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To compare the surgical outcomes of epiretinal membranes (ERMs) associated with retinal break and idiopathic ERMs.This retrospective study included patients with an idiopathic ERM or an ERM associated with retinal break, who were followed up for ≥ 6 months after ERM removal. The postoperative functional and anatomical outcomes were compared between the groups.A total of 160 and 38 eyes (198 patients) were in the idiopathic and retinal break groups, respectively. There was no significant difference in the baseline anatomical and functional parameters between the groups. At 6 months after surgery and at the final follow-up, best-corrected visual acuity, central foveal thickness, and ectopic inner foveal layer improved significantly in both groups, but there was no significant difference between the groups. In latter 49.0% of patients, tests for metamorphopsia and aniseikonia were performed. There was a significant improvement in the scores of metamorphopsia (0.40 ± 0.38 to 0.27 ± 0.28; p 0.001) and aniseikonia (6.07 ± 4.46 to 4.11 ± 3.52; p 0.001) in the idiopathic group at 6 months after surgery, but not in the retinal break group. The idiopathic group had significantly greater circularity of ERM extent compared to the retinal break group (p = 0.025).Visual and anatomical improvements after removal of ERMs associated with retinal break and idiopathic ERMs were comparable. However, metamorphopsia and aniseikonia improved only after removal of idiopathic ERMs.

To investigate the role of ultra-widefield fluorescein angiography (UWFA) for monitoring therapeutic response to adalimumab in patients with Behcet's uveitis.Patients with Behcet's uveitis treated with adalimumab for ≥30 weeks were included. Intraocular inflammation, best-corrected visual acuity, systemic medications, and UWFA scores were evaluated.Thirty-eight eyes of 20 patients were included. Significant decreases in grading of anterior chamber cells and vitreous haze were observed at 6, 14, and 30 weeks after adalimumab administration (UWFA scores significantly improved in Behcet's uveitis patients treated with adalimumab, and further improvement of UWFA scores was found in patients with a clinically quiescent inflammatory state.

To investigate the significance of systemic indicators, including neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), as long-term visual prognostic factors in patients with Behçet uveitis.This study comprised 114 eyes from 114 patients diagnosed with Behçet uveitis. Ophthalmologic evaluations and biochemical measurements including NLR and PLR values were consecutively obtained at each visit. Patients were divided into good and poor visual outcome groups, based on the visual acuity of 0.5 logarithm of the minimum angle of resolution in the worse-seeing eyes at the last visit. Factors associated with poor visual outcomes were analyzed, and optimal cutoff values of NLR and PLR were also evaluated.Sixty-six eyes (57.9%) were included in the good visual outcome group. Multivariate regression analysis showed that younger age of onset (odds ratio = 0.939; P = 0.010), longer disease duration (odds ratio = 1.164; P0.001), higher maximum NLR (odds ratio = 1.215; P = 0.033), and higher initial PLR (odds ratio = 1.014; P = 0.039) were significantly associated with poor visual outcomes. The optimal cutoff value for patients with poor visual outcome was 5.608 for NLR and 128.078 for PLR.A higher maximum NLR and higher initial PLR, as well as a younger age of onset and longer disease duration, were significantly associated with poor visual outcomes. Systemic inflammatory factors might be important indicators of visual prognosis in Behçet uveitis.

