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There are few reports on the association between apolipoprotein C-III (ApoC-III) and coronary calcification using intravascular modalities. This study aimed to investigate the impacts of ApoC-III levels on coronary calcification using grayscale intravascular ultrasound (IVUS). Consecutive 263 culprit lesions for 202 patients who underwent percutaneous coronary intervention using grayscale IVUS were included in this study and divided into four groups based on quartile ApoC-III values. This study assessed plaque characteristics, including severe calcification (>180° arc) at the minimum lumen area site and presence of calcified nodules within the culprit lesion using grayscale IVUS, and evaluated whether ApoC-III levels were associated with coronary calcified plaques. The highest ApoC-III quartile [Quartile 4 (Q4)] had a higher proportion of complex lesions, calcified plaques, severe calcification, calcified nodules, plaque burden, and total atheroma volume than the lowest ApoC-III quartile [Quartile 1 (Q1)]. Additionally, multivariable logistic regression analysis showed that Q4 was significantly associated with severe calcification and calcified nodules, with Q1 as the reference (odds ratio [OR]: 2.70, 95% confidence intervals [CIs]: 1.04–7.00, p = 0.042; and OR: 3.72, 95% CIs 1.26–11.0, p = 0.017, respectively). Furthermore, ApoC-III level (1-mg/dl increase) was a strong significant predictor of severe calcification (OR: 1.07, 95% CIs: 1.00–1.15, p = 0.040) and calcified nodules (OR: 1.09, 95% CIs: 1.01–1.19, p = 0.034) according to the multivariable logistic regression analysis. This study is the first to verify that elevated ApoC-III levels are associated with the development of severe calcification and progression to calcified nodules as detected by grayscale IVUS.

Abstract Background Since the complication of diabetes mellitus (DM) is a risk for adverse cardiovascular outcomes in patients with coronary artery disease (CAD), appropriate risk estimation is needed in diabetic patients following percutaneous coronary intervention (PCI). However, there is no useful biomarker to predict outcomes in this population. Although stromal cell derived factor-1α (SDF-1α), a circulating chemokine, was shown to have cardioprotective roles, the prognostic impact of SDF-1α in diabetic patients with CAD is yet to be fully elucidated. Moreover, roles of SDF-1α isoforms in outcome prediction remain unclear. Therefore, this study aimed to assess the prognostic implication of three forms of SDF-1α including total, active, and inactive forms of SDF-1α in patients with DM and after PCI. Methods This single-center retrospective analysis involved consecutive patients with diabetes who underwent PCI for the first time between 2008 and 2018 (n = 849). Primary and secondary outcome measures were all-cause death and the composite of cardiovascular death, non-fatal myocardial infarction, and ischemic stroke (3P-MACE), respectively. For determining plasma levels of SDF-1α, we measured not only total, but also the active type of SDF-1α by ELISA. Inactive isoform of the SDF-1α was calculated by subtracting the active isoform from total SDF-1α. Results Unadjusted Kaplan–Meier analyses revealed increased risk of both all-cause death and 3P-MACE in patients with elevated levels of inactive SDF-1α. However, plasma levels of total and active SDF-1α were not associated with cumulative incidences of outcome measures. Multivariate Cox hazard analyses repeatedly indicated the 1 higher log-transformed inactive SDF-1α was significantly associated with increased risk of all-cause death (hazard ratio (HR): 2.64, 95% confidence interval (CI): 1.28–5.34, p = 0.008) and 3P-MACE (HR: 2.51, 95% CI: 1.12–5.46, p = 0.02). Moreover, the predictive performance of inactive SDF-1α was higher than that of total SDF-1α (C-statistics of inactive and total SDF-1α for all-cause death: 0.631 vs 0.554, for 3P-MACE: 0.623 vs 0.524, respectively). Conclusion The study results indicate that elevated levels of plasma inactive SDF-1α might be a useful indicator of poor long-term outcomes in diabetic patients following PCI. Trial registration: This study describes a retrospective analysis of a prospective registry database of patients who underwent PCI at Juntendo University Hospital, Tokyo, Japan (Juntendo Physicians’ Alliance for Clinical Trials, J-PACT), which is publicly registered (University Medical Information Network Japan—Clinical Trials Registry, UMIN-CTR 000035587).

Introduction: The long-term impact of renin-angiotensin system (RAS) inhibitors for secondary prevention in patients with chronic kidney disease (CKD) and coexisting coronary artery disease remains unclear. Methods: Altogether, 1,160 consecutive patients with CKD (mean age, 70 ± 9 years; 78% men) who underwent their first percutaneous coronary intervention (PCI) between 2000 and 2018 were included and analyzed. Based on their RAS inhibitor use, 674 patients (58%) were allocated to the RAS inhibitor group, and 486 patients (42%) were allocated to the non-RAS inhibitor group. This study evaluated the incidence of 3-point major adverse cardiovascular events (3P-MACE), including cardiovascular death, nonfatal acute coronary syndrome and nonfatal stroke, admission for heart failure (HF), target vessel revascularization (TVR), and all-cause death. Results: During a median follow-up duration of 7.8 years, 280 patients (24.1%) developed 3P-MACE, 134 patients (11.6%) were hospitalized for HF, 171 patients (14.7%) underwent TVR, and 348 patients (30.0%) died of any causes. The cumulative incidence rate of 3P-MACE in the RAS inhibitor group was significantly lower than in the non-RAS inhibitor group (31.7% vs. 39.0%, log-rank test, p = 0.034); however, that of admission for HF in the RAS inhibitor group was significantly higher than in the non-RAS inhibitor group (28.1% vs. 13.3%, log-rank test, p < 0.001). The subgroup of preserved ejection fraction, non-acute myocardial infarction, and non-proteinuria tended to promote the onset of HF rather than cardiovascular prevention by RAS inhibitors. Conclusion: The long-term RAS inhibitor use for patients with CKD after PCI might prevent cardiovascular events but increase the risk of HF.

