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Purpose: To investigate the long-term efficacy and safety of intravitreal brolucizumab (BRZ) injections in patients with typical neovascular age-related macular degeneration (typical nAMD) and polypoidal choroidal vasculopathy (PCV)., Methods: This multicentre retrospective study included 401 eyes of 398 patients with nAMD who received BRZ injection(s), with a follow-up duration of ≥12 months. Changes in best-corrected visual acuity (BCVA), retinal fluid evaluation and central subfield thickness (CST) on optical coherence tomography were assessed. The efficacy of BRZ was compared between typical nAMD and PCV groups., Results: Analyses were conducted with 280 eyes of 278 patients with typical nAMD and 121 eyes of 120 patients with PCV (mean age, 71.1 ± 8.6 years). 29 eyes (7.2%) were treatment naïve. The mean follow-up period was 15.3 ± 2.8 months; the mean number of BRZ injections within 1 year was 4.5 ± 1.7. BCVA was maintained during the follow-up period, and CST significantly improved from the first injection month and was maintained for 12 months in both the typical nAMD and PCV groups. The dry macula proportion increased from 2.7% at baseline to 56.1% at 1 month and 42.9% at 12 months. Among the 18 eyes that underwent indocyanine green angiography both before and after treatment, 10 (55.6%) showed polyp regression. Overall, the incidence of intraocular inflammation (IOI), retinal vasculitis and occlusive retinal vasculitis was 9.4% (38 eyes), 1.2% (5 eyes) and 0.5% (2 eyes), respectively. IOI occurred from the first to the sixth injections, with an average IOI onset of 28.5 ± 1.4 days. All eyes achieved IOI resolution, although the two eyes with occlusive retinal vasculitis showed a severe visual decline after IOI resolution., Conclusion: Brolucizumab was effective in maintaining BCVA and managing fluid in eyes with nAMD for up to 1 year, exhibiting a high polyp regression rate. However, the not uncommon incidence of IOI and the severe visual decline caused by the rare occlusive retinal vasculitis following BRZ treatment underscore the importance of careful monitoring and timely management., (© 2024 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To describe the clinical and genetic features of Korean patients with peripheral retinal flecks unrelated to aging., Methods: A retrospective analysis was conducted on the clinical characteristics of patients with symmetric peripheral retinal flecks. Age-related deposits such as reticular pseudodrusen were excluded, as well as secondary deposits related to intraocular inflammation, tumor, and drug toxicity. Multimodal imaging, electrophysiological examinations, and genetic testing were analyzed., Results: A total of 10 patients (2 males and 8 females) with bilateral peripheral flecks were enrolled in this study. A mean age at diagnosis was 30.5±19.6 years (4-59 years). Within the 10 patients, 6 were genetically confirmed with monogenic retinal disorders. Biallelic pathogenic variants in RDH5 were found in 5 patients, and 1 patient was diagnosed with retinopathy related to Alport syndrome due to a pathogenic variant in COL4A5. Although not genetically confirmed, one case associated with nanophthalmos and another case showing chorioretinal mottling in a carrier of ocular albinism have been identified. In one patient, genetic testing also revealed unknown causes. The mean logMAR initial visual acuity was 0.12±0.18 and 0.07±0.18 in right and left eyes, respectively. Night blindness was reported by 4 patients (40%), with 3 showing decreased or delayed rod response in electroretinogram, particularly those with RDH5 mutations. Differences in the deposit layers and the patterns of flecks were observed on multimodal imaging., Conclusions: In the study population, we observed various causes and clinical differences in the retinal fleck patterns among Koreans, including RDH5-related fundus albipunctatus and Alport syndrome. Despite reports of night blindness symptoms in some cases, all patients demonstrated satisfactory corrected visual acuity.

Purpose: To investigate the risk of retinal vascular occlusion in patients with Moyamoya disease (MMD)., Design: Retrospective, longitudinal cohort study using the Korean National Health Insurance Service database., Participants: Newly diagnosed MMD patients (n=34,627), who were diagnosed between 2004 and 2022, and their propensity score matched controls (n=136,945) were included., Methods: We identified retinal vascular occlusion events using diagnostic codes for central retinal artery occlusion, other retinal artery occlusion, and retinal vein occlusion. After a washout-period from 2002 to 2003, information on the diagnosis of retinal vascular occlusion was extracted in both MMD and control group during the follow up period. The association between MMD and the risk of subsequent retinal vascular occlusion was investigated using a time-dependent Cox proportional hazard model and Kaplan-Meier survival analysis with log-rank test adjusted for age, sex, and comorbidities., Main Outcome Measures: Hazard ratios (HRs) and 95% confidence intervals (CIs) for retinal vascular occlusion development according to the MMD., Results: MMD was associated with an increased risk of subsequent retinal vascular occlusion even after adjusting for confounding variables (HR, 1.22; 95% CI, 1.09-1.36). Among the subtypes of retinal vascular occlusion, central retinal artery occlusion showed a highest HR (2.23; 95% CI, 1.35-3.7). Incidence probability of retinal vascular occlusion was significantly higher among MMD patients than controls (P < 0.001, log-rank test)., Conclusion: In this nationwide population-based cohort study, patients with MMD in Korea had an elevated risk of retinal vascular occlusion, suggesting that the MMD is one of the risk factors for retinal vascular occlusion., (Copyright © 2024. Published by Elsevier Inc.)

Pregestational diabetes is a risk factor for congenital anomalies, including heterotaxy syndrome, a rare birth defect characterized by the abnormal arrangement of organs relative to the left-right (L-R) body axis. To provide insight into the underlying mechanism by which diabetes induces heterotaxy, we here analyzed the L-R axis of mouse embryos of diabetic dams. Various Pitx2 expression patterns indicative of disruption of L-R axis formation were apparent in such embryos. Expression of Nodal at the node, which triggers a Nodal-Pitx2 expression cascade in lateral plate mesoderm, showed marked regression associated with L-R axis malformation. This regression was similar to that apparent in Wnt3a -/- embryos, and canonical Wnt signalling was indeed found to be downregulated in embryos of diabetic dams. RNA sequencing revealed dysregulation of glycolysis in embryos of diabetic dams, and high glucose lowered intracellular pH in the primitive streak, leading to the suppression of Wnt signalling and the regression of Nodal expression. Of note, maternal vitamin A intake increased the incidence of L-R axis defects in embryos of diabetic dams, with dysregulation of retinoic acid metabolism being apparent in these embryos and in Wnt3a -/- embryos. Our results shed light on the mechanisms underlying embryopathies associated with maternal diabetes and suggest the importance of diet for prevention of heterotaxy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

To identify genetic influences on subfoveal choroidal thickness of older adults using a genome-wide association study (GWAS). We recruited 300 participants from the population-based Korean Longitudinal Study on Health and Aging (KLoSHA) and Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD) cohort studies and 500 participants from the Bundang age-related macular degeneration (AMD) cohort study dataset. We conducted a GWAS on older adult populations in the KLoSHA and KLOSCAD cohorts. Single nucleotide polymorphisms (SNPs) associated with choroidal thickness were identified with P values < 1.0 × 10 -4 in both the right and left eyes, followed by validation using the Bundang AMD cohort dataset. This association was further confirmed by a functional in vitro study using human umbilical vein endothelial cells (HUVECs). The ages of the cohort participants in the discovery and validation datasets were 73.5 ± 3.3 and 71.3 ± 7.9 years, respectively. In the discovery dataset, three SNPs (rs1916762, rs7587019, and rs13320098) were significantly associated with choroidal thickness in both eyes. This association was confirmed for rs1916762 (genotypes GG, GA, and AA) and rs7587019 (genotypes GG, GA, and AA), but not for rs13320098. The mean choroidal thickness decreased by 56.7 μm (AA, 73.8%) and 31.1 μm (GA, 85.6%) compared with that of the GG genotype of rs1916762, and by 55.4 μm (AA, 74.2%) and 28.2 μm (GA, 86.7%) compared with that of the GG genotype of rs7587019. The SNPs rs1916762 and rs7587019 were located close to the FAM124B gene near its cis-regulatory region. Moreover, FAM124B was highly expressed in vascular endothelial cells. In vitro HUVEC experiments showed that the inhibition of FAM124B was associated with decreased vascular endothelial proliferation, suggesting a potential mechanism of choroidal thinning. FAM124B was identified as a susceptibility gene affecting subfoveal choroidal thickness in older adults. This gene may be involved in mechanisms underlying retinal diseases associated with altered choroidal thickness, such as age-related macular degeneration., (© 2024. The Author(s).)

