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Although coil embolization is commonly perceived as a minimally invasive procedure, the associated radiation exposure cannot be disregarded. To date, no specific study has investigated radiation exposure during coil embolization. This study aimed to investigate the potential of lowering the pulse rate to decrease radiation exposure during coil embolization while maintaining patient safety. Radiation data and clinical features of 70 patients who underwent coil embolization between 2015 and 2020 were retrospectively analyzed. Since July 2017, the pulse rate was regulated from 7.5 to 4 frames per second (f/s). Statistical analyses were performed to examine the correlation between pulse rate and radiation exposure. Out of the 70 procedures, 30 were performed at the standard pulse rate (7.5 f/s), and 40 were performed at the lower pulse rate (4 f/s). In the lower-pulse-rate group, the absorbed dose to the patient (AK) was 2580.7 (±217) mGy, whereas in the standard-pulse-rate group, it was 4760 (±411.1). Both the dose-area product (DAP) and AK were substantially reduced in the low pulse rate group (p = 0.000002). There was a significant correlation between DAP and AK and pulse rate (p = 0.004, p = 0.0017, respectively). Moreover, there was no significant correlation between pulse rate and perioperative complications. Our findings suggest that using a lower pulse rate (4 f/s) can effectively reduce radiation exposure during coil embolization for cerebral aneurysms while ensuring patient safety.

Abstract Apolipoprotein E (ApoE) is involved in cholesterol transport among cells and also plays an important role in amyloid formation, co-depositing with amyloid fibrils in various types of amyloidosis. Although the in vivo amyloidogenicity of ApoE has not been previously demonstrated, this study provides evidence of ApoE amyloidogenicity in leopard geckos (Eublepharis macularius), belonging to the class Reptilia. Histologically, amyloid deposits were localized within cholesterol granulomas and exhibited positive Congo red staining, with yellow to green birefringence under polarized light. On mass spectrometry-based proteomic analysis, ApoE was detected as a dominant component of amyloid; of the full length of the 274 amino acid residues, peptides derived from Leu185-Arg230 were frequently detected with non-tryptic truncations. Immunohistochemistry with anti-leopard gecko ApoE antibody showed positive reactions of amyloid deposits. These results show that ApoE is an amyloid precursor protein within the cholesterol granulomas of leopard geckos. Although further investigations are needed, the C-terminal region of ApoE involved in amyloid formation is a lipid-binding region, and there should be a relationship between amyloidogenesis and the development of cholesterol granulomas in leopard geckos. This study provides novel insights into the pathogenesis of ApoE-related diseases.

Aging is a high-risk factor for obstructive and fibrotic lung diseases. Fibrotic lung disease leading to decreased lung function is characterized by interstitial remodeling and tissue scarring (sclerosis), with destruction of alveoli and excess deposition of type I collagen, an extracellular matrix component secreted by fibroblasts. Therefore, regulating transforming growth factor-β (TGF-β) as a profibrotic signal is essential to suppress pulmonary fibrosis. In pulmonary fibrosis, TGF-β signaling is mediated by Smad and YAP/TAZ, and TAZ linked to the pathology of pulmonary function is observed in lung fibroblasts from patients with idiopathic pulmonary fibrosis. Although fibrosis is thought to be irreversible, it is an interventional condition. Decorin (DCN) blocks TGF-β signaling in pulmonary fibrosis, although there are no cellular pharmacological methods to stimulate DCN secretion. We previously showed that chicken eggshell membrane (ESM, a well-known wound-healing material) promotes dcn gene expression in fibroblasts. In this study, we investigated whether ESM stimulates DCN secretion as an endogenous mediator and ameliorates pulmonary fibrosis. Decorin secretion was significantly enhanced in the WI-38 lung fibroblast culture supernatants supplemented with ESM. This effect was increased with major component lysozyme and maximally promoted in experiments with lysozyme and ovotransferrin (the two main proteins in soluble ESM) at a 16:1 concentration ratio, the ratio in the ESM extract. Decorin secretion by ESM modulates TGF-β signaling in lung fibroblasts by reducing TAZ and pSmad2 nuclear localization. Decorin siRNA experiments confirmed that nuclear localization of TAZ is DCN-dependent. In a mouse model of bleomycin-induced pulmonary fibrosis, all fibrotic markers of ESM treatment group such as hydroxyproline (a collagen deposition marker), and both evaluation of fibrosis density by automated thresholding of picrosirius red-stained lung tissue scan images and Ashcroft fibrosis scores, and also the nuclear localization of TAZ were reduced after 2 weeks compared with control group. Furthermore, long-term (22 week) ESM consumption by healthy individuals significantly improved vital capacity and the forced expiratory volume in 1 s to forced vital capacity ratio (FEV1/FVC). This study reveals that ESM, a well-established wound-healing material, may be a potential preventive medicine for pulmonary fibrosis.