Background: Information regarding the outcomes of transcatheter aortic valve replacement (TAVR) in men is limited. This study aimed to investigate short- to mid-term outcomes and prognostic predictors in this population. Method and Results: The data of 519 men were analyzed from 1,693 consecutive patients with symptomatic severe aortic stenosis who underwent TAVR at six hospitals between April 2010 and July 2020. The primary endpoint was all-cause mortality at 30 days after TAVR. The mean age and Society of Thoracic Surgeons (STS) score were 83.7 ± 5.9 years and 6.3 ± 4.7%, respectively. Overall, 23.5% of patients consumed alcohol with a frequency of > 1 drinks/week, and 12.1% consumed alcohol with a frequency of > 8 drinks/week, while 66.1% were former smokers and 4.2% were current smokers. Mortality at 30 days was 0.8%. During the median follow-up period of 448 days, the estimated survival rates at 1 year post-TAVR was 90.7 ± 1.4%. In multivariate analysis, the serum albumin level [hazard ratio (HR): 2.20, 95% confidence interval (CI):1.36–3.62, p = 0.001], atrial fibrillation (HR: 1.79, 95% CI: 1.13–2.82, p = 0.012), and STS score (HR: 1.33, 95% CI: 1.06–1.67, p = 0.015) were independently associated with all-cause mortality following TAVR. Adjusted hazard ratios of current smoking, heavy drinking, and presence of cancer were 1.05 (95% CI: 0.36–2.98),1.37 (95% CI: 0.75–2.48), and 1.13 (95% CI: 0.75–2.48), respectively. Conclusion: Our study demonstrated that serum albumin levels, atrial fibrillation, and STS score were independently associated with all-cause mortality following TAVR in men.

Abstract Background This study aimed to compare the coronary plaque characterization by cardiovascular magnetic resonance (CMR) and near-infrared spectroscopy (NIRS)-intravascular ultrasound (IVUS) (NIRS-IVUS), and to determine whether pre–percutaneous coronary intervention (PCI) evaluation using CMR identifies high-intensity plaques (HIPs) at risk of peri-procedural myocardial infarction (pMI). Although there is little evidence in comparison with NIRS-IVUS findings, which have recently been shown to identify vulnerable plaques, we inferred that CMR-derived HIPs would be associated with vulnerable plaque features identified on NIRS-IVUS. Methods 52 patients with stable coronary artery disease who underwent CMR with non-contrast T1-weighted imaging and PCI using NIRS-IVUS were studied. HIP was defined as a signal intensity of the coronary plaque-to-myocardial signal intensity ratio (PMR) ≥ 1.4, which was measured from the data of CMR images. We evaluated whether HIPs were associated with the NIRS-derived maximum 4-mm lipid-core burden index (maxLCBI4mm) and plaque morphology on IVUS, and assessed the incidence and predictor of pMI defined by the current Universal Definition using high-sensitive cardiac troponin-T. Results Of 62 lesions, HIPs were observed in 30 lesions (48%). The HIP group had a significantly higher remodeling index, plaque burden, and proportion of echo-lucent plaque and maxLCBI4mm ≥ 400 (known as large lipid-rich plaque [LRP]) than the non-HIP group. The correlation between the maxLCBI4mm and PMR was significantly positive (r = 0.51). In multivariable logistic regression analysis for prediction of HIP, NIRS-derived large LRP (odds ratio [OR] = 5.41; 95% confidence intervals [CIs] 1.65–17.8, p = 0.005) and IVUS-derived echo-lucent plaque (OR = 5.12; 95% CIs 1.11–23.6, p = 0.036) were strong independent predictors. Furthermore, pMI occurred in 14 of 30 lesions (47%) with HIP, compared to only 5 of 32 lesions (16%) without HIP (p = 0.005). In multivariable logistic regression analysis for prediction of incidence of pMI, CMR-derived HIP (OR = 5.68; 95% CIs 1.53–21.1, p = 0.009) was a strong independent predictor, but not NIRS-derived large LRP and IVUS-derived echo-lucent plaque. Conclusions There is an important relationship between CMR-derived HIP and NIRS-derived large LRP. We also confirmed that non-contrast T1-weighted CMR imaging is useful for characterization of vulnerable plaque features as well as for pre-PCI risk stratification. Trial registration The ethics committee of Juntendo Clinical Research and Trial Center approved this study on January 26, 2021 (Reference Number 20-313).