Purpose: To investigate the significance of intravitreal anti-vascular endothelial growth factor treatment in patients with neovascular age-related macular degeneration and poor visual acuity., Methods: Retrospective study of patients with neovascular age-related macular degeneration with baseline best-corrected visual acuity of ≤20/200. Patients were divided into regular treatment and scarce treatment groups according to whether they underwent consecutive intravitreal anti-vascular endothelial growth factor treatments at intervals of ≤4 months or not., Results: A total of 131 eyes were included: 87 and 44 eyes in the regular treatment and scarce treatment groups, respectively. The regular treatment group showed significantly improved preservation of lesion size at both Years 1 and 2, with significantly fewer incidences of new subretinal hemorrhage. Improvements in visual acuity, reduction in central subfield macular thickness, and maximal height of choroidal neovascularization were significantly favorable in the regular treatment group at Year 1, and central subfield macular thickness was significantly decreased at Year 2. Survival analysis revealed that the regular treatment group had significantly greater preservation of visual acuity and lesion size than that in the scarce treatment group., Conclusion: Maintaining intravitreal anti-vascular endothelial growth factor treatment for patients with neovascular age-related macular degeneration and poor vision showed significant advantages in visual acuity and lesion size stability and reduced the incidence of new subretinal hemorrhage, which suggests preservation of paracentral vision.

Background and Objective: There is a relative lack of evidence from observational studies of older populations investigating the association between chronic periodontitis and cerebro-cardiovascular diseases. Accordingly, we investigated the risk of cerebro-cardiovascular diseases according to the severity of chronic periodontitis among older adults., Methods: Data on older adults with chronic periodontitis were extracted from the Korea National Health Insurance Service-Senior Cohort Database using diagnosis codes and dental procedures. Participants were divided into two exposure groups. Among 46 737 participants eligible for inclusion, 21 905 (46.9%) had newly diagnosed mild chronic periodontitis, and 24 832 (53.1%) had newly diagnosed severe chronic periodontitis. To determine the risk of cerebro-cardiovascular diseases, including ischemic stroke, haemorrhagic stroke, and myocardial infarction, multivariable-adjusted Cox proportional hazards modelling was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) in this retrospective follow-up study., Results: A total of 3453 (7.4%) outcomes were identified during a mean follow-up of 6.1 years. Kaplan-Meier analysis revealed that disease-free probability was lower in the severe group than in the mild group (log-rank P < .001). In the multivariable-adjusted model, the HR for cerebro-cardiovascular diseases in the severe group (relative to the mild group) was 1.16 (95% CI: 1.09-1.25). In individual outcome analysis, ischemic stroke and myocardial infarction were associated with chronic periodontitis severity, but haemorrhagic stroke was not., Conclusion: The severity of chronic periodontitis could be associated with the risk of cerebro-cardiovascular diseases in older adults., (© 2023 Gerodontology Association and John Wiley & Sons Ltd.)

Aquaporins (AQPs) are recognized as transmembrane water channels that facilitate selective water permeation through their monomeric pores. Among the AQP family, AQP6 has an intriguing characteristic as an anion channel, which is allosterically controlled by pH conditions and is eliminated by a single amino acid mutation. However, the molecular mechanism of anion permeation through AQP6 remains unclear. Using molecular dynamics simulations in the presence of a transmembrane voltage utilizing an ion concentration gradient, we show that chloride ions permeate through the pore corresponding to the central axis of the AQP6 homotetramer. Under low pH conditions, a subtle opening of the hydrophobic selectivity filter (SF), located near the extracellular part of the central pore, becomes wetted and enables anion permeation. Our simulations also indicate that a single mutation (N63G) in human AQP6, located at the central pore, significantly reduces anion conduction, consistent with experimental data. Moreover, we demonstrate that the pH-sensing mechanism in which the protonation of H184 and H189 under low pH conditions allosterically triggers the gating of the SF region. These results suggest a unique pH-dependent allosteric anion permeation mechanism in AQP6 and could clarify the role of the central pore in some of the AQP tetramers., Competing Interests: Declaration of interests The authors declare that they have no competing interests., (Copyright © 2024 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Purpose: Homozygous hypomorphic variants of the RP1 gene, including c.5797C>T, p.Arg1933Ter, have traditionally been considered non-pathogenic. This study aimed to elucidate the clinical manifestations of late-onset, slowly progressive cone/macular dystrophy in patients homozygous for p.Arg1933Ter in the RP1 gene., Methods: Five patients with biallelic p.Arg1933Ter in RP1 were retrospectively recruited, and their clinical profiles were analyzed. Copy number variation analysis and Alu insertion assessment of genes associated with inherited retinal diseases were conducted. The results of comprehensive ophthalmological examinations, multimodal imaging, and full-field electroretinogram tests were analyzed., Results: No specific sequencing errors or structural variations associated with the clinical phenotypes were identified. Alu element insertion in RP1 was not detected. The mean ± SD age at the first visit was 62.2 ± 9.8 years, with symptoms typically starting between 45 and 50 years of age. Two patients exhibited a mild form of cone/macular dystrophy, characterized by a relatively preserved fundus appearance and blurring of the ellipsoid zone on optical coherence tomography. Three patients had late-onset cone/macular dystrophy with significant atrophy., Conclusions: To our knowledge, this study is the first to report that a homozygous hypomorphic variant of RP1, previously considered non-pathogenic, leads to cone/macular dystrophy., Translational Relevance: The study introduces novel possibilities suggesting that the homozygous hypomorphic variant of RP1 may be linked to variant pathogenicity.

Purpose: To determine the association between pentosan polysulfate (PPS) use and the subsequent development of maculopathy in an Asian population., Design: A nationwide, population-based retrospective cohort study using the Health Insurance Review and Assessment Service database., Participants: A total of 103 553 individuals in the PPS user group and 205 792 individuals in the PPS nonuser group, all newly diagnosed with cystitis between 2009 and 2020., Methods: The association between PPS use and maculopathy was evaluated using a time-dependent Cox proportional hazard model. Additionally, 2 sensitivity analyses were conducted by defining PPS users as individuals with an observation period over 6 months from the initial prescription or those with a cumulative dose exceeding 9 g, using the same analysis., Main Outcome Measures: The outcome measures included the hazard ratios (HRs) representing the association between PPS use and maculopathy., Results: Use of PPS was associated with an increased risk of subsequent maculopathy in univariate (HR, 1.7; 95% confidence interval [CI], 1.66-1.75) and multivariate analysis (HR, 1.34; 95% CI, 1.31-1.38). These results were also confirmed in 2 sensitivity analyses. The mean cumulative dose of PPS for the cohort was 37.2 ± 76.7 g., Conclusions: In this nationwide cohort study involving an Asian population, individuals with cystitis using PPS exhibit an increased risk of developing subsequent maculopathy., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2024. Published by Elsevier Inc.)

Competing Interests: One of the co-authors, K.A.J., has recently moved to LG CNS. K.A.J.’s current involvement with LG CNS is unrelated to the examples provided in this article.

Background: The prevalence of diabetes is increasing globally, highlighting the importance of preventive healthcare. This study aimed to identify the diabetic retinopathy (DR) screening rates and risk factors linked to DR screening nonadherence in the Korean population through a nationally representative sample survey., Methods: Among the Korea National Health and Nutrition Examination Survey database from 2016 to 2021, participants aged ≥ 40 years with diabetes were included. The weighted estimate for nonadherence to DR screening within a year was calculated. Risk factor analyses were conducted using univariate and multivariate logistic regression., Results: Among the 3,717 participants, 1,109 (29.5%) underwent DR screening within the past year, and this national estimate exhibited no statistically significant difference from 2016 to 2021 ( P = 0.809). Nonadherence to annual DR screening was associated with residing in rural areas, age ≥ 80 years, low educational level, self-reported good health, absence of ocular disease, current smoking, lack of exercise and dietary diabetes treatment, and no activity limitation (all P < 0.05)., Conclusion: The recent DR screening rate in Korea was relatively low. Factors associated with apathy and complacency towards personal health were associated with the nonadherence to DR screening. Educational interventions have the potential to enhance the annual screening rate for diabetic patients., (© 2024 The Korean Academy of Medical Sciences.)

Background: Although several studies have demonstrated a bidirectional relationship between nonalcoholic fatty liver disease (NAFLD) and chronic periodontitis, few studies have reported that NAFLD causes chronic periodontitis, especially in the Asian population., Methods: This study was conducted on 129,087 individuals, and the NAFLD score was assessed using the Fatty Liver Index (FLI), Hepatic Steatosis Index (HSI), and Framingham Steatosis Index (FSI). The incidence of chronic periodontitis was defined as a diagnostic code with dental procedures. Multi-variable adjusted Cox proportional hazard regression analysis was performed with hazard ratio (HR) and 95% confidence intervals (CIs)., Results: Nine thousand one hundred and twenty-eight chronic periodontitis cases (7.1%) were identified during a mean 7.4 years follow-up period. Each NAFLD score was related to chronic periodontitis. In the FLI score, HR and 95% CIs for the incidence of chronic periodontitis compared with a low FLI group were as follows: indeterminate FLI: 1.19 (1.12-1.26), high FLI: 1.32 (1.18-1.47). In the HSI and FSI scores, HR and 95% CIs for the incidence of chronic periodontitis were 1.13 (1.05-1.22) and 1.23 (1.05-1.31), respectively., Conclusions: All NAFLD scores were associated with chronic periodontitis in the Korean population. As chronic periodontitis can aggravate the liver status, patients with NAFLD may need regular dental visits., (© 2024 American Academy of Periodontology.)

