Search

Anti-VEGF treatment for neovascular age-related macular degeneration (nAMD) has been evaluated in clinical trials. To select the best anti-VEGF drug and the best treatment regimen for nAMD, a thorough understanding of the characteristics of each anti-VEGF drug and treatment regimen is essential. In this review, we summarized visual acuity (VA) changes in 30 previous clinical trials of anti-VEGF treatment for nAMD. In most studies, ranibizumab, aflibercept, and brolucizumab improved the VA by 6 to 12 letters from the baseline VA of 50-65 letters and maintained the VA improvement regardless of the treatment regimen; the VA improved from 0.2-0.4 to 0.3-0.7 in Snellen equivalents. The improvement was rapid during the first month and became slower after the second injection, and 60% to 90% of the VA improvement was attained within the first 3 months. The upper limit of the VA improvement should be determined according to eyes with nAMD themselves, not according to anti-VEGF drugs or treatment regimens. Since a fixed regimen can result in overtreatment, whilst a pro re nata regimen can result in insufficient treatment, a treat-and-extend regimen would be optimal to treat nAMD. Insufficient treatment fails to improve VA to the upper limit and/or to maintain the improved VA, whereas overtreatment can cause macular atrophy. One study reported no difference in the risk of macular atrophy between ranibizumab and aflibercept, whilst many studies have suggested that aflibercept causes more choroidal thinning, one of the risk factors for macular atrophy, than does ranibizumab. Further evaluation of drugs and regimens should be performed from the viewpoint of complications and minimum number of injections required to improve and maintain VA.

Purpose To investigate long-term visual outcome in inferior posterior staphyloma (IPS) in each group classified based on macular complications and to examine the treatment effect for eyes with IPS with choroidal neovascularization (CNV). Design Prospective clinical cohort study. Participants We analyzed 56 eyes of 43 consecutive patients with IPS who were followed for 4 years. Methods We classified eligible eyes into 3 groups based on baseline findings: eyes without CNV or retinal exudate (no-exudate group), eyes without CNV and with retinal exudate (exudate group), and eyes with CNV (CNV group). We investigated the best-corrected visual acuity (BCVA) and associated parameters for 4 years. Results BCVA declined during 4 years only in the exudate group (P = .002), whereas it was maintained for 4 years in the no-exudate and CNV groups (P = .53 and .20, respectively). Baseline BCVA was lower in the CNV group than in the exudate group (P = .004); however, the 4-year BCVA was not (P = .84). The 4-year BCVA was associated with baseline BCVA in all groups. Eyes in the CNV group required 9.0 ± 8.7 anti–vascular endothelial growth factor therapy in 4 years. Conclusions Better baseline BCVA in eyes with exudative IPS without CNV spontaneously declined in 4 years, whereas worse baseline BCVA in eyes with IPS with CNV did not, probably because of treatment for retinal exudate from CNV. Anti–vascular endothelial growth factor therapy would be effective for long-term maintenance of BCVA in eyes with IPS with CNV, similar to other diseases with CNV.

To assess the value of the texture analysis of fluorine-18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) in predicting the treatment response of postoperative recurrent or metastatic oral squamous cell carcinoma (POR/M-OSCC) treated with cetuximab. A total of 14 patients undergoing 18F-FDG-PET/CT with POR/M-OSCC were divided into the responder and non-responder groups according to cetuximab response by Response Evaluation Criteria in Solid Tumors (RECIST). The regions of interest (ROI) were set at the POR/M-OSCC lesions with the highest uptake of 18F-FDG, and the volumetric and texture features were analyzed. The features with correlation coefficient of 0.6 or more were further evaluated using the logistic regression analysis to create a model. The SHAPEVolume(vx), SHAPEVolume(mL), metabolic tumor volume (MTV), and gray-level run-length matrix run-length nonuniformity (GLRLMRLNU) were significantly different between the responder (n = 6) and non-responder (n = 8) groups (p = 0.044, 0.042, 0.047, and 0.012, respectively). The model’s area under the curve (AUC) was found to be 0.83, 0.83, 0.79, and 0.92, respectively. The heatmap with PET feature dendrogram showed four distinct clusters including them in patient’s responder and non-responder groups. Higher MTV, GLRLMRLNU, SHAPEVolume(vx), and SHAPEVolume(mL) in 18F-FDG-PET images may have the prediction values for treatment response with POR/M-OSCC treated with cetuximab.

Purpose To describe the distribution of ocular biometry and refraction in Japanese adults. Design Cross-sectional analysis of a prospective cohort study. Participants A total of 9850 individuals participated in the first follow-up of the Nagahama Prospective Cohort for Comprehensive Human Bioscience (the Nagahama Study) conducted between 2013 and 2016. Participants were between 34 and 80 years of age. Methods All participants underwent axial length (AL; in millimeters), anterior chamber depth (ACD; in millimeters), corneal diameter (white to white; in millimeters), and central corneal thickness (CCT; in micrometers) measurement (IOL Master; Carl Zeiss Meditec, Dublin, CA) and refraction (spherical equivalent [SE]; in diopters [D]) and corneal curvature (CC; in millimeters) measurement (ARK-530A; Nidek, Aichi, Japan). Distribution of these ocular biometric parameters and prevalence of myopia, high myopia, and extreme myopia were summarized. Main Outcome Measures Distribution of ocular biometry and refraction. Results After standardization to the national population of 2015, estimates of mean AL and SE were 24.21 mm and –1.44 D, respectively. Estimates of mean CC, corneal diameter, CCT, and ACD were 7.69 mm, 12.01 mm, 543.96 μm, and 3.21 mm, respectively. After standardization of age and gender, the prevalence of myopia (SE, ≤–0.5 D) and high myopia (SE, ≤–6.0 D) were 49.97% and 7.89%, respectively. Approximately 70% of the younger participants (34–59 years of age) showed myopia, whereas high myopia was observed in approximately 10%. Although the number of individuals with myopia or high myopia was higher in the younger age groups, the prevalence of more extreme phenotypes remained stable across all ages, especially in women. Axial length of more than 30 mm was observed only in older women (n = 5 [0.05%]). Conclusions We showed detailed distributions of various ocular biometry and refraction parameters using a large general Japanese cohort. Prevalences of myopia and high myopia from 2013 through 2016 were higher than those in earlier studies, which reflects recent environmental change. However, constant prevalence of extreme myopia across all ages suggests high genetic predisposition of the extreme phenotype.

