI/PID resulted in poor dynamic response for large-scale WTs. However, to improve classical control techniques, AI algorithms could be used to tune the controller’s parameters to enhance its response, as a WT is a highly non-linear system. A graphical abstract is presented at the end of the paper showing the pros/cons of each control system category regarding each WT control system.

Objective We report the 2-year visual and psychological outcomes of the MERCURY study, examining the long-term effectiveness and safety of ranibizumab and subsequent therapy in Japanese patients with diabetic macular oedema with impaired visual acuity (VA) in the real-world setting.Methods and analysis This was a 24-month, phase 4, open-label, single-arm, multicentre, prospective, observational study. Following an initial dose of ranibizumab (0.5 mg) by intravitreal injection (0.05 mL), treatment was administered as needed after month 1. The primary treated eye (PTE) was the first eye that received a ranibizumab injection.Results In total, 209 patients were enrolled; 192 (91.9%) and 174 (83.3%) completed months 12 and 24, respectively. In the PTE set, mean±SD changes in best-corrected VA (BCVA) from baseline to months 12 (primary endpoint) and 24 were −0.08±0.35 (p=0.015) and −0.13±0.30 (p

Abstract Background Thyroid stimulating hormone (TSH) receptor and local infiltrate lymphocytes have been considered as major pathological factors for developing thyroid-related ophthalmopathy. Overexpression of insulin-like growth factor-I (IGF-I) receptor has emerged as a promising therapeutic target for refractory patients. However, the relationship between activation of growth hormone (GH)/IGF-I receptor signaling and development or exacerbation of thyroid ophthalmopathy has not been elucidated. Herein we describe a case that provides further clarification into the association between thyroid-related ophthalmopathy and GH/IGF-I receptor signaling. Case presentation A 62-year-old Japanese female diagnosed with thyroid-related ophthalmopathy was admitted to Kurume University Hospital. She had received daily administration of GH subcutaneously for severe GH deficiency; however, serum IGF-I levels were greater than + 2 standard deviation based on her age and sex. She exhibited mild thyrotoxicosis and elevation in levels of TSH-stimulating antibody. Discontinuation of GH administration attenuated the clinical activity scores of her thyroid-related ophthalmopathy. Additionally, concomitant use of glucocorticoid and radiation therapies resulted in further improvement of thyroid-related ophthalmopathy. The glucocorticoid administration was reduced sequentially, followed by successful termination. Thereafter, the patient did not undergo recurrence of thyroid-related ophthalmopathy and maintained serum IGF-I levels within normal physiological levels. Conclusions We describe here a case in which development of thyroid-related ophthalmopathy occurred upon initiation of GH administration. GH/IGF-I signaling was highlighted as a risk factor of developing thyroid-related ophthalmopathy. Additionally, aberrant TSH receptor expression was suggested to be a primary pathophysiological mechanism within the development of thyroid-related ophthalmopathy. Physicians should be aware of the risks incurred via GH administration, especially for patients of advanced age, for induction of thyroid-related ophthalmopathy.

PurposeThis study aims to reveal the altered expression profiles of circular RNAs (circRNAs) in the peripheral blood mononuclear cells (PBMCs) of patients with retinopathy of prematurity (ROP), and to identify potential biomarkers for ROP diagnosis.MethodsDifferentially expressed circRNAs in PBMCs of five infants with ROP and five controls were identified using microarray analysis. Twelve altered circRNAs were validated using reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR). Bioinformatic analyses were conducted to predict the circRNA/miRNA interactions, competing endogenous RNA (ceRNA) network, related biological functions, and signaling pathways. Four selected circRNAs in PBMCs were verified using RT-qPCR in another cohort, including 24 infants with ROP and 23 premature controls, and receiver operating characteristic (ROC) curves were used to estimate their potential as diagnostic biomarkers of ROP.ResultsA total of 54 and 143 circRNAs were significantly up- and down-regulated, respectively, in the PBMCs of patients with ROP compared with controls. Twelve of the significantly altered circRNAs were preliminarily validated by RT-qPCR, which confirmed the reliability of the microarray analysis. The circRNA/miRNA interactions and ceRNA network were displayed according to the altered circRNAs. Three circRNAs (hsa_circRNA_061346, hsa_circRNA_092369, and hsa_circRNA_103554) were identified as potential diagnostic biomarkers for ROP with certain clinical values.ConclusionsCircRNAs were significantly altered in PBMCs of treatment-requiring ROP patients. CircRNAs may be used as potential biomarkers and possible therapeutic targets for ROP.