Background: A left thoracotomy approach is anatomically appropriate for childhood aortic coarctation; however, the pediatric femoral arteriovenous diameters are too small for cardiopulmonary bypass cannulation. We aimed to determine the safety of a partial cardiopulmonary bypass through the main pulmonary artery and the descending aorta in pediatric aortic coarctation repair., Methods: We retrospectively reviewed 10 patients who underwent coarctation repair under partial main pulmonary artery-to-descending aorta cardiopulmonary bypass with a left thoracotomy as the CPB group. During the same period, 16 cases of simple coarctation of the aorta repair, with end-to-end anastomosis through a left thoracotomy without partial CPB assistance, were included as the non-CPB group to evaluate the impact of partial CPB., Results: The median age and weight at surgery of the CPB group were 3.1 years (range, 9 days to 17.9 years) and 14.0 (range, 2.8-40.7) kg, respectively. Indications for the partial cardiopulmonary bypass with overlap were as follows: age > 1 year (n = 7), mild aortic coarctation (n = 3), and predicted ischemic time > 30 min (n = 5). Coarctation repair using autologous tissue was performed in seven cases and graft replacement in three. The mean partial cardiopulmonary bypass time, descending aortic clamp time, and cardiopulmonary bypass flow rate were 73 ± 37 min, 57 ± 27 min, and 1.6 ± 0.2 L/min/m 2 , respectively. Urine output during descending aortic clamping was observed in most cases in the CPB group (mean: 9.1 ± 7.9 mL/kg/h), and the total intraoperative urine output was 3.2 ± 2.7 mL/kg/h and 1.2 ± 1.5 mL/kg/h in the CPB and non-CPB group, respectively (p = 0.020). The median ventilation time was 1 day (range, 0-15), and the intensive care unit stay duration was 4 days (range, 1-16) with no surgical deaths. No major complications, including paraplegia or recurrent coarctation, occurred postoperatively during a median observation period of 8.1 (range, 3.4-17.5) years in the CPB group. In contrast, reoperation with recurrent coarctation was observed in 2 cases in the non-CPB group (p = 0.37)., Conclusions: Partial cardiopulmonary bypass through the main pulmonary artery and descending aorta via a left thoracotomy is a safe and useful option for aortic coarctation repair in children., (© 2024. The Author(s).)

Psoriasis is a chronic inflammatory condition affecting 2% of the Western population. It includes diverse manifestations influenced by genetic predisposition, environmental factors, and immune status. The sustained activation of mTOR is a key element in psoriasis pathogenesis, leading to an uncontrolled proliferation of cytokines. Furthermore, mTOR activation has been linked with the transition from psoriasis to non-skin manifestations such as psoriatic arthritis and cardiovascular events. While therapies targeting pro-inflammatory cytokines have shown efficacy, additional pathways may offer therapeutic potential. The PI3K/Akt/mTOR pathway, known for its role in cell growth, proliferation, and metabolism, has emerged as a potential therapeutic target in psoriasis. This review explores the relevance of mTOR in psoriasis pathophysiology, focusing on its involvement in cutaneous and atheromatous plaque proliferation, psoriatic arthritis, and cardiovascular disease. The activation of mTOR promotes keratinocyte and synovial cell proliferation, contributing to plaque formation and joint inflammation. Moreover, mTOR activation may exacerbate the cardiovascular risk by promoting pro-inflammatory cytokine production and dysregulation lipid and glucose metabolism. The inhibition of mTOR has shown promise in preclinical studies, reducing skin inflammation and plaque proliferation. Furthermore, mTOR inhibition may mitigate cardiovascular risk by modulating cholesterol metabolism and attenuating atherosclerosis progression. Understanding the role of mTOR in psoriasis, psoriatic arthritis, and cardiovascular disease provides insight into the potential treatment avenues and sheds light on the complex interplay of the immune and metabolic pathways in these conditions.

Background: Bacterial infection of embryo culture medium is rare but may be detrimental. The main source of embryo culture contamination is semen. Assisted reproduction centers currently lack consensus regarding the methods for preventing and managing embryo culture infection. In our recent case, a successful pregnancy was achieved with intracytoplasmic sperm injection after failed conventional in vitro fertilization owing to bacterial contamination., Case Presentation: We present a case report of two consecutive in vitro fertilization-intracytoplasmic sperm injection cycles with photo and video documentation of the bacterial growth. A 36-year-old Hungarian woman and her 37-year-old Hungarian partner came to our department. They had two normal births followed by 2 years of infertility. The major causes of infertility were a closed fallopian tube and asthenozoospermia. Bacterial infection of the embryo culture medium was observed during in vitro fertilization and all oocytes degenerated. The source was found to be the semen. To prevent contamination, intracytoplasmic sperm injection was used for fertilization in the subsequent cycle. Intracytoplasmic bacterial proliferation was observed in one of the three fertilized eggs, but two good-quality embryos were successfully obtained. The transfer of one embryo resulted in a successful pregnancy and a healthy newborn was delivered., Conclusion: Intracytoplasmic sperm injection may be offered to couples who fail conventional in vitro fertilization treatment owing to bacteriospermia, as it seems to prevent infection of the embryo culture. Even if bacterial contamination appears, our case encourages us to continue treatment. Nevertheless, the development of new management guidelines for the prevention and management of bacterial contamination is essential., (© 2024. The Author(s).)

Purpose: To investigate the efficacy, safety, and indications for additional pneumatic retinopexy (PR) in patients with persistent retinal detachment after scleral buckling., Methods: This retrospective study included patients who underwent additional PR after scleral buckling for primary rhegmatogenous retinal detachment (n = 78). We defined "inadequate buckle" as retinal detachment persistence because of low buckle height despite accurate buckle placement and "buckle misplacement" as an uncovered tear because of incorrect buckle placement., Results: The anatomical success rate after additional PR was 52.6%. Development of proliferative vitreoretinopathy Grade B (hazard ratio, 5.73; P < 0.001) and inferior retinal tears (hazard ratio, 2.12; P = 0.040) were significant risk factors for anatomical failure. The most common cause of anatomical failure was proliferative vitreoretinopathy (19 of 37; 51.4%), and epiretinal membrane formation was a common complication after additional PR (22 of 78; 28.2%). The anatomical success rate with additional PR was significantly higher in the inadequate buckle group than in the misplacement group (8 of 9 [88.9%] vs. 1228 [42.9%]; P = 0.023)., Conclusion: Development of proliferative vitreoretinopathy Grade B and inferior retinal tears were significantly associated with anatomical failure after additional PR. Additional PR may benefit patients with superior retinal tears or low buckle height and those without proliferative vitreoretinopathy.

Purpose: To compare the posterior capsule rupture (PCR) rates of cataract surgery using a traditional ophthalmic surgical microscope (OSM) and a 3D heads-up visualization system (HUVS)., Setting: Single tertiary referral center., Design: Retrospective study., Methods: This study included 10 101 eyes that underwent phacoemulsification cataract surgery. Surgeries were performed using either 3D HUVS (1964 eyes, performed by 2 surgeons, HUVS group) or traditional OSM (8137 eyes, performed by 6 surgeons, OSM group) from February 2018 to June 2022. Data were collected based on the diagnosis-related group system, and the rate of PCR requiring vitrectomy and the surgical time were evaluated., Results: The PCR rates were not significantly different between the OSM (n = 63; 0.7%) and HUVS (n = 19; 0.9%, P = .392) groups. The mean surgical time was significantly longer in the HUVS group (14.7 ± 10.6 minutes) than in the OSM group (12.9 ± 9.9 minutes, P < .001). In the 3D HUVS group, there were no PCR cases among the initial 100 patients. In both groups, no significant difference was observed in the PCR rates over time. Although the difference was not statistically significant, the PCR rate decreased over time in the HUVS group., Conclusions: The results indicate that 3D HUVS-based cataract surgery performed by experienced cataract surgeons had a PCR rate similar to that of traditional OSM-based surgery during the 4-year study period. Although the surgical time was slightly longer with 3D HUVS, cataract surgery using 3D HUVS can be performed safely by experienced surgeons., (Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Purpose: This study aimed to analyze the genetic results of inherited retinal diseases (IRDs) and evaluate the diagnostic usefulness of whole genome sequencing (WGS) in the Korean National Project of Bio Big Data., Methods: As part of the Korean National Project of Bio Big Data, WGS was performed on 32 individuals with IRDs with no identified pathogenic variants through whole or targeted exome sequencing., Results: Individuals with retinitis pigmentosa (n = 23), cone dystrophy (n = 2), cone-rod dystrophy (n = 2), familial exudative vitreoretinopathy (n = 2), pigmented paravenous chorioretinal atrophy (n = 1), North Carolina macular dystrophy (n = 1), and bull's-eye macular dystrophy (n = 1) were included. WGS revealed genetic mutations in the IQCB1, PRPF31, USH2A, and GUCY2D genes in five cases (15.6%). Two large structural variations and an intronic variant were newly detected in three cases. Two individuals had biallelic missense mutations that were not identified in previous exome sequencing., Conclusion: With WGS, the causative variants in 15.6% of unsolved IRDs from the Korean National Project of Bio Big Data were identified. Further research with a larger cohort might unveil the diagnostic usefulness of WGS in IRDs and other diseases., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