Treatment strategies for unruptured intracranial aneurysms (UIAs) should be carefully considered with reference to rupture and complication rates. It is also important to minimize the length of hospital stay (LOS) and to ensure a high quality of medical care. In this study, we aim to clarify the factors that affect the LOS of patients treated for UIAs using the Inpatient Clinico-Occupational Database of the Rosai Hospital Group (ICOD-R). This was a nationwide-multicenter study based on ICOD-R data from 2000 to 2019. Patients diagnosed with UIAs who were treated with clipping or coiling were included in the study. Multivariate analysis was performed to identify the factors affecting LOS. LOS was also compared between groups classified by surgical procedure or treatment period. We identified 3294 patients on the database who underwent clipping or coiling of UIAs during the study period. Multivariate analysis revealed hospital admission during the early 2000s and the late 2010s, age, and treating institution to be significantly correlated with LOS (p < 0.05). There was a significant difference between the mean LOS of the clipping group (20.3 days) and the coiling group (9.65 days) (p < 0.001). Compared by treatment period, LOS significantly shortened over time. Our results suggest that the type of treatment, time of treatment, patient age, and the treating institution affect postoperative LOS for UIAs. Although coiling was found to lead to a lower average LOS than clipping, treatment selection should take the characteristics of each patient's aneurysm into consideration.

Bifrontal craniotomy frequently involves opening the frontal sinus and mucosal injury. We report a new technique for mucosal repair in the frontal sinus using surgical titanium microclips. Six consecutive patients who underwent bifrontal craniotomy with frontal sinus exposure and mucosal injury underwent mucosal repair using surgical titanium microclips between April 2019 and August 2022. In all cases, the frontal sinus mucosa was peeled from the inner walls of the frontal sinus to ensure sufficient mucosal margin for clipping using ORBEYE. The repair was accomplished with the microclips in all cases. We also sealed the mucosal wound using fibrin glue and sufficiently filled the frontal sinus with bone debris, resulting in zero incidence of postoperative liquorrhea in all cases. Repairing the mucosa using surgical titanium microclips using ORBEYE may be a simple and quick technique when the frontal sinus mucosa is injured during craniotomy.

Purpose: To evaluate the severity scales of diabetic macular ischemia (DMI) by analyzing the quantity and distribution of capillary nonperfusion using OCT angiography (OCTA) images. Design: A single-center, prospective case series. Participants: Three hundred one eyes from 301 patients with diabetic retinopathy. Methods: We acquired 3 × 3-mm swept-source OCTA images and created en face images within a central 2.5-mm circle. The circle was divided into 15 × 15-pixel squares and nonperfusion squares (NPSs) were defined as those without retinal vessels. Eyes with high-dimensional spatial data were arranged on a 2-dimensional space using the uniform manifold approximation and projection (UMAP) algorithm and classified by clustering into 5 groups: Initial, Mild, Superficial, Moderate, and Severe. Main Outcome Measures: Development of a severity scale for DMI. Results: Eyes arranged on a 2-dimensional UMAP space were divided into 5 clusters, based on the similarity of nonperfusion area distribution. Nonperfusion square counts in the deep layer increased in eyes of the Initial, Mild, Moderate, and Severe groups in a stepwise manner. In contrast, there were no significant changes in superficial NPS counts between eyes of the Initial and Mild groups. In the intermediate stage, eyes of the Superficial group exhibited higher NPS counts in the central sector of the superficial layer compared with those of the Moderate group. The foveal avascular zone extended into the temporal subfield of the deep layer in eyes of the Moderate group. Eyes of the Severe group had significantly poorer visual acuity that was more frequently accompanied with proliferative diabetic retinopathy. Conclusions: The application of dimensionality reduction and clustering has facilitated the development of a novel severity scale for DMI based on the distribution of capillary nonperfusion in OCTA images. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

There have been a number of anastomosis methods of bypass techniques reported for moyamoya disease. However, there are yet no randomized controlled trials conducted on the anastomosis method. Retrograde blood flow of the superficial temporal artery (STA) may be used as one of the donor options. Here, we examined the tolerability of retrograde bypass using a distal stump of the parietal STA (dsPSTA). Anastomosis between the dsPSTA and middle cerebral artery (MCA) was performed for consecutive patients with moyamoya disease whose parietal STA was visualized to be longer than 10 cm using contrast-enhanced computed tomography preoperatively. Retrospectively, we have examined its patency and clinical outcome. Retrograde dsPSTA-MCA bypass was performed in 22 hemispheres of 17 patients. The patency of retrograde dsPSTA-MCA bypass in all 22 anastomoses could be confirmed during follow-up periods (mean: 5.5, range: 2-15 years). No recurrence of ischemic events was observed. The dsPSTA-MCA bypass using retrograde blood flow has been determined as one of the many promising anastomosis methods, and long-term patency was achieved in moyamoya disease.

Purpose: The aim of this study was to examine the effects of foveal thickness (FT) fluctuation (FTF) on 2-year visual and morphological outcomes of eyes with central retinal vein occlusion (CRVO) undergoing anti-VEGF treatment for recurrent macular edema (ME) based on a pro re nata regimen. Design: Retrospective, observational case series. Participants: We analyzed 141 treatment-naive patients (141 eyes) with CRVO-ME at a multicenter retinal practice. Methods: We assessed FT using OCT at each study visit. Patients were divided into groups 0, 1, 2, and 3 according to increasing FTF. Main Outcome Measures: We evaluated the logarithm of the minimal angle of resolution (logMAR) best-corrected visual acuity (BCVA), the length of the foveal ellipsoid zone (EZ) band defect measured using OCT, and the association of FTF with VA and EZ band defect length. Results: The mean baseline logMAR BCVA and FT were 0.65 ± 0.52 (Snellen equivalent range: 20/20–20/2000) and 661.1 ± 257.4 μm, respectively. The mean number of anti-VEGF injections administered was 5.6 ± 3.6. At the final examination, the mean logMAR BCVA and FT values were significantly improved relative to the baseline values (both P