Uveitis is less common in children than in adults; however, pediatric uveitis has a relatively severe disease course that affects the quality of life. Although it is important to understand the epidemiological characteristics of pediatric uveitis, few studies have been conducted in large populations without referral bias. This study investigated the nationwide incidence and prevalence of pediatric uveitis in South Korea according to period, age, anatomic type, and systemic associations.This nationwide population-based cohort study used data from the Korean National Health Insurance Service from 2002 to 2018. This study included patients younger than 19 years of age with noninfectious uveitis with at least three claims of diagnostic codes of uveitis on separate days with at least once claim of prescription codes of steroid and immunosuppressive agents. All the cases were classified as anterior or non-anterior uveitis, and the overall incidence and prevalence were estimated by age, sex, and period. Patients with noninfectious uveitis were categorized by the presence of associated systemic conditions.A total of 10,862,616 patients over 128,688,078 person-years were evaluated from 2005 to 2016. Overall, 5,368 cases of anterior uveitis and 604 cases of non-anterior uveitis were identified. The incidence and prevalence of pediatric noninfectious uveitis were 4.64 per 100,000 person-years (95% confidence interval [CI], 4.52-4.76) and 8.25 per 100,000 persons (95% CI, 8.09-8.41). Both the incidence and prevalence of pediatric uveitis increased with age. Anterior uveitis accounted for 84.7% of pediatric noninfectious uveitis prevalent cases (6.99 per 100,000 persons). Cases of juvenile idiopathic arthritis (JIA)-associated uveitis accounted for 8.7% (926 cases) of pediatric noninfectious uveitis cases with a prevalence of 0.72 per 100,000 (95% CI, 0.67-0.77). The proportion of systemic associations was higher and JIA-related uveitis accounted for 11.2% (803 cases) of recurrent or chronic noninfectious uveitis cases with a prevalence of 0.62 per 100,000.This is the first population-based study investigating the largest population of pediatric patients with uveitis in Korea. The nationwide incidence and prevalence of pediatric noninfectious uveitis in 2005-2016 were 4.64 per 100,000 person-years and 8.25 per 100,000, respectively. The proportion of JIA in pediatric noninfectious uveitis was 8.7%. These population-based study findings provide a better understanding of the public health burden and aid in the planning of health-care strategies for pediatric patients with uveitis.

PURPOSE To evaluate the impact of posterior staphyloma identified using ultra-widefield fundus imaging on the long-term progression of myopic maculopathy in highly myopic patients. METHODS In this observational cohort study, highly myopic patients who were followed up for at least 5 years using ultra-widefield fundus imaging were analysed for fundus abnormalities and the progression of myopic maculopathy based on the International Meta-analysis of Pathologic Myopia classification. RESULTS This study included 390 eyes (210 patients) with the mean follow-up period of 69.2 ± 7.5 months (range, 60-88). Posterior staphyloma was identified in 198 eyes (50.8%) in the baseline ultra-widefield fundus images. The border of staphyloma was not identified within 50° view circle corresponding to conventional fundus photography in 42 eyes (21.2%) with staphyloma, most of that were wide macular type. Progression of myopic maculopathy during follow-up was observed in 202 eyes (51.8%), and eyes with staphyloma were more likely to show progression compared to those without (142/198 [71.7%] versus 60/192 [31.3%]; p

Background To evaluate whether subretinal or intravitreal injection of human CD34+ bone marrow-derived stem cells (BMSC) can have protective effects on retinal degeneration that may be enhanced by coadministration of exosomes harvested from human bone marrow mesenchymal stem cells (MSCs). Methods Human CD34+ cells were harvested from the mononuclear cell fraction of bone marrow using magnetic beads and labeled with EGFP. Exosomes were harvested from cultured human MSCs under hypoxic conditions. Royal College of Surgeons (RCS) 3-weeks-old rats, immunosuppressed with cyclosporine A, received subretinal or intravitreal injection of CD34+ cells (50,000 cells), CD34+ cells with exosomes (50,000 cells+10 µg), exosomes alone (10 µg), or PBS. Retinal function was examined using electroretinography (ERG), and the eyes were harvested for histologic and immunohistochemical analysis. Results The b-wave amplitude of ERG at 2 weeks after injection was significantly higher in eyes with subretinal or intravitreal CD34+ BMSC alone or in combination with exosomes when compared to PBS injected eyes or untreated contralateral eyes. At 4 weeks after injection, the ERG signal decreased in all groups but eyes with subretinal CD34+ BMSCs alone or combined with exosomes showed partially preserved ERG signal and preservation of the outer nuclear layer of the retina near the injection site on histology when compared to eyes with PBS injection. Immunohistochemical analysis identified the human cells in the outer retina. Subretinal or intravitreal exosome injection had no effect on retinal degeneration when administered alone or in combination with CD34+ cells. Conclusions Both subretinal and intravitreal injection of human CD34+ BMSCs can provide functional rescue of degenerating retina, although the effects were attenuated over time in this rat model. Regional preservation of the outer retina can occur near the subretinal injection site of CD34+ cells. These results suggest that CD34+ cells may have therapeutic potential in retinal degeneration.

