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Macular hole (MH) is a retinal break involving the fovea that causes impaired vision. Although advances in vitreoretinal surgical techniques achieve >90% MH closure rate, refractory cases still exist. For such cases, autologous retinal transplantation is an optional therapy showing good anatomic success, but visual improvement is limited and peripheral visual field defects are inevitable after graft harvesting. Here, using a non-human primate model, we evaluated whether human embryonic stem cell-derived retinal organoid (RO) sheet transplantation can be an effective option for treating MH. After transplantation, MH was successfully closed by continuous filling of the MH space with the RO sheet, resulting in improved visual function, although no host-graft synaptic connections were confirmed. Mild xeno-transplantation rejection was controlled by additional focal steroid injections and rod/cone photoreceptors developed in the graft. Overall, our findings suggest pluripotent stem cell-derived RO sheet transplantation as a practical option for refractory MH treatment., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to explore the potential benefits of retinal pigment epithelium replacement therapy in patients with Bietti crystalline dystrophy (BCD) by assessing the disease pathology with the distinctive relationship between fundus autofluorescence (FAF) abnormality and visual field defect., Methods: Sixteen eyes from 16 patients with BCD and 16 eyes from 16 patients with RHO-associated retinitis pigmentosa were included. Fundus autofluorescence, optical coherence tomography, and Goldmann perimetry results were retrospectively reviewed and assessed using image analyses., Results: In patients with BCD, the FAF abnormality area was not correlated with the overall visual field defect area and median overall visual field defect area (57.5%) was smaller than FAF abnormality area (98.5%). By contrast, the ellipsoid zone width was significantly correlated with the central visual field area (r = 0.806, P < 0.001). In patients with RHO-associated retinitis pigmentosa, the FAF abnormality area and ellipsoid zone width were significantly correlated with the overall visual field defect area (r = 0.833, P < 0.001) and central visual field area (r = 0.887, P < 0.001), respectively., Conclusion: The FAF abnormality shown in patients with BCD involves retinal pigment epithelium degeneration without complete loss of photoreceptors or visual function. These results suggest that patients with BCD are good candidates for retinal pigment epithelium replacement therapy for preservation of residual visual function., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Retinitis pigmentosa (RP) is the most common inherited retinal dystrophy and a major cause of blindness. RP is caused by several variants of multiple genes, and genetic diagnosis by identifying these variants is important for optimizing treatment and estimating patient prognosis. Next-generation sequencing (NGS), which is currently widely used for diagnosis, is considered useful but is known to have limitations in detecting copy number variations (CNVs). In this study, we re-evaluated CNVs in EYS, the main causative gene of RP, identified via NGS using multiplex ligation-dependent probe amplification (MLPA). CNVs were identified in NGS samples of eight patients. To identify potential CNVs, MLPA was also performed on samples from 42 patients who were undiagnosed by NGS but carried one of the five major pathogenic variants reported in Japanese EYS-RP cases. All suspected CNVs based on NGS data in the eight patients were confirmed via MLPA. CNVs were found in 2 of the 42 NGS-undiagnosed RP cases. Furthermore, results showed that 121 of the 661 patients with RP had EYS as the causative gene, and 8.3% (10/121 patients with EYS-RP) had CNVs. Although NGS using the CNV calling criteria utilized in this study failed to identify CNVs in two cases, no false-positive results were detected. Collectively, these findings suggest that NGS is useful for CNV detection during clinical diagnosis of RP., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hiraoka et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background Aortic valve (AV) repair is a challenging procedure due to its complexity, lower reproducibility, and steep learning curve. To examine its durability and validity, we investigated mid-term outcomes following AV repair without aortic root replacement. Methods Between March 2007 and May 2018, we retrospectively identified 14 patients who underwent AV repair without aortic root replacement at our institution. We investigated their baseline characteristics and postoperative outcomes, including the reoperation rate due to aortic regurgitation (AR) recurrence. Furthermore, we divided them into two groups: those who required reoperation due to AR recurrence (Group R) and those who did not require reoperation (Group F), and statistically compared them. Results The median age was 52.5 years (IQR: 42.0-60.8), with 11 male patients (78.6%). Eight patients (57.1%) had a bicuspid AV. Five cases (35.7%) underwent reoperation due to AR recurrence during a median follow-up period of 5.5 years. There were no significant differences in baseline characteristics between Group R (n=5, 35.7%) and Group F (n=9, 64.3%), including AR etiology, AV repair procedure, and intraoperative AR grade after the final declamp. All cases in Group R had at least mild to moderate AR on the echocardiogram before discharge. Regarding the AR grade before discharge, Group R had a significantly higher grade than Group F (p = 0.013). Conclusions The indication for AV repair for AR might need to be reassessed due to the considerable mid-term reoperation rate. Cases of AV repair with more than mild AR at discharge should be carefully monitored, as they are likely to require future reoperation for AR., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Teine Keijinkai Hospital Institutional Review Board issued approval 2-023421-00. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kato et al.)

Background: Cardiac metastasis including the right ventricle from renal cell carcinoma is rare. No standard treatment for cardiac metastasis and recurrence in renal cell carcinoma has been established., Case Presentation: We present the case of a 61-year-old man who underwent the resection of recurrent right ventricular metastasis caused by renal cell carcinoma following molecular targeted therapy. The first cardiac operation was performed for right ventricular metastasis due to renal cell carcinoma. The patient had a good postoperative course. Two years after the first operation, however, follow-up computed tomography revealed the recurrence of the right ventricular tumor and metastases in both lungs. Molecular targeted therapy was carried out and effectively controlled the lung metastasis but the right ventricular lesion remained unchanged, leading to reoperation. The recurrent right ventricular tumor was completely resected through a redo median sternotomy assisted by cardiopulmonary bypass. The patient had an uneventful postoperative course and was discharged on the 13th postoperative day. Follow-ups at 2 years showed no cardiac recurrence., Conclusion: Surgical intervention was considered useful in managing the recurrence of right ventricular metastasis from renal cell carcinoma after molecular targeted therapy., (© 2024. The Author(s).)

Memory T cells demonstrate superior in vivo persistence and antitumor efficacy. However, methods for manufacturing less differentiated T cells are not yet well-established. Here, we show that producing chimeric antigen receptor (CAR)-T cells using berbamine (BBM), a natural compound found in the Chinese herbal medicine Berberis amurensis, enhances the antitumor efficacy of CAR-T cells. BBM is identified through cell-based screening of chemical compounds using induced pluripotent stem cell-derived T cells, leading to improved viability with a memory T cell phenotype. Transcriptomics and metabolomics using stem cell memory T cells reveal that BBM broadly enhances lipid metabolism. Furthermore, the addition of BBM downregulates the phosphorylation of p38 mitogen-activated protein kinase and enhanced mitochondrial respiration. CD19-CAR-T cells cultured with BBM also extend the survival of leukaemia mouse models due to their superior in vivo persistence. This technology offers a straightforward approach to enhancing the antitumor efficacy of CAR-T cells., (© 2024. The Author(s).)

Clinical studies using suspensions or sheets of human pluripotent cell-derived retinal pigment epithelial cells (hiPSC-RPE) have been conducted globally for diseases such as age-related macular degeneration. Despite being minimally invasive, cell suspension transplantation faces challenges in targeted cell delivery and frequent cell leakage. Conversely, although the RPE sheet ensures targeted delivery with correct cell polarity, it requires invasive surgery, and graft preparation is time-consuming. We previously reported hiPSC-RPE strips as a form of quick cell aggregate that allows for reliable cell delivery to the target area with minimal invasiveness. In this study, we used a microsecond pulse laser to create a local RPE ablation model in cynomolgus monkey eyes. The hiPSC-RPE strips were transplanted into the RPE-ablated and intact sites. The hiPSC-RPE strip stably survived in all transplanted monkey eyes. The expansion area of the RPE from the engrafted strip was larger at the RPE injury site than at the intact site with no tumorigenic growth. Histological observation showed a monolayer expansion of the transplanted RPE cells with the expression of MERTK apically and collagen type 4 basally. The hiPSC-RPE strip is considered a beneficial transplantation option for RPE cell therapy., (© 2024. The Author(s).)

