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Purpose: To examine primary open-angle glaucoma patients after undergoing combined cataract surgery with microhook ab interno trabeculotomy (μLOT-Phaco) or iStent inject W implantation (iStent-Phaco), and then evaluate the surgical outcomes after a minimum of 6 months of follow-up., Methods: Between October 2020 and July 2022, 39 μLOT-Phaco eyes and 55 iStent-Phaco eyes that underwent surgery were evaluated in this retrospective, multicenter comparative case series. Data that included preoperative and postoperative intraocular pressure (IOP), number of glaucoma medications, and occurrence of complications were collected from medical records and then examined. Surgical failure was defined as patients exhibiting a  < 20% reduction in the preoperative IOP or an IOP > 18 mmHg on two consecutive follow-up visits, or when patients were required to undergo reoperation. Success rates were determined based on a Kaplan-Meier survival analysis., Results: At 3, 6 and 12 months postoperatively, there was a significant postoperative reduction in the IOP ( p  < 0.001) and in the medications scores ( p  < 0.001) for both of the groups. In the μLOT-Phaco and iStent-Phaco groups, the probabilities of success at 6 and 12 months were 55.3 and 45.5%, and 48.4 and 45.5% ( p  = 0.38; log-rank test), respectively. In the iStent-Phaco group, there was a significant decrease in the hyphema., Conclusion: Comparable surgical outcomes occurred for both the μLOT and iStent inject W procedures., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Onoe, Hirooka, Namiguchi, Mizoue, Hosokawa, Mochizuki, Okada, Tokumo, Okumichi and Kiuchi.)

Histologic evaluations revealed excessive accumulations of macrophages and absence of fibroblastic interstitial cells in explanted bioprosthetic valves. Comprehensive gene and protein expression analysis and histology unveiled an accumulation of fibrinogen and plasminogen, an activator of infiltrated macrophages, from degenerated valve surfaces in the interstitial spaces. These pathologies were completely reproduced in a goat model replaced with an autologous pericardium-derived aortic valve. Further preclinical animal experiments using goats demonstrated that preventing infiltration of macrophages and circulating proteins by increasing collagen density and leaflet strength is an effective treatment option., Competing Interests: This work was supported by Grants-in-Aid for Scientific Research (18K16396 to Dr Namiguchi, 16K10631, and 19H03740 to Dr Izutani, 19K17603 to Dr Hamaguchi, and 19K08585 and 16K109503 to Dr Aono) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan; the Takeda Science Foundation (grants 2016 and 2020 to Dr Sakaue); the Public Trust Cardiovascular Research Foundation (grant 2017 to Dr Sakaue); the SENSHIN Medical Research Foundation (grant 2016 to Drs Aono and 2020 to Dr Sakaue); and the MSD Life Science Foundation, Public Interest Incorporated Foundation (grant 2016 to Dr Aono). Dr Nakayama is an employee of Biotube. There are no financial relationships between Dr Nakayama and the other coauthors, and experimental materials and funding used in this study were not provided by industry. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Purpose: To elucidate the noninferiority of ab interno microhook trabeculotomy (μTLO) using a recently developed reusable stainless spatula-type microhook device to incise the trabecular meshwork to Trabectome (Neomeix, Inc) surgery in terms of the 1-year postoperative outcomes of Japanese patients with glaucoma by means of propensity score analyses., Design: Multicenter, retrospective cohort study., Participants: We enrolled 553 and 392 patients who underwent Trabectome surgery and μTLO, respectively, between January 2014 and March 2020 at 10 facilities., Methods: Logistic regression analysis was conducted to calculate the propensity score, which indicates the likelihood of treatment assignment (Trabectome or μTLO). We set the following factors as outcome-related covariates: age, sex, facility, glaucoma disease types, preoperative intraocular pressure (IOP), glaucoma drug score, mean deviation of Humphrey visual field test results, antithrombotic drug use, the presence or absence of combined cataract surgery, and incision range of the trabecular meshwork (1 or 2 quadrants). We analyzed 4 different methods (matching, inverse probability of treatment weighting [IPTW], stratification, and regression adjustment) using the propensity score. We set 15% as the noninferiority margin based on previous Trabectome meta-analysis results., Main Outcome Measures: The primary outcome was surgical success at 1 year after surgery. We defined surgical success as satisfying all 3 criteria: (1) IOP within 5 to 21 mmHg, (2) IOP reduction of 20% or more from preoperative IOP, and (3) no additional glaucoma surgery., Results: The 95% confidence interval of risk difference of surgical failure in μTLO in reference to Trabectome surgery was -12.1% to +9.5% in matching, -12.7% to +11.1% in IPTW, -12.2 to +7.0 in stratification, and -9.7% to +8.1% in regression adjustment, all of which fell within the predetermined noninferiority margin of 15%., Conclusions: Surgical success of μTLO at 1 year after was not inferior to that of Trabectome surgery., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objectives: The molecular mechanisms underlying post-operative pericardial adhesions remain poorly understood. We aimed to unveil the temporal molecular and cellular mechanisms underlying tissue dynamics during adhesion formation, including inflammation, angiogenesis, and fibrosis., Methods and Results: We visualized cell-based tissue dynamics during pericardial adhesion using histological evaluations. To determine the molecular mechanism, RNA-seq was performed. Chemical inhibitors were administered to confirm the molecular mechanism underlying adhesion formation. A high degree of adhesion formation was observed during the stages in which collagen production was promoted. Histological analyses showed that arterioles excessively sprouted from pericardial tissues after the accumulation of neutrophils on the heart surface in mice as well as humans. The combination of RNA-seq and histological analyses revealed that hyperproliferative endothelial and smooth muscle cells with dedifferentiation appeared in cytokine-exposed sprouting vessels and adhesion tissue but not in quiescent vessels in the heart. SMAD2/3 and ERK activation was observed in sprouting vessels. The simultaneous abrogation of PI3K/ERK or TGF-β/MMP9 signaling significantly decreased angiogenic sprouting, followed by inhibition of adhesion formation. Depleting MMP9-positive neutrophils shortened mice survival and decreased angiogenic sprouting and fibrosis in the adhesion. Our data suggest that TGF-β/matrix metalloproteinase-dependent tissue remodeling and PI3K/ERK signaling activation might contribute to unique angiogenesis with dedifferentiation of vascular smooth muscle cells from the contractile to the synthetic phenotype for fibrosis in the pericardial cavity., Conclusions: Our findings provide new insights in developing prevention strategies for pericardial adhesions by targeting the recruitment of vascular cells from heart tissues., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Namiguchi, Sakaue, Okazaki, Kanno, Komoda, Shikata, Kurata, Ota, Kubota, Kurobe, Nishimura, Masumoto, Higashiyama and Izutani.)

