Exosome-mediated secretion of miR-127-3p regulated by RAB27A accelerates metastasis in renal cell carcinoma.

BACKGROUND: The exosome-mediated extracellular secretion of miRNAs occurs in many cancers, and RAB27A is a potent regulator of exosome secretion. For metastatic renal cell carcinoma (RCC), this study examines the mechanisms of cancer metastasis via the RAB27A-regulated secretion of specific miRNAs. METHODS: RAB27A knockdown (KD) and overexpressing (OE) RCC cells were used to examine cell migration and adhesion. The particle counts and sizes of exosomes in RAB27A OE cells were analyzed using Exoview, and those of intraluminal vesicles (ILV) and multivesicular bodies (MVB) were measured using an electron microscope. Analysis of RNA sequences, protein-protein interaction networks, and the competing endogenous RNA (ceRNA) network were used to identify representative downregulated miRNAs that are likely to undergo cargo-sorting into exosomes and subsequent secretion. A molecular beacon of miR-137-3p, one of the most representatively downregulated genes with a fold change of 339, was produced, and its secretion was analyzed using Exoview. RAB27A OE and control cells were incubated in an exosome-containing media to determine the uptake of tumor suppressor miRNAs that affect cancer cell metastasis. RESULTS: Migration and cell adhesion were higher in RAB27A OE cells than in RAB27A KD cells. Electron microscopy revealed that the numbers of multivesicular bodies and intraluminal vesicles per cell were higher in RAB27A OE cells than in control cells, suggesting their secretion. The finding revealed that miR-127-3p was sorted into exosomes and disposed of extracellularly. Protein-protein interaction analysis revealed MYCN to be the most significant hub for RAB27A-OE RCC cells. ceRNA network analysis revealed that MAPK4 interacted strongly with miR-127-3p. CONCLUSION: The disposal of miR-127-3p through exosome secretion in RAB27A overexpressing cells may not inhibit the MAPK pathway to gain metastatic potential by activating MYCN. The exosomes containing miRNAs are valuable therapeutic targets for cancer treatment.

A case report of optic neuropathy following dacryocystorhinostomy in a 57-year-old female patient with May-Hegglin anomaly.

BACKGROUND: We report a rare case of optic neuropathy following dacryocystorhinostomy (DCR) in a 57-year-old female patient with May-Hegglin anomaly. CASE PRESENTATION: The patient was presented with sudden onset of vision loss for the left eye after DCR under general anesthesia. Her best corrected visual acuity was light perception in the left eye. Relative afferent pupillary defect was detected in her left eye. Magnetic resonance imaging of the orbit revealed an hyperintensity at the intra-orbital segment of the left optic nerve on T2-weighted image and Flair image. The patient was diagnosed with acute postoperative optic neuropathy and treated with methylprednisolone. Although her vision partially improved, she was left with a visual field defect in the left eye. CONCLUSIONS: In patients with hematologic diseases, postoperative vision loss can occur following even minor surgery under general anesthesia, such as DCR. Therefore, preoperative counseling regarding the risk of visual loss should be given to high-risk patients.

Corneal topography and angle parameters after laser iridotomy combined with iridoplasty assessed by dual Scheimpflug analyzer.

PURPOSE: To investigate the changes in corneal topography including parameters such as corneal curvature and corneal aberrations, along with anterior chamber angle (ACA) after laser iridotomy (LI) combined with peripheral iridoplasty (PI) using dual Scheimpflug analyzer. METHODS: In this prospective observational study, dual Scheimpflug analyzer images were acquired before and 1 week after LI plus PI. Corneal curvature of both axial and instantaneous maps from anterior and posterior surface, respectively, and total corneal power (TCP) were acquired. These corneal parameters from three zones (central, middle, and peripheral) and total corneal wavefront aberration, trefoil, and coma were obtained. The ACA from four quadrants, anterior chamber depth (ACD), anterior chamber volume (ACV), and intraocular pressure (IOP) were also inspected. RESULTS: ACD increased significantly from 2.15 ± 0.25 to 2.18 ± 0.24 mm (P = 0.002). ACV and ACA from all four quadrants increased significantly after the laser treatment (all P < 0.05). IOP decreased significantly from 16.9 ± 3.1 to 14.7 ± 2.9 mmHg following LI plus PI (P = 0.000). No significant changes were detected in corneal axial and instantaneous curvature from three zones on the anterior and posterior corneal surface after LI plus PI (all P > 0.05). The TCP, total corneal wavefront aberration, trefoil, and coma also revealed no significant changes after the laser procedure (all P > 0.05). CONCLUSIONS: Treatment with LI combined with PI did not affect the corneal topographic parameters from both anterior and posterior surfaces. However, LI plus PI improved ACA parameters significantly and effectively.