Purpose Although there have been many population-based studies of age-related macular degeneration (AMD), only limited information is available in Asia on the epidemiology of geographic atrophy (GA). We aimed to determine the prevalence and patterns of GA through an analysis of multiple studies conducted within the Asian Eye Epidemiology Consortium (AEEC). Design Cross-sectional meta-analyses. Participants A total of 97 213 individuals aged 40 years and older. Methods Data from 22 population-based studies from countries belonging to the AEEC were included. In all studies, AMD was defined on the basis of standardized grading systems. Geographic atrophy was defined as an area of pallor in the fundus with visibility of the underlying choroidal blood vessels and sharply defined borders. Random-effects meta-analysis was performed to estimate overall and age-, gender-, and region-specific pooled prevalence of GA. Main Outcome Measures Prevalence of GA per 1000 persons. Results The mean age was 60.8 ± 10.0 years, and 42 673 (43.9%) were male. Overall, a total of 223 individuals (0.2%) had GA. The pooled overall prevalence of GA was 1.57 per 1000 persons (95% confidence interval [CI], 1.04–2.10), which was 3 times less than that of neovascular AMD of 5.20 per 1000 persons (95% CI, 3.97–6.43). Compared with those aged 50 to 59 years, the prevalence of GA increased from 0.34 per 1000 persons (95% CI, 0.07–0.62) to 2.90 per 1000 persons (95% CI, 1.55–4.25) in those aged ≥70 years. The GA prevalence per 1000 persons was similar between urban (2.22; 95% CI, 1.22–3.23) and rural residents (1.33; 95% CI, 0.70–1.96). Geographic atrophy was more prevalent in South Asia (based on studies from India and Nepal, 3.82 per 1000 persons; 95% CI, 1.72–5.93) compared with East Asia (based on studies from China, Korea, Hong Kong, Taiwan, and Japan, and the Singapore Chinese Eye Study, 0.76 per 1000 persons; 95% CI, 0.31–1.22, P = 0.005). Conclusions Geographic atrophy is uncommon in Asian populations compared with those of European ancestry. Even within Asia, geographic differences in GA prevalence were seen. The findings of this meta-analysis suggest that better dissection of risk factors in the Asian population for GA may provide insights into the biological pathways that drive these late-stage manifestations, thus suggesting better targets for prevention.

PURPOSE To investigate whether the efficacy of anti-vascular endothelial growth factor (VEGF) monotherapy for polypoidal choroidal vasculopathy (PCV) differs between pachychoroid and non-pachychoroid phenotypes in the long term. METHODS This retrospective longitudinal study included 115 treatment-naive eyes in 115 consecutive patients with symptomatic PCV who were treated with anti-VEGF monotherapy and were followed up for 5 years. Eligible eyes were assigned to either a pachy-PCV group, with a pachychoroid phenotype, or a non-pachy-PCV group, without a pachychoroid phenotype. Best-corrected visual acuity (BCVA) and other parameters over a 5-year period were compared between the groups. RESULTS Forty-eight eyes and 67 eyes were classified into the pachy-PCV and non-pachy-PCV groups respectively. Baseline and 5-year BCVA (logarithm of the minimum angle of resolution) were 0.19 ± 0.20 and 0.16 ± 0.28 in the pachy-PCV group, respectively, and 0.25 ± 0.26 and 0.26 ± 0.36 in the non-pachy-PCV group respectively. BCVA did not change significantly in either group (p = 0.18 and 0.08 respectively). BCVA did not differ between the groups at any observation time-point. Subfoveal choroidal thickness (SFCT) at baseline and at 5 years was significantly higher in the pachy-PCV group than in the non-pachy-PCV group (both p

Purpose: To report fundamental epidemiologic data for choroidal parameters such as choroidal thickness and index of choroidal vascularity in Japanese individuals and to evaluate their correlations with age, sex, systemic parameters, and other ocular parameters. Design: Population-based cohort study. Participants: A total of 9850 individuals participated in the first follow-up of the Nagahama Prospective Cohort for Comprehensive Human Bioscience (the Nagahama Study) conducted between 2013 and 2016. Methods: All participants underwent standardized ophthalmic examinations, including OCT with enhanced depth imaging (EDI; RS-3000 Advance; Nidek). We manually segmented the choroidoscleral interface to measure subfoveal choroidal thickness (SFCT) and calculated the normalized choroidal intensity obtained with EDI (NCIEDI) and choroidal vascularity index (CVI). These are indices of choroidal brightness in OCT and reportedly represent the dilation of choroidal vessels. After summarizing the age-sex stratified distributions of SFCT, NCIEDI, and CVI, their associations with age, sex, axial length (AL), and spherical equivalent (SE) were evaluated using linear regression analysis with adjustments for possible confounders. Main Outcome Measures: Distribution of SFCT, NCIEDI, and CVI in the healthy Japanese population and their characteristics. Results: Age-sex standardized SFCT, NCIEDI, and CVI were 291.2 μm, 0.653, and 66.88%, respectively. In both men and women, SFCT was associated negatively with age (P < 0.001) and NCIEDI was associated positively with age (P < 0.001). Although both SFCT and NCIEDI did not differ significantly between men and women overall (P = 0.87 and P = 0.21, respectively), among younger participants (35–50 years of age), men showed significantly greater SFCT than women (P < 0.001). Only in men was CVI associated positively with age (P < 0.001). In the multivariable analysis, SFCT was associated significantly with age, sex, AL, SE, and the interaction term of age and sex (P < 0.001). Independent of SFCT, NCIEDI and CVI were associated significantly with age (P < 0.001). Conclusions: We report normative Japanese SFCT, NCIEDI, and CVI data using a large general Japanese cohort. The association analysis of SFCT with NCIEDI and CVI suggested that younger individuals have a more lumen-rich choroid for their choroidal thickness than older individuals.

Objective:The aim of this study was to identify disaster medical operation improvements from the 2016 Kumamoto Earthquake (Kumamoto Prefecture, Japan) and to extract further lessons learned to prepare for future expected major earthquakes.Methods:The records of communications logs, chronological transitions of chain of command, and team registration logs for the Disaster Medical Assistant Team (DMAT), as well as other disaster medical relief teams, were evaluated.Results:A total of 466 DMAT teams and 2,071 DMAT team members were deployed to the Kumamoto area, and 1,894 disaster medical relief teams and 8,471 disaster medical relief team member deployments followed. The DMAT established a medical coordination command post at several key disaster hospitals to designate medical coverage areas. The DMAT evacuated over 1,400 patients from damaged hospitals, transported medical supplies to affected hospitals, and coordinated 14 doctor helicopters used for severe patient transport. To keep constant medical and public health operations, DMAT provided medical coordination management until the local medical coordination was on-track. Several logistic teams, which are highly trained on operation and management of medical coordination command, were dispatched to assist management operation. The DMAT also helped to establish Disaster Coordination and Management Council at the prefectural- and municipal-level, and also coordinated command control for public health operations. The DMAT could provide not only medical assistance at the acute phase of the disaster, but also could provide medical coordination for public health and welfare.Conclusion:During the 2016 Kumamoto Earthquake, needs of public health and welfare increased enormously due to the sudden evacuation of a large number of residents. To provide constant medical assistance at the disaster area, DMAT, logistic teams, and other disaster medical relief teams must operate constant coordination at the medical headquarter command. For future expected major earthquakes in Japan, it will be required to educate and secure high enough numbers of disaster medical assistance and health care personnel to provide continuous medical and public health care for the affected area residents.Kondo H, Koido Y, Kawashima Y, Kohayagawa Y, Misaki M, Takahashi A, Kondo Y, Chishima K, Toyokuni Y. Consideration of medical and public health coordination – experience from the 2016 Kumamoto, Japan Earthquake. Prehosp Disaster Med. 2019;34(2):149–154