Abstract Morphological changes in capillaries are one of major clinical signs in diabetic retinopathy (DR). In this study, we quantified the dilated deep capillaries on optical coherence tomography angiography (OCTA) images. Central 3 × 3 mm en face images were obtained using a swept source OCTA device in 105 eyes of 99 patients with DR. Capillaries with a greater diameter in the deep layers were defined as the dilated deep capillaries, using stepwise image processing. The relative areas of automatically selected capillaries with a great diameter were calculated as the index of the dilated deep capillaries. Most eyes with DR had string-like or dot-like dilated deep capillaries in the OCTA images, which appeared to be dilated capillary segments or microaneurysms histologically. They were distributed more densely in the parafovea than in the central sector, while there were no differences between individual quadrants. The index of the dilated deep capillaries was higher in eyes with DR than in nondiabetic eyes. The index in the central subfield was modestly associated with visual acuity, diabetic macular edema, and proliferative diabetic retinopathy. The quantitative dilated deep capillaries are designated as a biomarker of vision-threatening DR.

Background: We report an unusual case of retinal vein occlusion (RVO) associated with vitreous hemorrhage (VH) without visible traction from the posterior vitreous membrane (PVM) at the bleeding point, challenging our current understanding of VH pathophysiology. Case presentation: A 52-year-old man presented with VH in the right eye. A detailed examination using optical coherence tomography angiography (OCTA) and ultra-widefield fluorescein angiography revealed branch RVO with non-perfused areas (NPAs) extending peripherally and neovascularization elsewhere (NVE). OCTA showed NVE infiltrating the vitreous cavity, leading to substantial bleeding without visible PVM traction at the bleeding point. The NVE was successfully removed following vitrectomy, and visual acuity improved from 20/20 to 20/13 preoperatively, along with a postoperative improvement in floaters. Conclusions: This unique case of RVO suggests the possibility of VH occurring independent of PVM contractions at the bleeding point, challenging the traditional understanding of VH. This finding underscores the potential role of OCTA in diagnosing and managing retinal vascular diseases, underscoring the need for further investigations into the underlying mechanisms, with potential implications for personalized therapeutic strategies.

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.

Abstract We included 97 patients with unilateral rhegmatogenous retinal detachment (RRD) with posterior vitreous detachment who underwent vitrectomy, and examined pigmentary lesion (PL) characteristics around the sites of original tears using pre- and postoperative ultra-widefield scanning light ophthalmoscopy, green light fundus autofluorescence (FAF) imaging, and intraoperative digital video. If PL did not involve RRD, we used OCT to preoperatively assess any pathologic changes to the lesion. A total of 116 retinal tears (mean count, 1.2 ± 0.5; range, 1–4 per eye) were observed in the detached retina. Overall, 102 (88%), 63 (54%), 14 (12%), and 25 (22%) tears were accompanied by lattice degeneration (LD) or PL, both LD and PL, only LD, and only PL, respectively. In green FAF images, LD showed normal to mild-hyper fluorescence, whereas all PL showed hypofluorescence. On OCT, PL were located at the RPE level, while choroid abnormalities were unclear. In the retinal areas of 22 eyes, which were not affected by RRD, we observed PL without retinal tears; some were accompanied by vitreous traction and tractional retinal detachment. Pre-, intra-, and post-operative assessments of original flap tears suggested that PL might be a risk factor for RRD, developing alongside or separately from LD.

Purpose: To investigate the distribution of clinically significant nonperfusion areas (NPAs) on widefield OCT angiography (OCTA) images in patients with diabetes. Design: Prospective, cross-sectional, observational study. Participants: One hundred and forty-four eyes of 114 patients with diabetes. Methods: Nominal 20 × 23 mm OCTA images were obtained using a swept-source OCTA device (Xephilio OCT-S1), followed by the creation of en face images 20-mm (1614 pixels) in diameter centering on the fovea. The nonperfusion squares (NPSs) were defined as the 10 × 10 pixel squares without retinal vessels, and the ratio of eyes with the NPSs to all eyes in each square was referred to as the NPS ratio. The areas with probabilistic differences (APD) for proliferative diabetic retinopathy (PDR) and nonproliferative diabetic retinopathy (NPDR) (APD[PDR] and APD[NPDR]) were defined as sets of squares with higher NPS ratios in eyes with PDR and NPDR, respectively. The P ratio (NPSs within APD[PDR] but not APD[NPDR]/all NPSs) was also calculated. Main Outcome Measures: The probabilistic distribution of the NPSs and the association with diabetic retinopathy (DR) severity. Results: The NPSs developed randomly in eyes with mild and moderate NPDR and were more prevalent in the extramacular areas and the temporal quadrant in eyes with severe NPDR and PDR. The APD(PDR) was distributed mainly in the extramacular areas, sparing the areas around the vascular arcades and radially peripapillary capillaries. The APD(PDR) contained retinal neovascularization more frequently than the non-APD(PDR) (P = 0.023). The P ratio was higher in eyes with PDR than in those with NPDR (P < 0.001). The multivariate analysis designated the P ratio (odds ratio, 8.293 × 107; 95% confidence interval, 6.529 × 102–1.053 × 1013; P = 0.002) and the total NPSs (odds ratio, 1.002; 95% confidence interval, 1.001–1.003; P < 0.001) as independent risk factors of PDR. Most eyes with NPDR and 4-2-1 rule findings of DR severity had higher P ratios but not necessarily greater NPS numbers. Conclusions: The APD(PDR) is uniquely distributed on widefield OCTA images, and the NPA location patterns are associated with DR severity, independent of the entire area of NPAs. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Abstract Microcirculatory disturbance plays a pivotal role in the pathogenesis in diabetic retinopathy (DR). We retrospectively quantified the total counts and morphological features of intercapillary spaces, i.e., intercapillary areas and nonperfusion areas (NPAs), on swept-source optical coherence tomography angiography (SS-OCTA) images and to evaluate their associations with DR severity grades. We acquired 3 × 3 mm OCTA images in 75 eyes of 62 diabetic patients and 22 eyes of 22 nondiabetic subjects. In the en-face superficial images within the central 2 mm, the areas enclosed by retinal vessels were automatically detected. Their total numbers decreased in some eyes with no apparent retinopathy and most eyes with DR, which allowed us to discriminate diabetic subjects from nondiabetic subjects [area under the receiver operating characteristic curve (AUC) = 0.907]. The areas and area/perimeter ratios continuously increased in DR, indicating a continuum between healthy intercapillary areas and NPAs. The number of intercapillary spaces with a high area/perimeter ratio increased according to DR severity, which showed modest performance in discriminating moderate NPDR or higher grades (AUC = 0.868). These quantified parameters of intercapillary spaces can feasibly be used for the early detection of microcirculatory impairment and the diagnosis of referable DR.