The characterization of aortic valve interstitial cells (VICs) cultured under optimal conditions is essential for understanding the molecular mechanisms underlying aortic valve stenosis. Here, we propose 2% hypoxia as an optimum VIC culture condition. Leaflets harvested from patients with aortic valve regurgitation were digested using collagenase and VICs were cultured under the 2% hypoxic condition. A significant increase in VIC growth was observed in 2% hypoxia (hypo-VICs), compared to normoxia (normo-VICs). RNA-sequencing revealed that downregulation of oxidative stress-marker genes (such as superoxide dismutase) and upregulation of cell cycle accelerators (such as cyclins) occurred in hypo-VICs. Accumulation of reactive oxygen species was observed in normo-VICs, indicating that low oxygen tension can avoid oxidative stress with cell-cycle arrest. Further mRNA quantifications revealed significant upregulation of several mesenchymal and hematopoietic progenitor markers, including CD34, in hypo-VICs. The stemness of hypo-VICs was confirmed using osteoblast differentiation assays, indicating that hypoxic culture is beneficial for maintaining growth and stemness, as well as for avoiding senescence via oxidative stress. The availability of hypoxic culture was also demonstrated in the molecular screening using proteomics. Therefore, hypoxic culture can be helpful for the identification of therapeutic targets and the evaluation of VIC molecular functions in vitro.

Background: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is an essential device in the field of emergency and intensive-care medicine. However, long-term use of VA-ECMO has various severe complications, including thrombosis., Case Presentation: A 60-year-old man underwent his third aortic root replacement using a homograft because of infectious endocarditis. Although the operation was difficult because of severe adhesion caused by the two previous interventions, aortic root replacement using a homograft was performed. At the time of withdrawal from cardiopulmonary bypass, the maintenance of hemodynamics was difficult because of bleeding from the surgical site, leading to hypovolemic shock. Cardiac function subsequently deteriorated; therefore, VA-ECMO was established and the operation was finished. Three days later, thrombus was formed inside the homograft and completely occluded ascending aorta. Evacuation of hematoma was performed, however, cardiac function was not ameliorated. Eventually, the patient had brain infarction and died. To prevent thrombus formation in very severe low cardiac output cases under VA-ECMO management after surgery, to prevent the stagnation of the blood flow from VA-ECMO will be necessary because anticoagulant therapy will be difficult. Impella ventricular assist device which is recently used widely generates anterograde blood flow and effectively prevents stagnation., Conclusions: To prevent thrombus formation in cases of very severe low cardiac output, Impella® should be combinatorially introduced from the beginning of VA-ECMO establishment to prevent thrombosis.