Purpose: To investigate the relationship between retinal traction force and impairment of the inner retinal layer in patients with epiretinal membrane (ERM). Design: Nonrandomized, retrospective consecutive case series. Participants: Two hundred nine eyes of 201 patients with idiopathic ERM who underwent vitrectomy for idiopathic ERM were enrolled. Methods: Retinal folds caused by ERM were visualized using en face OCT, and the maximum depth of retinal folds within the parafovea (MDRF) was measured. Focal macular electroretinogram (ERG) was used to measure the amplitude and implicit time of each component for the ERM eyes and the normal fellow eyes. B-scan OCT images were used to measure the thicknesses of the inner nuclear layer (INL) and outer nuclear layer (ONL) + outer plexiform layer (OPL). Expression of α-smooth muscle actin (α-SMA) in surgically removed ERM specimens was quantified by reverse-transcription polymerase chain reaction. Main Outcome Measures: We analyzed the relationship between MDRF and the relative amplitudes of focal macular ERG (affected eye/fellow eye), the relationships between MDRF and the mean INL thickness and ONL+OPL thickness, comparison of INL thickness and ONL+OPL thickness for each area when cases were classified according to MDRF localization in the ETDRS chart, and the relationship between MDRF and the relative expression of α-SMA in the ERM specimens. Results: The MDRF significantly correlated with the relative amplitudes (affected eye/fellow eye) of b-waves and oscillatory potentials (r = −0.657, P = 0.015; r = −0.569, P = 0.042, respectively) and the mean INL thickness and ONL+OPL thickness (r = 0.604, P

Abstract Dipeptidyl-peptidase-4 inhibitors (DPP4i) have been the most used antidiabetic medications worldwide due to their good safety profiles and tolerability with a low risk of hypoglycemia, however, large cardiovascular outcome trials (CVOTs) have not shown any significant the prognostic superiority. On the contrary, since observational studies have suggested the effects of DPP4i are enhanced some populations, such as Asians and those who without overweight, their prognostic benefit is still under debate. The aim of this study was thus to assess the prognostic impact of DPP4i in patients with both diabetes and coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI) through the insulin-like growth factor-1 (IGF-1) axis, a substrate of DPP4. This single-center analysis involved consecutive Japanese diabetic patients who underwent PCI for the first time between 2008 and 2018 (n = 885). Primary and secondary endpoints were set as cardiovascular (CV) death and the composite of CV death, non-fatal myocardial infarction and ischemic stroke (3P-MACE). Serum levels of IGF-1 and its main binding protein (insulin-like growth factor binding protein-3: IGFBP-3) were measured. In consequences, unadjusted Kaplan–Meier analyses revealed reduced incidences of CV-death and 3P-MACE by DPP4i, which was particularly enhanced in patients who were not overweight (BMI ≤ 25). Multivariate Cox hazard analyses consistently indicated reduced risks of CV death by DPP4i at PCI (hazard ratio (HR) 0.39, 95% confidence interval (CI) 0.16–0.82, p = 0.01) and 3P-MACE (HR 0.47, 95% CI 0.25–0.84, p = 0.01), respectively. Moreover, elevated IGF-1 activity indicated by the IGF-1/IGFBP-3 ratio was associated with decreased risks of both endpoints and it was significantly higher in patients with DPP4i (p

Abstract Aims Little is known about the long‐term outcomes of β‐blockers use in patients with coronary artery disease (CAD) without myocardial infarction (MI) and reduced ejection fraction (rEF). However, more attention should be paid to the oral administration of β‐blockers in elderly patients who are susceptible to heart failure (HF), sinus node dysfunction, or rate response insufficiency. We aimed to evaluate the long‐term impact of β‐blockers in elderly patients with CAD without MI or systolic HF who have undergone percutaneous coronary intervention. Methods and results A total of 1018 consecutive elderly patients with CAD (mean age, 72 ± 7 years; 77% men) who underwent their first intervention between 2010 and 2018 were included in this study. According to the presence or absence of the use of β‐blockers, 514 patients (50.5%) were allocated to the β‐blocker group, and 504 (49.5%) to the non‐β‐blocker group. We evaluated the incidence of 4‐point major adverse cardiovascular events (4P‐MACE), including cardiovascular death, non‐fatal MI, non‐fatal stroke, admission for HF, target vessel revascularization (TVR), and all‐cause death. We focused on the association between chronotropic incompetence of β‐blockers and incidence of a new HF and analysed the results using an exercise electrocardiogram regularly performed in the outpatient department after percutaneous coronary intervention. During a median follow‐up duration of 5.1 years, 83 patients (8.3%) developed 4P‐MACE, including cardiovascular death in 17, non‐fatal MI in 13, non‐fatal stroke in 25, and admission for HF in 39 patients. Additionally, 124 patients (12.2%) had a TVR and 104 (10.2%) died of other causes. Kaplan–Meier analysis showed that the cumulative incidence rate of 4P‐MACE in the β‐blocker group was significantly higher than that in the non‐β‐blocker group (15.4% vs. 10.0%, log‐rank test, P = 0.015). Above all, the cumulative incidence rate of admission for HF in the β‐blocker group was significantly higher (8.8% vs. 3.2%, log‐rank test, P

Background: Sarcopenia, which is evaluated based on appendicular skeletal muscle mass (ASM) using dual-energy X-ray absorptiometry and bioelectrical impedance analysis, is a prognostic predictor for adverse outcomes in patients with coronary artery disease (CAD). However, a simple equation for estimating ASM is yet to be validated in clinical practice. Methods: We enrolled 2211 patients with CAD who underwent percutaneous coronary intervention at our hospital between 2010 and 2017. The mean age was 68 years and 81.5 % were men. Patients were divided into 2 groups based on each ASM index (ASMI): low; male