Purpose: To evaluate midterm results of whether the strategy to occlude target lumbar arteries using n-butyl-2-cyanoacrylate (nBCA) injection during endovascular aneurysm repair (EVAR) reduced the incidence of Type II endoleak (T2EL) after EVAR., Materials and Methods: Between 2013 and 2020, 187 patients underwent EVAR; 106 in the treatment group received nBCA injection during EVAR, whereas 81 in the historical control group did not. The incidence of T2EL at 7 days, need for reintervention, and post-EVAR aneurysmal shrinkage were compared between the groups., Results: Between the treatment group and the control group, significant differences were achieved in the incidence of T2EL (2.8% vs 28.4%; P < .0001) and decreased aneurysmal diameter was observed at 1 year after EVAR (-5.2 vs -3.8 mm; P = .034). In multivariate analysis, nBCA injection (odds ratio [OR], 0.04; P = .001) and younger age (OR, 0.92; P = .036) were significantly associated with a reduced incidence of T2EL. As a possible adverse event associated with nBCA injection, 2 cases of transient lower-limb motor dysfunction (1.9%) were observed. Propensity score analysis revealed that the treatment group had a significantly lower incidence of T2EL than that in the control group (P = .0002) even though there was no difference in the incidence of inferior mesenteric artery coil embolization between the groups. The survival rate without aneurysm sac enlargement (100.0% vs 69.8%; P = .014) and the reintervention-free rate (100.0% vs 63.1%; P = .034) in the treatment group were significantly higher than those in the control group., Conclusions: Concomitant nBCA injection can provide durable EVAR without T2EL, as supported by the avoidance of reintervention associated with aneurysm sac enlargement., (Copyright © 2024 SIR. Published by Elsevier Inc. All rights reserved.)

Purpose: Recent reports of the Zenith Alpha abdominal endovascular graft (Zenith Alpha AAA, Cook, Inc., Bloomington, Indiana) have demonstrated an unexpectedly high incidence of limb graft occlusion (LGO). The purpose of this study was to prospectively evaluate the performance of the Zenith AAA in Japan, with a specific focus on LGO., Materials and Methods: All endovascular aneurysm repairs (EVARs) for abdominal aortic aneurysms performed using the Zenith Alpha AAA from July 2020 to October 2021 in 23 Japanese hospitals were prospectively evaluated. All computed tomographic images were analyzed in the core laboratory. Late complications were defined as any aneurysm-related events occurring >30 days after EVAR, including aneurysm sac enlargement of >5 mm and any reinterventions performed. Endoleaks without sac enlargement or reintervention were excluded as late complications., Results: During the study period, 147 EVARs were performed using the Zenith Alpha AAA. The mean patient age was 76.5±7.7 years, 84.4% of patients were male, and the mean aneurysm diameter was 52.4±9.2 mm. Instruction-for-use violations were observed in 76 patients (51.7%), primarily associated with a severely angulated proximal neck (>60°). There were six intraoperative complications and 62 additional intraoperative treatments reported, most of which involved preemptive coil embolization of the inferior mesenteric artery (37 cases). Technical success, defined as the absence of type 1 or 3 endoleaks on final angiography, was achieved in 99.3% of patients. At 12 months, there was only one case of type 1/3 endoleak (0.8%) and one aneurysm sac enlargement exceeding 5 mm (0.8%); however, a high incidence of type 2 endoleaks was observed in 35.2% of patients, and aneurysm sac regression exceeding 5 mm was achieved in 30.1% of patients. Nine late complications were observed, and the rate of freedom from late complications at 12 months was 93.5%, encompassing four LGOs and one limb graft stenosis (3.4%)., Conclusions: In contrast to recent reports, our Japanese multicenter prospective study demonstrated satisfactory early clinical results, including an acceptable LGO rate, for the low-profile Zenith Alpha AAA. Long-term follow-ups will be performed to confirm the persistence of these outcomes., Clinical Impact: This study prospectively evaluated the performance of 147 Zenith Alpha AAAs used for endovascular aneurysm repair with core-lab adjudication focusing especially on limb graft occlusion (LGO). At 12 months, aneurysm sac regression exceeding 5 mm was achieved in 30.1% of patients, and there was only one type 1/3 endoleak, one aneurysm sac enlargement (>5 mm), and nine late complications including five LGOs (3.4%), resulting in rate of freedom from late complications at 93.5%. Satisfactory early clinical results, including an acceptable rate of LGO can be achieved, particularly with cautious usage of the Zenith Alpha Spiral-Z Endovascular Leg." 5mm), and nine late complications including five LGOs (3.4%), resulting in rate of freedom from late complications at 93.5%. Satisfactory early clinical results, including an acceptable rate of LGO can be achieved, particularly with cautious usage of the Zenith Alpha Spiral-Z Endovascular Leg., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: NF receives consulting fee from Cook Medical, Endologix, Medtronic, and Terumo Aortic. YK receives consulting fee from Medtronic and Terumo Aortic.

This study aimed to investigate how the extent and central/peripheral location of the residual visual field (VF) in patients with late-stage inherited retinal diseases (IRDs) are related to retinal sensitivity detected using full-field stimulus testing (FST). We reviewed the results of Goldmann perimetry and FST from the medical records of patients with IRDs whose VF represents central (within 10°) and/or peripheral islands, or undetectable. In total, 19 patients (19 eyes) were analyzed in this study. The median value of residual VF area was 1.38%. The median values of rod and cone sensitivities were  - 14.9 dB and 7.4 dB, respectively. Patients with only the peripheral island (- 33.9 dB) had better median rod sensitivity than other groups (only central,  - 18.9 dB; both,  - 3.6 dB). VF area significantly correlated with rod sensitivity (r = - 0.943, p = 0.005) in patients with only peripheral island, but not with cone sensitivity. Peripheral VF islands were significant contributors to FST results, especially rod sensitivity. With reduced or loss of central vision, the extent of residual peripheral VF significantly affected rod sensitivity, suggesting that FST can be useful in quantitatively estimating the overall remaining vision in patients with late-stage IRD., (© 2024. The Author(s).)

