Flare levels after intravitreal injection of brolucizumab for diabetic macular edema.

PURPOSE: This study aimed to evaluate anterior flare intensity (AFI) after intravitreal injection of brolucizumab (IVBr) in patients with diabetic macular edema (DME), and to identify the factors associated with the change of AFI after IVBr. METHODS: This prospective multicenter study was conducted at five sites in Japan for patients with DME who underwent a single IVBr. AFI and central retinal thickness (CRT) were measured using a laser flare meter and spectral-domain optical coherence tomography, respectively, at weeks 0 and 6. RESULTS: Sixty-five patients (phakia, 37 eyes; pseudophakia, 28 eyes) were enrolled. Six weeks after IVBr, CRT and best-corrected visual acuity significantly improved (p < 0.0001). AFI (p = 0.0003) and age (p = 0.0054) were significantly higher in patients with pseudophakic eyes than those with phakic eyes. The AFI of the phakic eyes decreased after IVBr (p = 0.043). As the AFI before injection is higher (p = 0.0363) and the age is lower (p = 0.0016), the AFI decreases after IVBr. There was a significant positive correlation between the rates of change in CRT and AFI (p = 0.024). CONCLUSION: After IVBr, AFI decreases in phakic eyes but not in pseudophakic eyes. The age, AFI and CRT before injection and changes of CRT are involved in the change in AFI after IVBr.

ExistenceMap-PointPillars: A Multifusion Network for Robust 3D Object Detection with Object Existence Probability Map.

Recognition of surrounding objects is crucial for ensuring the safety of automated driving systems. In the realm of 3D object recognition through deep learning, several methods incorporate the fusion of Light Detection and Ranging (LiDAR) and camera data. The effectiveness of the LiDAR-camera fusion approach is widely acknowledged due to its ability to provide a richer source of information for object detection compared to methods that rely solely on individual sensors. Within the framework of the LiDAR-camera multistage fusion method, challenges arise in maintaining stable object recognition, especially under adverse conditions where object detection in camera images becomes challenging, such as during night-time or in rainy weather. In this research paper, we introduce "ExistenceMap-PointPillars", a novel and effective approach for 3D object detection that leverages information from multiple sensors. This approach involves a straightforward modification of the LiDAR-based 3D object detection network. The core concept of ExistenceMap-PointPillars revolves around the integration of pseudo 2D maps, which depict the estimated object existence regions derived from the fused sensor data in a probabilistic manner. These maps are then incorporated into a pseudo image generated from a 3D point cloud. Our experimental results, based on our proprietary dataset, demonstrate the substantial improvements achieved by ExistenceMap-PointPillars. Specifically, it enhances the mean Average Precision (mAP) by a noteworthy +4.19% compared to the conventional PointPillars method. Additionally, we conducted an evaluation of the network's response using Grad-CAM in conjunction with ExistenceMap-PointPillars, which exhibited a heightened focus on the existence regions of objects within the pseudo 2D map. This focus resulted in a reduction in the number of false positives. In summary, our research presents ExistenceMap-PointPillars as a valuable advancement in the field of 3D object detection, offering improved performance and robustness, especially in challenging environmental conditions.

Anti-VEGF Treatment Strategies for 3 Subtypes of Neovascular Age-Related Macular Degeneration in a Clinical Setting: A Multicenter Cohort Study in Japan.

PURPOSE: Neovascular age-related macular degeneration (nAMD) is classified into typical AMD (tAMD), polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP). This study investigated clinical features of the 3 subtypes and visual outcome associated with treatment regimens in a large cohort of patients with nAMD in a clinical setting. DESIGN: Retrospective multicenter cohort study. PARTICIPANTS: Five hundred patients with treatment-naive nAMD (268 tAMD, 200 PCV, and 32 RAP) initiated with anti-VEGF agents and followed for 1 year. METHODS: Medical records were reviewed to extract demographic data, best-corrected visual acuity at baseline and 1 year after treatment initiation, spectral-domain OCT findings, baseline fellow eye condition, systemic factors, treatment strategies, and number of intravitreal injections in the first year. MAIN OUTCOME MEASURES: Primary outcome measures were anti-VEGF treatment strategy (ranibizumab or aflibercept, anti-VEGF regimen, concomitant photodynamic therapy, drug switch), best-corrected visual acuity at 1 year, and factors associated with visual acuity. RESULTS: Patients with RAP were significantly older, were more commonly women, and had more macular lesions in fellow eye than patients with tAMD and PCV. Smoking history and diabetes prevalence were not different among the 3 subtypes. Frequencies of subretinal fluid were higher and intraretinal fluid were lower in tAMD and PCV than in RAP, whereas serous pigment epithelial detachment and subretinal hemorrhage were higher in PCV than in tAMD and RAP. Choice of anti-VEGF agents and treatment regimens did not differ among 3 subtypes. The aflibercept-to-ranibizumab ratio was approximately 7:3. The mean number of injections in 1 year was 5.3 ± 2.4 in nAMD overall, which was significantly less in pro re nata (PRN) than in treat and extend (TAE) regardless of the anti-VEGF agent. Best-corrected visual acuity improved in all 3 subtypes, although it was not significant in patients with RAP. CONCLUSIONS: This clinical study demonstrates that treatment regimens were similar in 3 subtypes and aflibercept was used in 70% of all patients. Approximately 5 injections were given in the first year regardless of the anti-VEGF agent, which was significantly less in PRN regimen than in TAE. Visual acuity improvement was observed after 1-year anti-VEGF therapy in all 3 subtypes, but was not significant in RAP. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Clinical relevance of fibrin membranous structures in the intra-photoreceptor outer segment separation on spectral domain optical coherence tomography (SD-OCT) in initial-onset acute Vogt-Koyanagi-Harada disease.