Purpose To evaluate long-term results of photodynamic therapy (PDT) as a rescue treatment in patients with type 1 neovascularization refractory to intravitreal anti-vascular endothelial growth factor (VEGF). Methods Patients who underwent reduced-fluence PDT for refractory type 1 neovascularization, which showed persistent subretinal and/or intraretinal fluid after three or more consecutive anti-VEGF treatments, and were followed up for ≥24 months were reviewed. Results Seventy-eight eyes of 78 patients were included, and 37 (47%) were classified as polypoidal choroidal vasculopathy (PCV). The mean number of anti-VEGF injections before rescue PDT was 8.5 ± 5.4, and the mean follow-up period after rescue PDT was 74.0 ± 29.4 months. At 3 months after rescue PDT, exudation completely resolved in 55 (71%) patients and vision significantly improved (p = 0.021). Resolution of exudation was associated with choroidal vascular hyperpermeability [odds ratio (OR), 3.82; p = 0.031] and lower maximal height of pigment epithelial detachment (OR, 0.69; p = 0.018). In these patients, exudation recurred in 49 (89%) after mean period of 13.5 months. Vision significantly worsened at 24 months after rescue PDT, and thereafter, and the vision decrease was more prominent in patients with PCV. Rescue PDT could be repeated for recurrent or persistent exudation without increasing the risk of complications. Conclusion In patients with type 1 neovascularization refractory to anti-VEGF, reduced-fluence PDT is an effective and safe rescue treatment. Therapeutic efficacy wore off during long-term follow-up, but rescue PDT may be repeated safely.

Purpose To assess the safety and efficacy of selective retina therapy (SRT) using a Q-switched neodymium-doped yttrium lithium fluoride laser with feedback systems in patients with idiopathic central serous chorioretinopathy (CSC). Methods This randomized clinical trial enrolled patients having at least 3-month symptom of CSC. From month 3 visit, all subjects in both groups were eligible for SRT retreatment if they showed persistent or recurrent subretinal fluid (SRF). The primary outcome was complete resolution of SRF by optical coherence tomography at 3 months after treatment. The secondary outcomes were changes in SRF, central macular thickness (CMT) and best-corrected visual acuity at the 1-, 3-, and 6-month examinations. Results Sixty-eight CSC patients were included (SRT, 31; control, 37). After 1 and 3 months, complete resolution of SRF was achieved in 25.8% and 54.8% of SRT group and 17.6% and 35.1% of controls. The differences were not statistically significant (p = 0.424 and p = 0.142, respectively). However, mixed model for repeated measures analyses showed that the reduction of SRF and CMT were observed earlier in SRT group than in the sham group (least squares mean difference, -59.7 µm; 95% confidence interval, -98.2 to -21.2; p = 0.0029; least squares mean difference -67.0 µm; 95% confidence interval, -104.8 to -29.2; p = 0.0007, respectively). Significant reduction of SRF (≥50% reduction from baseline) was more frequently observed in SRT group (80.6%) than the sham group (44.1%) at month 1 (p = 0.007). Early reduction of SRF and CMT was more abundant in SRT group with symptom duration less than 6 months. Treatment related serious adverse events were not observed. Conclusions SRT using a Q-switched neodymium-doped yttrium lithium fluoride laser with feedback system was safe in this trial and effective for early resolution of SRF in the CSC patients. Early intervention with SRT can be a safe alternative for patients with acute symptomatic CSC.