Purpose To explore novel prognostic factors associated with visual function and number of anti–vascular endothelial growth factor (VEGF) treatments in eyes with active myopic choroidal neovascularization (mCNV) using OCT angiography (OCTA). Design Prospective case series. Participants Twenty-eight treatment-naive eyes with active mCNV from 27 consecutive patients (mean age, 64.4 ± 11.1 years). Methods All eyes received through injection a single loading dose of intravitreal aflibercept (IVA), followed by additional IVA on a pro re nata (PRN) basis during the subsequent 12 months. At baseline, OCTA images of a 3 × 3-mm macular cube were acquired using an OCTA scanner. On binarized and skeletonized OCTA images of the outer retinal layer, OCTA-derived baseline parameters of mCNV—including lesion size, vessel density, vessel length density (VLD), vessel diameter index, and fractal dimension (FD)—were measured and evaluated for correlation with 12-month best-corrected visual acuity (BCVA) and number of additional injections. Main Outcome Measures The primary and secondary outcomes were BCVA 12 months after initial treatment and number of additional injections, respectively. Results There was no significant difference between baseline and 12-month BCVA (0.37 ± 0.30 and 0.30 ± 0.35 logarithm of the minimal angle of resolution, respectively; P = 0.23). The number of additional injections was 0.93 ± 1.02 (mean ± standard deviation). Baseline VLD, FD, and BCVA were correlated with 12-month BCVA (P = 0.02, r = 0.46; P = 0.02, r = 0.46; and P = 0.02, r = 0.45, respectively), and VLD also was correlated with the number of additional injections (P = 0.03, r = 0.42). Conclusions Exuberant mCNV, which is characterized by high VLD and FD derived using OCTA, is a predictor of poor visual outcomes after a single IVA injection followed by a PRN regimen. Only baseline VLD was correlated with the number of additional IVA injections, which indicates that this parameter could help to determine the optimal anti-VEGF treatment regimen for individual eyes with mCNV.

Unsupervised machine learning has received increased attention in clinical research because it allows researchers to identify novel and objective viewpoints for diseases with complex clinical characteristics. In this study, we applied a deep phenotyping method to classify Japanese patients with age-related macular degeneration (AMD), the leading cause of blindness in developed countries, showing high phenotypic heterogeneity. By applying unsupervised deep phenotype clustering, patients with AMD were classified into two groups. One of the groups had typical AMD features, whereas the other one showed the pachychoroid-related features that were recently identified as a potentially important factor in AMD pathogenesis. Based on these results, a scoring system for classification was established; a higher score was significantly associated with a rapid improvement in visual acuity after specific treatment. This needs to be validated in other datasets in the future. In conclusion, the current study demonstrates the usefulness of unsupervised classification and provides important knowledge for future AMD studies.

Genetic studies have investigated the pathogenesis of age-related macular degeneration (AMD). The pachychoroid concept has recently garnered attention as a possible explanation for AMD pathogenesis; the genetic characteristics of pachychoroid diseases have also been elucidated. In this review, we summarize previously reported genetic characteristics of AMD and pachychoroid diseases, and analyze these data to understand the pathogenesis of AMD and pachychoroid diseases. Previous studies show that VIPR2 and the CFH I62V A allele promote development of pachychoroid and central serous chorioretinopathy (CSC), while the CFH I62V G allele promotes development of drusen, pachychoroid neovasculopathy (PCN/PNV), and AMD. ARMS2/HTRA1 also promotes development of drusen, PCN/PNV, and AMD. TNFRSF10A and GATA5 are associated with CSC but not with pachychoroid, and TNFRSF10A is associated with AMD that includes PCN/PNV. These genetic characteristics suggest the following mechanisms of developing AMD and pachychoroid diseases. VIPR2 and the CFH I62V A allele promote pachychoroid development, which can result in CSC development. The CFH I62V G allele promotes a common step during PCN/PNV and AMD development induced by pachychoroid or drusen, such as damage of Bruch's membrane or retinal pigment epithelium (RPE). ARMS2/HTRA1 also promotes damage of Bruch's membrane or RPE, while the association with drusen formation is stronger in ARMS2/HTRA1 than in CFH. TNFRSF10A and GATA5 promote blood-retinal-barrier breakdown to induce CSC, which could lead to PCN/PNV development. Furthermore, recently reported genetic associations with the natural course of CSC suggest the importance of reconsidering the subtype classification of CSC. These associations would enable the development of personalized/precision medicine for CSC and.

To investigate the incidence and predictors of macular atrophy during treatment with aflibercept for neovascular age-related macular degeneration in Japanese patients.This study included patients with treatment-naive subfoveal neovascular age-related macular degeneration treated from December 2012 through January 2015. Patients were treated with bi-monthly aflibercept injections after 3 monthly loading injections for the first year. Diagnosis of retinal pigment epithelial atrophy was made based on color fundus photography, spectral-domain optical coherence tomography, and fundus autofluorescence. Baseline characteristics and morphological features were analyzed for their association with the development of macular atrophy.This study included 123 eyes that had no baseline macular atrophy and treated with aflibercept injections for 12 months. Thirteen eyes (10.6%) developed new macular atrophy at 12 months. Logistic regression analysis showed that the presence of intraretinal fluid and thinner subfoveal choroidal thickness at baseline were associated with the development of macular atrophy after aflibercept treatment.Macular atrophy developed in about 10% of eyes with neovascular age-related macular degeneration during 12 months of treatment with a fixed regimen of aflibercept. Intraretinal fluid and subfoveal choroidal thickness seem to be predictors for development of macular atrophy after anti-vascular endothelial growth factor (VEGF) therapy.