Background In‐stent restenosis, especially for neoatherosclerosis, is a major concern following percutaneous coronary intervention. This study aimed to elucidate the association of features of in‐stent restenosis lesions revealed by optical coherence tomography (OCT)/optical frequency domain imaging (OFDI) and the extent of lipid‐rich neointima (LRN) assessed by near‐infrared spectroscopy (NIRS) and intravascular ultrasound, especially for neoatherosclerosis. Methods and Results We analyzed patients undergoing percutaneous coronary intervention for in‐stent restenosis lesions using both OCT/OFDI and NIRS–intravascular ultrasound. OCT/OFDI‐derived neoatherosclerosis was defined as lipid neointima. The existence of large LRN (defined as a long segment with 4‐mm maximum lipid core burden index ≥400) was evaluated by NIRS. In 59 patients with 64 lesions, neoatherosclerosis and large LRN were observed in 17 (26.6%) and 21 lesions (32.8%), respectively. Naturally, large LRN showed higher 4‐mm maximum lipid core burden index (median [interquartile range], 623 [518–805] versus 176 [0–524]; P

Abstract This retrospective study was performed to classify diabetic macular edema (DME) based on the localization and area of the fluid and to investigate the relationship of the classification with visual acuity (VA). The fluid was visualized using en face optical coherence tomography (OCT) images constructed using swept-source OCT. A total of 128 eyes with DME were included. The retina was segmented into: Segment 1, mainly comprising the inner nuclear layer and outer plexiform layer, including Henle’s fiber layer; and Segment 2, mainly comprising the outer nuclear layer. DME was classified as: foveal cystoid space at Segment 1 and no fluid at Segment 2 (n = 24), parafoveal cystoid space at Segment 1 and no fluid at Segment 2 (n = 25), parafoveal cystoid space at Segment 1 and diffuse fluid at Segment 2 (n = 16), diffuse fluid at both segments (n = 37), and diffuse fluid at both segments with subretinal fluid (n = 26). Eyes with diffuse fluid at Segment 2 showed significantly poorer VA, higher ellipsoid zone disruption rates, and greater central subfield thickness than did those without fluid at Segment 2 (P

Abstract Background The aim of this study was to determine the difference in effects of beta-blockers on long-term clinical outcomes between ischemic heart disease (IHD) patients with mid-range ejection fraction (mrEF) and those with reduced ejection fraction (rEF). Methods Data were assessed of 3508 consecutive IHD patients who underwent percutaneous coronary intervention (PCI) between 1997 and 2011. Among them, 316 patients with mrEF (EF = 40–49%) and 201 patients with rEF (EF

Background: Malignancy is common in older adults undergoing transcatheter aortic valve implantation (TAVI), and may affect prognosis. The present study aimed to examine whether active cancer affects all-cause mortality rates among patients undergoing TAVI. Methods: This retrospective study examined data from 1,114 consecutive patients treated between April 2010 and June 2019. Patients with life expectancy of

Abstract This retrospective study investigated foveal and perifoveal retinal sensitivities using microperimetry before and after surgery for rhegmatogenous retinal detachment (RRD). Consecutive patients with RRD who underwent vitrectomy or scleral buckling were included. Comprehensive ophthalmological examinations, including microperimetry and swept-source optical coherence tomography, were performed before and 6 months after surgery. Pre- and postoperative retinal sensitivities at the fovea and 4 perifoveal measurement points farthest from the fixation point, both vertically and horizontally (superior, inferior, nasal, and temporal) were examined. A total of 34 foveal and 136 perifoveal measurement points in 34 eyes of 34 patients were evaluated. The postoperative retinal sensitivity was significantly higher than the preoperative value at foveal and perifoveal points with (P

Abstract Background Perfluorocarbon liquid (PFCL) is an effective surgical adjuvant in performing vitrectomy for severe vitreoretinal pathologies such as proliferative vitreoretinopathy and giant retinal tears. However, subretinal retention of PFCL can occur postoperatively and retained PFCL causes severe visual disorders, particularly when PFCL was retained under the fovea. Although several procedures have been proposed for subfoveal PFCL removal, such as direct aspiration or submacular injection of balanced salt solution (BSS) to dislodge the subfoveal PFCL, the retinal damage associated with these procedures has been a major problem. Here, we report a case of subfoveal retention of PFCL for which we performed a novel surgical technique that attempts to minimize retinal damage. Case presentation A 69-year-old man presented with subfoveal retained PFCL after surgery for retinal detachment. To remove the retained PFCL, the internal limiting membrane overlying the subretinal injection site is first peeled to allow low-pressure (8 psi) transretinal BSS infusion, using a 41-gauge cannula, to slowly detach the macula. A small drainage retinotomy is created with the diathermy tip at the inferior position of the macular bleb, sized to be slightly wider than that of the PFCL droplet. The head of the bed is then raised, and the surgeon gently vibrates the patient’s head to release the PFCL droplet to allow it to migrate inferiorly towards the drainage retinotomy. The bed is returned to the horizontal position, and the PFCL, now on the retinal surface, can be aspirated. The subfoveal PFCL is removed while minimizing iatrogenic foveal and macular damage. One month after PFCL removal, the foveal structure showed partial recovery on optical coherence tomography, and BCVA improved to 20/40. Conclusion Creating a macular bleb with low infusion pressure and using vibrational forces and gravity to migrate the PFCL towards a retinotomy can be considered as a relatively atraumatic technique to remove subfoveal retained PFCL.