To compare the efficacy of scleral buckling with adjuvant pneumatic retinopexy (SB with PR) and scleral buckling (SB) alone for primary rhegmatogenous retinal detachment (RRD). This retrospective and comparative study included patients who underwent SB with PR (n = 88) or SB alone (n = 161) for primary RRD. The primary anatomical success rate for SB with PR was 81.8%, whereas that for SB alone was 80.7% (P = 0.836). Among patients who achieved primary anatomical success, those in the SB with PR group showed postoperative epiretinal membrane (ERM) formation more frequently than those in the SB alone group (11 of 72 [15.3%] vs. 6 of 130 [4.6%]) (P = 0.009). The mean time to subretinal fluid absorption was not significantly different between the SB with PR and SB alone groups (11.2 ± 6.2 vs. 11.4 ± 5.8 months, P = 0.881). In the SB with PR group, retinal detachment involving ≥ three quadrants was a significant risk factor for surgical failure (hazard ratio, 3.04; P = 0.041). Adjuvant pneumatic retinopexy does not provide additional benefit in improving the surgical outcomes of SB for primary RRD repair., (© 2024. The Author(s).)

Purpose: Pathogenic variants in North Carolina macular dystrophy (NCMD) have rarely been reported in the East Asian population. Herein, we reported novel variants of NCMD in 2 Korean families., Methods: The regions associated with NCMD were analyzed with genome sequencing, and variants were filtered based on the minor allele frequency (0.5%) and heterozygosity. Non-coding variants were functionally annotated using multiple computational tools., Results: We identified two rare novel variants, chr6:g.99,598,914T>C (hg38; V17) and chr6:g.99,598,926G>A (hg38; V18) upstream of PRDM13 in families A and B, respectively. In Family 1, Grade 2 NCMD and a best-corrected visual acuity of 20/25 and 20/200 in the right and left eyes, respectively, were observed. In Family B, all affected individuals had Grade 1 NCMD with characteristic confluent drusen at the fovea and a best-corrected visual acuity of 20/20 in both eyes. These two variants are 10-22 bp downstream of the reported V10 variant within the DNase1 hypersensitivity site. This site is associated with progressive bifocal chorioretinal atrophy and congenital posterior polar chorioretinal hypertrophy and lies in the putative enhancer site of PRDM13 ., Conclusion: We identified two novel NCMD variants in the Korean population and further validated the regulatory role of the DNase1 hypersensitivity site upstream of  PRDM13 ., (Copyright © 2024 Molecular Vision.)

Purpose: To investigate the characteristics of subfoveal nodules in Korean patients with Coats disease and their association with visual outcomes., Methods: A retrospective analysis was conducted within the medical records of patients with stage 2B or 3A1 Coats disease, including clinical features, imaging, presence of either a subfoveal nodule or macular fibrosis, and visual outcome., Results: Twelve patients were present with stage 2B or 3A1 Coats disease, and nine patients (75%) presented with subfoveal nodule. Between the group without subfoveal nodule and the group with subfoveal nodule, there were no significant differences in age (mean, 14.0 ± 1.7 years vs. 27.7 ± 21.8 years; p = 0.482), sex (all men), stage of the disease (stage 2B: three patients vs. eight patients, p > 0.999; stage 3A1: none vs. one patient, p > 0.999), extension of retinal exudation (mean, 7.7 hours vs. 4.1 hours; p = 0.209) and peripheral telangiectasia (mean, 3.7 hours vs. 4.2 hours; p = 0.727), and follow-up duration (mean, 65.0 months vs. 46.1 months; p = 0.600). There were significantly more patients with severe visual loss (≤20 / 200) among the patients with subfoveal nodule (none vs. seven patients, p = 0.045), and the cause for severe visual loss was macular fibrosis in all cases. Macular fibrosis developed significantly more frequently in the patients with subfoveal nodule (none vs. seven = patients, p = 0.045)., Conclusions: This study is the first study covering the analysis of subfoveal nodules in Korean patients with Coats disease. The existence of a subfoveal nodule at the initial diagnosis serves as an indicator predicting the development of macular fibrosis and a less favorable visual outcome in the patients with Coats disease. A multicenter study with a larger patient pool and further studies toward the therapeutic approach for the subfoveal nodule and macular fibrosis are needed.

Electrolytes play a critical role in battery performance. They are associated with an increased risk of safety issues. The main challenge faced by many researchers is how to balance the physical and electrical properties of electrolytes. Gel polymer electrolytes (GPEs) have received increasing attention due to their satisfactory properties of ionic conductivity, mechanical stability, and safety. Herein, we develop a gel network polymer electrolyte (GNPE) to address the challenge mentioned earlier. This GNPE was formed by tri-epoxide monomer and bis(fluorosulfonyl)imide lithium salt (LiFSI) via an in situ cationic polymerization under mild thermal conditions. The obtained GNPE exhibited a relatively high ionic conductivity (σ) of 2.63 × 10 -4 S cm -1 , lithium transference number ( t Li + , 0.58) at room temperature (RT), and intimate electrode compatibility with LiFePO 4 and graphite. The LiFePO 4 /GNPE/graphite battery also showed a promising cyclic performance at RT, e.g., a suitable discharge specific capacity of 127 mAh g -1 and a high Coulombic efficiency (>97%) after 100 cycles at 0.2 C. Moreover, electrolyte films showed good mechanical stability and formed the SEI layer on the graphite anode. This study provides a facile method for preparing epoxy-based electrolytes for high-performance lithium-ion batteries (LIBs).

Purpose: To characterize the clinical effects of two RP1L1 hotspots in patients with East Asian occult macular dystrophy (OMD)., Methods: Fifty-one patients diagnosed with OMD harboring monoallelic pathogenic RP1L1 variants (Miyake disease) from Japan, South Korea, and China were enrolled. Patients were classified into two genotype groups: group A, p.R45W, and group B, missense variants located between amino acids (aa) 1196 and 1201. The clinical parameters of the two genotypes were compared, and deep learning based on spectral-domain optical coherence tomographic (SD-OCT) images was used to distinguish the morphologic differences., Results: Groups A and B included 29 and 22 patients, respectively. The median age of onset in groups A and B was 14.0 and 40.0 years, respectively. The median logMAR visual acuity of groups A and B was 0.70 and 0.51, respectively, and the survival curve analysis revealed a 15-year difference in vision loss (logMAR 0.22). A statistically significant difference was observed in the visual field classification, but no significant difference was found in the multifocal electroretinographic classification. High accuracy (75.4%) was achieved in classifying genotype groups based on SD-OCT images using machine learning., Conclusions: Distinct clinical severities and morphologic phenotypes supported by artificial intelligence-based classification were derived from the two investigated RP1L1 hotspots: a more severe phenotype (p.R45W) and a milder phenotype (1196-1201 aa). This newly identified genotype-phenotype association will be valuable for medical care and the design of therapeutic trials.