Objective: The aim of this study was to evaluate midterm outcomes of our novel strategy of postoperative initial 2-day blood pressure management (BPM) after endovascular aneurysm repair (EVAR) for the prevention of subsequent type II endoleak (T2EL) in a single-center series., Methods: Between 2008 and 2014, 137 patients who underwent EVAR for abdominal aortic aneurysm (AAA) were reviewed. Starting from 2013, the mean blood pressure was maintained between 75 and 90 mmHg for the initial 24 hours after EVAR followed by systolic pressure controlled below 120 mmHg during the next 24 hours in the treatment group (n = 76). The incidence of T2EL detected at 7 days, reintervention, and AAA sac diameter up to 5 years after EVAR were compared with those of the control group comprising of 60 consecutive patients who underwent standard EVAR without BPM prior to 2013., Results: Between the treatment group and the control group, significant differences were achieved in the incidence of T2EL at 7 days (19.7% vs 40.0%; P = .009), a mean decrease of AAA sac diameter at 1-year (-5.1 ± 4.9 vs -2.2 ± 6.7 mm; P = .013) and 2-year (-5.4 ± 7.7 vs -1.7 ± 10.8 mm; P = .045). In addition, there was a significant decrease in the incidence of T2EL detected at 7 days with the use of the Gore Excluder with 22.7% in the treatment group vs 80.0% in the control group (P < .001), which resulted in a significant decrease in the aneurysm sac diameter up to 4 years after EVAR. Survival rate without AAA sac enlargement at 5 years after EVAR (83.0% vs 70.0%; P = .021) in the treatment group was significantly higher than that of the control group, whereas no significant differences were observed in the freedom rates of reintervention, T2EL-related reintervention, and all-cause mortality between the groups., Conclusions: Postoperative initial 2-day BPM had a preventive effect on AAA sac enlargement until midterm periods, by reducing the incidence of T2EL at 7 days after EVAR. The usage of Gore Excluder under BPM was especially associated with sustained positive effects until the midterm follow-up., Competing Interests: Disclosures None., (Copyright © 2023 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Cystoid macular edema (CME) in retinitis pigmentosa (RP) is an important complication causing visual dysfunction. We investigated the effect of CME on photoreceptors in RP patients with previous or current CME, using an adaptive optics (AO) fundus camera., Methods: We retrospectively observed the CME and ellipsoid zone (EZ) length (average of horizontal and vertical sections) by optical coherence tomography. The density and regularity of the arrangement of photoreceptor cells (Voronoi analysis) were examined at four points around 1.5° from superior to inferior and temporal to nasal. We also performed a multivariate analysis using CME duration, central macular thickness and transversal length of CME., Results: We evaluated 18 patients with previous or current CME (18 eyes; age, 48.7 ± 15.6 years) and 24 patients without previous or current CME (24 eyes; age, 46.0 ± 14.5 years). There were no significant differences in age, logMAR visual acuity, or EZ length. In groups with and without CME, cell density was 11967 ± 3148 and 16239 ± 2935 cells/mm2, and sequence regularity was 85.5 ± 3.4% and 88.5 ± 2.8%, respectively; both parameters were significantly different. The correlation between photoreceptor density and age was more negative in group with CME. The CME group tended toward greater reductions in duration of CME., Conclusion: Complications of CME in RP patients may lead to a decrease in photoreceptor density and regularity. Additionally, a longer duration of CME may result in a greater reduction in photoreceptor density., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kitahata et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: This study aimed to evaluate the midterm results of zone 2 thoracic endovascular aortic repair (TEVAR) for uncomplicated type B aortic dissection (TBAD) by measuring the intra-false lumen pressure (IFLP) during TEVAR., Methods: Fifteen patients (9 men; mean age, 57 years) who underwent zone 2 TEVAR for uncomplicated TBAD were reviewed. Delta systolic pressure (defined as the difference between systemic pressure and IFLP) was measured before and after primary entry closure, and aortic remodeling and thrombo-occlusion of the false lumen (FL) were evaluated 12 months after TEVAR at 5 different levels of the aorta., Results: Median duration from onset to TEVAR was 34 days. The left subclavian artery was preserved in 13 patients (87%) by using stent graft fenestration. Although 1 patient (6%) had a transient cerebral infarction, there were no severe TEVAR-related complications. Entry closure significantly reduced delta systolic pressure (mm Hg) compared to preoperative pressure at all levels (distal arch: -22.2 ± 10.8 vs. -5.2 ± 9.6; Th8: -20.1 ± 12.4 vs. -6.9 ± 7.2; Th10: -14.3 ± 14.6 vs. -4.7 ± 7.5; Th12: -14.4 ± 14.5 vs. -4.9 ± 7.8; L2: -14.5 ± 14.2 vs. -3.4 ± 6.9). The percentages of aortic remodeling with expansion of the true lumen (distal arch: 82%; Th8: 80%; Th10: 54%; Th12: 45%; L2: 50%) and complete false lumen thrombosis (distal arch: 100%; Th8: 100%; Th10: 67%; Th12: 11%; L2: 0%) were approximately consistent with the change in delta systolic pressure. During a follow-up of 41 months, distal stent-induced new entry occurred in 2 patients (13%) requiring secondary intervention; however, there were no cases of FL enlargement or aorta-related mortality., Conclusions: Zone 2 TEVAR for uncomplicated TBAD may prevent TEVAR-related complications. Measuring IFLP could be a new predictive marker for assessing the extent of aortic remodeling., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Transplantation of induced pluripotent stem cell (iPSC)-derived retinal organoids into retinal disease animal models has yielded promising results, and several clinical trials on iPSC-derived retinal pigment epithelial cell transplantation have confirmed its safety. In this study, we performed allogeneic iPSC-derived retinal organoid sheet transplantation in two subjects with advanced retinitis pigmentosa (jRCTa050200027). The primary endpoint was the survival and safety of the transplanted retinal organoid sheets in the first year post-transplantation. The secondary endpoints were the safety of the transplantation procedure and visual function evaluation. The grafts survived in a stable condition for 2 years, and the retinal thickness increased at the transplant site without serious adverse events in both subjects. Changes in visual function were less progressive than those of the untreated eye during the follow-up. Allogeneic iPSC-derived retinal organoid sheet transplantation is a potential therapeutic approach, and the treatment's safety and efficacy for visual function should be investigated further., Competing Interests: Declaration of interests Y.H. reports that Kobe City Eye Hospital received a research grant from the Japan Agency for Medical Research and Development (AMED) (grant number: JP19bk0104082) and financial support from Sumitomo Pharma Co. Ltd. for this study. S.S., T.M., M.Y., and M.T. are employed by Vision Care, Inc. T.H., A.N., K.U., K.O., H.O., M. Fujiwara, S. Yamasaki, K.W., K.B., K.K., A.I., and A.K. are employed by Sumitomo Pharma Co. Ltd. T.K. is a board member of Sumitomo Pharma Co. Ltd. The authors are co-inventors on patent applications., (Copyright © 2023 Elsevier Inc. All rights reserved.)

We investigated the potential of ChatGPT in the ophthalmological field in the Japanese language using board examinations for specialists in the Japanese Ophthalmology Society. We tested GPT-3.5 and GPT-4-based ChatGPT on five sets of past board examination problems in July 2023. Japanese text was used as the prompt adopting two strategies: zero- and few-shot prompting. We compared the correct answer rate of ChatGPT with that of actual examinees, and the performance characteristics in 10 subspecialties were assessed. ChatGPT-3.5 and ChatGPT-4 correctly answered 112 (22.4%) and 229 (45.8%) out of 500 questions with simple zero-shot prompting, respectively, and ChatGPT-4 correctly answered 231 (46.2%) questions with few-shot prompting. The correct answer rates of ChatGPT-3.5 were approximately two to three times lower than those of the actual examinees for each examination set (p = 0.001). However, the correct answer rates for ChatGPT-4 were close to approximately 70% of those of the examinees. ChatGPT-4 had the highest correct answer rate (71.4% with zero-shot prompting and 61.9% with few-shot prompting) in "blepharoplasty, orbit, and ocular oncology," and the lowest answer rate (30.0% with zero-shot prompting and 23.3% with few-shot prompting) in "pediatric ophthalmology." We concluded that ChatGPT could be one of the advanced technologies for practical tools in Japanese ophthalmology., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Sakai et al.)

Purpose: To describe a novel case of bilateral rapidly progressive retinopathy after immunotherapy with pembrolizumab for metastatic urothelial carcinoma., Methods: Case report., Results: A 64-year-old man undergoing pembrolizumab immunotherapy was referred to our hospital because of bilateral acute vision loss. His best-corrected visual acuity was 20/30 in the right eye and 20/320 in the left eye, and a visual field test revealed central and paracentral scotomas in the right eye and central scotoma in the left eye. We suspected immune-related retinopathy based on the progressive photoreceptor damage with abnormal electroretinogram findings, absence of overt intraocular inflammation, and presence of malignancy. Cessation of pembrolizumab and steroid pulse therapy followed by decreasing oral prednisolone improved visual function and photoreceptor damage, although there was recurrence after pembrolizumab was restarted., Conclusion: We reported a case of rapidly progressive retinopathy that may have been triggered by pembrolizumab immunotherapy for metastatic urothelial carcinoma. High-dose corticosteroid pulse therapy was effective in reversing photoreceptor damage., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Electrochemical dehydrogenative C-O bond formation for the synthesis of sultones was achieved. In the presence of K 2 CO 3 and H 2 O, constant current electrolysis of [1,1'-biphenyl]-2-sulfonyl chloride afforded an aryl-fused sultone quantitatively. Under the optimized conditions, a variety of sultone derivatives were obtained. Control experiments suggest that the electrochemical oxidation of the sulfonates generated in situ would afford sulfo radical intermediates.