Introduction:Having experienced the Tokyo subway sarin attack in 1995, Japan has established extremely strict rules on handling injured victims before they are sent to a hospital. As a result, it takes a long time before rescue actions are taken. This report aims to propose a reform to change the system that focuses on saving lives.Methods:First, the issues in firefighting on sites that currently present problems in Japan were identified. Then, Japanese guidelines were compared with those that were considered in other countries. Based on this, an ideal way of running rescue operations was examined, and a proposal to save many lives was made. This research was conducted with funding from the Ministry of Health, Labour, and Welfare of Japan (MHLW; Chiyoda, Tokyo, Japan).Results:In addition to preventing secondary injuries, the temporal aspect of rescuing people early with the clear goal of saving many lives was emphasized. Priority was given to measures against nerve agents to prevent secondary injuries, which put the rescuers’ lives at risk. Possible decontamination methods were pursued before choosing the one that was most appropriate. A linear algorithm was used to determine which decontamination method could be started immediately, and then the gradual use of equipment was recommended. Even if Level A personal protective equipment (PPE) and other dedicated equipment and materials cannot be procured, the possibility of starting rescue activities under certain condition using regular equipment was pointed out. The need for a system for possible victims who would require support, such as foreigners, the handicapped, and elderly people, was also identified. Japan limits the scope of activities that can be undertaken by emergency medical technicians (EMTs) on-site. The way in which on-site medical care can be provided with future legal revisions in mind was also discussed.Conclusion:There is an urgent need to build a framework in which rescue activities can take place so that the number of deaths would not rise, even if sarin and other poisons are scattered.

Purpose To describe the clinical and genetic characteristics of pachychoroid geographic atrophy (GA) and to compare them with those of conventional GA associated with age-related macular degeneration (AMD). Design Observational case series. Participants Ninety-two eyes of 92 consecutive patients with GA who underwent a full ophthalmologic examination, including best-corrected visual acuity measurement, spectral-domain OCT, and fundus autofluorescence imaging. Their blood samples were genotyped for the major AMD-associated single nucleotide polymorphisms. Methods Pachychoroid GA was diagnosed if all of the following criteria were met: (1) GA in either eye; (2) clinical and anatomic features of the pachychoroid phenotype, such as reduced fundus tessellation and dilated choroidal vessels; and (3) no drusen in both eyes. Drusen-related GA was defined as conventional GA. Main Outcomes and Measures Comparison of clinical and genetic characteristics between pachychoroid GA and conventional GA. Results Twenty-one patients (22.8%) were diagnosed with pachychoroid GA. These patients were significantly younger than those with conventional GA (mean age, 70.5 vs. 78.5 years; P Conclusions Pachychoroid GA was diagnosed in 23% of patients with GA. Differences in the phenotypic and genetic characteristics of pachychoroid GA and conventional GA were identified. These 2 conditions should be differentiated when considering prevention and therapeutic strategies.

PURPOSE To examine the recurrence rate of choroidal neovascularization (CNV) lesion activity in age-related macular degeneration (AMD) and associated factors after 1-year aflibercept treatment. METHODS Age-related macular degeneration eyes with 1-year aflibercept fixed-regimen treatment and a follow-up period of at least 18 months from the initial aflibercept injection for treatment-naive exudative AMD were retrospectively evaluated. The recurrence rate was examined. Age, gender, visual acuity, AMD subtype, greatest linear dimension, and retinal and choroidal thicknesses at the 12th month examination were compared between eyes with and without recurrence. Presence of remnant polyps and pigment epithelial detachment (PED) morphology were also compared in polypoidal choroidal vasculopathy (PCV) eyes. RESULTS Of the 98 eyes studied, 69 displayed a dry macula at the 12th month examination; 43.7% exhibited recurrence during the subsequent 12-month period in Kaplan-Meier analysis. Although no factors associated with recurrence were detected in AMD, remnant polyps and pigment epithelial detachment morphology at the 12th month examination were significantly associated with recurrence in polypoidal choroidal vasculopathy (P = 0.018 and 0.048, respectively). CONCLUSION Continuous, proactive treatment would be considered overtreatment for more than half of the AMD eyes that achieved a dry macula. Angiography and optical coherence tomography analyses may be useful for predicting recurrence in polypoidal choroidal vasculopathy eyes.

Rationale: Bilateral diffuse uveal melanocytic proliferation (BDUMP) is an extremely rare retinal exudative disease with physical disorders and no established treatment standard. We describe treatment courses in 3 cases of BDUMP. Patients concerns: Three male patients complained active vision loss. One male patient in his 70s (patient 1) was treated with prednisolone, mesalazine, and ciclosporin for hypoplastic anemia and ulcerous colitis. One male patient in his 60s (patient 2) was on prednisolone therapy for adult Still disease. Another male patient in his 70s (patient 3) was on prednisolone therapy for polymyalgia rheumatica, giant cell arteritis, and pancreatic body tumor. Diagnoses: Retinal specialists diagnosed these patients with BDUMP based on characteristic fundus findings of multiple red patches and retinal exudate. Interventions: Two patients (patients 1 and 2) with poor response to anti-vascular endothelial growth factor (VEGF) monotherapy and/or triamcinolone acetonide sub-Tenon injection were treated with combined anti-VEGF therapy and photodynamic therapy. One patient (patient 3) was treated with 3 rounds of monthly anti-VEGF monotherapy. Outcomes: Retinal exudates were resolved in all patients. No recurrence of retinal exudates was observed for at least 10 months, 2 years, or 4 months after the therapy in patients 1, 2, and 3, respectively. However, best-corrected visual acuity of the right eye was low (20/200) compared with that of the left eye (20/22) in patient 2 despite exudate resolution, due to permanent outer retinal damage secondary to long-term retinal exudate. Lessons subsections: Combined anti-VEGF therapy and photodynamic therapy may be a feasible therapeutic option for treatment-resistant exudate in patients with BDUMP. Early diagnosis of BDUMP and prompt administration of combination therapy are crucial.

PURPOSE To investigate associations between parafoveal microcirculatory status and foveal pathomorphology in eyes with macular edema (ME) secondary to retinal vein occlusion (RVO). METHODS Ten consecutive patients (10 eyes) with acute retinal vein occlusion were enrolled, 9 eyes of which received intravitreal ranibizumab (IVR) injections. Foveal morphologic changes were examined via optical coherence tomography (OCT), and parafoveal circulatory status was assessed via adaptive optics scanning laser ophthalmoscopy (AO-SLO). RESULTS The mean parafoveal aggregated erythrocyte velocity (AEV) measured by adaptive optics scanning laser ophthalmoscopy in eyes with retinal vein occlusion was 0.99 ± 0.43 mm/second at baseline, which was significantly lower than that of age-matched healthy subjects (1.41 ± 0.28 mm/second, P = 0.042). The longitudinal adaptive optics scanning laser ophthalmoscopy examinations of each patient showed that parafoveal AEV was strongly inversely correlated with optical coherence tomography-measured central foveal thickness (CFT) over the entire observation period. Using parafoveal AEV and central foveal thickness measurements obtained at the first and second examinations, we investigated associations between differences in parafoveal AEV and central foveal thickness, which were significantly and highly correlated (r = -0.84, P = 0.002). CONCLUSION Using adaptive optics scanning laser ophthalmoscopy in eyes with retinal vein occlusion macular edema, we could quantitatively evaluate the parafoveal AEV. A reduction or an increase in parafoveal AEV may be a clinical marker for the resolution or development/progression of macular edema respectively.