PurposeWe sought to reveal the expression profiles of transfer RNA-derived small RNAs (tsRNAs) and microRNAs (miRNAs) in the vitreous humor of patients with proliferative diabetic retinopathy (PDR).MethodsVitreous humor samples were obtained from PDR patients and a control group for this study. Sequencing of small RNAs was conducted to assess the expression profiles of tsRNAs and miRNAs in both groups, which was followed by validation using reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR). Bioinformatics analyses were conducted to predict the target genes and their potential biological functions and signaling pathways.ResultsA total of 37 tsRNAs and 70 miRNAs with significant differences were screened out from the vitreous humor samples of PDR patients compared to controls. Following validation by RT-qPCR, the target genes of the validated tsRNAs and miRNAs were predicted, and Gene Ontology analysis indicated that the target genes of the tsRNAs were most enriched in the cellular macromolecule metabolic process, cytoplasm, and ion-binding, while those of the miRNAs were most abundant in the regulation of major metabolic process, cytoplasm, and protein-binding. In addition, Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the target genes of said tsRNAs and miRNAs were most enriched in the adenosine monophosphate-activated protein kinase signaling pathway and Th17 cell differentiation, respectively.ConclusionsThe present study identified altered tsRNAs and miRNAs in vitreous humor samples of PDR patients, which may play important roles in the pathogenesis of PDR and could be considered potential therapeutic targets in the treatment of PDR.

Abstract This prospective, open-label, single-arm, non-randomized clinical trial, assessed the efficacy of a 2-year treat-and-extend (T&E) regimen involving intravitreal aflibercept injection (IAI), with the longest treatment interval set to 16 weeks, and adjunct focal/grid laser in diabetic macula edema (DME) patients. We examined 40 eyes (40 adults) with fovea-involving DME from 8 Japanese centers between April 2015 and February 2017. Participants received IAI with an induction period featuring monthly injections and a subsequent T&E period featuring 8–16-week injection interval, adjusted based on optical coherence tomography findings. The primary endpoints were mean changes in the best-corrected visual acuity (BCVA) and central subfield macular thickness (CST) from baseline. Thirty patients (75%) completed the 2-year follow-up. The mean BCVA and CST changed from 60.5 ± 15.6 letters and 499.2 ± 105.6 µm at baseline to 66.6 ± 17.1 letters (P = 0.217) and 315.2 ± 79.0 µm (P

Abstract Background To evaluate the correlation between visual acuity improvement and vision-related QOL after ranibizumab treatment in Japanese patients with AMD. Methods In this one-year prospective, interventional, open-label, multicenter study involving four sites, patients with neovascular AMD were enrolled and observed for 12 months. Treatment-naïve patients received 0.5 mg ranibizumab as needed after three initial monthly doses. The best corrected visual acuity (BCVA) and central macular thickness (CMT) were measured at every visit. Evaluations with the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and patient satisfaction questionnaire were performed at baseline and 3 and 12 months after initial treatment. The primary endpoint was change in BCVA and QOL 3 months after ranibizumab treatment. QOL outcomes were also assessed in the better and poor BVCA subgroups. Results The study enrolled 100 patients. The mean logMAR BCVA after treatment improved significantly from 0.43 to 0.30 at 3 months (p 0.6, p=0.1) at 3 months. There were no significant differences in the satisfaction questionnaire score from baseline to at 3 months (p=0.54) and 12 months (p=0.23). The average CMT improved significantly from 340 to 264 μm at 3 months (p