Association between the Frequency of Optic Disk Hemorrhage and Progression of NTG Related with the Initial Location of RNFL Defect.

PURPOSE: This study aimed to investigate the association of the frequency of optic disk hemorrhage (DH) and progression of normal tension glaucoma (NTG) between each group based on the location of the initial retinal nerve fiber layer (RNFL) defect. METHODS: In this retrospective, observational cohort study, 142 NTG patients who underwent more than 5 reliable visual field tests with initial superior hemifield (group 2, n = 51), inferior hemifield (group 1, n = 44), or both hemifield (group 3, n = 47) defects were included. The number of DHs was inspected in serial optic disk photographs by 2 different ophthalmologists. Progression rates, which are the slope of mean thresholds from the 52 points, were calculated using a linear mixed effect model. RESULTS: The mean follow-up period was 8.19 ± 3.30 years. DHs related with the initial RNFL defect occurred significantly more frequently in group 2 (35 in inferior hemifield) than in group 1 (6 in superior hemifield) (p = 0.009) or group 3 (6 in inferior hemifield) (p = 0.006). The progression rate in group 2 was significantly faster than in group 1 (p = 0.019) or the superior hemifield of group 3 (p = 0.001). The progression rate of subjects showing recurrent DH was significantly faster than those showing single DH from all groups (-0.5460 vs. -0.2867 dB/year, p = 0.0053). CONCLUSIONS: More careful examination and caution are required when NTG patients show recurrent DH in the inferior hemifield related to the initial RNFL defect.

Visual and structural prognosis of the untreated fellow eyes of unilateral normal tension glaucoma patients.

PURPOSE: To investigate the visual and structural prognosis of untreated initial non-glaucomatous fellow eyes of unilateral normal tension glaucoma (NTG) patients. METHODS: In this retrospective observational cohort study, 50 NTG patients with unilateral visual field (VF) loss and no VF defect, retinal nerve fiber layer (RNFL) defect or neuroretinal rim (NRR) notching in the fellow eyes, and those who had initial non-glaucomatous fellow eyes untreated were included. For the fellow eyes, the development of VF defect, RNFL defect, and NRR notching was inspected retrospectively by two observers. Baseline clinical characteristics including initial intraocular pressure (IOP), central corneal thickness, and spherical equivalent (SE) were compared between glaucomatous and fellow eyes. RESULTS: During the mean follow-up period of 8.77 ± 2.92 years, five patients (10 %) developed RNFL defect and four patients (8 %) developed NRR notching in the fellow eye. Among six patients (12 %) who had developed either RNFL defect or NRR notching, only three patients (6 %) developed VF loss in 1.81, 3.09, and 9.27 years respectively. The initial IOP was significantly higher (p = 0.031), SE was more myopic (p = 0.025), and the occurrence of disc hemorrhage (p = 0.049) was significantly higher in glaucomatous eyes than that in fellow eyes. CONCLUSIONS: The incidence of glaucoma development in the fellow eye is rather low. Therefore, the initial non-glaucomatous fellow eye of the unilateral NTG patient may be observed without treatment until glaucoma develops.

Longitudinal Rates of Change in Structural Parameters of Optical Coherence Tomography in Primary Angle Closure Glaucoma following Laser Iridotomy along with Peripheral Iridoplasty.