Purpose: Novel therapeutic options, such as regenerative medicine and gene therapy, are now emerging as viable treatment options for patients with severe visual impairments, such as retinitis pigmentosa (RP). Gradable assessment of patients' visual function is essential to consider treatment options and to evaluate treatment outcomes; however, evaluation of visual function in patients with advanced low vision is often challenging because of patients' poor and sometimes unpredictable responses. In this study, we attempted to accurately assess visual capabilities and disease stage in patients with RP with a visual acuity (VA) of ≤ 0.01., Design: Retrospective analysis of visual function indicators, including VA, retinal thickness, full-field stimulus testing (FST), and chromatic pupillometry., Subjects: Overall, 43 patients (84 eyes) with advanced RP with a VA of ≤ 0.01 visited Kobe City Eye Hospital from 2019 to 2021., Methods: Hierarchical (multilevel) Bayesian modeling was used to estimate individual eye's pupil response and FST threshold, taking into account the ambiguity and randomness often observed in patients with ultralow vision. Using the estimated ability obtained from each test, the correlation between each test and retinal thickness was further analyzed to make a comprehensive assessment of the data., Main Outcome Measures: Visual acuity, retinal thickness, FST threshold, and pupil diameter change to different light stimuli., Results: Full-field stimulus testing and pupillometry measurements were moderately correlated with VA but exhibited a wide range of values within the same VA groups. Full-field stimulus testing was not correlated with central retinal thickness at counting fingers/hand motion VA range and seemed to reflect overall remaining photoreceptor function, including peripheral retina. Pupillometry may be able to distinguish between different levels of inner retinal function., Conclusions: The combination of pupillometry and FST allowed for graded evaluation of visual function within patients grouped in the same VA groups in patients with advanced RP with ultralow vision., Financial Disclosures: Proprietary or commercial disclosure may be found after the references., (© 2023 by the American Academy of Ophthalmology.)

Purpose: This study retrospectively evaluated the 12-month outcomes of the Zenith Alpha Abdominal Endovascular graft (Zenith Alpha AAA, Cook, Inc, Bloomington, Indiana), which was launched partially in Japan in March 2019, starting with 9 selected sites., Methods: A retrospective analysis was performed of all endovascular aneurysm repairs (EVAR) for abdominal aortic aneurysms using the Zenith Alpha AAA. Late complications were defined as any aneurysm-related events occurring >30 days after EVAR, including an aneurysm sac enlargement of >5 mm and any reinterventions performed. Endoleaks without sac enlargement or reinterventions were excluded from late complications., Results: During the study period, 79 EVARs using the Zenith Alpha AAA were performed. The mean age was 76.6±6.9 years old, 91.1% of patients were male, and the mean aneurysm diameter was 51.1±7.5 mm. Instructions for use violation was observed in 27 patients (34.2%), most frequently being a severely angulated proximal neck (>60°). There were 4 intraoperative complications, including 2 unintentional partial renal artery coverages caused by the premature anchoring of the exposed suprarenal stent barb to the aortic wall, which was a result of the design change of the top cap deletion. Since it was a partial coverage without flow impairment and since renal stenting was unsuccessful, it was left untreated and had no subsequent renal function impairment. During the mean follow-up of 444±123 days, 74 patients completed 12 months of follow-up. Freedom from late complications at 12 months was 90.8%, which included 2 limb occlusions (2.5%). Of 71 patients with a 12-month computed tomography scan, there was only 1 type 1a endoleak (1.3%), 1 sac enlargement of >5 mm (1.3%), and an aneurysm sac shrinkage of >5 mm was observed in 42.2% of patients. There was no type 3 endoleak during the follow-up., Conclusions: This study demonstrated that the new generation of low-profile Zenith Alpha AAA has satisfactory early clinical outcomes, comparable to those obtained with the conventional Zenith endovascular graft. Long-term follow-up is needed to determine whether these favorable outcomes persist.

The stereochemistry of pericyclic reactions is explained by orbital symmetry conservation, referred to as the Woodward-Hoffmann (WH) rule. Although this rule has been verified using the structures of reactants and products, the temporal evolution of the orbital symmetry during the reaction has not been clarified. Herein, we used femtosecond soft X-ray transient absorption spectroscopy to elucidate the thermal pericyclic reaction of 1,3-cyclohexadiene (CHD) molecules, i.e. , their isomerization to 1,3,5-hexatriene. In the present experimental scheme, the ring-opening reaction is driven by the thermal vibrational energy induced by photoexcitation to the Rydberg states at 6.2 eV and subsequent femtosecond relaxation to the ground state of CHD molecules. The direction of the ring opening, which can be conrotatory or disrotatory, was the primary focus, and the WH rule predicts the disrotatory pathway in the thermal process. We observed the shifts in K-edge absorption of the carbon atom from the 1s orbital to vacant molecular orbitals around 285 eV at a delay between 340 and 600 fs. Furthermore, a theoretical investigation predicts that the shifts depend on the molecular structures along the reaction pathways and the observed shifts in induced absorption are attributed to the structural change in the disrotatory pathway. This confirms that the orbital symmetry is dynamically conserved in the ring-opening reaction of CHD molecules as predicted using the WH rule.

Purpose: To investigate the long-term outcomes of cataract surgery for glaucoma management in patients with primary angle-closure disease (PACD)., Study Design: Retrospective case series., Methods: We reviewed the medical records of 87 eyes of 87 patients with PACD who underwent uncomplicated cataract surgery alone at the Kobe City Medical Center General Hospital. Only patients with a minimum follow-up of 10 years were included. The patients were divided into PACD spectrum categories: primary angle-closure glaucoma (PACG), primary-angle closure (PAC), and primary angle-closure suspect (PACS). The treatment outcomes were compared among the 3 groups. Intraocular pressure (IOP), number of glaucoma eye drops, requirement of additional glaucoma treatment, visual field progression, and progression to glaucoma during the follow-up period were evaluated., Results: Among the 87 patients, 39 had PACG; 26, PAC; and 22, PACS. Ten years after surgery, the IOP had significantly decreased from baseline in all 3 groups. The rate of requirement of additional glaucoma treatment during the follow-up period was significantly higher in the PACG group than in the other groups. Almost half of the patients with PACG required additional glaucoma treatment; of those patients, six (15.4%) underwent glaucoma surgery. Three patients (11.5%) with PAC required additional glaucoma medication. Visual field progression was observed in 28.1% of the patients with PACG. In 1 patient with PAC, the condition progressed to PACG, but there was no such progression in any of the patients with PACS., Conclusions: We confirmed that cataract surgery had a long-term (> 10 years) effect on IOP reduction in eyes with PACD. Early intervention with cataract surgery may be preferable for glaucoma management in patients with PACD., (© 2022. Japanese Ophthalmological Society.)

Purpose: To identify the genotypic and phenotypic characteristics of rhodopsin (RHO)-associated retinitis pigmentosa (RP) in the Japanese population., Study Design: Cross-sectional, single-center study METHODS: The medical records of 1336 patients with RP who underwent genetic testing at our clinic between November 2008 and September 2021 were reviewed, and patients with RHO variants were included. The patients were divided into class A and class B to assess genotype-phenotype correlations based on previous reports. The clinical findings, including best-corrected visual acuity (BCVA), OCT parameters (ellipsoid zone [EZ] width and central retinal thickness [CRT]), and presence of macular degeneration, of the 2 groups were compared., Results: The study included 28 patients diagnosed with RHO-associated RP (class A, 19; class B, 9). The BCVA was significantly worse in class A patients than in class B patients (P = 0.045). Superior EZ width was significantly shorter in class A than in class B patients (P = 0.016). Class A patients tended to have thinner CRT and shorter inferior EZ width than those of class B patients, although this difference was not significant. Macular degeneration was observed in 61.5% of class A and 12.5% of class B patients, demonstrating that macular degeneration can be a common complication in class A variants., Conclusion: Patients with class A variants presented with a severer form of RP than that of patients with class B variants in the Japanese population. These results suggest that the phenotype of RHO-associated RP is linked to the location of the variants and that such a genotype-phenotype correlation is less affected by ethnicities with different genetic backgrounds., (© 2023. Japanese Ophthalmological Society.)

Objective: To predict the visual prognosis of cataract surgery in patients with retinitis pigmentosa by measuring ellipsoid zone (EZ) width using spectral-domain optical coherence tomography., Methods: This retrospective study included patients with retinitis pigmentosa who underwent uncomplicated cataract surgery between December 2017 and June 2020. Preoperative best-corrected visual acuity (BCVA) and the best postoperative BCVA during follow-up were collected. EZ width was measured on preoperative cross-sectional optical coherence tomography images along the horizontal/vertical meridian through the fovea., Results: Thirty-eight eyes of 38 patients (22 female; mean [±standard deviation] age, 62.1 ± 11.8 years) were included. The median preoperative logarithm of the minimum angle of resolution BCVA of 0.52 (range, 0.00-3.00) significantly improved to 0.07 (range, -0.18-3.00) after surgery (P < 0.001). On preoperative spectral-domain optical coherence tomography images, the median horizontal, vertical, and average EZ widths were 783 (range, 0-9837), 761 (range, 0-10 250), and 769 (range, 0-10 043) μm, respectively. Postoperative BCVA significantly correlated with the horizontal (r = -0.784, P < 0.001), vertical (r = -0.777, P < 0.001), and average EZ widths (r = -0.777, P < 0.001). The area under the receiver operating characteristic curve for the ability of the horizontal, vertical, and average EZ widths to discriminate eyes with and without postoperative BCVA ≤ 0.3 was 0.971, 0.960, and 0.963, respectively, with best cut-off values of 513, 608, and 515 μm, respectively., Conclusions: EZ width measurement can help predict the visual prognosis of cataract surgery in patients with retinitis pigmentosa. A preferable visual acuity prognosis can be expected in patients with an EZ width of approximately 600 μm., (© 2021. The Author(s).)