Abstract The aim of this retrospective, observational study was to examine the intraretinal locations of ruptured retinal arterial macroaneurysms (RMAs) and investigate the associations with the visual prognosis. Fifty patients (50 eyes) with untreated RMA rupture who visited the Department of Ophthalmology at Kyoto University Hospital (April 2014–July 2019) were included. The intraretinal position of the ruptured RMAs relative to the affected retinal artery was examined using optical coherence tomography (OCT) and color fundus photography (CFP). The relative RMA positions were anterior to (anterior type, 44%), at the same level as (lateral type, 20%), or posterior to (posterior type, 34%) the affected artery. At the initial visit, the posterior type showed greater subretinal hemorrhage thickness than did the lateral and anterior types (P = 0.016 and 0.006, respectively), and poorer visual acuity (VA) than did the anterior type (P = 0.005). At the final visit, the length of the foveal ellipsoid zone band defect was longer (P = 0.005) and VA was poorer (P

PurposeTo examine whether extended interscan time (IST) on optical coherence tomography angiography (OCTA) can detect slow retinal blood flow, which is undetectable on default IST, in the healthy macula.MethodsOCTA (OCT-A1, Canon Inc.) scanning of a macular area measuring 4 × 4 mm2 of 14 healthy eyes of 14 healthy volunteers with no history or evidence of systemic and macular diseases was performed. ISTs were set at 7.6 (IST7.6, default setting), 12.0 (IST12.0), and 20.6 msec (IST20.6). Ten OCTA images were acquired at each IST, and an averaged image was created. For each averaged OCTA image obtained at IST7.6, IST12.0, and IST20.6, we defined the area surrounded by the innermost capillary ring as the foveal avascular zone (FAZ). We qualitatively evaluated the delineation of the capillaries consisting of the FAZ and quantitatively measured the FAZ area at each IST.ResultsExtensions from IST7.6 to IST12.0 and IST20.6 could newly delineated retinal capillaries that were undetectable at the default IST; new capillaries were detected in 10 (71%) eyes at IST12.0 and 11 (78%) eyes at IST20.0. The FAZ areas were 0.334 ± 0.137 mm2, 0.320 ± 0.132 mm2, and 0.319 ± 0.129 mm2 for IST7.6, IST12.0, and IST20.0, respectively; the FAZ areas at IST12.0 and IST20.0 were significantly decreased compared with that at IST7.6 (p = 0.004 and 0.002, respectively).ConclusionIn OCTA for healthy participants, extensions of the ISTs newly detected retinal capillaries with slow blood flow around FAZ. The FAZ shapes varied with different ISTs. Thus, the blood flow dynamics are not physiologically uniform around FAZ. Compared with conventional OCTA, this protocol enables a more detailed evaluation of retinal circulation and provides a better understanding of the physiological circulatory status of the healthy retina, and may enable the assessment of circulation in the very early stages in diseased eyes.

Abstract Objectives With the advent of new optical technologies, early pharyngolaryngeal cancerous lesions can be better visualized. Although the conventional transnasal approach offers great views of the hypopharynx and larynx, the visualization of the oropharynx and palatine tonsils is limited. Through the transoral insertion of a flexible video‐laryngoscope, direct views of the oropharynx and oral cavity can be obtained. Thus, transoral examination may contribute to primary detection of cancers of unknown primary (CUP). Methods Eighty‐five CUP patients from Tokai University were included retrospectively in this study, from 2006 to 2017. Starting in 2010, we employed the transoral examination in addition to our conventional method. The primary detection rates were compared before and after 2010. Oropharyngeal primaries were further analyzed for tumor subsite and p16 status. Results The overall primary detection rate did not improve with the addition of transoral examination. However, greater numbers of oropharyngeal primaries were detected. The oropharyngeal lesions detected by transoral examination were mainly p16 positive, located on the palatine tonsil. Conclusion Transoral examination is a noninvasive, easy method to adopt in an outpatient setting, and a promising technique to improve tumor detection in this era of human papillomavirus‐associated head and neck cancers. Level of Evidence 3.