The mammalian target of rapamycin (mTOR) signaling is critical to the regulation of stem cell maintenance and function in a cell-type and context-dependent manner. However, the effects of mTOR signaling on corneal epithelial stem cells (CESCs) under inflammatory conditions are not clear. Here, we demonstrate that mTOR inhibition with rapamycin promotes apoptosis of CESCs in a mouse model of sterile inflammation-induced CESC deficiency, and thereby aggravates the disease. Apoptosis induction in CESCs by rapamycin is not due to direct effect of rapamycin on the cells, but mediated by increase in neutrophilic inflammation. The interleukin (IL)-10/signal transducer and activator of transcription 3 anti-inflammatory pathway was downregulated in a Toll-like receptor 2-independent manner after rapamycin treatment and IL-10 replenishment abrogated the effects of rapamycin on inflammation and CESC apoptosis. Hence, our data reveal that the mTOR signaling is implicated in the control of the pro-inflammatory and anti-inflammatory balance in the cornea and that mTOR inhibition with rapamycin is detrimental to CESCs by accelerating inflammation-induced collateral damage to the cells. Stem Cells 2019;37:1212–1222

Rosacea is one of the most common dermatoses of adults. Although the detailed pathophysiology remains unknown, it is thought that rosacea is caused by a consistently aberrant, innate immune response, and that LL-37 plays an important role. However, involvement of the inflammatory cytokine IL-33 has not yet been studied. We explored the role played by IL-33 in the pathophysiology of rosacea. First, we immunohistochemically evaluated the expression of IL-33 and its receptor (ST2) in rosacea skin. Second, we exposed HaCaT cells to ultraviolet B (UVB) irradiation in the presence or absence of LL-37 and measured the expression of proinflammatory cytokines including IL-33. We also analysed VEGF (vascular endothelial growth factor) mRNA expression and protein release after costimulation of HaCaT cells by LL-37 and IL-33. Immunohistochemically, IL-33 expression was enhanced in the skin of rosacea patients, especially with erythematotelangiectatic subtype. In vitro, UVB and LL-37 synergistically increased mRNAs expression of proinflammatory cytokines, especially IL-33 and IL-1β. IL-33 protein release was also synergistically increased by LL-37 and UVB treatment. LL-37 and IL-33 stimulated VEGF mRNA expression and VEGF release from HaCaT cells. Our findings suggest that rosacea skin with abundant LL-37 may robustly produce and release IL-33 when exposed to UV radiation. IL-33 may participate in the angiogenesis and vasodilation of rosacea skin by enhancing VEGF release.

This study describes one of the technical solutions for Small Scale FLNG (SSFLNG)[1] development specifically designed to monetize Associated Gas (AG) of producing oil fields located within convenient distance of an existing LNG Plant or Port with LNG storage facility. Limited production capacity combined with short range small scale LNG carriers (SSLNGC), provide a cost effective means for LNG production. Ship to ship off-loading operation by loading arm has been considered in AG SSFLNG. Produced LNG is to be off-loaded from the SSFLNG to side-by-side moored SSLNGC. Relative motion and dynamic load acting on loading arm system in side-by-side mooring arrangement is one of key factors to estimate the offloading operability of the AG SSFLNG. In this paper, a numerical two-body motion analysis for the side-by-side moored SSFLNG in frequency- and time-domain is carried out. Also, the basic engineering work is carried out for the marine loading arms (MLA). Since the MLA reacts approximately as a linear system, it is calculated by a full spectral RAO analysis for each of the worst load cases issued from the spectral ranking. All loads and stresses inside the MLA are verified in accordance with EN1474-1[2] for the situations identified in the previous step. A high level fatigue analysis focused on the cryogenic swivel joints is carried out. Based on the numerical calculation for relative motion in side-by-side moored FLNG, we have been performed structural assessment for MLA in several environment conditions. The structural integrity of both MLA and the LNGC manifold are validated during offloading for Offshore West Africa.