Abstract Intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) is the standard treatment modality in various types of retinal diseases. However, endophthalmitis remains the most serious complication. Despite the lack of evidence that antibiotics prevent endophthalmitis, topical antibiotics are still used routinely in Japan. We conducted a retrospective multicenter study by analyzing records from patients who underwent IVI of anti-VEGF agents with or without antibiotic treatment. In the analysis of a total of 147,440 eyes, the incidence of endophthalmitis was 0.007%: 0.005% with no use of antibiotics, 0.009% with antibiotic pretreatment, 0.012% with posttreatment, and 0.005% with pre- and posttreatment. There was no statistically significant difference among the four groups (chi-square test, p = 0.57). Most facilities used masks, sterilized gloves, and drapes. Nine of the 10 eyes that developed endophthalmitis received topical antibiotics, and all infected eyes underwent IVI with aflibercept, not the prefilled syringe delivery system. In four patients who received multiple IVI, the detection of causative bacteria revealed resistance to used antibiotics. Data from this large population, treated with or without antibiotics, suggests that antibiotic prophylaxis does not reduce the rate of endophthalmitis after IVI.

AIM: To conduct a Meta-analysis for the change of interleukin-10 (IL-10) concentration in vitreous samples of patients with diabetic retinopathy (DR). METHODS: Systemic search for literature was conducted from the databases of PubMed, Web of Science and Cochrane Library by August 2019. Statistical analyses including standard mean difference (SMD) and its 95% confidence interval (CI) were performed by using RevMan 5.3 software. RESULTS: Totally 194 studies were screened and finally 11 studies were included in the Meta-analysis. The concentration of IL-10 in the DR group was higher than in the control group (P=0.003, SMD: 0.77, 95%CI: 0.25-1.28). Significant heterogeneity was found among all studies (P

Retinopathy of prematurity (ROP) is the main risk factor for vision-threatening disease in premature infants with low birth weight. An accumulating number of independent studies have focused on ROP pathogenesis and have demonstrated that laser photocoagulation therapy and/or anti-VEGF treatment are effective. However, early diagnosis of ROP is still critical. At present, the main method of ROP screening is based on binocular indirect ophthalmoscopy. However, the judgment of whether ROP occurs and whether treatment is necessary depends largely on ophthalmologists with a great deal of experience. Therefore, it is essential to develop a simple, accurate and effective diagnostic method. This review describes recent findings on novel biomarkers for the prediction, diagnosis and prognosis of ROP patients. The novel biomarkers were separated into the following categories: metabolites, cytokines and growth factors, non-coding RNAs, iconography, gut microbiota, oxidative stress biomarkers, and others. Biomarkers with high sensitivity and specificity are urgently needed for the clinical applications of ROP. In addition, using non-invasive or minimally invasive methods to obtain samples is also important. Our review provides an overview of potential biomarkers of ROP.

In this paper, we present the development of a non-linear model predictive controller for the trajectory tracking of a quadrotor using the CasADi optimization framework. The non-linear dynamic model of the quadrotor was derived using Newton–Euler equations, and the control algorithm and drone dynamics were wrapped in Matlab. The proposed controller was tested by simulating the tracking of a 3D helical reference trajectory, and its efficiency was evaluated in terms of numerical performance and tracking accuracy. The results showed that the proposed controller leads to faster computational times, approximately 20 times faster than the Matlab toolbox (nlmpc), and provides better tracking accuracy than both the Matlab toolbox and classical PID controller. The robustness of the proposed control algorithm was also tested and verified under model uncertainties and external disturbances, demonstrating its ability to effectively eliminate tracking errors.