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

Diabetic retinopathy is a form of diabetic microangiopathy, and vascular hyperpermeability in the macula leads to retinal thickening and concomitant reduction of visual acuity in diabetic macular edema (DME). In this review, we discuss multimodal fundus imaging, comparing the pathogenesis and interventions. Clinicians diagnose DME using two major criteria, clinically significant macular edema by fundus examination and center-involving diabetic macular edema using optical coherence tomography (OCT), to determine the appropriate treatment. In addition to fundus photography, fluorescein angiography (FA) is a classical modality to evaluate morphological and functional changes in retinal capillaries, e.g., microaneurysms, capillary nonperfusion, and fluorescein leakage. Recently, optical coherence tomography angiography (OCTA) has allowed us to evaluate the three-dimensional structure of the retinal vasculature and newly demonstrated that lamellar capillary nonperfusion in the deep layer is associated with retinal edema. The clinical application of OCT has accelerated our understanding of various neuronal damages in DME. Retinal thickness measured by OCT enables us to quantitatively assess therapeutic effects. Sectional OCT images depict the deformation of neural tissues, e.g., cystoid macular edema, serous retinal detachment, and sponge-like retinal swelling. The disorganization of retinal inner layers (DRIL) and foveal photoreceptor damage, biomarkers of neurodegeneration, are associated with visual impairment. Fundus autofluorescence derives from the retinal pigment epithelium (RPE) and its qualitative and quantitative changes suggest that the RPE damage contributes to the neuronal changes in DME. These clinical findings on multimodal imaging help to elucidate the pathology in the neurovascular units and lead to the next generation of clinical and translational research in DME.

Purpose: To highlight a potential pathogenetic mechanism of retinal arterial macroaneurysm. Observations: A 79-year-old woman presented with a ruptured retinal arterial macroaneurysm in the right eye. One year after treatment, high-resolution multimodal imaging with optical coherence tomography (OCT), OCT angiography, and adaptive optics scanning light ophthalmoscope showed that a narrow passage developed in the vessel wall of the pre-existing retinal arterial macroaneurysm and another macroaneurysm had developed adjacent to the pre-existing one. Conclusions and Importance: These images suggest the pathogenesis of retinal arterial macroaneurysm (RAM) associated with crack-like changes in the retinal arterial wall, similar to pathologies seen in systemic arteries.

Amyloid-producing ameloblastoma (APAB) is characterized by abundant amyloid deposits in ameloblastoma, but the amyloid precursor protein is unknown. To explore this, we conducted histopathologic and proteomic analyses on formalin-fixed and paraffin-embedded samples from five cases of APAB (three dogs and two cats). Histologically, the samples exhibited a proliferation of the odontogenic epithelium, with moderate to severe interstitial amyloid deposits. By using Congo red and polarized light, the amyloid deposits were found to show characteristic birefringence. Amyloid deposits were dissected from tissue sections and analyzed by LC/MS/MS, and high levels of ameloblastin were detected in all tissues. Mass spectrometry also revealed that the N-terminal region of ameloblastin is predominantly present in amyloid deposits. Immunohistochemistry was performed using two anti-ameloblastin (N terminal, middle region) antibodies and showed that amyloid deposits were positive for ameloblastin N terminal but negative for ameloblastin middle region. These results suggest that ameloblastin is the amyloid precursor protein of APABs in dogs and cats, and the N-terminal region may be involved in the amyloidogenesis of ameloblastin.

High resolution imaging with optical coherence tomography angiography and offset pinhole adaptive optics scanning light ophthalmoscope helped us visualize the hemodynamic and structural changes in a ruptured retinal arterial macroaneurysm in a 78-year-old woman. Intravitreal injection of anti-vascular endothelial growth factor was administered to ameliorate the condition.

Background The effect of intra‐arterial infusion of fasudil hydrochloride in patients with post‐traumatic cerebral vasospasm remains unclear. Here we report a case of intra‐arterial infusion of fasudil hydrochloride for post‐traumatic cerebral vasospasm. Case presentation A 47‐year‐old man was transferred to our hospital with a fractured skull and traumatic subarachnoid hemorrhage. As rhinorrhea of cerebrospinal fluid had not improved, repair surgery was carried out on day 4. Aphasia appeared on day 13. Magnetic resonance imaging and angiography showed an ischemic region in the left temporal lobe and vasospasm of the left middle cerebral artery. We immediately carried out angiography and diagnosed severe vasospasm of the M1 region of the left middle cerebral artery. After placing a microcatheter into the proximal middle cerebral artery, we injected fasudil hydrochloride intra‐arterially. Vasospasm improved and aphasia resolved. Conclusion In this case, intra‐arterial infusion of fasudil hydrochloride was effective against post‐traumatic cerebral vasospasm.