Transplantation of embryonic/induced pluripotent stem cell-derived retina (ESC/iPSC-retina) restores host retinal ganglion cell light responses in end-stage retinal degeneration models with host-graft synapse formation. We studied the immunological features of iPSC-retina transplantation using major histocompatibility complex (MHC)-homozygote monkey iPSC-retinas in monkeys with laser-induced retinal degeneration in MHC-matched and -mismatched transplantation. MHC-mismatched transplantation without immune suppression showed no evident clinical signs of rejection and histologically showed graft maturation without lymphocytic infiltration, although immunological tests using peripheral blood monocytes suggested subclinical rejection in three of four MHC-mismatched monkeys. Although extensive photoreceptor rosette formation was observed on histology, evaluation of functional integration using mouse models such as mouse ESC-retina (C57BL/6) transplanted into rd1(C3H/HeJ, MHC-mismatched model) elicited light responses in the host retinal ganglion cells after transplantation but with less responsiveness than that in rd1-2J mice (C57BL/6, MHC-matched model). These results suggest the reasonable use of ESC/iPSC-retina in MHC-mismatched transplantation, albeit with caution., Competing Interests: Conflicts of interests S.Y. is an employee at Sumitomo Pharma Co., Ltd. M.T. is a founder and the president of Vision Care, Inc., and a board member of Sysmex., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Blue carbon ecosystems (BCEs) are a promising resource for the mitigation of global warming; however, climate spectrums and anthropogenic activities could influence the fragile balance of BCEs as carbon sinks or sources. We assess how oyster farming affects dissolved inorganic carbon (DIC) and total alkalinity (TA) on CO 2 fluxes in a mangrove-dominated lagoon. Water physical, chemical and biological parameters were recorded by in-situ buoys within the lagoon and at its inflow. Structural equation modeling was adopted to clarify the factors/processes controlling the partial pressure of CO 2 (pCO 2 ). A three-dimensional environmental model followed by a conceptual DIC model was used to quantify the spatiotemporal patterns of capture and release of DIC and TA by oyster production. The results showed that 49% of TA and DIC released from mangroves was depleted by oyster shell formation. DIC was reduced by algal photosynthesis and algal was served as a food source supporting oyster production. Annual oyster production through phytoplankton photosynthesis accounted for 11% of the atmosphere carbon inflows, suggesting that oyster production served as a significant atmospheric/terrestrial carbon sink in the lagoon. The results indicate that mangroves benefit local oyster production by acting as an important source of DIC and TA, and that the oyster aquaculture contributed to carbon capture in a mangrove-dominated lagoon ecosystem., Competing Interests: Declaration of competing interest The authors declared that they have no competing interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

cis,cis-Muconate (ccMA) is a promising platform for use in synthesizing various polymers. A glucose-free ccMA production using Pseudomonas sp. NGC7 from hardwood lignin-derived aromatic compounds was previously reported. In that system, syringyl nucleus compounds were essential for growth. Here, it is shown that NGC7 is available for glucose-free ccMA production even from a mixture of lignin-derived aromatics that does not contain syringyl nucleus compounds. By introducing a gene set for the protocatechuate (PCA)-shunt consisting of PCA 3,4-dioxygenase and PCA decarboxylase into an NGC7-derived strain deficient in PCA 3,4-dioxygenase and ccMA cycloisomerase, it was succeeded in constructing a ccMA-producing strain that grows on a lignin-derived aromatics mixture containing no syringyl nucleus compounds. Finally, it is demonstrated that the engineered strain produced ccMA from sugar cane bagasse alkaline extract in 18.7 mol%. NGC7 is thus shown to be a promising microbial chassis for biochemicals production from lignin-derived aromatics., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

This study aimed to evaluate the distribution of retinal pigment epithelium (RPE) melanin in patients with retinitis pigmentosa (RP) using entropy measurements by custom-made polarization-sensitive optical coherence tomography (PS-OCT) images, and compare entropy with the intensity of short-wavelength (SW) and near-infrared (NIR) autofluorescence (AF). We retrospectively reviewed the retinal images, including PS-OCT, SW-AF, and NIR-AF of patients with RP who had a hyperautofluorescent ring on AF. A total of 12 eyes of 12 patients (8 women and 4 men; mean age: 37.9 years) were included. There was a strong positive correlation between entropy value and NIR-AF intensity (r = 0.626, p < 0.001), and there was a very weak negative correlation between entropy value and SW-AF (r = - 0.197, p = 0.001). The mean values of the entropy in the foveal, temporal (2 mm from the fovea), and nasal (2 mm from the fovea) sections were 0.41 (± 0.09), 0.29 (± 0.08), and 0.26 (± 0.08), respectively. The entropy was significantly higher in the foveal section than in the temporal and nasal sections (p = 0.002 and p = 0.003, respectively). There was no significant difference between the entropies values for the temporal and nasal sections (p = 0.157). Age, logMAR best-corrected visual acuity, ellipsoid zone width, and central retinal thickness were not correlated with foveal entropy. We presented RPE melanin imaging in patients with RP using PS-OCT for the first time. PS-OCT can be a useful tool for monitoring patients with RP., (© 2022. The Author(s).)

Aim: To investigate the one-year outcomes and factors that influence the results of microhook ab interno trabeculotomy (µLOT)., Methods: The medical records of consecutive patients with open angle glaucoma who underwent µLOT (including combination of µLOT and cataract surgery) between February 2018 and July 2019 were retrospectively reviewed. Surgical success was defined as the following: an intraocular pressure (IOP)≤21 mm Hg or IOP≤preoperative IOP with a reduced number of glaucoma eye drops, without additional glaucoma surgery, and assessed using Kaplan-Meier survival analysis. A multivariate Cox proportional-hazards regression model was used to investigate the factors associated with surgical failure., Results: The 59 eyes of 59 patients comprising 28 eyes with primary open angle glaucoma (POAG) and 31 with secondary open angle glaucoma (SOAG) were included. The mean IOP and number of glaucoma eye drops significantly decreased from 25.3±7.2 mm Hg and 3.9±1.1, preoperatively to 16.1±4.4 mm Hg ( P <0.01) and 2.1±1.8 ( P <0.01), respectively, 12mo postoperatively, with a cumulative success rate of 63.1%. The one-year success rate was significantly higher in POAG eyes than in SOAG eyes (80.0% vs 48.0%; P =0.011, log-rank test). Multivariate analyses revealed SOAG [ P =0.017, adjusted hazard ratio (aHR): 3.468, 95%CI: 1.246-9.654] and the postoperative IOP spike (IOP>25 mm Hg within 2wk post-surgery; P <0.001, aHR: 5.382, 95%CI: 2.113-13.707) as independent factors associated with surgical failure., Conclusion: The µLOT is a good treatment option for POAG eyes. However, the postoperative course should be carefully followed in cases with postoperative IOP spike., (International Journal of Ophthalmology Press.)