Purpose: We describe the ocular findings in a patient with Alagille syndrome, included those obtained with ultra-widefield and anterior-segment optical coherence tomography (AS-OCT) imaging. Observations: A previously asymptomatic 29-year-old woman with a heterozygous pathogenic variant in the JAG1 gene was referred for an ophthalmic evaluation. The ocular abnormalities included bilateral posterior embryotoxon, iris atrophy, retinal pigmentary changes in the peripheral and peripapillary regions, and optic disc elevation. Ultra-widefield OCT showed bilateral retinal thinning with increased choroidal hyperreflectivity in the areas of peripheral retinopathy and optic disc elevation. AS-OCT confirmed bilateral iris atrophy. Conclusions and Importance: The ocular abnormalities observed in the present case represent clinical features characteristic of Alagille syndrome. Both ultra-widefield and AS-OCT were useful for assessing the ocular abnormalities in Alagille syndrome.

Diabetic retinopathy (DR) is a major cause of blindness worldwide and may be non-proliferative (NPDR) or proliferative (PDR). To investigate the metabolomic and lipidomic characteristics of plasma in DR patients, plasma samples were collected from patients with type 2 diabetes mellitus (DR group) with PDR (n = 27), NPDR (n = 18), or no retinopathy (controls, n = 21). Levels of 54 and 41 metabolites were significantly altered in the plasma of DR patients under positive and negative ion modes, respectively. By subgroup analysis, 74 and 29 significantly changed plasma metabolites were detected in PDR patients compared with NPDR patients under positive and negative ion modes, respectively. KEGG analysis indicated that pathways such as biosynthesis of amino acids and neuroactive ligand-receptor interaction were among the most enriched pathways in altered metabolites in the DR group and PDR subgroup. Moreover, a total of 26 and 41 lipids were significantly changed in the DR group and the PDR subgroup, respectively. The panel using the 29-item index could discriminate effectively between diabetic patients with and without retinopathy, and the panel of 22 items showed effective discrimination between PDR and NPDR. These results provide a basis for further research into the therapeutic targets associated with these metabolite and lipid alterations.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

PurposeChoroidal neovascularization (CNV) is the defining feature of neovascular age-related macular degeneration (nAMD). Gut microbiota might be deeply involved in the pathogenesis of nAMD. This study aimed to reveal the roles of the gut microbiome and fecal metabolome in a mouse model of laser-induced CNV.MethodsThe feces of C57BL/6J mice with or without laser-induced CNV were collected. Multi-omics analyses, including 16S rRNA gene sequencing and untargeted metabolomics, were conducted to analyze the changes in the gut microbial composition and the fecal metabolomic profiles in CNV mice.ResultsThe gut microbiota was significantly altered in CNV mice. The abundance of Candidatus_Saccharimonas was significantly upregulated in the feces of CNV mice, while 16 genera, including Prevotellaceae_NK3B31_group, Candidatus_Soleaferrea, and Truepera, were significantly more abundant in the controls than in the CNV group. Fecal metabolomics identified 73 altered metabolites (including 52 strongly significantly altered metabolites) in CNV mice compared to control mice. Correlation analysis indicated significant correlations between the altered fecal metabolites and gut microbiota genera, such as Lachnospiraceae_UCG-001 and Candidatus_Saccharimonas. Moreover, KEGG analysis revealed six pathways associated with these altered metabolites, such as the ABC transporter, primary bile acid biosynthesis and steroid hormone biosynthesis pathways.ConclusionThe study identified an altered fecal microbiome and metabolome in a CNV mouse model. The altered microbes, metabolites and the involved pathways might be associated with the pathogenesis of nAMD.