Summary Background Since transforming growth factor (TGF)-β1-induced cardiac fibrosis following myocardial infarction (MI) leads to heart failure and poor clinical prognosis, we aimed to identify a novel and unknown target for cardiac fibrosis related to the TGF-β signaling. Method and result We performed and investigated RNA-Seq using infarcted mouse hearts, culminating in cartilage intermediate layer protein 1 (CILP1). Interestingly, Cilp1 expression was increased along with TGF-β1 expression in infarcted hearts, and was also upregulated after TGF-β1 stimulation in cardiac fibroblasts in vitro . Histological analysis revealed that Cilp1 was localized at the fibrotic regions of infarcted hearts. Full length CILP1 (F-CILP1) was cleaved into both N-terminal CILP1 (N-CILP1) and C-terminal CILP1 at the furin cleavage site, and both F-CILP1 and N-CILP1 were extracellularly secreted. We further found that CILP1 bound to TGF-β1 via thrombospondin type 1 domain, and suppressed both smad3 phosphorylation and fibroblasts differentiation to myofibroblasts induced by TGF-β1. Conclusion We identified CILP1 as a potential regulator of cardiac fibrosis by inhibiting TGF-β signaling, and these results suggest the promise of CILP1 as a novel therapeutic target for preventing cardiac fibrosis and heart failure in MI patients.

To evaluate peripheral retinal hemorrhagic patterns in eyes with acute central retinal vein occlusion, and to explore their clinical relevance in differentiating for the retinal perfusion status, through a prospective, and cross-sectional study.Fifty eyes with acute central retinal vein occlusion were included. Retinal hemorrhagic patterns at the equator and retinal perfusion status were evaluated by ultra-wide field fundus photography and fluorescein angiography.Retinal perfusion was categorized as nonischemic in 29 eyes, ischemic in 18 eyes, and undeterminable in 3 eyes. None of the examined eyes had flame-shaped retinal hemorrhages in the periphery. All hemorrhages were rounded-dot or blot and were variable in size. Particle analysis was performed to quantify hemorrhage size, and showed higher values in eyes having larger blot hemorrhages, and lower values in eyes having dot or smaller blot hemorrhages. Mean size of maximum peripheral dot or blot hemorrhage was larger in eyes classified as ischemic (10,763.0 ± 5,946.3 pixels) than as nonischemic (2,839.9 ± 1,153.6 pixels, P0.001). The authors calculated area under the curve to investigate the ability of continuous variables to discriminate retinal perfusion status, which was 0.963 (P0.001) for mean size of maximum peripheral blot hemorrhages.The authors objectively evaluated retinal hemorrhagic patterns at the equator in eyes with acute central retinal vein occlusion using particle analysis. The resulting hemorrhage size measurement was considered to be often useful in determining retinal perfusion status. Because they can be noninvasively evaluated with readily available equipment, peripheral hemorrhagic patterns might be good clinical markers of retinal perfusion.

Background and aims Ultrasound-guided peripheral nerve block (USGPNB) is a safe and reliable procedure. However, it is not easy for the novice to perform an appropriate procedure from the start. The aim of this study was to evaluate whether laser-guided ultrasound probe facilitated the performance of USGPNB for the novice practitioners compared with standard ultrasound probe. Methods 32 medical students and residents who have never performed USGPNB were enrolled in this study. The participants were randomly allocated into two groups: GroupL using laser-guided probe and GroupS using standard probe. Each participant performed USGPNB with each probe of the group on porcine phantom a total of six times, three times with linear probe for the simulated nerve embedded in the shallow layer and three times with convex probe for the nerve in the deep layer. A blinded researcher measured the time required for each procedure. Finally, the participants answered a 5-point impression scale of the difficulty for USGPNB. We evaluated the differences in the time required for the procedure and in the impression scale of the difficulty. The date was statistically analyzed with Mann-Whitney U test. Results The time required for the procedure (min, median[IQR]) was significantly shorter in GroupL than GroupS in using linear probe (GroupL: 65[37.5–96.5], GroupS: 92.5[55.5–162.25], P=0.013) and convex probe (GroupL: 54.5[34.5–88.5], GroupS: 93.5[61.25–143], P=0.003). There was no difference between two groups about the impression scale of the difficulty for USGPNB. Conclusions Our study demonstrated that laser-guided ultrasound probe might facilitate the performance of USGPNB from the start of their training for the novice.

The recently emerged pachychoroid concept has changed the understanding of age-related macular degeneration (AMD), which is a major cause of blindness; recent studies attributed AMD in part to pachychoroid disease central serous chorioretinopathy (CSC), suggesting the importance of elucidating the CSC pathogenesis. Our large genome-wide association study followed by validation studies in three independent Japanese and European cohorts, consisting of 1546 CSC samples and 13, 029 controls, identified two novel CSC susceptibility loci: TNFRSF10A-LOC389641 and near GATA5 (rs13278062, odds ratio = 1.35, P = 1.26 × 10−13; rs6061548, odds ratio = 1.63, P = 5.36 × 10−15). A T allele at TNFRSF10A-LOC389641 rs13278062, a risk allele for CSC, is known to be a risk allele for AMD. This study not only identified new susceptibility genes for CSC, but also improves the understanding of the pathogenesis of AMD., 特殊な網膜剥離の発症に関わる遺伝子変異を発見 --中心性漿液性脈絡網膜症のゲノムワイド関連解析--. 京都大学プレスリリース. 2019-12-13.

Purpose To compare the efficacy of photodynamic therapy (PDT) in eyes with polypoidal choroidal vasculopathy (PCV) associated with and without pachychoroid phenotypes (pachychoroid PCV and nonpachychoroid PCV, respectively). Design Retrospective chart review. Participants Patients previously diagnosed with PCV and initially treated with PDT. Methods Patients were classified as having pachychoroid- or nonpachychoroid-driven conditions. The long-term visual outcome and its associated factors were investigated. Main Outcome Measures Visual acuity (VA) outcomes at 1, 2, 3, 4, and 5 years after initial PDT in pachychoroid and nonpachychoroid PCV. Results Of the 158 eyes, 88 (55.7%) met the criteria for pachychoroid PCV; 70 (44.3%) did not (nonpachychoroid PCV). In cases of pachychoroid PCV, VA improved significantly at 1 year (P = 0.042) and maintained baseline level at 5 years (P = 0.38). By contrast, VA continued to deteriorate in the nonpachychoroid PCV group during the follow-up period and had already declined significantly by the second year (P = 0.022, compared with baseline). Despite no difference in baseline VA between pachychoroid and nonpachychoroid PCV groups (P = 0.11), the VA at 5 years was significantly better in the pachychoroid PCV group compared with the nonpachychoroid PCV group (0.54±0.47 vs. 0.93±0.63, respectively; P = 0.23 × 10–3). The incidence of massive submacular hemorrhage (SMH) or vitreous hemorrhage (VH) was not different between groups at 5 years (P = 0.67), and their occurrence was associated with decreased VA in both the nonpachychoroid and pachychoroid PCV groups (coefficient β, 0.361 and 0.481; P = 0.59 × 10–3 and P Conclusions Five years after PDT treatment, VA was maintained at the baseline level in the pachychoroid PCV group but not in the nonpachychoroid PCV group. Massive SMH or VH during the follow-up period affected the final visual outcomes in both conditions.