Introduction: The objective of this study was to investigate the clinical characteristics and genetic spectrum of adult-onset cone/cone-rod dystrophy (AOCD/AOCRD) in Korean individuals., Methods: This is a single-center, retrospective cross-sectional study. We analyzed 22 individuals with genetically confirmed cone dystrophy, with symptoms beginning after 30 years of age. All patients underwent comprehensive ophthalmic and electrophysiological examinations. Exome sequencing of 296 genes associated with inherited retinal disease was performed. The clinical features of patients with AOCD/AOCRD and the causative genes and variants detected by exome sequencing were analyzed., Results: The median age at the first visit was 52 years (range, 31-76 years), and the most common initial symptom was reduced visual acuity. In most cases, fundus photography showed a bull's eye pattern with foveal sparing, consistent with perifoveal photoreceptor loss on optical coherence tomography. We identified disease-causing variants in six genes: RP1, CRX, CDHR1, PROM1, CRB1, and GUCY2D. Pathogenic variants in RP1, CRX, and CDHR1 were identified in 77% of the AOCD/AOCRD cases, including p.Cys1399LeufsTer5, p.Arg1933Ter, and p.Ile2061SerfsTer12 in RP1; p.Ter300GlnextTer118 in CRX; and p.Glu201Lys in CDHR1. No characteristic imaging differences were observed for any of the causative genes. Most of the RP1-related AOCD/AOCRD cases showed a decreased amplitude only in the photopic electroretinogram (ERG), whereas CRX-related AOCD/AOCRD cases showed a slightly decreased amplitude in both the scotopic and photopic ERGs., Conclusion: In case of visual impairment with bull's eye pattern of RPE atrophy recognized after the middle age, a comprehensive ophthalmic examination and genetic test should be considered, with the possibility of AOCD/AOCRD in East Asians., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Motivation: Predicting protein structures with high accuracy is a critical challenge for the broad community of life sciences and industry. Despite progress made by deep neural networks like AlphaFold2, there is a need for further improvements in the quality of detailed structures, such as side-chains, along with protein backbone structures., Results: Building upon the successes of AlphaFold2, the modifications we made include changing the losses of side-chain torsion angles and frame aligned point error, adding loss functions for side chain confidence and secondary structure prediction, and replacing template feature generation with a new alignment method based on conditional random fields. We also performed re-optimization by conformational space annealing using a molecular mechanics energy function which integrates the potential energies obtained from distogram and side-chain prediction. In the CASP15 blind test for single protein and domain modeling (109 domains), DeepFold ranked fourth among 132 groups with improvements in the details of the structure in terms of backbone, side-chain, and Molprobity. In terms of protein backbone accuracy, DeepFold achieved a median GDT-TS score of 88.64 compared with 85.88 of AlphaFold2. For TBM-easy/hard targets, DeepFold ranked at the top based on Z-scores for GDT-TS. This shows its practical value to the structural biology community, which demands highly accurate structures. In addition, a thorough analysis of 55 domains from 39 targets with publicly available structures indicates that DeepFold shows superior side-chain accuracy and Molprobity scores among the top-performing groups., Availability and Implementation: DeepFold tools are open-source software available at https://github.com/newtonjoo/deepfold., (© The Author(s) 2023. Published by Oxford University Press.)

Purpose: To characterize the genotype and phenotype of a patient with CAPN5-related neovascular inflammatory vitreoretinopathy (NIV) who have undergone surgery for macular holes., Methods: We observed a patient presenting with retinitis pigmentosa and posterior uveitis who later developed vitreoretinal macular traction and a macular hole. Genetic testing was performed using a targeted gene panel. Fundus photography and spectral-domain optical coherence tomography were also performed., Results: In a targeted gene panel, a monoallelic pathogenic variant, c.750G > T, p.Lys250Asn, in the CAPN5 gene was identified, and CAPN5-NIV was diagnosed. At the first visit, peripheral retinal degeneration and mild posterior uveitis were observed. At that time, neovascularization, epiretinal or fibrous membranes were not observed. After 5 years, vitreomacular traction developed and progressed to a full-thickness macular hole in both eyes. After pars plana vitrectomy, the macular hole was successfully closed without aggravation of uveitis., Conclusion: In this case, a pathogenic variant of CAPN5 lead to a distinct phenotype of retinitis pigmentosa, posterior uveitis, vitreomacular traction, and macular hole without typical inflammatory neovascularization or tractional membranes. Therefore, the clinical variability of CAPN5-NIV and genetic diagnosis should be considered in cases of atypical retinitis pigmentosa with bilateral macular hole., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Conformational space annealing (CSA), a global optimization method, has been applied to various protein structure modeling tasks. In this paper, we applied CSA to the cryo-EM structure modeling task by combining the python subroutine of CSA (PyCSA) and the fast relax (FastRelax) protocol of PyRosetta. Refinement of initial structures generated from two methods, rigid fitting of predicted structures to the Cryo-EM map and de novo protein modeling by tracing the Cryo-EM map, was performed by CSA. In the refinement of the rigid-fitted structures, the final models showed that CSA can generate reliable atomic structures of proteins, even when large movements of protein domains were required. In the de novo modeling case, although the overall structural qualities of the final models were rather dependent on the initial models, the final models generated by CSA showed improved MolProbity scores and cross-correlation coefficients to the maps. These results suggest that CSA can accomplish flexible fitting and refinement together by sampling diverse conformations effectively and thus can be utilized for cryo-EM structure modeling., (© 2023 Wiley Periodicals LLC.)

Manhattan and Atlanta worlds hold for the structured scenes with only vertical and horizontal dominant directions (DDs). To describe the scenes with additional sloping DDs, a mixture of independent Manhattan worlds seems plausible, but may lead to unaligned and unrelated DDs. By contrast, we propose a novel structural model called Hong Kong world. It is more general than Manhattan and Atlanta worlds since it can represent the environments with slopes, e.g., a city with hilly terrain, a house with sloping roof, and a loft apartment with staircase. Moreover, it is more compact and accurate than a mixture of independent Manhattan worlds by enforcing the orthogonality constraints between not only vertical and horizontal DDs, but also horizontal and sloping DDs. We further leverage the structural regularity of Hong Kong world for the line-based SLAM. Our SLAM method is reliable thanks to three technical novelties. First, we estimate DDs/vanishing points in Hong Kong world in a semi-searching way. We use a new consensus voting strategy for search, instead of traditional branch and bound. This method is the first one that can simultaneously determine the number of DDs, and achieve quasi-global optimality in terms of the number of inliers. Second, we compute the camera pose by exploiting the spatial relations between DDs in Hong Kong world. This method generates concise polynomials, and thus is more accurate and efficient than existing approaches designed for unstructured scenes. Third, we refine the estimated DDs in Hong Kong world by a novel filter-based method. Then we use these refined DDs to optimize the camera poses and 3D lines, leading to higher accuracy and robustness than existing optimization algorithms. In addition, we establish the first dataset of sequential images in Hong Kong world. Experiments showed that our approach outperforms state-of-the-art methods in terms of accuracy and/or efficiency.

Background: The integration of Artificial Intelligence (AI) technology in cancer care has gained unprecedented global attention over the past few decades. This has impacted the way that cancer care is practiced and delivered across settings. The purpose of this study was to explore the perspectives and experiences of healthcare professionals (HCPs) on cancer treatment and the need for AI. This study is a part of the INCISIVE European Union H2020 project's development of user requirements, which aims to fully explore the potential of AI-based cancer imaging technologies., Methods: A mixed-methods research design was employed. HCPs participating in cancer care in the UK, Greece, Italy, Spain, Cyprus, and Serbia were first surveyed anonymously online. Twenty-seven HCPs then participated in semi-structured interviews. Appropriate statistical method was adopted to report the survey results by using SPSS. The interviews were audio recorded, verbatim transcribed, and then thematically analysed supported by NVIVO., Results: The survey drew responses from 95 HCPs. The occurrence of diagnostic delay was reported by 56% (n = 28/50) for breast cancer, 64% (n = 27/42) for lung cancer, 76% (n = 34/45) for colorectal cancer and 42% (n = 16/38) for prostate cancer. A proportion of participants reported the occurrence of false positives in the accuracy of the current imaging techniques used: 64% (n = 32/50) reported this for breast cancer, 60% (n = 25/42) for lung cancer, 51% (n = 23/45) for colorectal cancer and 45% (n = 17/38) for prostate cancer. All participants agreed that the use of technology would enhance the care pathway for cancer patients. Despite the positive perspectives toward AI, certain limitations were also recorded. The majority (73%) of respondents (n = 69/95) reported they had never utilised technology in the care pathway which necessitates the need for education and training in the qualitative finding; compared to 27% (n = 26/95) who had and were still using it. Most, 89% of respondents (n = 85/95) said they would be opened to providing AI-based services in the future to improve medical imaging for cancer care. Interviews with HCPs revealed lack of widespread preparedness for AI in oncology, several barriers to introducing AI, and a need for education and training. Provision of AI training, increasing public awareness of AI, using evidence-based technology, and developing AI based interventions that will not replace HCPs were some of the recommendations., Conclusion: HCPs reported favourable opinions of AI-based cancer imaging technologies and noted a number of care pathway concerns where AI can be useful. For the future design and execution of the INCISIVE project and other comparable AI-based projects, the characteristics and recommendations offered in the current research can serve as a reference., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: Intracytoplasmic sperm injection (ICSI) was introduced to achieve fertilization in cases of severe male factor infertility. However, ICSI is often used in cases of non-male factor infertility, such as advanced maternal age or low oocyte number, but the clinical benefit of the method in these indications has not been proven., Material and Methods: A prospective randomized study was conducted in a university clinic between 2018 and 2020. Patients with ≥40 years of age and/or ≤4 oocytes with non-sever male factor infertility were randomized into conventional IVF or ICSI groups. Fertilization rate, embryo quality, implantation, clinical pregnancy and live birth rates were compared., Results: A total of 336 IVF cycles (169 conventional IVF and 167 ICSI) were involved in the study. The fertilization rate was higher in the conventional IVF group compared to the ICSI group (IVF: 61.7%, ICSI: 53.4%, P=0.001). Embryo development and morphology did not show considerable difference between groups. Implantation, clinical pregnancy and live birth rate were 13.1%, 24.3% and 11.4% in the conventional IVF and 10.4%, 19.0%, 12.0% in the ICSI group. The differences were not significant. Subgroup analysis showed a significantly better clinical outcome following conventional IVF when advanced maternal age was accompanied by low oocyte number (Implantation: 11.7% vs 2.6%, P=0.027; Clinical pregnancy: 18.5% vs 4%, P=0.020)., Discussion: A significantly higher fertilization rate, a tendency for higher clinical pregnancy rate was found in conventional IVF treatments compared to ICSI. When advanced maternal age was associated with low oocyte number, ICSI resulted in a substantially lower chance of fertilization and clinical pregnancy. These data suggest that ICSI offers no advantage over conventional IVF in terms of fertilization, embryo quality, implantation and pregnancy rates for couples with advanced maternal age or with low oocyte number., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Occult macular dystrophy (OMD) is the most prevalent form of macular dystrophy in East Asia. Beyond RP1L1 , causative genes and mechanisms remain largely uncharacterised. This study aimed to delineate the clinical and genetic characteristics of OMD syndrome (OMDS). Patients clinically diagnosed with OMDS in Japan, South Korea, and China were enrolled. The inclusion criteria were as follows: (1) macular dysfunction and (2) normal fundus appearance. Comprehensive clinical evaluation and genetic assessment were performed to identify the disease-causing variants. Clinical parameters were compared among the genotype groups. Seventy-two patients with OMDS from fifty families were included. The causative genes were RP1L1 in forty-seven patients from thirty families (30/50, 60.0%), CRX in two patients from one family (1/50, 2.0%), GUCY2D in two patients from two families (2/50, 4.0%), and no genes were identified in twenty-one patients from seventeen families (17/50, 34.0%). Different severities were observed in terms of disease onset and the prognosis of visual acuity reduction. This multicentre large cohort study furthers our understanding of the phenotypic and genotypic spectra of patients with macular dystrophy and normal fundus. Evidently, OMDS encompasses multiple Mendelian retinal disorders, each representing unique pathologies that dictate their respective severity and prognostic patterns.