Abstract The early remission of diabetic macular edema (DME) often occurs in eyes treated with anti-vascular endothelial growth factor (VEGF) treatment. We retrospectively reviewed and characterized eyes with early remission of DME at six months in 80 eyes under pro re nata (PRN) intravitreal ranibizumab (IVR) injections. The number of eyes without center-involved DME gradually increased and 14 and 20 eyes achieved remission of DME at 3 or 6 months, respectively, under the PRN regimen following three monthly loading doses. In particular, eyes with early remission at 6 months had smaller CSF thickness than those without the remission before and after the treatment except at the 1-month visit (P

Mycobacterium marinum is a free-living nontuberculous mycobacterium that is widely distributed in freshwater and seawater around the world. Granulomatous skin infection from M. marinum in people who are exposed to fish or aquatic environments is a rare condition known as fish tank granuloma. The granuloma mainly occurs on the skin of the upper limb, in a few cases on the face, and rarely in the nasal cavity. We describe a case of M. marinum infection that presented as a nasal cavity mass. A 57-year-old woman who was receiving infliximab for psoriatic arthritis visited our hospital with a complaint of right nasal obstruction. A granulomatous mass with an irregular surface was found in the anterior part of the right nasal cavity. Tissue biopsy revealed granulation tissue. Since the application of steroid ointment did not reduce the size of the mass, the tumor was resected under local anesthesia, and the base was cauterized. The pathological finding was an inflammatory granuloma with negative Ziehl–Neelsen staining. The granuloma recurred 3 months after resection. The interferon-gamma release assay (IGRA) test was positive, and therefore, a mycobacterial tissue culture test was performed because of suspected nasal tuberculosis, which identified M. marinum. The nasal cavity mass disappeared 2 months after the administration of minocycline, followed by clarithromycin, and subsequent discontinuation of infliximab. M. marinum infection can cause an intranasal mass. IGRA and the mycobacterial tissue culture test are useful for diagnosis. As in this case, the nasal lesion may be excised as an inflammatory nasal granuloma, and therefore, there may be many more “hidden” cases of M. marinum infection. If nasal granulation is present, the possibility of M. marinum infection should be considered.

Objective: An Arterial Stiffness Index (ASI) can be obtained by measuring finger photoplethysmogram using the SB200 pulse oximeter, giving a level between 1 and 6. However, it was unclear whether this method accurately reflected arterial stiffness. Brachial–Ankle Pulse Wave Velocity (baPWV) is an established method for the assessment of arterial stiffness, allowing us to compare baPWV and our own ASI. Methods: We retrospectively collected data from 18 patients scheduled for neuroendovascular therapy in the Department of Neurosurgery at Osaka University Hospital between March 2016 and December 2016, for whom both baPWV and SB200 measurements were performed prior to their procedure. This allowed us to assess the relationship between the ASI and the baPWV. We defined patients with an ASI ≥ 3 on the SB200 as the progressed arterial stiffness group, while patients with a level of ≤2 were considered normal. BaPWV was compared across the two groups. We also analyzed the receiver operating characteristic curve for predicting baPWV values ≥ 1700 cm/s by the ASI measurement. Results: The progressed arterial stiffness group showed significantly higher baPWV values (p = 0.0087). The area under the curve for the ASI was 0.84. The ASI of 3 had a sensitivity of 71.4% and a specificity of 90.1% for predicting baPWV ≥ 1700 cm/s. Conclusion: We conclude that the non-invasive and portable SB200 device successfully measured arterial stiffness.

Abstract Diabetes induces lesions of the retinal and choroidal capillaries, which promote the pathogenesis of diabetic retinopathy (DR). The decorrelation signals in optical coherence tomography angiography (OCTA) represent the blood flow and vascular structure, and three-dimensional OCTA images enable individual capillary layers to be evaluated separately. The current study documented that en-face OCTA images revealed spots of flow void in the choriocapillaris layer in eyes with DR. Quantitative investigation demonstrated that non-flow areas within the central subfield (CSF) increased in eyes with more severe DR grades. The non-flow areas in the choriocapillaris layer were also associated with poorer visual acuity (VA) in all 108 eyes. A modest correlation was noted between the areas of flow void and poorer VA in 69 eyes without DME, whereas the non-flow areas were not related to VA or to CSF thickness measured by OCT in 39 eyes with DME. In 12 eyes with ischemic maculopathy, the choriocapillaris layer beneath the disrupted ellipsoid zone of the photoreceptor (EZ) had greater areas of flow void than did the area beneath an intact EZ. These data suggested that disrupted choroidal circulation has clinical relevance and contributes to the pathogenesis of DR.

To investigate whether baseline optical coherence tomography (OCT) parameters can predict the treatment frequency of intravitreal ranibizumab (IVR) injections during the first year in patients with diabetic macular edema (DME) treated with pro re nata (PRN) IVR injections.We retrospectively reviewed 68 eyes of 63 patients with center-involved DME who received IVR injections for 12 months or longer according to three monthly IVR injections followed by the PRN dosing. We measured the mean retinal thicknesses in the individual subfields of the Early Treatment Diabetic Retinopathy Study grid and evaluated the qualitative and quantitative parameters on OCT sectional images. We investigated the relationship between these OCT parameters at baseline and the number of IVR injections during the 12-month follow-up.Three loading doses were administered to 10 eyes; four to seven annualized IVR injections were administered to 34 eyes. The number of eyes that received IVR injections decreased gradually until month 6 and was almost constant from months 7 to 11. No relationships were seen between the treatment frequency and baseline systemic factors and the ophthalmic examination findings. Univariate analyses showed that the number of IVR injections during the first year was associated with the mean retinal thickness in the individual subfields and the transverse length of the disrupted external limiting membrane (ELM) and ellipsoid zone of the photoreceptors. Multivariate analysis showed a significant association with the thickness in the inferior subfield alone. The treatment frequency during the 12-month follow-up was not correlated with improved visual acuity but was associated with the decrease in the central subfield thickness and disrupted ELM.The retinal thickness in the inferior subfield predicts the treatment frequency during the first year in eyes with DME treated with PRN IVR injections.