To assess whether optical coherence tomography angiography (OCTA) can be used as an alternative to conventional fundus fluorescein angiography (FFA) for the detection of myopic choroidal neovascularization (CNV).Validity and reliability analysis.Twenty-eight eyes of 26 consecutive Japanese patients with exudative lesions associated with pathologic myopia were included in this institutional study. Myopic CNV was detected in 23 eyes of 22 patients; 5 eyes exhibited simple hemorrhage. The main outcome measure was CNV detection by OCTA and FFA. The CNV area was individually measured by FFA and OCTA. Intraclass correlation coefficients (ICCs) for the CNV area, independently measured by 2 investigators using OCTA and FFA, were determined.OCTA images with sufficient quality for CNV assessment were obtained for 17 eyes with CNV and 4 without. FFA alone detected CNV in all 17 eyes, while OCTA alone detected CNV in 16 (94.1%). The 1 eye for which CNV was not detected by OCTA exhibited a 0.01 mm(2) area on FFA. Both FFA and OCTA did not detect CNV in eyes with simple hemorrhage. The mean CNV areas on FFA and OCTA were 0.59 ± 0.56 mm(2) and 0.51 ± 0.55 mm(2), respectively; the 2 values were significantly correlated (P.001, r = .86). The ICC (2, 1) values for FFA and OCTA were 0.944 and 0.997, respectively.Our results indicate that OCTA can detect most myopic CNVs if high-quality images are acquired and can preclude the requirement for FFA in these settings.

Resveratrol is a natural polyphenol produced by plants in response to environmental stress. This compound has been shown to have pharmacological effects against a wide range of diseases including neurological, hepatic, cardiovascular and autoimmune conditions. The non-obese diabetic (NOD) mouse, in which loss of lacrimal and salivary gland function occurs, has been studied as an animal model for Sjögren’s syndrome. In this study, we confirmed that administration of resveratrol results in increased secretion of saliva in NOD mice. Although resveratrol enhanced Sirt1 activity, inflammatory cell infiltration was not affected. Moreover, expression of the anti-inflammatory cytokine IL-10 in salivary glands was enhanced in the resveratrol-administered group. Thus, we confirmed a novel therapeutic effect for resveratrol on salivary dysfunction in Sjögren’s syndrome.

Intravitreal injections of anti-vascular endothelial growth factor agents such as ranibizumab and aflibercept are the first-line treatment for neovascular age-related macular degeneration (AMD). However, data about long-term outcome in real-world clinical practice is scarce. We recruited 98 AMD patients and investigated four-year visual outcome. During the four years, 25 patients dropped out. The survivors received 7.0 ± 0.1 injections during the first year and 8.0 ± 7.4 injections in the following three years. The logarithm of minimum angle of resolution (logMAR) at baseline, year one, and year four was 0.28, 0.14 (P = 0.033), and 0.22 (P = 0.697), respectively. The gain of vision was not different among AMD subtypes (typical AMD, polypoidal choroidal vasculopathy, and retinal angiomatous proliferation; P = 0.513) Among the investigated factors, the presence of external limiting membrane (ELM), the absence of vitreoretinal adhesion, and thicker choroid at baseline were associated with better logMAR values at year four (coefficient beta = −0.388, 0.201, and −0.001; P = 7.34 × 10−6; 0.01, and 0.028, respectively). In the present study, vision was retained at baseline level after the four-year treatment with aflibercept. The status of ELM, vitreoretinal adhesion, and choroidal thickness were predictive factors for final vision.

PURPOSE To compare therapeutic responses to intravitreal aflibercept and ranibizumab in neovascular age-related macular degeneration (AMD)-affected eyes with and without choroidal vascular hyperpermeability (CVH). METHODS Medical records of 216 consecutive patients (216 eyes) with treatment-naive exudative AMD who had received three monthly intravitreal injections of aflibercept (2 mg) and ranibizumab (0.5 mg) at a single institution were analyzed. The associations of CVH with functional and morphologic changes were compared between the treatment groups. RESULTS Although foveal thickness (P = 0.85) and visual acuity (P = 0.13) changes were not significantly different between the treatment groups, subfoveal choroidal thickness (CT) (P = 0.001) and pigment epithelial detachment (PED) height (P = 0.043) decreased more profoundly in the aflibercept-treated group. The incidence of dry macula after treatments was lower in the ranibizumab-treated eyes with CVH than in those without CVH (P = 0.043), but it showed no significant difference between the aflibercept-treated eyes with and without CVH (P = 0.74). The aflibercept-treated eyes with CVH showed a higher incidence of dry macula (P = 0.04) and greater decrease in subfoveal CT (P = 0.002) than the ranibizumab-treated eyes with CVH. CONCLUSIONS Intravitreal aflibercept can achieve remission of exudative retinal changes in eyes with AMD even in the presence of CVH. In addition, it showed greater effects on the choroid and PED than intravitreal ranibizumab. The possible relationship between CVH suppression and decrease in CT warrants further study.

To investigate the incidence rate and risk factors for development of retinal pigment epithelial (RPE) atrophy during anti-vascular endothelial growth factor (anti-VEGF) treatment for retinal angiomatous proliferation.This study included 46 eyes with treatment-naive retinal angiomatous proliferation. All patients were treated with ranibizumab or aflibercept injections. Color fundus photography, spectral-domain optical coherence tomography, and fundus autofluorescence were evaluated for RPE atrophy diagnosis. Baseline characteristics and gene polymorphisms of ARMS2 A69S, and CFH I62V were analyzed for association with development and progression of RPE atrophy.Among 21 eyes treated with ranibizumab without preexisting RPE atrophy at baseline, 5 eyes (23.8%) developed RPE atrophy at 12 months. Among 20 eyes treated with aflibercept without preexisting RPE atrophy at baseline, 10 eyes (50.0%) developed RPE atrophy at 12 months. Refractile drusen at baseline was associated with RPE atrophy development at 12 months (P = 0.014), and the progression rate of RPE atrophy area was negatively correlated with subfoveal choroidal thickness at baseline (R = -0.595, P = 0.019). Gene polymorphisms were not associated with RPE atrophy.Retinal pigment epithelial atrophy developed in 36.6% during 12 months after anti-VEGF treatment for retinal angiomatous proliferation. The presence of refractile drusen at baseline was identified as a novel significant risk factor for RPE atrophy development.