Abstract Background In the secondary prevention of cardiovascular (CV) disease in patients with diabetes, an optimal level of HbA1c, the most widely-used glycemic control indicator, for favorable clinical consequences still remains to be established. This study assessed the association between preprocedural HbA1c level and CV mortality in Japanese diabetic patients undergoing percutaneous coronary intervention (PCI). Methods This is a retrospective observational study using a single-center prospective PCI database involving consecutive 4542 patients who underwent PCI between 2000 and 2016. Patients with any antidiabetic medication including insulin at PCI were included in the analysis (n = 1328). We divided the patients into 5 and 2 groups according to HbA1c level; HbA1c: and ≤ 7.0%, respectively. The primary outcome was CV mortality including sudden death. The median follow-up duration was 6.2 years. Results In the follow-up period, CV and sudden death occurred in 81 and 23 patients, respectively. While unadjusted Kaplan–Meier analysis showed no difference in cumulative CV mortality rate between patients binarized by preprocedural HbA1c 7.0%, analysis of the 5 groups of HbA1c showed significantly higher cumulative CV death in patients with HbA1c

Background: Asians have a much lower incidence of adverse coronary events than Caucasians. We sought to evaluate the characteristics of coronary lipid-rich plaques (LRP) in Asian patients with acute coronary syndrome (ACS) and stable angina (SA). We also aimed to identify surrogate markers for the extent of LRP. Methods: We evaluated 207 patients (ACS, n = 75; SA, n = 132) who underwent percutaneous coronary intervention under near infrared spectroscopy intravascular ultrasound (NIRS-IVUS). Plaque characteristics and the extent of LRP [defined as a long segment with a 4-mm maximum lipid-core burden index (maxLCBI4mm)] on NIRS in de-novo culprit and non-culprit segments were analyzed. Results: The ACS culprit lesions had a significantly higher maxLCBI4mm (median [interquartile range (IQR)]: 533 [385–745] vs. 361 [174–527], p

BackgroundPeroxisome proliferator-activated receptor α (PPARα) is a nuclear receptor that has key roles of lipid metabolism and inflammation. The PPARα may affects the initiation and progression of atherosclerosis by reducing inflammatory responses. Pemafibrate (K-877) is a novel selective PPARα modulator (SPPARMα), which was designed to possess higher PPARα potency and selectivity than existing PPARα agonists. The aim of this study is to evaluate the effect of pemafibrate on vascular response in coronary atherosclerosis model using low density lipoprotein receptor knock-out (LDLR-KO) pigs with balloon injury.Methods and resultsTen LDLR-KO pigs were randomly allocated to two groups [pemafibrate (n = 5) and control (n = 5)] and fed with a diet containing 2.0% cholesterol and 20% lard throughout the study. Balloon injury was created in 40 coronary segments two weeks after starting the oral administration of pemafibrate or placebo. Necropsy was conducted 8 weeks later. Coronary artery sections were reviewed to evaluate lesion progression and the mRNA expression levels for C-Jun, NFκ B, CCL2, CCR7, CD163 and MMP9 determined using real-time RT-PCR. LDL cholesterol at baseline was about 700 mg/dL. The mean ratio of macrophages to plaque area was significantly lower in pemafibrate group compared with control one (7.63±1.16 vs 14.04±4.51, P = 0.02) whereas no differences were observed in intimal area between groups. The mRNA levels of C-Jun, NFκB and MMP9 were significantly decreased in pemafibrate group.ConclusionsPemafibrate was associated with inhibition of inflammatory responses in coronary artery atherosclerosis model using LDLR-KO swine with balloon injury.

Abstract Background We recently reported that lamellar macular hole (LMH) with lamellar hole-associated epiretinal proliferation (LHEP) can be effectively treated by embedding the LHEP into the retinal cleavage to improve foveal contour and visual acuity. Here, we report a case of LMH with LHEP for which we performed embedding of the LHEP combined with internal limiting membrane (ILM) inversion. We then evaluated the effects of this surgery on macular morphology and visual functions. Case presentation A 62-year-old man presented with visual disturbance (20/29) and metamorphopsia in his right eye. B-scan optical coherence tomography (OCT) imaging revealed the presence of both partial-thickness defect of the macula with degenerative retinal cleavage and LHEP at the surface of the retina. En face OCT imaging showed the absence of retinal fold. We performed phacoemulsification with intraocular lens implantation, vitrectomy, embedding of LHEP into the retinal cleavage, and ILM inversion. Three months after the surgery, both foveal contour and visual acuity (20/20) were improved and metamorphopsia was reduced. Conclusion Embedding of the LHEP combined with ILM inversion may be an effective treatment for LMH with LHEP.

Abstract Background Coats disease is a retinal disease characterized by exudative retinal detachment due to abnormal retinal blood vessels. Coats disease is generally treated using laser photocoagulation and cryotherapy to ablate the abnormal retinal blood vessels. However, if abnormal blood vessels are present near the posterior pole of the eye and there is a severe exudative change there, it is difficult to perform these standard treatments. We describe a case of Coats disease with severe exudative retinal change and retinal vascular abnormality near the posterior pole for which we performed photodynamic therapy and successfully suppressed the disease and improved vision. Case presentation A 15-year-old Japanese boy presented to hospital with a chief complaint of decreased vision in his right eye. At the initial examination, corrected visual acuity of the right eye was 20/100. On the right fundus, exudative retinal detachment with subretinal haemorrhage was observed from the upper intermediate periphery to the posterior pole. Abnormal telangiectatic vessels and microaneurysms were found at the nasal peripheral retina. From these findings, we diagnosed the case as Coats disease. We conducted photodynamic therapy for the right eye. At 10 months after treatment, both the subretinal haemorrhage and the exudative retinal detachment had disappeared completely. Further, the retinal structure of the macula had recovered, and right vision had improved to 20/20. Conclusion Photodynamic therapy may be an effective and safe treatment for Coats disease in cases that present with abnormal retinal vessels close to the posterior pole of the eye.