AIM: To identify disease-related miRNAs in retinas of mice with oxygen-induced retinopathy (OIR), and to explore their potential roles in retinal pathological neovascularization. METHODS: The retinal miRNA expression profile in mice with OIR and room air controls at postnatal day 17 (P17) were determined through miRNA microarray analysis. Several miRNAs were significantly up- and down-regulated in retinas of mice with OIR compared to controls by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Two databases including Targetscan7.1 and MirdbV5 were used to predict target genes that associated with those significantly altered miRNAs in retinas of mice with OIR. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were also conducted to identify possible biological functions of the target genes. RESULTS: In comparison with room air controls, 3 and 8 miRNAs were significantly up- and down-regulated, respectively, in retinas of mice with OIR. The qRT-PCR data confirmed that mmu-miR-350-3p and mmu-miR-202-3p were significantly up-regulated, while mmu-miR-711 and mmu-miR-30c-1-3p were significantly down-regulated in mice with OIR compared to controls. GO analysis demonstrated that the identified target genes were related to functions such as cellular macromolecule metabolic process. KEGG pathway analysis showed a group of pathways, such as Wnt signaling pathway, transcriptional misregulation in cancer, Mucin type O-glycan biosynthesis, and mitogen-activated protein kinase (MAPK) signaling pathway might be involved in pathological process of retinal neovascularization. CONCLUSION: Our findings suggest that the differentially expressed miRNAs in retinas of mice with OIR might provide potential therapeutic targets for treating retinal neovascularization.

AIM: To investigate the regulation and mechanisms of periostin expression in retinal Müller glia, and to explore the relevance to retinal neovascularization. METHODS: The oxygen-induced retinopathy (OIR) mouse model and the human Moorfield/Institute of Ophthalmology-Müller 1 (MIO-M1) cell line were used in the study. Immunofluorescence staining was used to determine the distribution and expression of periostin and a Müller glial cell marker glutamine synthetase (GS). Cytokines TNF-α and IFN-γ were added to stimulate the MIO-M1 cells. ShRNA was used to knockdown periostin expression in MIO-M1 cells. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was conducted to assess the mRNA expression of periostin. RESULTS: Immunofluorescence staining showed that periostin was expressed by MIO-M1 Müller glia. GS-positive Müller glia and periostin increased in OIR retinas, and were partially overlaid. The stimulation of TNF-α and IFN-γ reduced the mRNA expression of periostin significantly and dose-dependently in MIO-M1 cells. Knockdown of periostin reduced mRNA expression of vascular endothelial growth factor A (VEGFA) in MIO-M1 cells, while VEGFA expression was not changed in periostin knock-out OIR retinas. CONCLUSION: Müller glia could be one of the main sources of periostin in the retina, and might contribute to the pathogenesis of retinal neovascularization. Proinflammatory cytokines TNF-α and IFN-γ attenuate the periostin expression in retinal Müller glia, which provides a potential and novel method in treating retinal neovascular diseases.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare monogenic autosomal recessive disorder caused by mutation in the autoimmune regulator (AIRE) gene. Patients usually are diagnosed at ages between 5 and 15 years when they show 3 or more manifestations, most typically mucocutaneous candidiasis, Addison’s disease, and hypoparathyroidism. APECED-associated hepatitis (APAH) develops in only 10% to 40% of patients, with severity varying from subclinical chronic active hepatitis to potentially fatal acute liver failure (ALF). Ocular abnormalities are fairly common, most often keratopathy but sometimes retinopathy. Here we report a 2-year-old Japanese girl with an AIRE gene mutation who developed APAH with ALF, preceded by autoimmune retinopathy associated with anti-recoverin antibody before major symptoms suggested a diagnosis of APECED. Intravenous pulse methylprednisolone therapy followed by a corticosteroid combined with azathioprine treatment resolved ALF and achieved control of APAH. To our knowledge, our patient is the youngest reported to have ALF resulting from an AIRE gene mutation. Pulse methylprednisolone induction therapy followed by treatment with corticosteroid plus azathioprine may well be effective in other children with APAH and AIRE gene mutations.