A 47-year-old woman with a history of mitral valve replacement (MVR) through a median sternotomy was admitted to our hospital due to dyspnea on exertion. Echocardiography showed bioprosthetic valve dysfunction with mitral stenosis. Right heart catheter examination revealed severe pulmonary hypertension and right ventricular dysfunction. We considered that she could not tolerate the hemodynamic changes during induction of general anesthesia without any cardiopulmonary support. Therefore, the percutaneous cardiopulmonary support was started before induction of anesthesia. To avoid the risk of injury to cardiac structures, we performed redo mitral valve replacement via right mini-horacotomy in the 4th intercostal space. Severe calcification was found in the leaflets of the prosthetic valve. She was discharged home on postoperative day 42.

Purpose: To compare the success rates of eye drop instillation in the sitting position and supine position among Japanese patients with ocular diseases (cataract, glaucoma, or retinal and vitreous diseases)., Methods: Patients who were hospitalized in Okayama University Hospital for eye surgery were studied. Instillation procedures of each patient in both the sitting and supine positions were recorded using a video camera at the time of instillation. We defined "success" when one drop fell accurately onto the ocular surface at the first attempt. Instillation of two or more drops, drops delivered to a site other than the eye surface, and touching the eyelashes, eyelids, or conjunctiva with the tip of the eye drop bottle were regarded as "failure". We excluded patients with vision below counting finger., Results: One-hundred and two patients (54 males and 58 females, aged 70.2 ± 12.3 years) with ocular disease who were hospitalized for surgery (cataract: 61.8%, glaucoma: 15.7%, retinal and vitreous diseases: 22.5%) were included in this prospective observational study. The mean duration of eye drop use was 3.1 ± 5.2 years. The success rate of eye drop instillation was significantly higher in the supine position than in the sitting position (64.7% vs. 50%, P = 0.0039). The mean age was significantly higher in the failure group than in the success group (74.0 ± 11.5 vs. 67.7 ± 12.4 years, P = 0.0085) for the sitting position, but not significantly different for the supine position (72.3 ± 12.9 vs. 70.1 ± 12.0 years, P = 0.3849). No significant differences in mean duration of drop use, mean corrected VA, and mean spherical equivalent refraction were observed between success and failure groups, for both sitting and supine positions., Conclusions: In the present study, the success rate of eye drop instillation was significantly higher when applied in the supine position than in the sitting position., Competing Interests: The authors have declared that no competing interests exist.

Objective: To determine the effect of botulinum toxin A (BTX-A) on the eyelid pressure in patients with benign essential blepharospasm (BEB)., Methods: Twenty normal volunteers (10 men, 10 women; average age 59.7 ± 11.3 years) and 33 patients (12 men, 21 women; average age 61.1 ± 14.7 years) with BEB were studied. The upper and lower eyelid pressures were measured with a blepharo-tensiometer in the normal subjects (N group). The eyelid pressures and intraocular pressures (IOP) were measured before and after the BTX-A injections in the BEB patients (B group)., Results: The mean eyelid pressure in the N group was 31.0 ± 6.8 mmHg for the upper eyelid and 29.9 ± 6.5 mmHg for the lower eyelid (P > 0.05). The mean eyelid pressure in the B group before treatment was 35.3 ± 7.0 mmHg for the upper eyelid and 37.8 ± 6.6 mmHg for the lower eyelid. The eyelid pressure in the B group was significantly higher than in the N group for the upper and lower eyelids (both P < 0.001). The eyelid pressure was significantly decreased after BTX-A treatment for the upper (29.9 ± 7.5 mmHg) and the lower (32.8 ± 7.0 mmHg) eyelids (both P < 0.001). The mean IOP was 15.1 ± 2.9 mmHg before, and it significantly decreased to 14.5 ± 2.8 mmHg (P = 0.020) after the BTX-A injections. The IOP was significantly correlated with the lower eyelid pressure (P = 0.0435), but not with the upper eyelid pressure (P = 0.175)., Conclusion: The eyelid pressure was higher in the patients with BEB. The eyelid pressure and the IOP were significantly reduced after the BTX-A injections. In addition, the IOPs were significantly correlated with the eyelid pressure of the lower eyelid.