Background: This study aimed to investigate longitudinal rates of change (LRCs) of structural parameters from optical coherence tomography (OCT) in patients with primary angle closure glaucoma (PACG) after laser iridotomy (LI) along with laser peripheral iridoplasty (PI). Methods: Among 146 patients diagnosed with PACG, thirty-two subjects (32 eyes) who underwent LI plus PI and accomplished more than five times of reliable OCT tests were included in the current retrospective study. Retinal nerve fiber layer (RNFL) and Bruch's membrane opening-minimum rim width (BMO-MRW) were measured by spectral-domain OCT with three month interval. LRCs of global and six Garway-Heath sectors were investigated using the linear mixed-effects model which adjusted BMO area, sex, and age. Imaging of dual Scheimpflug analyzer was performed before and at 1 week after LI with PI and yearly thereafter. Results: The mean follow-up period was 32.28 ± 13.34 months with a mean number of 10.18 ± 3.33 OCT images. Baseline characteristics are as follows: age, 63 ± 7.9 years; female, 62.5%; intraocular pressure(IOP), 15.48 ± 4.79 mmHg; anterior chamber depth, 2.09 ± 0.18 mm; and mean deviation, -7.97 ± 8.48 dB. Global LRC of BMO-MRW was 0.86 ± 1.34 µm/yr and RNFL was -0.64 ± 0.22 µm/yr. IOP decreased significantly to 13.06 ± 2.21 mmHg (p=0.001) while anterior chamber volume (p=0.011) and mean anterior chamber angle (p=0.022) increased significantly after LI along with PI compared to the baseline at the final visit. Conclusions: LRC of a new parameter, BMO-MRW, and LRC of RNFL were relatively low in patients with PACG, following LI along with PI. After widening of the anterior chamber angle and decrease of IOP due to LI plus PI, PACG might show stable structural prognosis assessed by OCT.

Evaluation of lysyl oxidase-like 1 gene polymorphisms in pseudoexfoliation syndrome in a Korean population.

PURPOSE: The purpose of this study was to evaluate association profiles of lysyl oxidase-like 1 (LOXL1) gene polymorphisms with pseudoexfoliation syndrome (XFS) in a Korean population. METHODS: A total of 110 Korean patients with XFS and 127 control subjects were included in this study. Genotypes of three single nucleotide polymorphisms (SNPs) of LOXL1 (rs1048661, rs3825942, and rs2165241) were analyzed with direct sequencing, and a case-control association study was performed. Genotype frequencies of each SNP were compared according to the XFS phenotypes. RESULTS: All three SNPs were significantly associated with XFS. The T allele at rs1048661 (odds ratio [OR] = 14.29, 95% confidence interval [CI] = 6.25-33.3) and the C allele at rs2165241 (OR = 7.14, 95% CI = 1.59-33.3) were risk alleles in Korean subjects, which was consistent with findings in other Asian populations. However, our findings were opposite to results from Caucasian populations in which the risk alleles at rs1048661 and rs2165241 were G and T, respectively. At the rs3825942, the G allele (OR = 12.50, 95% CI = 2.94-50.0) was a risk allele for XFS, which was similar to results from most other ethnic groups except black South Africans in whom the A allele increased the risk. In the haplotype analysis, the T-G-C haplotype composed of all three risk alleles was significantly overrepresented in XFS and conferred an 11.36 fold (95% CI = 5.97-23.49) increased likelihood of XFS. There was no significant association between the genotype frequencies of the three SNPs and the XFS phenotypes. CONCLUSIONS: Three SNPs of LOXL1 (rs1048661, rs3825942, and 2,165,241) are highly associated with XFS in a Korean population. The risk alleles of these SNPs were similar to those of other Asian populations, such as Japanese or Chinese, but differed from non-Asian populations, suggesting that still unidentified genetic or environmental factors may contribute to disease expression.

Deep learning visual field global index prediction with optical coherence tomography parameters in glaucoma patients.

The aim of this study was to predict three visual filed (VF) global indexes, mean deviation (MD), pattern standard deviation (PSD), and visual field index (VFI), from optical coherence tomography (OCT) parameters including Bruch's Membrane Opening-Minimum Rim Width (BMO-MRW) and retinal nerve fiber layer (RNFL) based on a deep-learning model. Subjects consisted of 224 eyes with Glaucoma suspects (GS), 245 eyes with early NTG, 58 eyes with moderate stage of NTG, 36 eyes with PACG, 57 eyes with PEXG, and 99 eyes with POAG. A deep neural network (DNN) algorithm was developed to predict values of VF global indexes such as MD, VFI, and PSD. To evaluate performance of the model, mean absolute error (MAE) was determined. The MAE range of the DNN model on cross validation was 1.9-2.9 (dB) for MD, 1.6-2.0 (dB) for PSD, and 5.0 to 7.0 (%) for VFI. Ranges of Pearson's correlation coefficients were 0.76-0.85, 0.74-0.82, and 0.70-0.81 for MD, PSD, and VFI, respectively. Our deep-learning model might be useful in the management of glaucoma for diagnosis and follow-up, especially in situations when immediate VF results are not available because VF test requires time and space with a subjective nature.

