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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.

To describe the distribution of ocular biometry and refraction in Japanese adults.Cross-sectional analysis of a prospective cohort study.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.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.Distribution of ocular biometry and refraction.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%]).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.

Quality of single optical coherence tomography angiography (OCTA) images of myopic choroidal neovascularisation (mCNV) is poorer than in averaged images, although obtaining averaged images takes much time. This study evaluated the clinical usefulness of novel denoising process for depicting mCNV. This study included 20 eyes of 20 patients with mCNV. Ten en face images taken in a 3 × 3 mm macular cube were obtained from outer-retina-to-choriocapillaris layer. Three image types were prepared for analysis; single images before and after the denoising process accomplished deep learning (single and denoising groups, respectively) and up to 10 images were averaged (averaging group). Pairwise comparisons showed vessel density, vessel length density, and fractal dimension (FD) were higher; whereas, vessel density index (VDI) was lower in single group than in denoising and averaging groups. Detectable CNV indices, contrast-to-nose ratio, and CNV diagnostic scores were higher in denoising and averaging groups than in single group. No significant differences were detected in VDI, FD, or CNV diagnostic scores between denoising and averaging groups. The denoising process can utilise single OCTA images to provide results comparable to averaged OCTA images, which is clinically useful for shortening examination times with quality similar to averaging.

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.

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.

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.

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.

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.

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.

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.

In Drosophila, mature sperm are transferred from males to females during copulation, stored in the sperm storage organs of females, and then utilized for fertilization. Here, we report a gene named sheepish (shps) of Drosophila melanogaster that is essential for sperm storage in females. shps mutant males, although producing morphologically normal and motile sperm that are effectively transferred to females, produce very few offspring. Direct counts of sperm indicated that the primary defect was correlated to failure of shps sperm to migrate into the female sperm storage organs. Increased sperm motion parameters were seen in the control after transfer to females, whereas sperm from shps males have characteristics of the motion parameters different from the control. The few sperm that occasionally entered the female sperm storage organs showed no obvious defects in fertilization and early embryo development. The female postmating responses after copulation with shps males appeared normal, at least with respect to conformational changes of uterus, mating plug formation, and female remating rates. The shps gene encodes a protein with homology to amine oxidases, including as observed in mammals, with a transmembrane region at the C-terminal end. The shps mutation was characterized by a nonsense replacement in the third exon of CG13611, and shps was rescued by transformants of the wild-type copy of CG13611. Thus, shps may define a new class of gene responsible for sperm storage.

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 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 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.

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.

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 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.

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.

Bone scintigraphy (bone scan) is useful in detecting metastatic bone lesions through visual assessment of hot spots. A semi-quantitative analysis method that evaluates bone scan images has been eagerly anticipated. BONENAVI is software that enables automatic assessment of bone scan index (BSI). BSI is useful for stratifying cancer patients and monitoring their therapeutic response. The purpose of this study was to evaluate the BONENAVI reading in determining BSI and hot spots at different time intervals after radioisotope injection. We evaluated 32 patients, including 22 males and 10 females. Ten patients had breast cancer, 20 patients had prostate cancer, and 2 had malignant pheochromocytoma. Patients were injected with 740 MBq of 99mTc-methylene diphosphonate and bone scintigraphy was performed at 2, 4, and 6 h after injection on each patient. The BSI and the number of hot spots were obtained from BONENAVI software. Bone scan images were also visually assessed to exclude false positives due to artifacts. Analyses were performed in all lesions, selected true lesions, segment based and cancer type based. Non-parametric statistical analyses for pairwise multiple group comparison were performed using Friedman test followed with post hoc analysis. The BSIs and the number of hot spots were significantly increased with time, with significant differences between each of time points (P