Objective: The purpose of our study was to determine the 4-year visual and anatomic outcomes of intravitreal aflibercept treatment for neovascular age-related macular degeneration (AMD) using a treat-and-extend (TAE) regimen. Methods: We retrospectively reviewed the medical records of 39 patients with neovascular AMD who were treated continuously with intravitreal aflibercept injections using the TAE regimen for at least 4 years. The outcome measures were the best-corrected visual acuity (BCVA) and central macular thickness (CMT) on spectral-domain optical coherence tomography. The BCVAs were measured as decimal values and converted to the corresponding Early Treatment Diabetic Retinopathy Study (ETDRS) letter scores for statistical analysis. The Wilcoxon signed-rank test was used to compare the differences in BCVAs and CMTs. Results: The mean ETDRS letter scores improved significantly from 63.9 at baseline to 70.4, 67.8, 67.2, and 67.3 at 1, 2, 3, and 4 years, respectively. The mean baseline CMT was 380 µm, which decreased significantly to 229, 231, 221, and 210 µm at 1, 2, 3, and 4 years, respectively. The mean numbers of injections were 7.9, 6.0, 5.5, and 5.4 at 1, 2, 3, and 4 years, respectively. The percentages of patients with a treatment interval of 12 weeks or more were 46.2%, 46.2%, 43.6%, and 46.2% at 1, 2, 3, and 4 years, respectively. At year 4, 30.8% of the patients had a treatment interval of 7 weeks or less, whereas 25.6% had 16 weeks or more. Conclusion: Intravitreal aflibercept TAE treatment may be an effective and efficient method for treating patients with neovascular AMD up to 4 years of follow-up. The TAE regimen is a potential tool to optimize appropriate treatment intervals, avoiding both undertreatment and overtreatment of neovascular AMD.

Purpose: We report the clinical courses of two patients with papillomacular retinoschisis in eyes with advanced glaucomatous optic neuropathy. Observations: In case 1, a 67-year-old woman was diagnosed with papillomacular retinoschisis and normal tension glaucoma in the left eye. Her medication was switched from topical latanoprost to brinzolamide, resulting in gradual improvement in the papillomacular retinoschisis thereafter. In case 2, a 76-year-old man was diagnosed with papillomacular retinoschisis, foveal detachment, and normal tension glaucoma in the left eye. His medication was switched from topical tafluprost/timolol to brinzolamide, resulting in gradual improvement in the papillomacular retinoschisis and foveal detachment thereafter. Conclusionsand Importance: Papillomacular retinoschisis may occur in eyes with advanced glaucomatous optic neuropathy. Topical brinzolamide therapy may lead to improvement of papillomacular retinoschisis.

This study aims to investigate the changes in metamorphopsia after administering the treat-and-extend regimen of anti-vascular endothelial growth factor therapy for branch retinal vein occlusion-associated macular edema. We retrospectively examined 27 patients (27 eyes) with macula edema due to branch retinal vein occlusion who received intravitreal injections of anti-vascular endothelial growth factor agents using the treat-and-extend regimen for ≥18 months. We evaluated best-corrected visual acuity, central macular thickness, macular edema recurrence, and amount of metamorphopsia quantified by M-CHARTS. The best-corrected visual acuity (logarithm of minimum angle of resolution) and central macular thickness significantly improved at 18 months compared to baseline, the median value (interquartile range [IQR]), 0.30 (0.15-0.52) and 459 (373-542) μm at baseline, and 0 (-0.08-0.16) and 267 (232-306) μm at 18 months. The M-CHARTS score (the mean of vertical and horizontal scores) significantly decreased at 1, 6, and 12 months compared to baseline, but worsened at 18 month, the median value (IQR), 0.45 (0.250-0.925), 0.4 (0.15-0.70), 0.4 (0.150-0.625), 0.4 (0.225-0.550) and 0.45 (0.225-0.750) at baseline, 1 month, 6 months, 12 months and 18 months, respectively. The median cumulative number of macular edema recurrences was 2 (IQR, 0.5-3.0) at 18 months. Simple linear regression and multivariate analyses revealed that the change in the mean M-CHARTS score at 18 months was significantly correlated with the baseline score and the cumulative number of macular edema recurrences. Anti-vascular endothelial growth factor therapy using the treat-and-extend regimen improved metamorphopsia in branch retinal vein occlusion-related macular edema in the short to mid-term follow-up period, but not in the long term. Macular edema recurrence may be associated with persistent metamorphopsia.