Background: Acute dietary nitrate (NO3-) supplementation with beetroot juice (BRJ) can lower blood pressure (BP) at rest and during exercise in healthy individuals; however, the effects on endothelial function and BP response to dynamic exercise are not known in prehypertensive individuals. We compared the effects of 15 days BRJ supplementation on hemodynamic responses during progressive dynamic exercise. Methods: In a double-blind, randomized, crossover design, 11 healthy, prehypertensive men were supplemented with either BRJ (5.6 mmol, 70 ml BRJ) or a placebo (PL)(70 ml control drink) every day for 15 days. Participants completed two bouts of cycling exercise at each of the two workout intensities, corresponding to 30% and 60% of their predetermined VO2peak values. Flowmediated dilation (FMD) of the brachial artery and plasma concentration of NOx (NO3- and NO2-) were measured, and the mean arterial pressure (MAP), cardiac output (CO), and total vascular conductance (TVC) were assessed at rest and during exercise before and after each treatment. Results: BRJ supplementation significantly increased resting plasma NOx concentrations (123.0±11.3 vs. 181.9±19.5 μM) and the brachial artery FMD (9.8±1.0 vs. 13.5±1.4%) compared to no change after ingestion of the PL. Compared with the PL, BRJ supplementation reduced the MAP (101±1 vs. 99±1 mmHg) at rest and this reduction occurred across workloads, while the TVC was increased only during exercise (p

Purpose To compare the effects of bifocal versus trifocal diffractive intraocular lens (IOL) implantation on visual quality after phacoemulsification in patients with cataracts. Methods Eighty-eight eyes from 63 patients were analyzed. Trifocal (AT LISA tri 839MP), bifocal (AcrySof IQ ReSTOR) and bifocal (Tecnis MF ZLB00) IOLs were implanted into 53, 18, and 17 eyes, respectively. Uncorrected distance, intermediate and near visual acuity, refractive errors, contrast sensitivity, and patient satisfaction were measured at 1 week and 1 month after surgery. Refractive error was converted to a spherical equivalent and compared to predicted refraction calculated by IOL calculation formulas. Results Uncorrected distance, intermediate, and near visual acuity did not differ significantly between groups. One month after surgery, the mean refractive errors were −0.07 diopters (D) in the AT LISA tri 839MP group, +0.18 D in the AcrySof IQ ReSTOR group, and +0.31 D in the Tecnis MF ZLB00 group (p < 0.001). The predictive accuracy of IOL calculation formulas did not differ between groups. Contrast sensitivity, satisfaction, and spectacle independence in the trifocal group were comparable with those of the two bifocal groups. Conclusions Trifocal IOL and two different types of bifocal IOL implantation were all effective for improving visual quality, although refractive error in patients with trifocal IOL shows myopic tendencies.

Purpose of the study The purpose of the study was to report cases with acute primary angle closure where optic disc swelling was documented after intraocular pressure (IOP) lowering by laser iridotomy. Patients and methods Two patients with acute primary angle closure underwent funduscopic examination of the optic disc and spectral-domain optical coherence tomography circumpapillary scanning at the time of acute primary angle closure attack before laser iridotomy, and after the laser iridotomy treatment. Results Optic disc swelling was developed in both patients following IOP lowering by laser iridotomy, which was documented by spectral-domain optical coherence tomography imaging as a diffuse thickening of the circumpapillary retinal nerve fiber layer. Conclusions This is the first report demonstrating a temporal relationship between IOP lowering and optic disc swelling in patients with acute primary angle closure. Optic disc swelling documented after acute episode of acute primary angle closure may suggest choroidal effusion or axoplasmic overflow associated with sudden IOP lowering, rather than coexistence of other optic neuropathy.

The purpose of this study is to investigate the effects of astronomical animation module on students` conceptual change regarding the concepts of diurnal motion of stars. Four students participated in this study, who never learned about the diurnal motion of stars. An animation module was developed by using Flash MX to readily understand the concept of space. In addition, we inserted a teacher`s voice with supplementary materials into the animation module to help students learn individually. The animation module was comprised of the movement of the Earth, the Moon and the planet. The earth science gifted students` preconception on diurnal motion of stars was analyzed with pre-test using questionnaires and interviews. After the instruction with animation module, the effect of conceptual change was examined by comparing pre and post-test. The results indicated that three students correctly presented about the motion of the star by all directions in middle latitude. Four students showed their understanding that stars travelled straight in all directions. Finally, all of four students whose preconceptions were that the star rotated perpendicularly showed the conceptual change of diurnal motion that the star traveled diagonally.