Purpose To investigate the efficacy of periodic injection of aflibercept in each subtype of age-related macular degeneration (AMD) and to explore the predictive factors for visual outcome in clinical settings. Design Prospective nonrandomized interventional case series. Methods Patients with AMD were recruited and were administered aflibercept injections once a month for 3 months followed by once every 2 months for 8 months. The logarithm of the minimal angle of resolution (logMAR) at 12 months and improvement of vision from baseline were compared among polypoidal choroidal vasculopathy (PCV), retinal angiomatous proliferation (RAP), and typical AMD. Regression rate of polypoidal lesions was assessed. We also performed regression analysis with logMAR at 12 months as the dependent variable. Results The study sample consisted of 98 patients: 46 had typical AMD, 42 had PCV, and 10 had RAP. Mean logMAR improved from 0.36 to 0.21 in 12 months. While there was no difference in visual improvement between typical AMD and PCV, final logMAR was better in PCV (0.32 ± 0.09 vs 0.08 ± 0.04, P = .016). Thirty-nine PCV patients underwent follow-up angiography, and regression of polyps was observed in 27 cases (69.2%). Multiple regression analysis showed that the presence of external limiting membrane (ELM), smaller greatest linear dimension, and the presence of polypoidal lesion were associated with better visual outcome (R2 = 0.53, P = 2.73 × 10−14). Conclusions Periodic injection of aflibercept is effective for PCV as well as for typical AMD. The statuses of ELM, greatest linear dimension, and polypoidal lesion are predictive for visual outcome.

To evaluate visual and anatomic outcomes in response to the conversion of treatment in patients with neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) refractory to previous treatment. We also investigated the effect of genetic factors. We recruited patients with AMD or PCV refractory to ranibizumab and initiated aflibercept treatment. Changes in the logarithm of minimum angle of resolution (logMAR) and central retinal thickness (CRT) measured using optical coherence tomography (OCT) 6 months after the conversion were compared between the AMD and PCV groups. We also genotyped each patient for the ARMS2 A69S, CFH Y402H, and I62V alleles, and investigated the association between genotype and treatment response. Mean age of the participants was 75.6 ± 8.0 years. There were 15 patients with AMD and 26 patients with PCV. While PCV patients gained about 1 line of vision (0.40 ± 0.37 to 0.31 ± 0.40, P = 0.003), AMD patients did not show significant improvement (0.41 ± 0.37 to 0.42 ± 0.39, P = 0.699) despite the decrease in CRT (202.1 ± 113.7 to 131.2 ± 55.7 μm, P = 0.003). The prevalence of dry retina after treatment was higher among PCV patients (80.8 vs 46.7 %, P = 0.024). There was no significant difference between patients with risk and non-risk alleles for ARMS2 A69S, CFH Y402H, and I62V. In AMD or PCV patients refractory to ranibizumab, switching to aflibercept is generally effective regardless of patient genotype. PCV patients may benefit more significantly than AMD patients.

To investigate the 2-year outcomes of photodynamic therapy (PDT) combined with intravitreal injections of ranibizumab for polypoidal choroidal vasculopathy (PCV). Ninety-five eyes with subfoveal PCV treated with combined therapy were followed for ≥24 months. The association between visual outcomes and single nucleotide polymorphisms in ARMS2 A69S and CFH I62V genes were examined without adjusting for multiple comparisons. Visual acuity (VA) improvement was observed at month 3 (P = 0.009). The improvement persisted until month 12 (P = 0.003), when VA began the decline back to baseline values at month 24. To investigate the factors associated with VA reduction during the second year, patients were divided into those with and those without a second-year VA reduction. Both patients with and without a second-year VA reduction showed similar VA changes over the first year. The first-year VA improvement was not predictive of the VA decline over the second year. Genetic analyses showed no significant difference in the frequency of the A risk allele of CFH I62V between patients with and without a second-year VA reduction. However, patients with the T risk allele of A69S had a higher rate of recurrence and were more likely to experience a reduction in VA during the second year when compared to patients without (P = 0.020 and P = 0.048, respectively). PDT combined therapy resulted in significant visual recovery in the first year, which was not sustained during the second year. VA reduction in the second year was affected by genetic factors.