PURPOSE: The purpose of the study was to investigate clinical relevance of fibrin membranous structure (FMS) in the photoreceptor outer segments on spectral-domain optical coherence tomography (SD-OCT) in untreated initial-onset acute Vogt-Koyanagi-Harada (VKH) disease. METHODS: Clinical charts of 39 patients (78 eyes) diagnosed with initial-onset VKH disease were retrospectively reviewed. Age, gender, period from the onset of symptoms to first visit, visual acuity (VA), intraocular pressure (IOP), anterior chamber cells, serous retinal detachment (SRD), SD-OCT findings, as well as fluorescein (FA), and indocyanine green angiography (ICGA) were collected. RESULTS: FMS was observed in 24 out of 39 VKH patients in either eye (61.5%). VKH patients with FMS (FMS group) were significantly younger and had the shorter period from the onset of symptoms to the first visit compared with those without FMS (non-FMS group). Mean logMAR VA and proportion of pooling of dye, mean central retinal thickness (CRT) were significantly higher in FMS group than in non-FMS group. In contrast, hyperfluorescence of the optic disc on FA was more in non-FMS group than in FMS group. Significant positive correlations between CRT and logMAR VA or IOP were only observed in the FMS group. Total amount of corticosteroids was significantly greater in FMS group than in non-FMS group. However, there were no significant differences in LogMAR VA and IOP between two groups at 6 months after treatment initiation. CONCLUSION: FMS on SD-OCT is a critical feature observed in the early stage of initial-onset acute VKH disease, which is more common in younger patients and is related to the disease activity.

LiDAR- and Radar-Based Robust Vehicle Localization with Confidence Estimation of Matching Results.

Localization is an important technology for autonomous driving. Map-matching using road surface pattern features gives accurate position estimation and has been used in autonomous driving tests on public roads. To provide highly safe autonomous driving, localization technology that is not affected by the environment is required. In particular, in snowy environments, the features of the road surface pattern may not be used for matching because the road surface is hidden. In such cases, it is necessary to construct a robust system by rejecting the matching results or making up for them with other sensors. On the other hand, millimeter-wave radar-based localization methods are not as accurate as LiDAR-based methods due to their ranging accuracy, but it has successfully achieved autonomous driving in snowy environments. Therefore, this paper proposes a localization method that combines LiDAR and millimeter-wave radar. We constructed a system that emphasizes LiDAR-based matching results during normal conditions when the road surface pattern is visible and emphasizes radar matching results when the road surface is not visible due to snow cover or other factors. This method achieves an accuracy that allows autonomous driving to continue regardless of normal or snowy conditions and more robust position estimation.

Robust Traffic Light and Arrow Detection Using Digital Map with Spatial Prior Information for Automated Driving.

Traffic light recognition is an indispensable elemental technology for automated driving in urban areas. In this study, we propose an algorithm that recognizes traffic lights and arrow lights by image processing using the digital map and precise vehicle pose which is estimated by a localization module. The use of a digital map allows the determination of a region-of-interest in an image to reduce the computational cost and false detection. In addition, this study develops an algorithm to recognize arrow lights using relative positions of traffic lights, and the arrow light is used as prior spatial information. This allows for the recognition of distant arrow lights that are difficult for humans to see clearly. Experiments were conducted to evaluate the recognition performance of the proposed method and to verify if it matches the performance required for automated driving. Quantitative evaluations indicate that the proposed method achieved 91.8% and 56.7% of the average f-value for traffic lights and arrow lights, respectively. It was confirmed that the arrow-light detection could recognize small arrow objects even if their size was smaller than 10 pixels. The verification experiments indicate that the performance of the proposed method meets the necessary requirements for smooth acceleration or deceleration at intersections in automated driving.

Antisense-induced guanine quadruplexes inhibit reverse transcription by HIV-1 reverse transcriptase.

Guanine quadruplex structures in DNA and RNA affect normal cellular processes such as replication, recombination, and translation. Thus, controlling guanine quadruplex structures could make it possible to manipulate the biological function of nucleic acids. Here, we report a novel antisense strategy using guanine-tethered antisense oligonucleotides (g-ASs) that introduces an RNA-DNA heteroquadruplex structure on RNA templates in a predictable and sequence-specific manner, which in practice effectively inhibited reverse transcription on a variety of RNA sequences, including the HIV-1 RNA genome. Reverse transcriptase-mediated enzymatic analysis, together with other biophysical analyses, elucidated a cooperative binding of duplex and quadruplex in g-AS-RNA complexes. The remarkable ability of g-ASs to inhibit reverse transcription could make possible the development of novel anti-retroviral gene therapies based on blocking the replication of RNA genomes to complementary DNA, which is a critical step for integration into the host's genome.

A reverse transcriptase stop assay revealed diverse quadruplex formations in UTRs in mRNA.

Here, we developed a reverse transcriptase based method (RTase stop assay) to characterize quadruplex formations in guanine-rich RNAs with high sensitivity and specificity. By using the RTase stop assay, we also revealed a plausible structural polymorphism in biologically important RNAs. The RTase stop assay would provide helpful insight into RNA quadruplex structures and functions, together with other analytical methods, including various footprinting techniques.