Purpose: To investigate the clinical features, natural course, and genetic characteristics of Koreans with rhodopsin-associated retinitis pigmentosa ( RHO -associated RP). Design: We conducted a retrospective, multicenter, observational cohort study. Participants: We reviewed the medical records of 42 patients with RHO -associated RP of 36 families who visited 4 hospitals in Korea. Methods: Patients with molecular confirmation of pathogenic variants of the RHO gene were included. The patients were divided into two subgroups: the generalized and sector RP groups. A central visual field of the better-seeing eye of <10° or a best-corrected visual acuity of the better-seeing eye <20/40 indicated the progression to late-stage RP. Results: The mean age at which symptoms first appeared was 26.3 ± 17.9 years (range: 8-78 years), and the mean follow-up period was 80.9 ± 68.7 months (range: 6-268 months). At the last follow-up visit, the generalized RP group showed a significantly higher rate of visual field impairment progression to late-stage RP than that of the sector RP group (22 of 35 [62.9%] vs. 0 of 7 [0.0%], p = 0.003). No cases in the sector RP group progressed to generalized RP. Best-corrected visual acuity deterioration to late-stage RP was observed only in the generalized RP group (13 of 35 patients; 37.1%), whereas no deterioration was observed in the sector RP group. We identified 16 known and three novel RHO mutations, including two missense mutations (p.T108P and p.G121R) and one deletion mutation (p.P347&#95;A348del). The pathogenic variants were most frequently detected in exon 1 (14 of 36 [38.9%]). The most common pathogenic variants were p.P347L and T17M (5 of 36 [13.9%] families). Among 42 patients of 36 families, 35 patients of 29 families (80.6%) presented with the generalized RP phenotype, and seven patients of seven families (19.4%) presented with the sector RP phenotype. Three variants (p.T17M, p.G101E, and p.E181K) presented with both the generalized and sector RP phenotypes. Conclusion: This multicenter cohort study provided information on the clinical and genetic features of RHO -associated RP in Koreans. It is clinically important to expand the genetic spectrum and understand genotype-phenotype correlations to ultimately facilitate the development of gene therapy., 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 © 2023 Jung, Kwak, Joo, Lee, Park, Kim, Lee, Byeon, Lee, Han, Lee, Yoon and Woo.)

The polarized cross-section ratio σ&#95;{LT^{'}}/σ&#95;{0} from hard exclusive π^{-}Δ^{++} electroproduction off an unpolarized hydrogen target has been extracted based on beam-spin asymmetry measurements using a 10.2  GeV/10.6  GeV incident electron beam and the CLAS12 spectrometer at Jefferson Lab. The study, which provides the first observation of this channel in the deep-inelastic regime, focuses on very forward-pion kinematics in the valence regime, and photon virtualities ranging from 1.5  GeV^{2} up to 7  GeV^{2}. The reaction provides a novel access to the d-quark content of the nucleon and to p→Δ^{++} transition generalized parton distributions. A comparison to existing results for hard exclusive π^{+}n and π^{0}p electroproduction is provided, which shows a clear impact of the excitation mechanism, encoded in transition generalized parton distributions, on the asymmetry.

Objectives: During human in vitro fertilisation (IVF) treatments, embryologists attempt to select the most viable embryos for embryo transfer (ET). Previously, embryos were evaluated based on light microscopic morphological parameters. However, this is currently accomplished by morphokinetic analysis of time-lapse recordings. This technique provides us the opportunity to observe cytoplasmic strings at the blastocyst stage. The aim of this work was to examine the relationship between the presence of cytoplasmic strings (CS) and the embryo viability in human in vitro fertilised embryos. Study design: Herein, we present an evaluation of the morphokinetic data on the development of embryos obtained during IVF treatments performed at the Division of Assisted Reproduction between December 2020 and March 2021. The dynamics of embryo development, embryo morphology, and morphokinetic scores generated by a time-lapse system were compared between the presence of cytoplasmic strings (CS+) and their absence (CS-) at the blastocyst stage. Results: The development of 208 embryos from 78 patients was examined. Moreover, 81.2% of the embryos had CS in the blastocyst stage; 77% of CS existed in embryos created by conventional IVF, while 86% of CS existed in embryos fertilised by intracytoplasmic sperm injection (ICSI) ( p = 0.08). A greater number of CS+ embryos developed into a higher quality blastocyst (52.1% vs. 20.5%, p = 0.02). The morphokinetic score values characterising the development of embryos, such as Known Implantation Data Score (KIDScore) and Intelligent Data Analysis (iDAScore), were higher in CS+ groups (KID: 6.1 ± 2.1 vs. 4.7 ± 2.07; iDA: 8.0 ± 1.9 vs. 6.8 ± 2.3, p < 0.01). The dynamics of the early embryo development were similar between the two groups; however, CS+ embryos reached the blastocyst stage significantly earlier (tB: 103.9 h vs. tB: 107.6 h; p = 0.001). Conclusion: Based on our results, the number of embryos with cytoplasmic strings was higher than that without cytoplasmic strings, and its presence is not related to the fertilisation method. These embryos reached the blastocyst stage earlier, and their morphokinetic (KIDScore and iDAScore) parameters were better. All these results suggest that the presence of CS indicates higher embryo viability. The examination of this feature may help us make decisions about the embryos with higher implantation potential., 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 © 2023 Joo, Nemes, Dudas, Berkes-Bara, Murber, Urbancsek and Fancsovits.)

Introduction: This single-center retrospective cohort study investigated the incidence rate and risk factors for the discontinuation of anti-vascular endothelial growth factor (VEGF) injections and retreatment in typical neovascular age-related macular degeneration (tnAMD) and polypoidal choroidal vasculopathy (PCV) in the real-world setting., Methods: A total of 488 eyes with either tnAMD ( n = 334) or PCV ( n = 154) followed up for ≥3 years were analyzed. The discontinuation of treatment was defined as the cessation of anti-VEGF injections for 1 year or longer. Eyes with discontinuing treatment were subdivided into group A: eyes with stable responses (complete or incomplete resolution) and group B: those with no expectation of visual gain or poor response. The proportion and median time of discontinuation of treatment or retreatment were analyzed. The visual prognosis and the associated risk factors for the discontinuation of treatment or retreatment were also investigated., Results: The mean follow-up period was 8.1 ± 3.4 years. Of 488 eyes, discontinuation of the treatment occurred in 322 eyes (66.0%), and the median time to discontinuation was 1.5 years after the initial injection. Of 297 eyes with discontinuation of treatment excluding 25 eyes with vitrectomy or photodynamic therapy after the discontinuation of the injection, 277 eyes belonged to group A and the remaining 20 eyes belonged to group B. Of the 277 eyes discontinuing treatment with a stable response, 185 eyes (66.8%) were given retreatment. The median time to retreatment was 3.3 years after the discontinuation of the injections. PCV and the lower annual number of injections were the significant factors associated with discontinuation. Younger age, male gender, and PCV were the significant factors for the retreatment., Conclusion: Our long-term real-world study showed that two-thirds of eyes with neovascular age-related macular degeneration (nAMD) had the discontinuation of the anti-VEGF injections and two-thirds of eyes discontinuing treatment with stable responses experienced retreatment. Long-term follow-up and regular monitoring are needed to detect the recurrence., 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 © 2023 Cho, Park, Park, Joo and Woo.)