To investigate the choroidal thickness/volume of eyes with reticular pseudodrusen using high-penetration swept-source optical coherence tomography (SS-OCT) and to evaluate the choroidal vasculature changes using en face images.Prospective cross-sectional study.Thirty-eight eyes with reticular pseudodrusen and 14 normal eyes were studied with prototype SS-OCT. Eyes with reticular pseudodrusen were classified into 3 subgroups: eyes without late age-related macular degeneration (AMD) (Group1), eyes with neovascular AMD (Group2), and eyes with geographic atrophy (Group3). Mean regional choroidal thickness/volume measurements were obtained by 3-dimensional (3D) raster scanning. The choroidal vascular area was measured using en face images reconstructed from a 3D SS-OCT data set.Mean age and axial length did not differ between eyes with reticular pseudodrusen and normal eyes. The mean choroidal thickness and volume of each sector was significantly reduced in eyes with reticular pseudodrusen compared with normal eyes (P.020 for all). Mean choroidal thickness and volume of each area showed no significant difference between the 3 groups; however, most of them showed decreased thickness compared with normal eyes. En face images through the choroid revealed narrow and sparse choroidal vessels in eyes with reticular pseudodrusen. The area of choroidal vasculature was significantly reduced in eyes with reticular pseudodrusen compared with normal eyes (P = .037).In eyes with reticular pseudodrusen, macular choroidal thickness/volume was reduced regardless of choroidal neovascularization/geographic atrophy. Thinned vessels in the choroid suggest choroidal involvement in the pathogenesis of reticular pseudodrusen.

[Objective] To evaluate macular function using multimodality in eyes with age-related macular degeneration (AMD) at various stages. [Methods] Macular function in 20 control eyes (20 subjects), 17 eyes (17 patients) with large drusen, 18 eyes (18 patients) with drusenoid pigment epithelial detachment (PED), and 19 eyes (19 patients) with neovascular AMD was examined using a Landolt chart for visual acuity; retinal sensitivity was measured by microperimetry; and focal macular electroretinography (fmERG) was performed. In all of these eyes, retinal morphology was examined using optical coherence tomography. [Results] Eyes with neovascular AMD showed morphologic changes in the neurosensory retina as well as marked deterioration of macular function in all parameters measured with a Landolt chart, fmERG, and microperimetry. Eyes with large drusen showed only minimal morphologic changes in the neurosensory retina. In this large drusen group, although retinal sensitivity at the central point was significantly decreased (P = 0.0063), the other parameters of macular function were well preserved. In eyes with drusenoid PED, the structure of the neurosensory retina was well preserved, while the foveal thickness was significantly increased (P = 0.013). The macular function of these eyes was significantly deteriorated, with the VA, amplitude of the a-wave and b-wave, and retinal sensitivity being markedly decreased. In addition, the area of PED correlated with the latency of the a-wave and b-wave and with the retinal sensitivity within the central 4° or 8° region. [Conclusion] Multimodal evaluation demonstrated a significant decrease in macular function in drusenoid PED and in neovascular AMD.

Purpose To investigate the difference in intraocular vascular endothelial growth factor (VEGF) concentration between pachychoroid neovasculopathy and neovascular age-related macular degeneration (nAMD) and its associations with responses to three monthly anti-VEGF injections as an initial treatment for the two conditions. Methods This study included nine eyes with treatment-naive pachychoroid neovasculopathy and 21 eyes with treatment-naive nAMD. Before the initial intravitreal anti-VEGF injection, aqueous humor samples were collected and the concentration of VEGF was measured using enzyme-linked immunosorbent assay. The concentration was compared between the two conditions, and its associations with responses to anti-VEGF therapy were investigated. Results The mean VEGF concentration in pachychoroid neovasculopathy was significantly lower than that in nAMD (63.4 ± 17.8 pg/ml and 89.8 ± 45.0 pg/ml, respectively; P = 0.035). The VEGF concentration was associated with the presence or absence of drusen (β = 0.503, P = 0.004). After anti-VEGF therapy, 6 (66.7%) of 9 eyes with pachychoroid neovasculopathy and 17 (81.0%) of 21 eyes with nAMD achieved dry macula (P = 0.640). Dry macula at 3 months and 12 months was significantly associated with a low VEGF concentration in pachychoroid neovasculopathy (P = 0.013 and P = 0.042, respectively), but not in nAMD (P = 0.108 and P = 0.219). Conclusions The mean VEGF concentration in pachychoroid neovasculopathy was lower than that in nAMD, suggesting that the way in which VEGF is involved in angiogenesis may differ between pachychoroid neovasculopathy and nAMD.