From the standpoint of poultry meat hygiene, amyloid deposition and bacterial contamination in livers of 197 mature white layer chickens from a slaughterhouse and 100 young broiler breeder chickens from 5 different retail butcher shops were examined. Amyloid deposition was detected in 1 liver from 2-years-old layer using alkaline Congo red staining and immunohistochemical examination, but no amyloid deposition was observed in 100 livers from young broiler. Total bacterial counts in the chicken livers were examined using nutrient, desoxycholate hydrogen sulfate and mCCDA agar plates, but no close relationship between amyloid deposition and bacterial contamination (counts and species) was observed in this study. These results suggest there is low incidence of systemic amyloid deposition in chicken liver from meat market.

To characterize white dots in diabetic retinopathy (DR) and their association with disease severity using ultra-wide-field scanning laser ophthalmoscopy.We randomly selected 125 eyes of 77 patients (25 eyes from individual categories of the international classification of DR severity) for which ultrawide field photographs were obtained. We characterized white dots, which were delineated by higher signal levels on green but not red laser images, and evaluated the relationship between the number of white dots and the international severity scale of DR.Most white dots were located in nonperfused areas, and the number of total white dots was significantly correlated to that of dots in nonperfused areas. White dots corresponded to microaneurysms around the boundary between nonperfused areas and perfused areas or unknown lesions in nonperfused areas. Eyes with DR had significantly more white dots than those with no apparent retinopathy. The numbers of white dots in moderate nonproliferative diabetic retinopathy (NPDR) or more severe grades were significantly higher than in mild NPDR. The area under the receiver operating characteristics curve (AROC) analyses demonstrated that the number of white dots had the significance in the diagnosis of DR (0.908-0.986) and moderate NPDR or more severe grades (0.888-0.974).These data suggest the clinical relevance of white dots seen on ultrawide field images in the diagnosis of the severity of DR.

Diabetes induces microvascular diseases including diabetic retinopathy and choroidopathy which reciprocally promote the pathogenesis, although optical coherence tomography images of diabetic choroidopathy remains to be documented. Here we evaluated the qualitative characteristics of choroidal vascular lesions in patients with diabetes and their association with diabetic retinopathy on swept-source optical coherence tomography (SS-OCT) images. We retrospectively reviewed 110 consecutive eyes of 110 patients with diabetes and 35 eyes of 35 healthy subjects for whom SS-OCT images (6x6-mm scans centered on the fovea) of sufficient quality were acquired. The curve of chorioretinal sections was flattened using Bruch's membrane as a reference surface, followed by generation of en-face images. We characterized choroidal vascular lesions and evaluated their association with the logarithm of the minimum angle of resolution visual acuity (logMAR VA), retinal and choroidal thicknesses, and diabetic retinopathy severity. En-face SS-OCT images showed unvisualized vessels in Sattler's layer in 33 eyes (30.0%). Focal narrowing was seen in choroidal vessels in Haller's layer in 56 eyes (50.9%). The choroidal vessels ended in the superficial or middle portion of Haller's layer, referred to as vascular stumps, in 20 eyes (18.2%). Diabetic eyes had these findings more frequently than nondiabetic eyes. The subfoveal choroid was thicker in eyes with focal vascular narrowing and vascular stumps than in eyes without such lesions. Vascular stumps in Haller's layer were significantly related to diabetic retinopathy severity, logMAR VA, and central retinal and choroidal thicknesses. These novel findings on SS-OCT images would promote the better understanding of complicated pathogenesis in diabetic retinopathy and choroidopathy.

To investigate the functional and morphologic prognoses of eyes with subfoveal hemorrhage from acute branch retinal vein occlusion (BRVO), and to examine the effect of intravitreal ranibizumab injection (IVR) on these prognoses, we assessed 81 eyes with acute BRVO, of which 38 did not receive IVR [IVR(-) group], and 43 were treated with IVR [IVR(+) group] for macular edema. The foveal morphologic changes were examined via optical coherence tomography (OCT). At initial examination, 63 eyes exhibited subfoveal hemorrhage. At final examination, the defect lengths in the foveal external limiting membrane (ELM) and ellipsoid lines in these eyes were longer, and final VA was significantly poorer, compared with eyes without subfoveal hemorrhage. In comparisons between the final measurements in eyes with subfoveal hemorrhage in the IVR(-) and IVR(+) groups, while there were no differences in initial ocular conditions, final VA was significantly better in the IVR(+) group. The defects in the ELM and ellipsoid lines in the IVR(+) group were shorter than those of the IVR(-) group (p = 0.002 in both). Final VA was correlated with the defect lengths of foveal ELM and ellipsoid lines in both the IVR(-) and IVR(+) groups (both p < 0.001). In addition, the defect lengths of foveal ELM and ellipsoid lines were closely correlated with the duration of subfoveal hemorrhage (both p < 0.001). BRVO-associated subfoveal hemorrhage caused damage to the foveal photoreceptors, and visual dysfunction. However, IVR improved these prognoses, by accelerating the absorption of the subfoveal hemorrhage.