Background: Congenital long QT syndrome (LQTS) can cause ventricular arrhythmic events with syncope and sudden death resulting from malignant torsades de pointes (TdP) followed by ventricular fibrillations (VFs). However, the syndrome is often overlooked prior to the development of arrhythmic events in patients with congenital heart diseases demonstrating right bundle branch block on electrocardiogram (ECG). We present a case of an adult patient with congenital heart disease who developed VFs postoperatively, potentially due to his mutation in a LQTS related gene, which was not identified on preoperative assessment due to incomplete evaluation of his family history., Case Presentation: A 64-year-old man was diagnosed as having multiple atrial septal defects. He presented with no symptoms of heart failure. His preoperative ECG showed complete right bundle branch block (CRBBB) with a corrected QT interval time of 478 ms. He underwent open-heart surgery to close the defects through median sternotomy access. Three hours after the operation, he developed multiple events of TdP and VFs in the intensive care unit. Cardiopulmonary resuscitation and multiple cardioversions were attempted for his repetitive TdP and VFs. He eventually reverted to sinus rhythm, and intravenous beta-blocker was administered to maintain the sinus rhythm. After this event, his family history was reviewed, and it was confirmed that his daughter and grandson had a medical history of arrhythmia. A genetic test confirmed that he had a missense mutation in CACNA1C, p.K1580 T, which is the cause for type 8., Conclusions: This case highlights the importance of paying attention to other ECG findings in patients with CRBBB, which can mask prolonged QT intervals.

Background: To investigate the success rate of eye drop instillation in glaucoma patients with visual field defect as well as non-glaucoma volunteers. Factors that may affect the success rate of eye drop instillation were also evaluated., Design: A prospective, observational study., Participants: Seventy-eight glaucoma patients and 85 non-glaucoma volunteers were recruited in this study., Methods: Open angle glaucoma patients with visual field defect as well as non-glaucoma volunteers were asked to video record their procedures of eye drop instillation using a 5-mL plastic bottle of artificial tear solution. Success of eye drop instillation was judged on video based on the first one drop of solution successfully applied on the cornea, by two investigators., Main Outcome Measures: Success rate of eye drop instillation in glaucoma patients and non-glaucoma volunteers. Factors related to success rate of eye drop instillation, such as visual field defect and clinical characteristics, were also analyzed using multivariable logistic regression., Results: No significant deference in mean age was observed between two groups (glaucoma: 64.5 ± 14.4 years, non-glaucoma: 60.9 ± 14.1 years, P = 0.1156). Success rate of eye drop instillation was significantly lower (P = 0.0215) in glaucoma patients (30/78; 38.5%) than in non-glaucoma volunteers (48/85; 56.5%). The most frequent reason of instillation failure in glaucoma patients was touching the bulbar conjunctiva, cornea, eyelid or eyelashes with the tip of the bottle (29.5%). Multivariable logistic regression analysis identified lower corrected visual acuity (VA) (≤ 1.0; odds ratio [OR] = 0.20, 95% confidence interval [CI] 0.04-0.93, P = 0.0411), lower mean deviation (MD) (< -12 dB; OR = 0.20, 95% CI 0.05-0.86, P = 0.0307) and visual field defect (VFD) in the inferior hemifield (OR = 0.11, 95% CI 0.02-0.34, P < 0.001) to be significantly related to instillation failure in glaucoma patients., Conclusions: Success rate of eye drop instillation was significantly lower in glaucoma patients than in non-glaucoma volunteers. Corrected VA ≤ 1.0, MD < -12 dB and/or VFD in the inferior hemifield may be related to failure of eye drop instillation.