Granular cell tumors (GCTs) are uncommon soft tissue tumors that mostly occur in patients between 40 and 60 years of age and can occur at various body sites. Malignant granular cell tumors (MGCTs) comprise less than 2 % of GCTs and are mostly found on the lower extremities, especially the thighs. These tumors grow more rapidly than benign GCTs, and most importantly, they can metastasize. We describe an MGCT that presented as a right breast mass in a 79-year-old Japanese woman. Local excision was performed for the primary tumor, which was diagnosed as an atypical GCT, but 15 months later, the tumor recurred at the same site. Thereafter, right mastectomy with axillary lymph node dissection was performed. Metastatic disease was identified in 2 of 12 lymph nodes. The pathological examination revealed that the tumor had progressed to an MGCT after recurrence. Multiple liver, lung and bone metastases were revealed 4 months after the second surgery, and the patient died 34 months after the primary surgery. Our findings highlighted the difficulty in diagnosing MGCTs using histological features alone and suggested the usefulness of Ki67 values. A tumor with a high level of Ki67 should be treated as malignant, even if the tumor has few pathological features of malignancy.

Reduced left ventricular torsion (LV-tor) has been reported to be associated with acute rejection in heart transplant (HTx) recipients. We investigated the utility of LV-tor analysis derived from 2-dimensional speckle-tracking echocardiography (2D-STE) for detecting allograft rejection.A total of 301 endomyocardial biopsies (EMBs), right heart catheterizations and echocardiograms were performed in 32 HTx recipients. Echocardiography was done within 3 hours from EMB or simultaneously with the procedures. The LV-tor was defined as the difference between apical and basal end-systolic rotations. The LV-tor values with and without cellular rejection were compared. In addition, we investigated whether the change in LV-tor values predicts the change in rejection grade in each patient. The baseline LV-tor value in each patient was defined as a mean value of the first 3 LV-tor measurements obtained when the patient was free from rejection.According to the conventional International Society for Heart and Lung Transplantation criteria, 274 biopsies showed a rejection Grade of 0, 1a or 1b (Group AR(-)), whereas 27 biopsies were Grade 2 or higher (Group AR(+)). LV-tor decreased more in Group AR(+) than in Group AR(-) (9.3 ± 0.7 vs 12.2 ± 0.2 degrees, p0.0001). In the LV-tor measurement for each patient, the 25% reduction in LV-tor value from baseline predicted Grade 2 or higher rejection with a predictive accuracy of 92.9%.LV-tor derived from 2D-STE could be of clinical value for non-invasive monitoring of acute rejection in HTx recipients.

Although various management methods have been developed for heart failure, it is necessary to investigate the diagnostic or therapeutic targets of heart failure. Accordingly, we have developed different approaches for managing heart failure by using conventional microarray analyses. We analyzed gene expression profiles of myocardial samples from 12 patients with heart failure and constructed datasets of heart failure-associated genes using clinical parameters such as pulmonary artery pressure (PAP) and ejection fraction (EF). From these 12 genes, we selected four genes with high expression levels in the heart, and examined their novelty by performing a literature-based search. In addition, we included four G-protein-coupled receptor (GPCR)-encoding genes, three enzyme-encoding genes, and one ion-channel protein-encoding gene to identify a drug target for heart failure using in silico microarray database. After the in vitro functional screening using adenovirus transfections of 12 genes into rat cardiomyocytes, we generated gene-targeting mice of five candidate genes, namely, MYLK3, GPR37L1, GPR35, MMP23, and NBC1. The results revealed that systolic blood pressure differed significantly between GPR35-KO and GPR35-WT mice as well as between GPR37L1-Tg and GPR37L1-KO mice. Further, the heart weight/body weight ratio between MYLK3-Tg and MYLK3-WT mice and between GPR37L1-Tg and GPR37L1-KO mice differed significantly. Hence, microarray analysis combined with clinical parameters can be an effective method to identify novel therapeutic targets for the prevention or management of heart failure.