The co-existence of expansive arterial remodelling in both coronary arteries (CAs) and the abdominal aorta has already been reported, although the clinical indicators and quantitative analysis have not been well studied. We therefore aimed to clarify the clinical and anatomical characteristics of patients with abdominal aortic aneurysms (AAAs). 123 AAA patients who underwent coronary angiography were compared to 123 control patients selected by propensity score matching. CA diameters of all 3 vessels were measured by quantitative coronary angiographic analysis. Coronary artery ectasia (CAE) was defined as local or generalized aneurysmal change of the CAs. Excessive expansive CA remodelling was defined as the maximal diameter of the right or left circumflex artery in the upper 75th percentile (>4.8 mm). Multivariable logistic regression analyses were used to determine predictors of CAE and excessive expansive CA remodelling. The prevalences of CAE and excessive expansive CA remodelling were significantly higher in the AAA group than in the non-AAA group (28% vs. 8% and 31% vs. 19%; both p

PurposeTo investigate the influence of subretinal injection pressure on the microstructure of the retina in a monkey model.MethodsAfter vitrectomy, balanced salt solution was injected subretinally into one eye each of four cynomolgus monkeys while controlling the injection pressure. Initially, a pressure of 2 psi was used, and this was gradually increased to determine the minimum required pressure. Subsequent injections were performed at two pressures: minimum (n = 13) and high (n = 6). To compare the influence of these injection pressures on retinal structure, optical coherence tomography (OCT) was performed before surgery and every week afterwards. The monkeys were euthanized and their eyes were enucleated at 1 or 6 weeks after the injections. The eyes were processed for light microscopy and transmission electron microscopy (TEM) as well as for TdT-mediated dUTP nick end labeling.ResultsThe minimum pressure required to perform subretinal injection was 6 psi. After injection at this pressure, both OCT and microscopy showed that the retinal structure was well-preserved throughout the experimental period at all injection sites. Conversely, after injection at high pressure (20 psi) OCT images at all injection sites showed disruption of the ellipsoid zone (EZ) after 1 week. Microscopy indicated damage to the photoreceptor outer segment (OS) and stratification of the retinal pigment epithelium (RPE). After 6 weeks, OCT demonstrated that the EZ had become continuous and TEM confirmed that the OS and RPE had recovered. Photoreceptor apoptosis was absent after subretinal injection at both pressures.ConclusionsThe retinal damage caused by subretinal injection increases depending on pressure, indicating that clinicians should perform subretinal injection at pressures as low as possible to ensure safety.

To investigate the tilt and decentration of the crystalline lens and the intraocular lens (IOL) relative to the corneal topographic axis using anterior segment ocular coherence tomography (AS-OCT).A sample set of 100 eyes from 49 subjects (41 eyes with crystalline lenses and 59 eyes with IOLs) were imaged using second generation AS-OCT (CASIA2, TOMEY) in June and July 2016 at Okayama University. Both mydriatic and non-mydriatic images were obtained, and the tilt and decentration of the crystalline lens and the IOL were quantified. The effects of pupil dilation on measurements were also assessed.The crystalline lens showed an average tilt of 5.15° towards the inferotemporal direction relative to the corneal topographic axis under non-mydriatic conditions and 5.25° under mydriatic conditions. Additionally, an average decentration of 0.11 mm towards the temporal direction was observed under non-mydriatic conditions and 0.08 mm under mydriatic conditions. The average tilt for the IOL was 4.31° towards the inferotemporal direction relative to the corneal topographic axis under non-mydriatic conditions and 4.65° in the same direction under mydriatic conditions. The average decentration was 0.05 mm towards the temporal direction under non-mydriatic conditions and 0.08 mm in the same direction under mydriatic conditions. A strong correlation was found between the average tilt and decentration values of the crystalline lens and the IOL under both non-mydriatic and mydriatic conditions (all Spearman correlation coefficients, r ≥ 0.800; all P < 0.001).When measured using second generation AS-OCT, both the crystalline lens and the IOL showed an average tilt of 4-6° toward the inferotemporal direction relative to the corneal topographic axis and an average decentration of less than 0.12 mm towards the temporal direction. These results were not influenced by pupil dilation and they showed good repeatability.

To examine the usefulness of room temperature vulcanizing (RTV) silicone rubber as a barrier material for cell exclusion zone assays.We created barriers using three types of RTV silicone rubber with differing viscosities. We then assessed the adherence of these barriers to culture dishes and their ease of removal from the dishes. We tested the effect of the newly created barriers on the extracellular matrix (ECM) protein fibronectin by attaching and then removing them from fibronectin-coated culture dishes. We also conducted cell exclusion zone assays with MIO-M1 cells using this new barrier in order to measure cell migration. We used real time reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical staining to measure the effect of fibronectin on MIO-M1 cell migration and the effect of migration (with fibronectin coating) on basic fibroblast growth factor (bFGF) expression in MIO-M1 cells.Of the three types of RTV silicon rubber tested, KE-3495-T was the best in terms of adherence to the dish and ease of removal from the dish. When barrier attachment and removal tests were performed, this rubber type did not have an effect on the fibronectin that coated the dish. In the cell exclusion assay, removal of the barrier revealed that a cell-free area with a distinct margin had been created, which allowed us to conduct a quantitative assessment of migration. Fibronectin significantly promoted the migration of MIO-M1 cells (P = 0.02). In addition, both real time RT-PCR and immunohistological staining indicated that bFGF expression in migrating MIO-M1 cells was significantly higher than that in non-migrating cells (P = 0.03).RTV silicone rubber can be used to create an effective barrier in cell exclusion zone assays and allows simple and low-cost multi-parametric analysis of cell migration.