The effect of interpolation and super-resolution (SR) algorithms on quantitative and qualitative assessments of enlarged optical coherence tomography (OCT) images was investigated in this report. Spectral-domain OCT images from 30 eyes in 30 consecutive patients with diabetic macular edema (DME) and 20 healthy eyes in 20 consecutive volunteers were analyzed. Original image (OR) resolution was reduced by a factor of four. Images were then magnified by a factor of four with and without application of one of the following algorithms: bilinear (BL), bicubic (BC), Lanczos3 (LA), and SR. Differences in peak signal-to-noise ratio (PSNR), retinal nerve fiber layer (RNFL) thickness, photoreceptor layer status, and parallelism (reflects the complexity of photoreceptor layer alterations) were analyzed in each image type. The order of PSNRs from highest to lowest was SR > LA > BC > BL > non-processed enlarged images (NONE). The PSNR was statistically different in all groups. The NONE, BC, and LA images resulted in significantly thicker RNFL measurements than the OR image. In eyes with DME, the photoreceptor layer, which was hardly identifiable in NONE images, became detectable with algorithm application. However, OCT photoreceptor parameters were still assessed as more undetectable than in OR images. Parallelism was not statistically different in OR and NONE images, but other image groups had significantly higher parallelism than OR images. Our results indicated that interpolation and SR algorithms increased OCT image resolution. However, qualitative and quantitative assessments were influenced by algorithm use. Additionally, each algorithm affected the assessments differently.

Optical coherence tomography (OCT) has enabled objective measurement of the total retinal thickness in diabetic macular edema (DME). The central retinal thickness is correlated modestly with visual impairment and changes paradoxically after treatments compared to the visual acuity. This suggests the clinical relevance of the central retinal thickness in DME and the presence of other factors that affect visual disturbance. Recent advances in spectral-domain (SD) OCT have provided better delineation of the structural changes and fine lesions in the individual retinal layers. Cystoid spaces in the inner nuclear layer and outer plexiform layer are related to quantitative and qualitative parameters in fluorescein angiography. OCT often shows vitreoretinal interface abnormalities in eyes with sponge-like retinal swelling. Serous retinal detachment is sometimes accompanied by hyperreflective foci in the subretinal fluid, which exacerbates the pathogenesis at the interface of the photoreceptors and retinal pigment epithelium. Photoreceptor damage at the fovea is thought to be represented by disruption of the external limiting membrane or the junction between the inner and outer segment lines and is correlated with visual impairment. Hyperreflective foci in the outer retinal layers on SD-OCT images, another marker of visual disturbance, are associated with foveal photoreceptor damage.

Sarcocystis spp. cause pigeon protozoan encephalitis, a neuronal disease. A female pigeon exhibiting torticollis had a necrotic area in the cerebral hemisphere surrounded by lesions with perivascular cuffing, gliosis, granulomatous foci, and meningitis. Non-necrotic lesions were also observed in the brainstem. Intact and degenerative schizonts were observed within the neuropils and neurons in the lesions. Deoxyribonucleic acid (DNA) was extracted from paraffin-embedded brain tissues and genetically analyzed after gel electrophoresis to determine Sarcocystis spp. using specific primer sets for 28S ribosomal ribonucleic acid and internal transcribed spacer region-1. DNA sequencing confirmed a significant homology with S. calchasi. This is the first report of meningoencephalitis with malacia caused by S. calchasi in a rock pigeon in Japan. [ABSTRACT FROM AUTHOR]

Cryptococcosis, a globally distributed mycotic disease caused by Cryptococcus neoformans or C. gattii, has been extensively studied in various domestic animals and humans. However, non-domestic species have often been overlooked in the literature, with limited attention given to their susceptibility and contribution to the epidemiology of the disease. In this study, a captive two-year-old Cape hyrax in a Japanese zoo exhibited neurological symptoms and torticollis, ultimately succumbing to the infection. Necropsy and pathological analyses, including histopathological techniques and PCR, revealed the presence of C. neoformans in the lungs, cerebrum, and internal auditory canal. While cryptococcosis has been reported in various wild animals globally, this case represents the first documented cryptococcosis in Cape hyrax. [ABSTRACT FROM AUTHOR]

Cryptococcosis, a globally distributed mycotic disease caused by Cryptococcus neoformans or C. gattii, has been extensively studied in various domestic animals and humans. However, non-domestic species have often been overlooked in the literature, with limited attention given to their susceptibility and contribution to the epidemiology of the disease. In this study, a captive two-year-old Cape hyrax in a Japanese zoo exhibited neurological symptoms and torticollis, ultimately succumbing to the infection. Necropsy and pathological analyses, including histopathological techniques and PCR, revealed the presence of C. neoformans in the lungs, cerebrum, and internal auditory canal. While cryptococcosis has been reported in various wild animals globally, this case represents the first documented cryptococcosis in Cape hyrax. [ABSTRACT FROM AUTHOR]

The brain of a rhesus monkey that died at 43 years of age with symptoms of suspected cognitive dysfunction was analyzed. pathological analyses revealed characteristic Alzheimer’s disease-related lesions: the aggregation of amyloid β (Aβ) in the form of senile plaques and phosphorylated tau proteins. We also revealed that Aβ43, which is prone to aggregation and toxicity in humans, is involved in senile plaques in the brain of the rhesus monkey, as well as several other Aβ species. Comparative studies of neuropathology using aged nonhuman primates lack behavioral descriptions compared to human medicine. This case report showed behavioral abnormalities and the detailed pathological changes that may have caused it in a super-aged rhesus monkey [ABSTRACT FROM AUTHOR]