SummaryBackground and purposeThe majority of heart transplant (HTx) candidates require left ventricular assist device (LVAD) support for more than 2 years before transplantation in Japan. However, the only currently available device is the extracorporeal pulsatile LVAD. The long-term management of extracorporeal LVAD support has improved remarkably over the years. To determine which post-operative management factors are related to the long-term survival of patients on such LVAD, we retrospectively compared the incidence of complications and their management strategies between the initial and recent eras of LVAD use, classified by the year of LVAD surgery.MethodsSixty-nine consecutive patients supported by extracorporeal pulsatile LVAD as a bridge to HTx between 1994 and 2007 were reviewed retrospectively. The patients were assigned according to the time of LVAD surgery to either group A (n=30; between 1994 and 2000) or group B (n=39; between 2001 and 2007).ResultsPatients in group B survived significantly longer on LVAD support than those in group A (674.6 vs. 369.3 days; p

The normal cranial nerves (CNs) of the cavernous sinus can be clearly demonstrated using contrast-enhanced constructive interference in steady-state (CISS) magnetic resonance imaging (MRI). This study used the method to evaluate pathological CNs III, IV, V1, V2, and VI in cavernous sinuses affected by inflammatory and neoplastic diseases. MR images from 17 patients with diseases involving the cavernous sinuses and/or causing neuropathy in CNs III–VI were retrospectively evaluated. The patients were divided into inflammatory (n = 11) and neoplastic (n = 6) groups. We defined CNs as abnormal when they exhibited enlargement or enhancement. CNs were evaluated using both contrast-enhanced CISS and T1-weighted MRI. In the inflammatory group, abnormal CNs were identified by contrast-enhanced CISS MRI in 13 of 25 symptomatic CNs (52%) in eight patients, but in only two CNs (8%) in two patients by contrast-enhanced T1-weighted MRI. In the neoplastic group, both sequences of contrast-enhanced CISS and T1-weighted MRI detected abnormalities in the same three of eight symptomatic CNs (37.5%), i.e., the three CNs were all in the same patient with adenoid cystic carcinoma. Contrast-enhanced CISS MRI is useful for detecting CN abnormalities in inflammatory pathological conditions of the cavernous sinuses.

Purpose To determine the utility of diffusion-weighted MR imaging (DWI) for the diagnosis of adrenal tumors. Materials and Methods Forty-two patients (24 men and 18 women; age, 61.5 ± 12.7 years old; range, 34–86 years) with 43 adrenal tumors (11 functioning cortical adenomas, 20 nonfunctioning cortical adenomas, 7 metastatic tumors, and 5 pheochromocytomas) were retrospectively investigated. DWIs were obtained by single-shot spin-echo type echo-planar imaging sequence (1.5 Tesla [T]; TR = 8000 ms, TE = 72, b-factor = 0 and 1000 s/mm2), and apparent diffusion coefficient (ADC) value was calculated. Chemical shift images were obtained by gradient echo sequence (TR = 161, TE = 2.38 [out-of-phase, OP] and 4.76 [in-phase, IP], FA = 60), and the signal intensity index (SII; [IP-OP]/IP *100%) was calculated. Results There was no difference in ADC values between adenomas (1.09 ± 0.29*10−3 mm2/s; range, 0.52–1.64) and metastatic tumors (0.85 ± 0.26*10−3; 0.51–1.23; p = 0.14). Pheochromocytomas showed the higher mean ADC value (1.59 ± 0.34*10−3; 1.04–1.96) compared with those of adenomas or metastatic tumors (P < 0.05 and P < 0.005, respectively). The mean SII of adenomas (62.1 ± 17.9%; 14.5–88.4) was significantly higher than those of pheochromocytomas (4.0 ± 10.0%; −19.6–3.3; P < 0.005) or metastatic tumors (−1.5 ± 11.7%; −18.3–8.2; P < 0.01). There was no correlation between ADC values and SII. Conclusion Although pheochromocytomas showed higher ADC values, we did not find that ADC value had diagnostic utility for differentiating adenomas and metastatic tumors. J. Magn. Reson. Imaging 2009;29:112–117. © 2008 Wiley-Liss, Inc.