Purpose: To compare the accuracy of intraoperative aberrometry (IA) for predicting postoperative refraction between eyes with emmetropia and myopia targets., Patients and Methods: This retrospective analysis included patients with axial myopia (axial length ≥ 25.0 mm) who underwent uncomplicated phacoemulsification cataract surgery with IA to achieve emmetropia (plano to -0.5 D) or intentional myopia (-2.5 D to -5.0 D). Preoperative ocular biometry was performed in all eyes using an IOLMaster. Refractive prediction errors in IA were compared between eyes with emmetropia and myopia targets. Refractive prediction errors in IA for both groups were also compared with those predicted by intraocular lens power calculation formulas including the SRK/T, Holladay 1, Hoffer Q, Holladay 2, Haigis, and Barrett Universal II formulas., Results: Thirty-nine eyes of 39 patients with a target of emmetropia and 22 eyes of 22 patients with a target of intentional myopia were included in the final analysis. The mean numerical error was significantly different from zero (myopic trend) in myopia-targeted eyes (-0.37 ± 0.54 D, one-sample t -test, P = 0.004, 95% confidence interval: -0.61 to -0.14), while it was close to zero in emmetropia-targeted eyes. The mean absolute error was significantly smaller in emmetropia-targeted eyes (0.28 ± 0.27 D) than in myopia-targeted eyes (0.51 ± 0.41 D, P = 0.01). IA was revealed as the most accurate method for predicting postoperative refraction in eyes with emmetropia target, whereas Barrett Universal II formula was found to be the most accurate for eyes with myopia target., Conclusion: In patients with axial myopia, the performance of IA was altered when targeting intentional myopia compared with emmetropia. Myopic shift in the refractive outcome should be considered when IA is used to target myopia., Competing Interests: Dr Yasuo Kurimoto reports grants and/or personal fees from Astellas, Santen, Tomey, Nikon, Sumitomo Dainippon Pharma, AMO Japan, Senju, Kowa, Alkon Japan, Bayer, Pfizer, Novartis, and Viatris, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2022 Sakai et al.)

A 67-year-old man had left upper lung cancer with invasion into the descending aorta. He underwent pre-emptive thoracic endovascular aortic repair using a Valiant Navion followed by left lung upper lobectomy with resection of the aortic wall. Because of continuous bleeding, he underwent re-thoracotomy. Since the surgically resected aortic wall was largely cleaved, bleeding around the stent-graft that herniated into the left pleural cavity was observed. Re-thoracic endovascular aortic repair using a GORE TAG was immediately performed to prevent further stent-graft herniation and impending lethal haemorrhage. It may be necessary to consider reinforcement of the resected aortic wall to prevent thoracic endovascular aortic repair-related complications., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Purpose: To investigate the relationships between indications for thoracic endovascular aortic repair for acute/subacute complicated Stanford type B aortic dissection and clinical outcomes, and complications specific to thoracic endovascular aortic repair., Material and Methods: The J-predictive study retrospectively collected data of patients treated with thoracic endovascular aortic repair for complicated Stanford type B aortic dissection at 20 institutions from January 2012 to March 2017. From the database, those treated for acute/subacute complicated Stanford type B aortic dissection were extracted (n = 118; 96 men; average age, 66.1 years; standard deviation, ± 13) and classified into groups 1, 2, and 3 according to thoracic endovascular aortic repair indications (rupture, superior mesenteric artery malperfusion, and renal or lower extremity malperfusion, respectively). Primary and secondary measures were mortality (overall and aortic-related) and complications related to thoracic endovascular aortic repair, respectively. For each outcome, the risks of being in groups 1 and 2 were statistically compared with that of being in group 3 as a control using Fisher's exact test., Results: Mortality rate (odds ratio, 5.22; 95% confidence interval [CI], 1.33-20.53) and prevalence of paraparesis/paraplegia (odds ratio, 30.46; confidence interval, 1.71-541.77) were higher in group 1 than in group 3. Compared to group 3, group 2 showed no statistically significant differences in mortality or complications related to thoracic endovascular aortic repair., Conclusions: Rupture as an indication for thoracic endovascular aortic repair for type B aortic dissection was more likely to result in worse mortality and high prevalence of spinal cord ischemia., Level of Evidence: Level 4, Case series., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

Background: This study aimed to identify the features of ocular biometry in patients with EYS-related retinitis pigmentosa using IOLMaster 700., Methods: We retrospectively reviewed the medical records of patients with retinitis pigmentosa. Patients with records of the following were included: (1) ocular biometry measurements using the IOLMaster 700 and (2) genetic diagnostic tests. Axial length, keratometry, anterior chamber depth, aqueous depth, lens thickness, central corneal thickness (CCT), and corneal diameter (white to white) measurements were extracted. Based on keratometry measurements, (1) standard keratometric astigmatism, (2) posterior corneal astigmatism, and (3) total corneal astigmatism were obtained. Demographics and biometric parameters were compared between patients with EYS-related retinitis pigmentosa and other patients with retinitis pigmentosa., Results: A total of 86 eyes of 44 patients (23 females and 21 males; mean age: 47.7 years) with retinitis pigmentosa were included. Of these, 18 were identified as having EYS variants. CCT was significantly thinner (P < 0.001) and the posterior corneal curvature at the steepest meridian was significantly smaller (P = 0.024) in patients with EYS-related retinitis pigmentosa than in other patients with retinitis pigmentosa. The magnitudes of all corneal astigmatism measurements was higher in patients with EYS-related RP, although these differences were not statistically significant., Conclusion: Patients with EYS-related retinitis pigmentosa had unique features in ocular biometry, such as thinner central corneal thickness and smaller posterior corneal curvature radius at the steepest meridian compared with other patients with retinitis pigmentosa. The findings suggest that patients with retinitis pigmentosa have different ocular dimension features among the different causative genes., (© 2022. The Author(s).)

The retinal pigment epithelium (RPE) is essential for the survival and function of retinal photoreceptor cells. RPE dysfunction causes various retinal diseases including age-related macular degeneration (AMD). Clinical studies on ES/iPS cell-derived RPE transplantation for RPE dysfunction-triggered diseases are currently underway. Quantification of the diseased RPE area is important to evaluate disease progression or the therapeutic effect of RPE transplantation. However, there are no standard protocols. To address this issue, we developed a 2-step software that enables objective and efficient quantification of RPE-disease area changes by analyzing the early-phase hyperfluorescent area in fluorescein angiography (FA) images. We extracted the Abnormal region. This extraction was based on deep learning-based discrimination. We scored the binarized extracted area using an automated program. Our program's performance for the same eye from the serial image captures was within 3.1 ± 7.8% error. In progressive AMD, the trend was consistent with human assessment, even when FA images from two different visits were compared. This method was applicable to quantifying RPE-disease area changes over time, evaluating iPSC-RPE transplantation images, and a disease other than AMD. Our program may contribute to the assessment of the clinical course of RPE-disease areas in routine clinics and reduce the workload of researchers., (© 2022. The Author(s).)

Purpose: To compare the accuracy of the intraocular lens (IOL) power calculation formulas for predicting the postoperative refraction in eyes with a target of emmetropia or intentional myopia., Patients and Methods: This is a retrospective study conducted at Kobe City Eye Hospital, Kobe, Japan. Fifty eyes of 50 patients with axial myopia who underwent uncomplicated phacoemulsification and single-type IOL implantation for a target of emmetropia (plano to -0.5 D) or intentional myopia (-2.0 D to -3.0 D) were selected. Preoperative ocular biometry was performed using IOLMaster700 in all eyes. Refractive prediction errors of 6 IOL formulas integrated into IOLMaster700 were compared between eyes with a target of emmetropia and intentional myopia., Results: The mean numerical errors of SRK/T (Sanders, Retzlaff, and Kraft/theoretical), Holladay 1, Hoffer Q, and Holladay 2 significantly differed between the two groups (p < 0.001, p = 0.008, 0.02, and 0.007, respectively). The values for mean numerical errors in eyes with a target of intentional myopia were smaller, showing relatively myopic outcome, as compared with those in eyes with a target of emmetropia. In eyes with a target of emmetropia, the mean numerical errors of Holladay 1 (p < 0.001, 95% confidence interval [CI]: 0.32 to 0.63), Hoffer Q (p = 0.001, 95% CI: 0.12 to 0.42), and Barrett Universal II (p = 0.007, 95% CI: 0.06 to 0.35) were significantly different from zero (hyperopic trend). Furthermore, in eyes with a target of intentional myopia, the mean numerical error of SRK/T (p = 0.001, 95% CI: -0.61 to -0.17) and Holladay 2 (p = 0.023, 95% CI: -0.43 to -0.04) were significantly different from zero (myopic trend)., Conclusion: In patients with axial myopia, some IOL formulas may show a myopic trend in the refractive outcome when targeting intentional myopia as compared to emmetropia., Competing Interests: The authors declare no conflicts of interest., (© 2021 Sakai et al.)