Decreased gamma-aminobutyric acid (GABA)-mediated phasic inhibitory transmission in the spinal cord is thought to be responsible for the development of neuropathic pain. However, the role of GABAergic tonic current in substantia gelatinosa (SG) neurons remains to be fully elucidated. Using real-time polymerase chain reaction, we investigated the expression of the GABAA receptor δ subunit, which contributes to tonic current in the SG, in chronic constriction injury (CCI; a well-known model of neuropathic pain) and naive mice. The expression of the δ subunit mRNA was reduced by 40% in the ipsilateral SG of the dorsal horn of CCI mice compared to naive mice. We also performed behavioral experiments to assess the effect of the δ subunit-preferring agonist 4,5,6,7- tetrahydroisoxazolo(5,4-c)pyridine-3-ol (THIP) on thermal hypersensitivity with the Hargreaves test. Intrathecal administration of THIP significantly improved thermal thresholds of the ipsilateral hindpaw (4.55 ± 0.78 to 6.56 ± 1.09 s from baseline to after injection, respectively, P 0.1). GABAA receptor δ subunit-mediatedtonic current contributes to thermal hypersensitivity of CCI mice, and THIP may represent a therapeutic tool to improve thermal hypersensitivity.

To investigate the 2-year outcomes of intravitreal injections of ranibizumab in typical neovascular age-related macular degeneration (tAMD) and polypoidal choroidal vasculopathy (PCV). Factors associated with visual outcomes are examined. We retrospectively reviewed medical records of 128 consecutive eyes with treatment-naive subfoveal AMD treated with ranibizumab and followed for ≥24 months. The association between visual outcomes and single nucleotide polymorphisms (SNPs) in ARMS2 A69S and CFH I62V genes were examined. Fifty-eight eyes were diagnosed with tAMD and 70 eyes with PCV. In tAMD eyes, visual acuity (VA) improved at 3 months (P = 0.020) but returned to the baseline level at 6 months. Thereafter, VA was maintained until 24 months. In PCV eyes, VA significantly improved at 3 months (P = 0.015) and persisted at 12 months (P = 0.025), but the VA improvement dissipated by 24 months. With regard to genetic associations with VA and VA change, neither VA nor VA change showed significant associations with these SNPs at all time points in tAMD. In the PCV eyes, there were significant associations between ARMS2 A69S and VA at baseline and 1 year (P = 0.017 and P = 0.025, respectively). However, VA change showed no significant difference among these genotypes in PCV. Intravitreal ranibizumab significantly improved the VA initially, but this improvement did not persist at 2 years post-treatment. In PCV, ARMS2 A69S polymorphism is associated with the baseline and 12-month VA, but is not associated with the visual prognosis at 24 months.

To investigate the incidence rate, risk factors, and final outcomes of patients with age-related macular degeneration (AMD) who have experienced vision loss despite periodic aflibercept treatment. Subjects with treatment-naive AMD were prospectively recruited and treated with three monthly injections followed by two monthly injections of aflibercept. The incidence rate and risk factors of more than two lines of vision loss at any visit were investigated. We included 196 eyes of 196 patients. Vision loss was observed in 16 patients (8.2%). Eleven of 16 patients developed vision loss during the initial 3 months (68.8%). Vision loss remained in 11 eyes (68.8%) at the final visit. The maximum pigment epithelium detachment (PED) height (odds ratio = 1.46 for a 100-μm increase in the PED height) and disruption of the external limiting membrane (odds ratio = 4.45) were identified as risk factors for developing vision loss on logistic regression analysis. The incidence rate of vision loss during aflibercept treatment was relatively low. Identifying high-risk patients, those with a high PED height and disruption of the external limiting membrane, would be helpful in ensuring appropriate informed consent before treatment. Further studies are needed to establish optimal treatment for these patients.

Incretin hormones, including glucagon-like peptide-1 (GLP-1), a target for diabetes mellitus (DM) treatment, are associated with cardioprotection. As dipeptidyl-peptidase IV (DPP-IV) inhibition increases plasma GLP-1 levels in vivo, we investigated the cardioprotective effects of the DPP-IV inhibitor vildagliptin in a murine heart failure (HF) model. We induced transverse aortic constriction (TAC) in C57BL/6J mice, simulating pressure-overloaded cardiac hypertrophy and HF. TAC or sham-operated mice were treated with or without vildagliptin. An intraperitoneal glucose tolerance test revealed that blood glucose levels were higher in the TAC than in sham-operated mice, and these levels improved with vildagliptin administration in both groups. Vildagliptin increased plasma GLP-1 levels in the TAC mice and ameliorated TAC-induced left ventricular enlargement and dysfunction. Vildagliptin palliated both myocardial apoptosis and fibrosis in TAC mice, demonstrated by histological, gene and protein expression analyses, and improved survival rate on day 28 (TAC with vildagliptin, 67.5%; TAC without vildagliptin, 41.5%; P < 0.05). Vildagliptin improved cardiac dysfunction and overall survival in the TAC mice, both by improving impaired glucose tolerance and by increasing GLP-1 levels. DPP-IV inhibitors represent a candidate treatment for HF patients with or without DM.

To compare the 12-month-efficacy of 1 initial intravitreal ranibizumab injection (IVR) followed by pro re nata (PRN) dosing with that of three initial monthly IVR followed by PRN dosing in patients with macular edema (ME) after branch retinal vein occlusion.Prospective, interventional study.Of 81 eyes, 42 received 1 initial IVR injection (1+PRN group) and 39 eyes received 3 monthly IVRs (3+PRN). Pro re nata injections were performed when fovea exudative changes were evident.At Month 12, the visual acuity (VA) changes from baseline were -0.245 ± 0.227 and -0.287 ± 0.222, in the 1+PRN and 3+PRN groups, respectively; there were no significant difference between groups (P = 0.728). The stratified analysis showed that patients with better VA (baseline VA20/40) had similar significant improvement in VA at Month 12 (P0.001) to that of those with poorer VA (≤20/40). Better VA at Month 12 was significantly associated with younger age, better baseline VA, and thinner baseline central foveal thickness (P = 0.003,0.001, and0.001, respectively). Mean total number of IVR injections in the 1+PRN and 3+PRN groups were 3.8 ± 1.8 and 4.6 ± 1.4, respectively (P = 0.060). In both groups, shorter durations to the first PRN injection were associated with greater total PRN injection number (1+PRN, P = 0.006; 3+PRN; group, P0.001).In IVR treatment for ME after branch retinal vein occlusion, 1+PRN and 3+PRN regimens achieved similar 12-month functional outcomes. Patients with shorter durations to initial PRN injection may require more PRN treatments.