Facial expressions influence our experience and perception of emotions—they not only tell other people what we are feeling but also might tell us what to feel via sensory feedback. We conducted three experiments to investigate the interaction between facial feedback phenomena and different environmental stimuli, by asking participants to remember emotional autobiographical memories. Moreover, we examined how people with schizotypal traits would be affected by their experience of emotional facial simulations. We found that using a directed approach (gripping a pencil with teeth/lips) while remembering a specific autobiographical memory could successfully evoke participants’ positive (e.g., happy and excited)/negative (e.g., angry and sad) emotions (i.e., Experiment 1). When using indirective environmental stimuli (e.g., teardrop glasses), the results of our experiments (i.e., Experiments 2 and 3) investigating facial feedback and the effect of teardrop glasses showed that participants who scored low in schizotypy reported little effect from wearing teardrop glasses, while those with high schizotypy reported a much greater effect in both between- and within-subject conditions. The results are discussed from the perspective of sense of ownership, which people with schizophrenia are believed to have deficits in.

Macrophages are involved in angiogenesis, and might also contribute to the pathogenesis of intraocular neovascular diseases. Recent studies indicated that macrophages exert different functions in the process of intraocular neovascularization, and the polarization of M1 and M2 phenotypes plays extremely essential roles in the diverse functions of macrophages. Moreover, a large number of cytokines released by macrophages not only participate in macrophage polarization, but also associate with retinal and choroidal neovascular diseases. Therefore, macrophage might be considered as a novel therapeutic target to the treatment of pathological neovascularization in the eye. This review mainly summarizes diverse roles of macrophages and discusses the possible mechanisms in retinal and choroidal neovascularization.

The large number of interdigitated electrodes (IDEs) in a macro fiber composite (MFC) piezoelectric actuator dictates using a very fine finite element (FE) mesh that requires extremely large computational costs, especially with a large number of actuators. The situation becomes infeasible if repeated finite element simulations are required, as in control tasks. In this paper, an efficient technique is proposed for modeling MFC using a finite element method. The proposed technique replaces the MFC actuator with an equivalent simple monolithic piezoceramic actuator using two electrodes only, which dramatically reduces the computational costs. The proposed technique was proven theoretically since it generates the same electric field, strain, and displacement as the physical MFC. Then, it was validated with the detailed FE model using the actual number of IDEs, as well as with experimental tests using triaxial rosette strain gauges. The computational costs for the simplified model compared with the detailed model were dramatically reduced by about 74% for memory usage, 99% for result file size, and 98.6% for computational time. Furthermore, the experimental results successfully verified the proposed technique with good consistency. To show the effectiveness of the proposed technique, it was used to simulate a morphing wing covered almost entirely by MFCs with low computational cost.

Retinal neovascularization (NV) due to retinal ischemia remains one of the principal causes of vision impairment in patients with ischemic retinal diseases. We recently reported that periostin (POSTN) may play a role in the development of preretinal fibrovascular membranes, but its role in retinal NV has not been determined. The purpose of this study was to examine the expression of POSTN in the ischemic retinas of a mouse model of oxygen-induced retinal NV. We also studied the function of POSTN on retinal NV using Postn KO mice and human retinal endothelial cells (HRECs) in culture. In addition, we used a novel RNAi agent, NK0144, which targets POSTN to determine its effect on the development of retinal NV. Our results showed that the expression of POSTN was increased in the vascular endothelial cells, pericytes, and M2 macrophages in ischemic retinas. POSTN promoted the ischemia-induced retinal NV by Akt phosphorylation through integrin αvβ3. NK0144 had a greater inhibitory effect than canonical double-stranded siRNA on preretinal pathological NV in vivo and in vitro. These findings suggest a causal relationship between POSTN and retinal NV, and indicate a potential therapeutic role of intravitreal injection of NK0144 for retinal neovascular diseases. Keywords: periostin, RNAi, neovascularization, diabetic retinopathy