Purpose: To evaluate tangential morphological changes in the outer retina and assess their correlation with the degree of metamorphopsia in patients with idiopathic epiretinal membrane (ERM)., Methods: This retrospective study included patients with idiopathic ERM who underwent vitrectomy between January 2018 and December 2019. We evaluated the preoperative examination results. Using cross-sectional spectral-domain optical coherence tomography (OCT) images along the horizontal/vertical meridian through the fovea, we defined a new parameter, tangential displacement (TD), as the tangential component of the position vector of the distorted outer nuclear layer caused by ERM. Visual function measurements included M-CHARTS results (vertical/horizontal metamorphopsia score [MV/MH]) and best-corrected visual acuity (BCVA). The correlations among the OCT parameters including TD and central foveal thickness (CFT) with visual function measurements were determined., Results: Overall, 78 eyes of 76 patients (49 females; mean age, 67.9 [± standard deviation, 7.5 years]) were included. The mean horizontal TD was 24.0 ± 73.9 μm, which was significantly different from 0 (p = 0.005). The mean vertical TD was 6.0 ± 76.2 μm, which was not significantly different from 0. The absolute value of horizontal TD was significantly correlated with MV (r = 0.513, p < 0.01) and MH (r = 0.423, p < 0.01). The absolute value of vertical TD was also significantly correlated with MV (r = 0.274, p = 0.02) and MH (r = 0.413, p < 0.01). However, neither value was significantly correlated with BCVA. Multiple regression analysis showed that the horizontal absolute TD was an independent factor associated with both MV (β = 0.635, p < 0.001) and MH (β = 0.259, p = 0.048)., Conclusion: We found that ERM tended to distort the outer retinal layer toward the temporal side of the fovea. The tangential distortion of this layer was associated with the degree of metamorphopsia, suggesting that misalignment of parafoveal photoreceptors causes metamorphopsia in patients with ERM., (© 2021. The Author(s).)

The first Cu-catalyzed dehydrogenative C-O cyclization for the synthesis of furan-fused thienoacenes is described. A variety of heteroacenes including a thieno[3,2- b ]furan or a thieno[2,3- b ]furan skeleton were synthesized by intramolecular C-H/O-H coupling. The use of a mixed solvent of N -methyl-2-pyrrolidone, ethylene glycol monomethyl ether, and toluene was essential for suppressing side reactions and efficiently promoting the reaction. Double C-O cyclization was also conducted to afford highly π-expanded furan-fused thienoacenes.

Background: Primary angle closure disease (PACD) is a type of glaucoma in which the intraocular pressure (IOP) is increased because of the blockage of the anterior chamber angle. Medications contraindicated for patients with PACD, such as anticholinergics, cause mydriasis, and can elevate IOP. However, anticholinergics are currently contraindicated only for primary angle closure glaucoma (PACG) in Japanese package inserts. In this study, we investigated the prescription status of medications contraindicated for PACD, such as anticholinergics, in patients with PACD scheduled for eye surgeries., Methods: Forty-three Japanese patients diagnosed with PACD at Kobe City Eye Hospital, Japan, and scheduled hospitalization for eye surgeries between December 2017 and July 2018, were included. Data, including sex, age, diagnosis, IOP, anterior chamber depth, and patients' regular medications prior to hospitalization, were collected for each patient from the electronic medical records., Results: The number of patients with chronic primary angle closure (CPAC) and acute primary angle closure (APAC) was 35 (81.4%) and 8 (18.6%), respectively. Among all the 43 patients with PACD, 8 (18.6%) received 15 medications that are potentially contraindicated for PACD by non-ophthalmologist. According to medication categories, benzodiazepine hypnotics were the most commonly prescribed. Among the 8 patients with APAC, 2 (25.0%) had routinely received medications contraindicated for PACD. The median number of all kinds of prescriptions on the day of hospitalization was significantly higher for patients who received medications contraindicated for PACD than for those who did not receive them (p = 0.010)., Conclusions: About 20% of patients with PACD received medications potentially contraindicated for PACD, such as anticholinergics. Attention should be paid to patients prescribed multiple drugs for adverse events, such as increase in intraocular pressure.

Purpose: Patients with an eye disease often report nyctalopia, hemianopia, and/or photophobia. We hypothesized that such symptoms are related to the disease impacting the dynamic range of lightness perception (DRL). However, there is currently no standardized approach for measuring DRL for clinical use. We developed an efficient measurement method to estimate DRL., Study Design: Clinical trial METHODS: Fifty-five photophobic patients with eye disease and 46 controls participated. Each participant judged the appearance of visual stimuli, a thick bar with luminance that gradually changed from maximum to minimum was displayed on uniform background. On different trials the background luminance changed pseudo-randomly between three levels. The participants repeatedly tapped a border on the bar that divided the appearance of grayish white/black and perfect white/black. We defined the DRL as the ratio between the luminance values at the tapped point of the border between gray and white/black., Results: The mean DRL of the patients was approximately 15 dB, significantly smaller than that of the controls (20 dB). The center of each patient's DRL shift depending on background luminance, which we named index of contextual susceptibility (iCS), was significantly larger than controls. The DRL of retinitis pigmentosa was smaller than controls for every luminance condition. Only the iCS of glaucoma was significantly larger than controls., Conclusions: This measurement technique detects an abnormality of the DRL. The results support our hypothesis that the DRL abnormality characterizes lightness-relevant symptoms that may elucidate the causes of nyctalopia, hemeralopia, and photophobia.

Age-related macular degeneration (AMD) is a highly prevalent irreversible impairment in the elderly population worldwide. Stem cell therapies have been considered potentially viable for treating AMD through the direct replacement of degenerated cells or secretion of trophic factors that facilitate the survival of existing cells. Among them, the safety of pluripotent stem cell-derived retinal pigment epithelial (RPE) cell transplantation against AMD, and some hereditary retinal degenerative diseases, has been discussed to a certain extent in clinical studies of RPE cell transplantation. Preparations are in progress for its clinical application. On the other hand, clinical trials using somatic stem cells are also being conducted, though these had controversial outcomes. Retinal regenerative medicine using stem cells is expected to make steady progress toward practical use while new technologies are incorporated from various fields, thereby making the role of ophthalmologists in this field increasingly important.

The first electrochemical synthesis of diarylphosphole oxides (DPOs) was achieved under mild conditions. The practical protocol employs commercially available and inexpensive DABCO as a hydrogen atom transfer (HAT) mediator, leading to various DPOs in moderate to good yields. This procedure can also be applied to the synthesis of six-membered phosphacycles, such as phenophosphazine derivatives. Mechanistic studies suggested that the reaction proceeds via an electro-generated phosphinyl radical.

Objectives: We investigated the validity of the surgical strategy for aortic arch aneurysm depending on the patient's condition., Methods: Between 2014 and 2019, 70 patients underwent total arch replacement (TAR) and 14 patients underwent fenestrated thoracic endovascular aortic repair( fTEVAR) for aortic arch aneurysm. We selected the surgical strategy on the basis of the patient's condition with or without frailty and if surgical risks including cancer or a respiratory condition precluded open surgery., Results: The preoperative average ages were 73.3±7.8 years in the TAR group and 73.9±6.1 years in the fTEVAR group (p=0.93). EuroSCORE Ⅱ was 4.3±3.6 in the TAR group and 6.0±3.3 in the fTEVAR group (p=0.03). Frailty was observed in 11 patients (15.7%) in the TAR group and fivepatients (35.7%) in the fTEVAR group (p=0.08). In the fTEVAR group, there were three patients (21.4%) with cancer and three patients (21.4%) with a respiratory condition that precluded open surgery. The overall 30-day mortality rate was 0% for both groups, and the in-hospital mortality rate was 2.9% in the TAR group and 0% in the fTEVAR group (p=0.52). The incidence of stroke was 2.9% (two patients) in the TAR group and 7.1%( one patient) in the fTEVAR group( p=0.43). However, all stroke patients were able to walk at discharge. The cumulative survival rate was 88.9% and 83.5% in the TAR group and 85.1% and 68.1% in the fTEVAR group at two and five years, respectively (p=0.173). There were both 98.1% of patients in the TAR group and 85.7% and 75.0% of patients in the fTEVAR group who were free from reoperations at two and five years, respectively( p<0.01)., Conclusions: Our surgical strategy and outcomes for aortic arch aneurysm were generally appropriate. It is important to select open surgery or TEVAR depending on the patient's condition.