To examine factors affecting foveal avascular zone (FAZ) area in healthy eyes using swept-source optical coherence tomography angiography (OCTA).This prospective, cross-sectional study included 144 eyes of 144 individuals (77 women, 67 men) with a best corrected visual acuity of at least 20/20 and no history of ocular disorders. The area of the superficial FAZ was assessed using OCTA. Age, gender, central retinal thickness (CRT), retinal vascular density, refractive error, and axial length were examined to determine associations with FAZ area.The mean age of the subjects was 42.1 ± 20.2 years (range: 10-79 years). The mean FAZ area was 0.32 ± 0.11 mm2, while the mean retinal vascular density was 35.53 ± 0.92%. Multivariate regression analysis was performed using FAZ area as the dependent variable and age, gender, CRT, retinal vascular density, refractive error, and axial length as independent variables. The results of this analysis demonstrate that CRT and retinal vascular density were significantly associated with FAZ area in our sample (P < 0.001, R2 = 0.425). Age, gender, refractive error, and axial length were not significantly correlated with FAZ area, while CRT and retinal vascular density were negatively correlated with FAZ area (CRT: P < 0.001, R2 = 0.356; retinal vascular density: P < 0.001, R2 = 0.189).OCTA results suggest that CRT and retinal vascular density negatively affect FAZ area in healthy eyes.

The epithelial-mesenchymal transition (EMT) in retinal pigment epithelial (RPE) cells plays a central role in the development of proliferative vitreoretinopathy (PVR). The purpose of this study was to investigate the effect of AMP-activated protein kinase (AMPK), a key regulator of energy homeostasis, on the EMT in RPE cells. In this study, EMT-associated formation of cellular aggregates was induced by co-stimulation of cultured ARPE-19 cells with tumor necrosis factor (TNF)-α (10 ng/ml) and transforming growth factor (TGF)-β2 (5 ng/ml). 5-Aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR), a potent activator of AMPK, significantly suppressed TNF-α and TGF-β2-induced cellular aggregate formation (p < 0.01). Dipyridamole almost completely reversed the suppressive effect of AICAR, whereas 5'-amino-5'-deoxyadenosine restored aggregate formation by approximately 50%. AICAR suppressed the downregulation of E-cadherin and the upregulation of fibronectin and α-smooth muscle actin by TNF-α and TGF-β2. The levels of matrix metalloproteinase (MMP)-2, MMP-9, interleukin-6, and vascular endothelial growth factor were significantly decreased by AICAR. Activation of the mitogen-activated protein kinase and mammalian target of rapamycin pathways, but not the Smad pathway, was inhibited by AICAR. These findings indicate that AICAR suppresses the EMT in RPE cells at least partially via activation of AMPK. AMPK is a potential target molecule for the prevention and treatment of PVR, so AICAR may be a promising candidate for PVR therapy.

To investigate the occurrence ratio, localization, and surgical outcomes of intraretinal cystic spaces in idiopathic epiretinal membranes (ERMs).We retrospectively reviewed the charts of 432 eyes of 398 consecutive patients with idiopathic ERM who underwent vitrectomy and ERM peeling from January 2012 to September 2015. We selected cases with intraretinal cystic space prior to surgery, detected by spectral-domain optical coherence tomography. We then evaluated the effects of ERM peeling on intraretinal cystic spaces, best corrected visual acuity, and central retinal thickness at 6 months after surgery.Twenty-four eyes (5.5%) showed intraretinal cystic spaces before surgery, present in the inner retinal layer (the inner group) in 9 eyes, in the outer retinal layer (the outer group) in 6 eyes, and in both the inner and the outer retinal layers (the combined group) in 9 eyes. Additionally, 30 eyes with ERM but without any presence of intraretinal cystic space were selected randomly and classified as the no cyst group. At 6 months after surgery, the disappearance rate of cystic spaces was significantly greater for the outer group than for the inner group (83.3% and 11.1%, respectively, P = 0.011). The mean best corrected visual acuity improved significantly after surgery in the inner group, the outer group, and the no cyst group (P < 0.05 for all three groups) but did not improve in the combined group (P = 0.58). The mean central retinal thickness decreased significantly after surgery in the inner group, the combined group, and the no cyst group (P < 0.05).Intraretinal cystic spaces were observed in 5.5% of preoperative idiopathic ERM cases. Following surgery, the cystic spaces in the outer retinal layer disappeared at higher rates than those in the inner retinal layer, suggesting that the pathophysiologies of these cystic spaces are different.

The TCB index (triglycerides × total cholesterol × body weight), a novel simply calculated nutritional index based on serum triglycerides (TGs), serum total cholesterol (TC), and body weight (BW), was recently reported to be a useful prognostic indicator in patients with coronary artery disease. Thus, this study aimed to investigate the relationship between TCBI and long-term mortality in acute decompensated heart failure (ADHF) patients. Patients with a diagnosis of ADHF who were consecutively admitted to the cardiac intensive care unit in our institution from 2007 to 2011 were targeted. TCBI was calculated using the formula TG (mg/dL) × TC (mg/dL) × BW (kg)/1000. Patients were divided into two groups according to the median TCBI value. An association between admission TCBI and mortality was assessed using univariable and multivariable Cox proportional hazard analyses. Overall, 417 eligible patients were enrolled, and 94 (22.5%) patients died during a median follow-up period of 2.2 years. The cumulative survival rate with respect to all-cause, cardiovascular, and cancer-related mortalities was worse in patients with low TCBI than in those with high TCBI. In the multivariable analysis, although TCBI was not associated with cardiovascular and cancer mortalities, the association between TCBI and reduced all-cause mortality (hazard ratio: 0.64, 95% confidence interval: 0.44–0.94, p = 0.024) was observed. We computed net reclassification improvement (NRI) when TCBI or Geriatric Nutritional Risk Index (GNRI) was added on established predictors such as hemoglobin, serum sodium level, and both. TCBI improved discrimination for all-cause mortality (NRI: 0.42, p < 0.001; when added on hemoglobin and serum sodium level). GNRI can improve discrimination for cancer mortality (NRI: 0.96, p = 0.002; when added on hemoglobin and serum sodium level). TCBI, a novel and simply calculated nutritional index, can be useful to stratify patients with ADHF who were at risk for worse long-term overall mortality. [ABSTRACT FROM AUTHOR]