본 연구는 일반병동에 입원하여 3일 이상 경장영양을 시행한 성인 환자 95명을 대상으로 영양집중지원팀의 중재 효과를 평가하기 위해 영양중재를 받은 중재군과 받지 못한 군으로 분류하여 열량 및 단백질 지원율과 생화학적 지표를 비교·분석 하였다. 연구결과를 통해 환자의 입원 초기부터 적절한 영양관리를 계획하고, 영양집중지원팀의 영양중재로 체계적인 관리를 실시하면 환자의 영양상태가 개선되는 것을 확인할 수 있었다. 결론적으로 영양불량 문제가 있는 환자에게 영양집중지원팀의 중재를 받아 문제를 개선할 수 있도록 절차를 마련한다면, 이는 환자의 임상적 치료에 긍정적인 영향을 줄 것으로 생각된다. 본 연구는 국내에서 경장영양을 시행한 일반병동 환자를 대상으로 영양집중 지원팀의 중재 효과에 대한 초기 연구이며, 집중영양치료료 수가 신설 이후 진행된 연구다. 추후 일반병동 환자를 대상으로 영양집중지원팀의 중재효과에 대한 연구가 다양하게 시행된다면 의료진의 관심이 증대 될 것이고, 나아가 영양집중지원팀의 중재를 통해 진료의 질을 높일 수 있을 것이다.

Purpose To describe the characteristics and frequency of ophthalmologic findings in patients with Lennox-Gastaut syndrome (LGS). Methods The medical records of patients diagnosed with LGS at Seoul National University Children's Hospital from January 2004 to August 2014 were retrospectively reviewed. The records of 34 patients (mean age ± standard deviation, 2.66 ± 3.51 years; male, 58.8%) were reviewed. The primary measure was the incidence of ophthalmologic manifestations. Results Of the 34 patients, 88.2% had at least one ocular abnormality. Refractive error (52.9%) was the most frequently observed ophthalmologic manifestation in patients with LGS, followed by strabismus (32.4%), cortical visual impairment (23.5%), and retinopathy of prematurity (8.8%). Among these cases, seven patients had exotropia and three had esotropia. Conclusions LGS is a childhood-onset epileptic encephalopathy with variable ophthalmologic manifestations, the most frequent being refractive errors. Patients with suspected LGS should be examined regularly because ophthalmological features can change during their disease course.

Miller Fisher syndrome is typically associated with a preceding infection, especially with Campylobacter jejuni. We describe a patient with Miller Fisher syndrome following Orientia tsutsugamushi infection, which to our knowledge has not been previously reported.

Purpose: To determine the sensitivity and specificity of MR elastography (MRE) in the staging of hepatic fibrosis (HF) using histopathology as the reference standard in an Asian population. Materials and Methods: MRE was performed on 55 patients with chronic liver diseases or biliary diseases and on 5 living related liver donors (48 men and 12 women; mean age, 55.7 years). MRE was performed with modified, phase-contrast, gradient-echo sequences, and the mean stiffness values were measured on the elastograms in kilopascals(kPa). Receiver operating characteristic curve analysis was performed to determine the cutoff value and accuracy of MRE for staging HF. Histopathologic staging of HF according to the METAVIR scoring system served as the reference. Results: Liver stiffness increased systematically along with the fibrosis stage. With a shear stiffness cutoff value of 3.05 kPa, the predicted sensitivity and specificity for differentiating significant liver fibrosis (≥ F2) from mild fibrosis (F1) were 89.7% and 87.1%, respectively. In addition, MRE was able to discriminate between patients with severe fibrosis (F3) and those with liver cirrhosis (sensitivity, 100%; specificity, 92.2%), with a shear stiffness cutoff value of 5.32 kPa. Conclusion: MRE could be a promising, noninvasive technique with excellent diagnostic accuracy for detecting significant HF and liver cirrhosis. J. Magn. Reson. Imaging 2011. © 2011 Wiley Periodicals, Inc.