Surgical indication and treatment for patients with Kommerell diverticulum and aberrant subclavian artery are still not well established. A patient with esophageal and tracheal compression resulting from these anatomical abnormalities was successfully treated with a hybrid approach of total arch replacement, frozen elephant trunk technique, aberrant left subclavian artery transection, and left subclavian artery reconstruction through median sternotomy. Compressive symptoms were relieved without resecting the enlarged diverticulum. In this case, the importance of preoperative investigation for the main cause of compressive symptoms is illustrated and a novel treatment strategy is outlined., Competing Interests: Disclosure StatementAll authors declare no conflict of interest., (© 2021 The Editorial Committee of Annals of Vascular Diseases.)

Introduction: Nitrofurantoin is a well-established antibiotic, and is an important first-line oral treatment for uncomplicated urinary tract infections. However, little information is available with respect to its antibacterial activity in Japan, in vivo efficacy, or the in vivo biological cost of resistant strains., Methods: We compared the susceptibility of six representative antibacterial agents-nitrofurantoin, sulfamethoxazole/trimethoprim, fosfomycin, mecillinam, ciprofloxacin, and cefdinir-against E. coli clinically isolated in Japan during 2017. We evaluated the in vivo efficacy of nitrofurantoin using a model of mouse urinary tract infection caused by ciprofloxacin resistant E. coli. We obtained nitrofurantoin resistant isolates through tests generating spontaneous mutations, and assessed the in vivo fitness of nitrofurantoin resistant isolates., Results: The MIC 90 of nitrofurantoin was 16 μg/mL, and was the lowest among the drugs tested. It was found that, in the mouse urinary tract infection model, 30 mg/kg and 100 mg/kg of nitrofurantoin reduced the count of viable bacterial cells in the kidney, while 100 mg/kg of ciprofloxacin did not. All spontaneous bacterial mutants resistant to nitrofurantoin had deletions in the nfsA gene, and we found that the resistant strain had lower growth in the mouse urinary tract infection model than in the parent strain., Conclusions: We demonstrated promising in vitro and in vivo activity of nitrofurantoin against E. coli clinical isolates in Japan, and lower in vivo fitness of the resistant strain of nitrofurantoin., Competing Interests: Declaration of competing interest Satoshi Nakagawa, Yusuke Kurimoto, Masayuki Ezumi, Keisuke Nakatani, and Shingo Mizunaga are researchers of FUJIFILM Corporation. Mikamo H received research funding from Sumitomo Dai-nippon Pharma Co., Ltd., ASAHIKASEI Pharma Co. Ltd., AstellasPharma, MSD K.K., Shionogi & Co. Ltd., Taisho Pharma Co., Ltd., Daiichi-Sankyo, FUJIFILM Toyama Chemical Co. Ltd., Pfizer, MIYARISAN Pharmaceutical Co., Ltd., Meiji Seika Pharma; Consulting fee/honorarium from MSD K.K., Astellas Pharma, Daiichi-Sankyo, MSD K.K., MIYARISAN Pharmaceutical Co., Ltd., Shionogi., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objective : The treatment for arch aneurysms by endovascular repair is often difficult. This study evaluated the long-term outcomes of thoracic endovascular aortic repair for aortic arch aneurysms treated with the Najuta stent-graft system. Materials and Methods : From January 2009 to December 2019, 37 patients underwent treatment for aortic aneurysms with the Najuta stent graft system at two institutes, including our hospital. We retrospectively analyzed the short- and long-term clinical outcomes. Results : Of all 37 cases, the technical success rate was 97.3% (36 of 37). The mean proximal neck length was 20.1±5.3 mm. The postoperative results revealed 10 patients with type Ia endoleaks (27.8%), 6 with stroke (16.7%), and one with paraplegia (2.8%). In the chronic phase, the overall survival rates and the rates of freedom from aorta-related events at 7 years were 71.3% and 50.7%, respectively. Between two groups divided based on the proximal neck diameter of 20 mm, the <20-mm group had significantly higher rates of aorta-related events in terms of freedom from aortic events (P=0.046). Conclusion : The fenestrated stent graft can be a less invasive option for the treatment of high-risk patients with aortic aneurysms., Competing Interests: Disclosure StatementThe authors declare no conflict of interest., (© 2020 The Editorial Committee of Annals of Vascular Diseases.)

Objectives: Salivary glands produce brain-derived neurotrophic factor (BDNF), which increases plasma BDNF content. Salivary BDNF influences the hippocampus and enhances anxiety-like behaviors. Dyslipidemia affects the brain, promoting depression and anxiety-like behaviors. This study was performed to investigate whether hypertriglyceridemia influences salivary BDNF expression., Methods: Hypertriglyceridemia was induced in rats by high-fat diet intake for 10 weeks. BDNF protein levels in the saliva and submandibular glands were measured using enzyme-linked immunosorbent assay (ELISA). Bdnf mRNA levels in the submandibular gland were determined using real-time polymerase chain reaction., Results: A hypertriglyceridemia rat model was established. Body weight did not differ between the control and hypertriglyceridemia groups. Bdnf mRNA and protein expression was increased in the submandibular gland in the hypertriglyceridemia group compared to the control group. BDNF expression was also significantly increased in the saliva of the hypertriglyceridemia group., Conclusions: This is first study to show that hypertriglyceridemia induces BDNF expression in the rat submandibular gland and suggests that salivary BDNF is associated with lipid metabolism., Competing Interests: Conflicts of interest No potential conflict of interest was reported by the authors., (Copyright © 2020 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved.)

Imaging of melanin in the eye is important as the melanin is structurally associated with some ocular diseases, such as age-related macular degeneration. Although optical coherence tomography (OCT) cannot distinguish tissues containing the melanin from other tissues intrinsically, polarization-sensitive OCT (PS-OCT) can detect the melanin through spatial depolarization of the backscattered light from the melanin granules. Entropy is one of the depolarization metrics that can be used to detect malanin granules in PS-OCT and valuable quantitative information on ocular tissue abnormalities can be retrived by correlating entropy with the melanin concentration. In this study, we investigate a relationship between the melanin concentration and some depolarization metrics including the entropy, and show that the entropy is linearly proportional to the melanin concentration in double logarithmic scale when noise bias is corrected for the entropy. In addition, we also confirm that the entropy does not depend on the incident state of polarization using the experimental data, which is one of important attributes that depolarization metrics should have. The dependence on the incident state of polarization is also analyzed for other depolarization metrics.

Background: The Fitzgerald classification expresses the extension of hematoma from the ruptured abdominal aortic aneurysm (rAAA) and is related to a patient's preoperative status. The objective of this study was to propose a new decision-making method for emergency surgeries, endovascular aortic repair (EVAR), or open repair (OR) for rAAA based on the Fitzgerald classification using preoperative computed tomography images., Materials and Methods: A multicenter observational study was performed with a questionnaire survey of rAAA from August 2010 to July 2015 in Hokkaido, Japan, and sent to 20 institutions participating in the Hokkaido Society of Aortic Stent Graft. We included 205 patients who could be stratified by the Fitzgerald classification as the subjects of this study. We categorized these patients into Fitzgerald classes I and II (first category, n = 72) and classes III and IV (second category, n = 133). The short-term results of both EVAR and OR cases were examined in the 2 categories., Results: In the first category, patients in the EVAR group were older than those in the OR group. Nonetheless, the in-hospital mortality rate was lower in the EVAR group than in the OR group (0% vs. 18%; P = 0.019). In the second category, there was no difference in preoperative factors between the groups. The EVAR group showed a higher incidence rate of postoperative abdominal compartment syndrome than the OR group (12% vs. 2%; P = 0.042). The in-hospital mortality rate was comparable between the groups (24% vs. 25%; P = 0.80). Although there were no deaths in the EVAR group without preoperative shock, in-hospital mortality in the EVAR group of the second category with shock was 41% (vs. 28% in the OR group; P = 0.27). Furthermore, mortality in the EVAR group with Fitzgerald class IV was 100% (vs. 29% in the OR group; P = 0.049)., Conclusions: EVAR is recommended in Fitzgerald class I or II and also in Fitzgerald class III or IV without shock because the results of EVAR were better than those of OR. Because all patients who underwent EVAR died in Fitzgerald class IV, OR would be beneficial in this patient population., (Copyright © 2020 Elsevier Inc. All rights reserved.)