Introduction: We examined the sustainability of the intraocular pressure (IOP)-lowering efficacy of travoprost (0.004%) ophthalmic solution in subjects with normal tension glaucoma (NTG)., Methods: Travoprost ophthalmic solution was given once daily at 9 PM to subjects with newly diagnosed NTG or with NTG who had not received any ocular hypotensives within the previous 30 days. IOP was measured at three time points (9 AM, 1 PM, and 5 PM) at baseline and week 12 visits, and at one time point (9 AM) at week 4 and week 8 visits. Conjunctival hyperemia, superficial punctate keratopathy, and other adverse events were evaluated during the observation period., Results: Thirty subjects (12 males and 18 females; mean age 65.6 years) from 32 subjects enrolled were included in the efficacy analysis. The mean IOPs (±standard deviation) of 16.6 ± 1.4, 15.7 ± 1.8, and 15.7 ± 2.2 mmHg at 9 AM, 1 PM, and 5 PM, respectively, at baseline reduced significantly to the mean IOPs of 13.0 ± 1.8, 12.7 ± 1.8, and 12.8 ± 1.6 mmHg, respectively, at week 12 (P < 0.0001 for every time point). Together with the mean IOPs of 13.4 ± 1.9 mmHg at week 4 and 13.2 ± 1.9 mmHg at week 8, the pooled IOP during the observation period for up to 12 weeks showed a statistically and clinically significant reduction of IOP at 9 AM. (3.4 mmHg or 20.3% reduction from baseline, P < 0.0001). There were no adverse events leading to treatment discontinuation., Conclusion: This multi-center collaborative study suggests that IOP-lowering efficacy of travoprost ophthalmic solution persists during the day at the clinically relevant level in subjects with NTG., Funding: Alcon Japan Ltd., Trial Registration: University Hospital Medical Information Network, UMIN ID: 000011621.

Purpose . To quantify changes in anterior segment (AS) parameters after laser peripheral iridotomy (LPI) using AS-optical coherence tomography (OCT) of iris bombe. Method . AS images of eight eyes were captured before and after iris bombe and more than 2 weeks after LPI (post-LPI) using AS-OCT. We compared the following AS parameters: anterior chamber depth (ACD), anterior chamber volume (ACV), iris curvature (IC), iris thickness at 500  μ m from the scleral spur (IT-1) in the middle between the iris root and pupillary margin (IT-2) and 500  μ m from the pupillary margin (IT-3) to the anterior chamber angle (ACA) (angle opening distance [AOD750]), and trabecular iris space area. Results . Mean IT-1 and IT-3, but not IT-2, were lower after iris bombe (IT-1, P = 0.001; IT-2, P = 0.081; and IT-3, P = 0.001). There were no significant differences between ACD at pre-LPI and before iris bombe ( P = 0.096). The mean ACV and AOD750 of iris bombe increased at post-LPI (ACV, P < 0.01, and AOD750, P < 0.05). The mean IT-1, IT-2, and IT-3 increased at post-LPI (all, P ≤ 0.01). IC decreased at post-LPI ( P < 0.001), and ACD at post-LPI did not change. Conclusions . The iris extends and becomes thinner during iris bombe. LPI during bombe decreases the IC and increases the ACV and ACA.

Collateral vascular arteries from the descending aorta to the pulmonary arteries are uncommon after arterial switch operation. Here, we report the case of a baby girl treated with coil embolization for abnormal blood flow from the descending aorta to the pulmonary arteries after arterial switch operation. A baby girl weighing 1324 g was delivered at 32 weeks 4 days of gestation, and she had D-transposition of the great arteries and a ventricular septal defect. She underwent nitrogen inhalation to reduce pulmonary blood flow before arterial switch operation. After the operation, she presented with left heart failure due to the presence of abnormal blood flow from the descending aorta to the pulmonary arteries, and she was successfully treated with coil embolization. After the treatment, her condition improved dramatically, and she was discharged without any complications.

Purpose: To compare the morphology of the anterior chamber angle (ACA) and iris in eyes with pseudoexfoliation (PEX) syndrome to that of their clinically unaffected fellow eyes and normal control eyes., Methods: Forty-two patients with unilateral PEX syndrome and 42 normal subjects were studied. Eyes were separated into those with PEX, their clinically unaffected fellow eyes, and normal eyes. The dark-light changes of the ACA and iris were documented by anterior segment optical coherence tomography (AS-OCT) video recordings. The nasal ACA parameters including the angle opening distance at 500 μm (AOD500), the trabecular-iris space at 500 μm (TISA500), and the trabecular-iris angle at 500 μm (TIA500); anterior chamber depth (ACD); iris-lens contact distance (ILCD), and iris configuration were analyzed with the built-in software and a customized program., Results: The ACA parameters were not significantly different among all three groups in the dark. The PEX eyes had significantly smaller ACA parameters than their fellow eyes and normal control eyes in the light. PEX eyes also had significantly shallower ACD, longer ILCD, and greater iris convexity (both in dark and light), and thinner iris (in dark) than their fellow eyes. The fellow eyes had significantly lower ACD both in the dark and light, and smaller angle opening distance at 500 μm and ILCD in the light than normal controls. There were no significant differences in the iris area among the three groups., Conclusions: Differences in the anterior segmental morphology are present between PEX and fellow eyes. These disparities may be related to the asymmetry in patients with the unilateral PEX syndrome.