BACKGROUND AND PURPOSE: Fluid-attenuated inversion recovery (FLAIR) MR imaging has advantages to detect meningeal lesions. FLAIR MR imaging was used to detect pachymeningeal thickening and thin bilateral subdural effusion/hematomas in patients with spontaneous intracranial hypotension (SIH). MATERIALS AND METHODS: Eight patients were treated under clinical diagnoses of SIH. Chronologic MR imaging studies, including the FLAIR sequence, were retrospectively reviewed. RESULTS: Initial MR imaging showed diffuse pachymeningeal thickening as isointense in 6 cases, hypoisointense in 1 case, and isohyperintense in 1 case on the T1-weighted MR images, and hyperintense in all cases on both T2-weighted and FLAIR MR images. Dural (pachymeningeal) hyperintensity on FLAIR MR imaging had the highest contrast to CSF, and was observed as linear in all patients, usually located in the supratentorial convexity and also parallel to the falx, the dura of the posterior fossa convexity, and the tentorium, and improved after treatment. These characteristics of diffuse pachymeningeal hyperintensity on FLAIR MR imaging were similar to diffuse pachymeningeal enhancement (DPME) on T1-weighted imaging with gadolinium. Initial FLAIR imaging clearly showed subdural effusion/hematomas in 6 of 8 patients. The thickness of subdural effusion/hematomas sometimes increased transiently after successful treatment and resolution of clinical symptoms. CONCLUSION: Diffuse pachymeningeal hyperintensity on FLAIR MR imaging is a similar sign to DPME for the diagnosis of SIH but does not require injection of contrast medium. FLAIR is useful sequence for the detection of subdural effusion/hematomas in patients with SIH.

The fluoroscopic computed tomography (CT)-guidance technique increases the accuracy and safety of needle placement for percutaneous lumbar sympathectomy. The aim of the present study was to provide anatomic data from CT images and to discuss the safest route for needle insertion.We retrospectively analyzed CT images that were obtained from 25 patients (14 men, 11 women; 37-89 years of age [mean, 68.4 years]) during fluoroscopic CT-guided percutaneous lumbar sympathectomy. The anatomy around the inserted needle was measured and the correlations between patient characteristics and the procedure-related distances were assessed.The distance from the midline (spinous process) to the entry point and the depth to the target site correlated with body size, especially height and weight. The maximal distance from midline to the insertion point in the range of safe needle insertion at L2 was less than 7.0 cm in approximately 20% of the patients.The present study was performed to determine the anatomic details required to guide safe percutaneous lumbar sympathectomy based on CT images. The use of CT guidance is recommended for lumbar sympathectomy, especially at the L2 spinal level.

Importance Paravascular retinal abnormalities are common in highly myopic eyes. However, affected areas may be underestimated, and the pathogenesis and effects on retinal function remain unclear. Objective To prospectively investigate the characteristics and pathogenesis of paravascular inner retinal defects (PIRDs). Design, Setting, and Participants Prospective and observational case series (between April 2013 and April 2014) at a referral retinal practice among 28 patients (41 eyes) with PIRDs. The entire affected retinal area was examined in 4 quadrants in sequential thin sections using optical coherence tomography. The effect of PIRDs on retinal function was examined using Goldmann perimetry. Main Outcomes and Measures Morphological changes on optical coherence tomography sections and visual field test by Goldmann perimetry. Results On fundus photography, PIRDs appeared as spindle-shaped or caterpillar-shaped dark areas along the major retinal vessels disconnected from the optic disc. On optical coherence tomography cross-sections of retinal vessels, PIRDs often appeared as cystoid or fissure-like spaces; however, longitudinal optical coherence tomography sections along retinal vessels revealed that most PIRDs were actually wide defects in the inner retina or located beneath the major retinal vessels, often deviating into the vitreous cavity. Of 41 eyes with PIRDs, 37 (90%) were myopic; 21 eyes (51%) had high myopia. The mean refractive error of the eyes with PIRDs was −7.94 (95% CI, −9.48 to −6.40) diopters. The mean axial length of the eyes with PIRDs was 26.96 (95% CI, 25.42-28.49) mm. Twenty-one eyes (51%) showed epiretinal membrane in the macular area. In these eyes, PIRDs had formed along the temporal arcade vessels, which increasingly deviated toward the fovea by epiretinal membrane traction. Of 41 eyes with PIRDs, 35 showed visual field defects corresponding to the PIRD locations. The most common visual field defects were relative Bjerrum scotoma (in 75% [60 of 80]; 95% CI, 66%-85%) and nasal steps (in 59% [47 of 80]; 95% CI, 48%-70%) corresponding to the PIRD predilection locations. Conclusions and Relevance Paravascular inner retinal defects primarily occur in eyes with high myopia or epiretinal membrane. Deviated retinal vessels due to axial elongation or epiretinal membrane traction may be involved in the pathogenesis. Paravascular inner retinal defects often cause retinal dysfunction corresponding to the location. A PIRD may partially overlap with retinal lesions previously reported as cleavage of the retinal nerve fiber layer, inner retinal cleavage, paravascular retinal cysts, or lamellar holes. However, the term PIRD more precisely describes the characteristic features of the lesion.