ObjectiveAccurate scleral marking of retinal breaks is essential for successful scleral buckling. This study aimed to investigate the use of wide-field fundus images obtained with an Optos for preoperative estimation of the distance from the limbus to the retinal breaks.Methods and analysisThis is a retrospective review of 29 eyes from 26 patients with rhegmatogenous retinal detachment who received scleral buckling with anatomically successful repair. They underwent wide-field fundus photography with Optos California. In the pre- and postoperative fundus images, we measured distances from the macula to the retinal tears (TM), to the center of the vortex veins (VM), to the optic disc (DM), and to the posterior edge of the scleral buckle (BM).Results(BM-VM) / DM was significantly correlated with the distance from the limbus to the posterior edge of the scleral buckle that had been determined intraoperatively. (r = 0.705; pConclusionPreoperative analysis of Optos images may be useful for estimating the distance from the limbus to retinal breaks, which might aid scleral marking during scleral buckling surgery.

Bacterial endophthalmitis is an intraocular infection that causes rapid vison loss. Pathogens can infect the intraocular space directly (exogenous endophthalmitis (ExE)) or indirectly (endogenous endophthalmitis (EnE)). To identify predictive factors for the visual prognosis of Japanese patients with bacterial endophthalmitis, we retrospectively examined the bacterial endophthalmitis characteristics of 314 Japanese patients and performed statistics using these clinical data. Older patients, with significantly more severe clinical symptoms, were prevalent in the ExE group compared with the EnE group. However, the final best-corrected visual acuity (BCVA) was not significantly different between the ExE and EnE groups. Bacteria isolated from patients were not associated with age, sex, or presence of eye symptoms. Genus Streptococcus, Streptococcus pneumoniae, and Enterococcus were more prevalent in ExE patients than EnE patients and contributed to poor final BCVA. The presence of eye pain, bacterial identification, and poor BCVA at baseline were risk factors for final visual impairment.

The diffuser total efficiency was formulated and defined based on the generalized actuator disc model for the index of the efficiency of the diffuser-alone of the diffuser-augmented wind turbines. An optimization method to maximize the diffuser total efficiency was developed using a genetic algorithm and axisymmetric computational fluid dynamics. A case study was conducted for a 10% chord-to-diameter ratio, 2% thickness-to-chord plate, and the crest position at 50% chord of the diffuser. The optimal result showed a diffuser total efficiency of 1.087. Furthermore, 1392 (=48 population × 29 generations) simulation cases of the optimization process showed that high diffuser total efficiency appears at a low-drag coefficient, high-lift coefficient, and 15–25% low diffuser height-to-chord ratio.

A dynamic stall model for tower shadow effects is developed for downwind turbines. Although Munduate’s model shows good agreement with a 1.0 m wind tunnel test model, two problems exist: (1) it does not express load increase before the entrance of the tower wake, and (2) it uses the empirical tower wake model to determine the wind speed profile behind the tower. The present research solves these problems by combining Moriarty’s tower wake model and the entrance condition of the tower wake. Moriarty’s model does not require any empirical parameter other than tower drag coefficient and it expresses positive wind speed around the tower also. Positive wind speed change is also allowed as the tower wake entrance condition in addition to the negative change observed in the previous model. It demonstrates better agreement with a wind tunnel test and contributes to the accuracy of the fatigue load, as it expresses a slight increase in load around the entrance of the tower wake. Furthermore, the scale effects are also evaluated; lift deviation becomes smaller as the scale increases, i.e., lower rotor speed.