This study aimed to investigate the clinical characteristics of Korean patients with retinal dystrophy associated with pathogenic variants of cone rod homeobox-containing gene (CRX). We retrospectively enrolled Korean patients with CRX-associated retinal dystrophy (CRX-RD) who visited two tertiary referral hospitals. Pathogenic variants were identified using targeted panel sequencing or whole-exome sequencing. We analyzed clinical features and phenotypic spectra according to genotype. Eleven patients with CRX-RD were included in this study. Six patients with cone-rod dystrophy (CORD), two with macular dystrophy (MD), two with Leber congenital amaurosis (LCA), and one with retinitis pigmentosa (RP) were included. One patient (9.1%) had autosomal recessive inheritance, and the other ten patients (90.9%) had autosomal dominant inheritance. Six patients (54.5%) were male, and the mean age of symptom onset was 27.0 ± 17.9 years. At the first presentation, the mean age was 39.4 ± 20.6 years, and best-corrected visual acuity (BCVA) (logMAR) was 0.76 ± 0.90 in the better eye. Negative electroretinography (ERG) was observed in seven (63.6%) patients. Nine pathogenic variants were identified, including two novel variants, c.101-1G>A and c.898T>C:p.(*300Glnext*118). Taken together with the variants reported in prior studies, all variants within the homeodomain are missense variants, whereas most variants downstream of the homeodomain are truncating variants (88%). The clinical features of pathogenic variants within the homeodomain are either CORD or MD with bull's eye maculopathy, whereas variants downstream of the homeodomain cause more diverse phenotypes, with CORD and MD in 36%, LCA in 40%, and RP in 24%. This is the first case series in Korea to investigate the CRX-RD genotype-phenotype correlation. Pathogenic variants downstream of the homeodomain of the CRX gene are present as RP, LCA, and CORD, whereas pathogenic variants within the homeodomain are mainly present as CORD or MD with bull's eye maculopathy. This trend was similar to previous genotype-phenotype analyses of CRX-RD. Further molecular biologic research on this correlation is required.

Mutations in the RPE65 gene, associated with Leber congenital amaurosis, early-onset severe retinal dystrophy, and retinitis pigmentosa, gained growing attention since gene therapy for patients with RPE65-associated retinal dystrophy is available in clinical practice. RPE65 gene accounts for a very small proportion of patients with inherited retinal degeneration, especially Asian patients. Because RPE65-associated retinal dystrophy shares common clinical characteristics, such as early-onset severe nyctalopia, nystagmus, low vision, and progressive visual field constriction, with retinitis pigmentosa by other genetic mutations, appropriate genetic testing is essential to make a correct diagnosis. Also, fundus abnormalities can be minimal in early childhood, and the phenotype is highly variable depending on the type of mutations in RPE65-associated retinal dystrophy, which makes a diagnostic difficulty. The aim of this paper is to review the epidemiology of RPE65-associated retinal dystrophy, mutation spectrum, genetic diagnosis, clinical characteristics, and voretigene neparvovec, a gene therapy product for the treatment of RPE65-related retinal dystrophy.

This multicenter study aimed to characterize Korean patients with achromatopsia. The patients' genotypes and phenotypes were retrospectively evaluated. Twenty-one patients (with a mean age at the baseline of 10.9 years) were enrolled and followed up for a mean of 7.3 years. A targeted gene panel or exome sequencing was performed. The pathogenic variants of the four genes and their frequencies were identified. CNGA3 and PDE6C were equally the most prevalent genes: CNGA3 (N = 8, 38.1%), PDE6C (N = 8, 38.1%), CNGB3 (N = 3, 14.3%), and GNAT2 (N = 2, 9.5%). The degree of functional and structural defects varied among the patients. The patients' age exhibited no significant correlation with structural defects. During the follow-up, the visual acuity and retinal thickness did not change significantly. In CNGA3 -achromatopsia patients, a proportion of patients with a normal foveal ellipsoid zone on the OCT was significantly higher than that of patients with other causative genes (62.5% vs. 16.7%; p = 0.023). In PDE6C -achromatopsia patients, the same proportion was significantly lower than that of patients with other causative genes (0% vs. 58.3%; p = 0.003). Korean patients with achromatopsia showed similar clinical features but a higher prevalence of PDE6C variants than those of other ethnic groups. The retinal phenotypes of the PDE6C variants were more likely to be worse than those of other genes.

We report the first measurements of deep inelastic scattering spin-dependent azimuthal asymmetries in back-to-back dihadron electroproduction in the deep inelastic scattering process. In this reaction, two hadrons are produced in opposite hemispheres along the z axis in the virtual photon-target nucleon center-of-mass frame, with the first hadron produced in the current-fragmentation region and the second in the target-fragmentation region. The data were taken with longitudinally polarized electron beams of 10.2 and 10.6 GeV incident on an unpolarized liquid-hydrogen target using the CLAS12 spectrometer at Jefferson Lab. Observed nonzero sinΔϕ modulations in ep→e^{'}pπ^{+}X events, where Δϕ is the difference of the azimuthal angles of the proton and pion in the virtual photon and target nucleon center-of-mass frame, indicate that correlations between the spin and transverse momenta of hadrons produced in the target- and current-fragmentation regions may be significant. The measured beam-spin asymmetries provide a first access in dihadron production to a previously unexplored leading-twist spin- and transverse-momentum-dependent fracture function. The fracture functions describe the hadronization of the target remnant after the hard scattering of a virtual photon off a quark in the target particle and provide a new avenue for studying nucleonic structure and hadronization.

Introduction: The aim of the study was to determine the short-term real-world safety and efficacy of intravitreal brolucizumab injections in Korean patients with neovascular age-related macular degeneration (nAMD)., Methods: This multicenter retrospective study involved 294 eyes (treatment naïve 20 eye [6.8%] and nontreatment naïve 274 eyes [93.2%]) of 290 patients from 13 hospitals or retinal centers in South Korea. Patients with nAMD who received brolucizumab injection(s) between April 1 and November 30, 2021, with a follow-up ≥1 month, were included. Primary outcomes were safety, incidence of intraocular inflammation (IOI), and potential risk factors. The secondary outcome was efficacy, i.e., change in best-corrected visual acuity (BCVA) and optical coherence tomography-measured macular thickness and retinal fluid., Results: The mean age was 71.63 ± 8.66. The follow-up period was 2.38 ± 0.79 months. The mean number of brolucizumab injections during the follow-up was 1.52 ± 0.58. The overall incidence of IOI was 13.9% (n = 41 eyes). Most IOI cases were of anterior uveitis (8.8%, 26 eyes), followed by retinal vasculitis (2.4%, seven eyes) and occlusive retinal vasculitis (0.3%, one eye). Most eyes showed IOI resolution (n = 40, 97.5%) and BCVA restoration (n = 39, 95.1%) with or without corticosteroid treatment during the follow-up. Age, sex, IOI history, or other anti-vascular endothelial growth factor injection histories were not associated with the occurrence of IOI. However, only thin subfoveal choroidal thickness (SFCT) was associated with the occurrence of IOI (odds ratio = 0.995, p = 0.020). BCVA at 1 month improved from baseline (baseline 0.518 ± 0.356 vs. 1 month 0.503 ± 0.383, p = 0.023), but the improvement was not maintained. Anatomical improvement was significant after 3 months., Conclusion: In Korean patients with nAMD, the incidence of IOI following brolucizumab injections was 13.9%. IOI was well-controlled with or without steroid treatment. Most IOI eyes (95.1%) were restored to the level of vision before. IOI occurrence and occlusive vasculitis was rare. In the short term, brolucizumab injection effectively improved vision at 1 month and dried retinal fluid for 3 months., (© 2023 S. Karger AG, Basel.)