To investigate the clinical background of needle biopsy of suspected bone metastasis under guidance with CT fluoroscopy.During a 3-year period (from April 2000 to March 2003), 103 needle biopsies on 101 lesions of 90 patients were performed for pathological evaluation of suspected bone metastasis. The clinical course of these patients prior to biopsy and its relation to the biopsy results were retrospectively reviewed.Sixty-two patients (69% of total cases) were referred for biopsy from orthopedic surgeons, and 51 of these patients consulted orthopedic surgeons on the initial presentation. Malignancy was pathologically proved in 47 (76%) of the 62 orthopedic patients, and in 19 (68%) of the 28 patients referred from other clinicians. Thirteen (21%) of the orthopedic patients had a history of malignancy, while 22 (78%) of the non-orthopedic patients were cancer patients. Metastasis was pathologically proved in 23 (66%) of the 35 patients with a history of malignancy, while malignancy was pathologically proved in 43 (78%) of the 55 patients without known malignancy. Diagnostic accuracy of the needle bone biopsy was 96%, and its complication rate was 0.7%.In the era of CT fluoroscopy, needle biopsy for suspected bone metastasis was most frequently requested for the patients who consulted orthopedic surgeons for the occurrence of local bone pain as the initial symptom of unknown malignancy. Frequency of malignancy proved by the biopsy in those patients was as high as that in the cancer patients referred from other clinicians.

Diffuse pachymeningeal enhancement on magnetic resonance (MR) imaging is important in identifying spontaneous and secondary intracranial hypotension (IH) [cerebrospinal fluid (CSF) hypovolemia] in patients with postural headache, because CSF pressure at lumbar puncture is variable. We examined the pachymeningeal enhancement pattern in patients with IH. MR imaging findings of pachymeningeal enhancement were examined before and after treatment in seven consecutive patients with spontaneous IH and one patient with IH after lumbar puncture. Diffuse non-nodular dural enhancement was observed in all patients. Characteristic thick, uninterrupted, enhancement was observed, mainly in the dura of the frontal, temporal, and retroclival regions, and the tentorium. Thin and uninterrupted, or partially interrupted, enhancement was observed, mainly in the parieto-occipital region and cerebellar convexity. Curved linear enhancement was observed along the calvarium of all patients. A wave-like appearance, a clear pattern of dural unevenness parallel to the brain, was detected in the frontal and temporal regions, near the base, in all patients. A wave-like appearance, especially in the frontal and temporal base, may be a characteristic MR imaging indicator of IH.

Gliomatosis cerebri is a rare condition in which an infiltrative glial neoplasm spreads through the brain with preservation of the underlying structure. CT and MRI show diffuse abnormal density or signal, without mass effect, and because these findings are nonspecific, it is difficult to make a definitive diagnosis. Our purpose was to assess the usefulness of a new tumour-detecting amino acid tracer for positron-emission tomography (PET), L-[3-(18)F] alpha-methyl tyrosine (FMT), in patients with gliomatosis cerebri. We performed FMT PET, fluorodeoxyglucose FDG PET and MRI eight patients with gliomatosis cerebri and six with non-neoplastic disease, whose MRI also showed diffuse high signal on T2-weighted images. Standardised uptake (SUV) of FMT and FDG in the area of gliomatosis was obtained and the tumour-to-normal cortex (T/N) ratio of this was compared. The tumours were shown on FMT PET as areas of increased uptake, except in one patient with severe intracranial hypertension. There were significant differences between the SUV of FMT and the T/N ratio of FMT in patients and in controls (both P0.01), and between the T/N ratio of FMT and FDG in patients ( P0.01). Increased uptake of FMT PET strongly suggests neoplasia. FMT PET is valuable for differentiating gliomatosis cerebri from non-neoplastic diseases showing similar diffuse high signal on T2-weighted images and little contrast enhancement.