This prospective study included 63 eyes with acute branch retinal vein occlusion (BRVO) to evaluate the retinal hemorrhagic patterns at the posterior poles and explore their clinical relevance in macular perfusion differentiation. Retinal hemorrhagic patterns and macular perfusion status were evaluated via fundus photography and fluorescein angiography, respectively. Macular perfusion was judged as nonischemic in 30, ischemic in 28 and undeterminable in 5 among the 63 eyes. Predominant hemorrhagic patterns were flame-shaped in 39 (67.2%) and non-flame-shaped in 19 (32.8%) eyes. All 39 eyes with a flame-shaped hemorrhage showed a nonischemic macula. Of the 19 eyes classified as having a non-flame-shaped hemorrhage, 13 (68.4%) had an ischemic macula and 6 (31.6%) had a nonischemic macula (P P P P

To quantify the area of photoreceptor damage surrounding geographic atrophy (GA) and evaluate the relationship between structural abnormalities and retinal function in eyes with GA.Prospective cross-sectional study.Twenty-five eyes of 25 patients with GA associated with age-related macular degeneration underwent a full ophthalmologic examination, including spectral-domain optical coherence tomography (SDOCT), fundus autofluorescence (FAF), and microperimetry. ImageJ software was used to quantify the disruption of the ellipsoid zone on SDOCT images. Hypofluorescent areas of the FAF images indicated areas of retinal pigment epithelium (RPE) loss. Areas of interest graded by SDOCT (photoreceptor damage) and FAF (RPE loss) were registered with microperimetry within a 6-mm circle centered on the fovea.The mean area of photoreceptor damage was 7.69 ± 5.36 mm(2), which was significantly greater than the mean area of RPE loss (4.57 ± 4.07 mm(2), P.001). The average retinal sensitivity of the area with photoreceptor damage outside the area of RPE loss was lower than that of the area without photoreceptor damage (6.57 ± 4.13 dB vs 11.27 ± 3.78 dB, P.001). The area of photoreceptor damage surrounding the area of RPE loss was larger in eyes with pseudodrusen than in eyes without pseudodrusen (4.96 mm(2) vs 1.91 mm(2), P = .008). The only significant predictor of decreased retinal sensitivity was the area of the photoreceptor damage (P.001).Widespread photoreceptor damage surrounding sites of RPE loss occurred in eyes with GA, and it correlated with visual function. Evaluation of photoreceptor damage surrounding sites of RPE loss using OCT is important in patients with GA associated with AMD.

Background and Purpose— The majority of patients with ventricular wall motion abnormality (WMA) associated with subarachnoid hemorrhage (SAH) are postmenopausal women. In addition to elevated catecholamine, the role of estrogen in the pathogenesis of WMA has recently been implicated. The objective of this study is to clarify the interrelation among catecholamine, estrogen, and WMA in patients with SAH. Methods— A retrospective analysis was performed on the medical records of 77 patients with SAH (23 men, 54 women) whose plasma levels of epinephrine, norepinephrine, and estradiol had been measured and echocardiograms had been obtained within 48 hours of SAH onset. Results— Twenty-four patients (31%) were found to sustain WMA on admission. Multivariate regression analysis revealed that decreased estradiol ( P =0.018; OR, 0.902) and elevated norepinephrine levels ( P =0.027; OR, 1.002) were associated with WMA. After quadrichotomization of 77 patients based on sex/WMA, plasma norepinephrine levels were markedly elevated in men with WMA, whereas estradiol levels were markedly decreased in women with WMA. Plasma norepinephrine and estradiol levels were not correlated. Fifty-four female patients with SAH were further quadrichotomized based on norepinephrine/estradiol levels with a threshold value of 1375 pg/mL for norepinephrine and 11 pg/mL for estradiol. The incidence of WMA in the high-norepinephrine/low-estradiol group was significantly higher than the low-norepinephrine/high-estradiol group. Conclusions— To our knowledge, this is the first study to evaluate the interrelation among catecholamine, estrogen, and SAH-induced WMA. Lack of estradiol in postmenopausal women may predispose them to develop WMA after poor-grade SAH. However, the precise role of multiple sex hormones in SAH-induced WMA should be evaluated in future prospective studies.

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.

Pachychoroid neovasculopathy is a recently proposed clinical entity of choroidal neovascularization (CNV). As it often masquerades as neovascular age-related macular degeneration (AMD), it is currently controversial whether pachychoroid neovasculopathy should be distinguished from neovascular AMD. This is because its characteristics have yet to be well described. To estimate the relative prevalence of pachychoroid neovasculopathy in comparison with neovascular AMD and to investigate the phenotypic/genetic differences of the two diseases, we evaluated 200 consecutive Japanese patients who agreed to participate in the genetic study and diagnosed with pachychoroid neovasculopathy or neovascular AMD. Pachychoroid neovasculopathy was observed in 39 individuals (19.5%), which corresponds to one fourth of neovascular AMD. Patients with pachychoroid neovasculopathy were significantly younger (p = 5.1 × 10−5) and showed a greater subfoveal choroidal thickness (p = 3.4 × 10−14). Their genetic susceptibility to AMD was significantly lower than that of neovascular AMD; ARMS2 rs10490924 (p = 0.029), CFH rs800292 (p = 0.013) and genetic risk score calculated from 11 AMD susceptibility genes (p = 3.8 × 10−3). Current results implicate that the etiologies of the two conditions must be different. Thus, it will be necessary to distinguish these two conditions in future studies.

To review the published reports concerning the apparent diffusion coefficient (ADC) value evaluation for the differentiation between malignant and benign breast tumors, articles were searched with the inclusion criteria: (a) a 1.5-T unit was used; (b) the diagnostic criteria were clearly stated; (c) diffusion-weighted images (DWIs) were obtained, and ADC value was calculated; (d) ADC values of breast tumors were reported with mean +/- standard deviation (SD). Meta-analysis from 12 articles revealed that the pooled sensitivity and specificity were 0.89 (95% confidence interval [CI], 0.85-0.91) and 0.77 (95% CI, 0.69-0.84), respectively, and that only the maximum b factor correlated with the mean ADC values of malignant and benign tumors, and the noncancerous breast tissue (P< 0.05,P < 0.01,P< 0.05, respectively). In conclusion, ADC evaluation is useful for the differentiation between malignant and benign breast tumors.

全身麻酔は意識消失, 不動化, 鎮痛などさまざまな要素が組み合わさった現象である. 近年の麻酔メカニズム研究では, 麻酔薬は神経細胞表面の受容体蛋白質に作用し, その効果を発揮すると考えられている. 神経細胞にはさまざまな受容体蛋白質が存在するが, その中でも特にGABAA受容体は麻酔メカニズム研究の中心的存在である. 最近, GABAA受容体を介する抑制性電流にはPhasic電流とTonic電流の2種類が存在することが明らかにされ, 特にTonic電流は麻酔メカニズムの新しいターゲットとして非常に注目を浴びている. 本稿では, Tonic電流を含むGABAA受容体を中心とした麻酔メカニズム研究の新しい知見についてまとめる.