Purpose: To evaluate plasma antiretinal autoantibody (ARA) profiling and diagnostic efficacy for autoimmune retinopathy (AIR)., Design: A multicenter, diagnostic evaluation study., Methods: Forty-nine patients with a clinical diagnosis of AIR, disease controls including 20 patients with retinitis pigmentosa (RP), and 30 normal controls were included. Plasma samples from patients were analyzed for the presence of 6 ARAs, including recoverin, α-enolase, carbonic anhydrase II, heat shock protein 60, aldolase C, and cone-rod homeobox/cone-rod retinal dystrophy 2 using western blotting., Results: Autoantibody detection rates against cone-rod homeobox/cone-rod retinal dystrophy 2, heat shock protein 60, and aldolase C in AIR were 67.3%, 40.8%, and 42.9%, respectively, which were higher than those in RP and normal controls (P < .001, P < .001, and P = .007, respectively), but recoverin, α-enolase, and carbonic anhydrase II were not different from other control groups (P = .117, P = .774, and P = .467, respectively). Among ARAs, antirecoverin antibody was the most specific, as it was found in 3 (6.1%) patients with AIR and none of the control groups. As the number of detected ARAs increased, the probability of AIR increased (odds ratio: 1.913; P < .001; 95% confidence interval: 1.456-2.785). The positive number of ARAs was significantly higher when photoreceptor disruption was observed on optical coherence tomography, or severe dysfunction was observed in electroretinography (P = .022 and P = .029, respectively)., Conclusions: The profiles of ARAs in the AIR group were different from those in the RP and normal controls. The higher number of positive ARAs suggests a higher possibility of AIR diagnosis. ARAs should be used as adjunct tools for the clinical diagnosis of AIR., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: The aim of this study was to report surgical outcomes and risk factors for primary surgical failure following rhegmatogenous retinal detachment (RRD) repair., Methods: In this retrospective cohort study, RRD patients who underwent primary surgery at a tertiary center between January 1, 2006, and December 31, 2020, were enrolled. Surgical failure was defined as reoperation within 60 days postoperatively due to retinal re-detachment and putative risk factors for surgical failure were analyzed., Results: Of 2,383 eyes (2,335 patients), 1,342 (56.3%) underwent vitrectomy and 1,041 (43.7%) underwent scleral buckling. The surgical failure rate was 9.1% overall, and 6.0% and 13.1% for the vitrectomy and scleral buckling groups, respectively. In the multivariate logistic regression analysis, surgical failure was associated with surgical experience (first-year fellow vs. senior professor) (odds ratio [OR]: 1.66; p = 0.018), scleral buckling (OR: 2.33; p &lt; 0.001), and longer axial length (AL; ≥26.5 mm) (OR: 1.49; p = 0.017). In each surgical approach, age &lt;40 years (OR: 2.11; p = 0.029) in the vitrectomy group and age &gt;40 years (OR, 1.84; p = 0.004), male sex (OR: 1.65; p = 0.015), and first-year fellows compared to senior professors (OR: 1.95; p = 0.013) in the scleral buckling group were associated with surgical failure. Lens status were not associated with the surgical failure rate., Conclusion: In this large retrospective study using data from Korea, vitrectomy was superior to scleral buckling in terms of primary anatomical outcomes in the management of RRD. First-year fellows were a risk factor for surgical failure, especially for scleral buckling. Longer AL was a significant parameter for predicting the success rates., (© 2023 S. Karger AG, Basel.)

A 57-year-old man was transferred with sudden onset chest pain and evolving paralysis and numbness in the left leg. Contrast computed tomography (CT) revealed Stanford type A acute aortic dissection from the ascending aorta to bilateral internal and external iliac arteries with blood flow obstruction to the left kidney and left lower limb. Surgery was initiated 10 hours after onset of ischemic symptoms in the leg. Femoro-femoral bypass was carried out first, and we ensured sufficient phlebotomy from the ischemic limb during reperfusion and continuous hemodiafiltration to prevent myonephropathic metabolic syndrome. Total aortic arch replacement was then performed. Our treatment strategy was effective in this case of Stanford type A aortic dissection with prolonged lower limb ischemia. Although left hip disarticulation was subsequently required due to intractable infection, the patient became able to walk with an artificial limb after post-rehabilitation.

Purpose: We investigated the clinical features of Korean patients with retinal capillary hemangioblastoma (RCH) and genetic variants of the von Hippel-Lindau (VHL) gene., Methods: A retrospective analysis was performed on patients with RCH from 2003 to 2021 at Seoul National University Bundang Hospital. Sporadic and hereditary RCH associated with VHL disease were classified based on the specific tumors and family history. Clinical features, including the location and number of RCH and bilateral involvement, were investigated. Multiplex ligation-dependent probe amplification and direct sequencing targeting the VHL gene were performed for six RCH cases associated with VHL disease., Results: A total of 18 patients (23 eyes) were enrolled in this study. The mean age at diagnosis was 37 ± 15 years. Twelve patients had hereditary RCH associated with VHL disease, and six patients had sporadic RCH. All five patients with bilateral RCH were clinically diagnosed with VHL disease, and 13 patients had unilateral RCH. Juxtapapillary RCH was only observed in patients with VHL. The most common complication of RCH was the epiretinal membrane, followed by the subretinal fluid. Pathogenic variants were identified in four patients. All three patients with type 1 VHL had the well-known missense mutation p.Glu70Lys, and one patient with type 2 VHL had the nonsense mutation p.Trp88Ter., Conclusions: In Korean patients with RCH, bilateral involvement and juxtapapillary RCH are highly likely to be associated with VHL disease. Because RCH may be the first clinical manifestation in patients with VHL, active genetic testing of the VHL gene and systemic evaluation are required.

The single nucleotide polymorphisms (SNPs) of complement factor H (CFH) gene are well-known genetic risk factors for age-related macular degeneration (AMD). To identify whether the measurement of plasma protein concentrations of CFH variants using the multiple reaction monitoring (MRM) assay can determine the genotypes of CFH SNP rs1061170 and rs800292, 120 patients with AMD and 26 controls were included in this study. The number of cases were TT:TC:CC = 121:24:1 in CFH SNP Y402H and GG:AG:AA = 72:57:17 in CFH SNP I62V. Plasma concentrations of tryptic peptides were measured using the MRM assay, and tyrosine/histidine (Y/H) and valine/isoleucine (V/I) CFH variant protein ratios were obtained. To discriminate the genotypes by the plasma protein ratios, cut-off values were set for Y/H ratios (TT: > 4.428; TC: 1.00-4.428; CC: < 1.00) and V/I ratios (GG: > 1.09; AG: 0.0089-1.08; AA: < 0.0089). Correlation analysis revealed that the plasma CFH variant protein ratios and genotypes of CFH were exactly matched (100%) without overlap in the total patients and controls. The measurement of plasma protein CFH variants using the MRM assay can accurately identify the genotypes of CFH SNPs of Y402H and I62V., (© 2022. The Author(s).)

The movement toward smart farming, which has productivity and eco-friendly roles, is emerging in the foodservice industry in the form of indoor smart farm restaurants. The purpose of this study was to investigate the consumer decision-making processes in the context of indoor smart farm restaurants. The investigational framework was designed around the norm activation model (NAM) and the theory of planned behavior (TPB), with the moderating role of age. In particular, this study merged NAM and TPB to assess the effect of awareness of consumption consequences on consumers' attitudes as well as the role played by subjective norms in the formation of personal norms. Data were collected from 304 respondents in South Korea. As a result of structural equation modeling, the proposed hypotheses of causal relationships were generally supported, excluding only the relationship between subjective norm and behavioral intention. The moderating role of age was identified in the relationships between (1) subjective norm and attitude, and (2) personal norm and behavioral intention. This study presents not only theoretical contributions as the first empirical study on consumer behavior in the context of indoor smart farm restaurants but also presents practical suggestions from the perspective of green marketing.

We propose a new linear RGB-D simultaneous localization and mapping (SLAM) formulation by utilizing planar features of the structured environments. The key idea is to understand a given structured scene and exploit its structural regularities such as the Manhattan world. This understanding allows us to decouple the camera rotation by tracking structural regularities, which makes SLAM problems free from being highly nonlinear. Additionally, it provides a simple yet effective cue for representing planar features, which leads to a linear SLAM formulation. Given an accurate camera rotation, we jointly estimate the camera translation and planar landmarks in the global planar map using a linear Kalman filter. Our linear SLAM method, called L-SLAM, can understand not only the Manhattan world but the more general scenario of the Atlanta world, which consists of a vertical direction and a set of horizontal directions orthogonal to the vertical direction. To this end, we introduce a novel tracking-by-detection scheme that infers the underlying scene structure by Atlanta representation. With efficient Atlanta representation, we formulate a unified linear SLAM framework for structured environments. We evaluate L-SLAM on a synthetic dataset and RGB-D benchmarks, demonstrating comparable performance to other state-of-the-art SLAM methods without using expensive nonlinear optimization. We assess the accuracy of L-SLAM on a practical application of augmented reality.

We present the first measurement of dihadron angular correlations in electron-nucleus scattering. The data were taken with the CLAS detector and a 5.0 GeV electron beam incident on deuterium, carbon, iron, and lead targets. Relative to deuterium, the nuclear yields of charged-pion pairs show a strong suppression for azimuthally opposite pairs, no suppression for azimuthally nearby pairs, and an enhancement of pairs with large invariant mass. These effects grow with increased nuclear size. The data are qualitatively described by the gibuu model, which suggests that hadrons form near the nuclear surface and undergo multiple scattering in nuclei.These results show that angular correlation studies can open a new way to elucidate how hadrons form and interact inside nuclei.