To study longitudinal changes in the posterior pole in eyes with dome-shaped macular configuration within the staphyloma.Prospective, longitudinal study.We prospectively examined the macular area in 35 eyes (26 patients) with dome-shaped macular configuration and high myopia (mean spherical equivalent, -14.83 ± 4.50 diopters) using swept-source optical coherence tomography. Scleral and choroidal thicknesses were measured at the fovea and at 4 parafoveal locations 2000 μm from the foveal center. Height of the macular bulge was measured as well.During the mean follow-up of 24.8 ± 2.5 months, the scleral thickness significantly decreased at the fovea from 496.1 ± 95.7 μm to 484.7 ± 96.2 μm (P.001) and at all 4 parafoveal locations (P.001, respectively). The scleral thinning was asymmetric, with an estimated decrease per year of 5.6 μm at the foveal center, 11.1 μm superiorly, 12.1 μm inferiorly, 10.4 μm temporally, and 5.8 μm nasally. The ocular concavities deepened over time, and mean macular bulge height increased from 136.5 ± 60.9 μm to 157.6 ± 67.0 μm (P.001). The choroid within the staphyloma showed generalized thinning during follow-up. Mean choroidal thickness decreased significantly at the fovea from 28.3 ± 17.2 μm at baseline to 22.9 ± 17.2 μm (P.001).Progressive asymmetric scleral thinning occurred in the macular region of eyes with dome-shaped macular configuration. The scleral thinning was more pronounced in the parafoveal area than at the foveal center, resulting in an increase of the macular bulge height.

In this report we describe 2 patients with exercise-induced, second-degree atrioventricular (AV) block. Case 1 was a 49-year-old man with normal AV conduction at rest but who developed dyspnea on exertion. Treadmill testing showed an exercise-induced 2:1 AV block. Electrophysiologic study (EPS) demonstrated rate-dependent, presumably intrahissian, AV block. Case 2 was a 31-year-old woman with first-degree AV block and complete right bundle branch block with dyspnea on exertion and occasional syncope. She had twice undergone surgical patch closure of an ostium primum atrial septal defect. Exercise testing induced type II second-degree AV block. Atrial pacing during EPS did not disclose rate-dependent type II AV block, but disopyramide induced second-degree AV block.

Purpose To study the prevalence and 3-dimensional (3-D) tomographic features of focal choroidal excavations in eyes with central serous chorioretinopathy (CSC) using swept-source optical coherence tomography (OCT). Design Prospective, cross-sectional study. Methods We examined 116 consecutive eyes with CSC with a prototype 3-D swept-source OCT. 3-D images of the shape of the macular area, covering 6 × 6 mm 2 , were reconstructed by segmentation of the outer surface of the retinal pigment epithelium (RPE). Results The 3-D swept-source OCT detected focal choroidal excavations in 9 eyes (7.8%). The 3-D scanning protocol, coupled with en face scans, allowed for clear visualization of the excavation morphology. In 5 eyes with focal excavations, unusual choroidal tissue was found beneath the excavation, bridging the bottom of the excavation and the outer choroidal boundary. Additionally, 3 of those 5 eyes showed a suprachoroidal space below the excavation, as if the outer choroidal boundary is pulled inward by this bridging tissue. The focal choroidal excavations were located within fluorescein leakage points and areas of choroidal hyperpermeability. Eyes with focal choroidal excavations were more myopic (−4.42 ± 2.92 diopters) than eyes without excavations (−0.27 ± 1.80 diopters, P = .001). Subfoveal choroidal thickness was significantly thinner (301.3 ± 60.1 μm) in eyes with focal excavations than in eyes without the excavations (376.6 ± 104.8 μm, P = .036). Conclusions Focal choroidal excavations were present in 7.8% of eyes with CSC. In these eyes, focal choroidal excavations may have formed from RPE retraction caused by focal scarring of choroidal connective tissue.