Background: The natural course of submacular hemorrhage resulting from traumatic choroidal rupture generally has a poor outcome unless treated. The intravitreal injection of gas only or gas with recombinant tissue plasminogen activator (rt-PA) has been reported to be effective, but has also been reported to induce severe complications such as retinal detachment and vitreous hemorrhage. Recently, we reported a safe and effective procedure for treating submacular hemorrhage due to polypoidal choroidal vasculopathy (PCV) with a low dose of rt-PA. Here we report the application of this procedure to a case of traumatic submacular hemorrhage in a 13-year-old boy, which achieved a good visual outcome. Case presentation: A 13-year-old Japanese boy presented with a thick submacular hemorrhage in his left eye as a result of blunt trauma from being hit by a sinker. Best-corrected visual acuity (BCVA) was assessed as only able to perceive hand motions. We carried out a vitrectomy, subretinal injection of 4,000 IU rt-PA (6.9 μg) and air tamponade. The day after surgery, most of the submacular hemorrhage had moved to the inferior periphery. One month after the surgery, we observed cataract formation, thin remnants of the submacular hemorrhage and juxtafoveal choroidal rupture. We carried out cataract surgery and injected bevacizumab intravitreally to prevent the development of choroidal neovascularization. Two months after the second surgery, the submacular hemorrhage had totally disappeared and the patient had a BCVA of 20/40. Conclusion: Vitrectomy, subretinal injection of rt-PA, and intravitreal air tamponade may be a promising strategy for treating traumatic submacular hemorrhage in young patients. [ABSTRACT FROM AUTHOR]

Background: Macular holes (MHs) are one of the complications of posterior uveitis that can significantly disturb vision. Conventional MH surgery (vitrectomy, internal limiting membrane (ILM) peeling, and gas tamponade) has been reported to show lower closure rates in patients with MHs secondary to uveitis than in patients with idiopathic MHs. Recently, the inverted ILM flap technique has been reported to be effective for treating refractory MHs. Here, we describe the application of this technique in a patient with a large MH secondary to uveitis, and its successful closure. Case presentation: An 80-year-old woman presented with a chronic, large MH secondary to uveitis. The minimum aperture diameter of the MH was 569 _m and extensive post-inflammatory chorioretinal atrophy was present, which included the juxtafoveal region. Vitrectomy with the inverted ILM flap technique assisted by low molecular weight hyaluronic acid was performed. Three days after surgery, the MH was closed successfully, without excessive gliosis. Conclusion: The inverted ILM flap technique may be the preferred surgical procedure for the treatment of large MHs secondary to uveitis. [ABSTRACT FROM AUTHOR]

PURPOSE: To evaluate vitrectomy with subretinal tissue plasminogen activator (t-PA) injection, and air tamponade, followed by intravitreal anti-vascular endothelial growth factor (VEGF) therapy for submacular hemorrhage in polypoidal choroidal vasculopathy (PCV). DESIGN: Prospective, interventional case series. METHODS: SETTING: Two clinics. PATIENTS: Fifteen eyes of 15 consecutive patients (mean age 72 ± 7 years) with submacular hemorrhage attributable to PCV. INCLUSION CRITERIA: PCV diagnosis with unorganized submacular hemorrhage greater than 500 mm thick. EXCLUSION CRITERIA: Submacular hemorrhage attributable to macular diseases (eg, high myopia, typical age-related macular degeneration, retinal angiomatous proliferation, and angioid streaks). INTERVENTION: Vitrectomy with 4000 IU t-PA injected subretinally and fluid/air exchange. Patients remained facedown for 3 days after surgery. Anti-VEGF drugs were administered as exudative changes required. MAIN OUTCOME MEASURES: Submacular hemorrhage displacement from the macula and changes in best-corrected visual acuities (BCVAs). RESULTS: Mean time from onset to surgery was 9.5 ± 4.5 (range, 5-21) days. Mean follow-up period was 9.4 ± 3.1 (range, 6-17) months. Surgery successfully displaced submacular hemorrhages from the macula in all eyes. Mean BCVA at baseline (0.98 ± 0.44) had improved significantly both 1 month after surgery (0.41 ± 0.25, P < .01) and at final visits (0.23 ± 0.25, P < .001). In all eyes, exudative retinal changes relapsed after surgery but were completely resolved by anti-VEGF injections. No complications occurred in any patients. CONCLUSION: Treating submacular hemorrhage with vitrectomy and subretinal t-PA injection, followed by intravitreal anti-VEGF therapy, is a promising strategy for improving visual acuity in PCV patients warranting further investigation. [ABSTRACT FROM AUTHOR]