Association between atrial fibrillation and the risk of glaucoma development: a 12-year Nationwide cohort study.

OBJECTIVE: To investigate the risk of glaucoma development in patients with atrial fibrillation (A-fib) using Korean National Health Insurance Service data. METHODS: The present study used a National Sample Cohort consisting of approximately one million random subjects who were tracked from 2002 to 2013 (12 years). Newly diagnosed glaucoma and A-fib were included based on the Korean Classification of Disease codes. The A-fib group consisted of patients who received an initial A-fib diagnosis between January 2003 and December 2007 as an index period (n = 8765). The control group (n = 43,352) was selected using a 1:5 propensity-score matching for social and demographic factors. Each subject was followed up until 2013. Multivariate Cox proportional hazard regression analysis was performed to compare the risk of glaucoma development between the A-fib group and the control group. RESULTS: The rate of glaucoma development was 3.54% in the A-fib group and 2.96% in the control group (P < 0.0001). A-fib increased the risk of glaucoma development [hazard ratio = 1.31; 95% confidence interval (CI): 1.15 to 1.48] after adjusting for age, sex, comorbidities, residence, household income, and year of enrollment. In multivariable Cox regression analysis, patients with comorbidity of diabetes mellitus and chronic renal failure and those aged ≥50 years showed significantly higher risk of glaucoma development (all P < 0.001). CONCLUSIONS: A-fib was significantly associated with the development of glaucoma after adjusting for potential confounding factors. Physicians may need to monitor patients with A-fib carefully for possible glaucoma development.

The effect of additional topical cyclosporine or vitamin A on the ocular surface during antiglaucoma medication administration.

PURPOSE: To investigate the effects of topical application of cyclosporine or vitamin A on the ocular surface during the concurrent administration of antiglaucoma drugs. METHODS: Thirty rabbits were randomized into 5 groups. Group 1 was administered timolol, group 2 received travoprost, group 3 received a travoprost/timolol fixed combination solution, group 4 received timolol and travoprost, and group 5 received timolol, travoprost, and dorzolamide. Each group was divided into a subgroup that received only the antiglaucoma medication (subgroup A), a subgroup that received topical cyclosporine in addition to the antiglaucoma medication (subgroup B), and a subgroup that received topical vitamin A in addition to the antiglaucoma medication (subgroup C). Conjunctival impression cytology specimens were collected at baseline and at weeks 1, 3, and 6. Conjunctival biopsy specimens were collected at week 6. RESULTS: The impression cytologic study results are as follows: statistically significant differences were found between groups 4A and 4B and between groups 4A and 4C at week 6 (p = 0.004, p = 0.006, respectively) and between groups 5A and 5B and between groups 5A and 5C at weeks 3 and 6 (p = 0.006, p = 0.008 at week 3, p = 0.003, p = 0.004 at week 6, respectively). No statistically significant differences were found between subgroup B and subgroup C in any of the groups at any of the times evaluated (p > 0.05). The conjunctival biopsy specimens from groups 1, 2, and 3 showed no distortion, but groups 4A and 5A showed distortion of the conjunctival epithelial structures. Groups 4B, 4C, 5B, and 5C showed less distortion of the conjunctival epithelial structures. CONCLUSION: Administration of cyclosporine or vitamin A may reduce the adverse ocular surface changes caused by long-term administration of antiglaucoma drugs.

Long-Term Outcome of Corneal and Anterior Chamber Angle Parameters after Combined Laser Iridotomy and Iridoplasty Using Dual Scheimpflug Analyzer: 1 Year Results.

BACKGROUND: To investigate the outcomes of corneal and anterior chamber angle (ACA) parameters after laser iridotomy (LI) combined with peripheral iridoplasty (PI) using dual Scheimpflug analyzer in the long term. METHODS: Fifty-eight eyes (58 subjects) with shallow AC were included in this prospective cohort study. Images of the Dual Scheimpflug analyzer were obtained before, 1 week, and 1 year after LI and PI. Pachymetry from three zones (central, middle, and peripheral), corneal aberration, and spherical equivalent (SE) were acquired. AC depth (ACD), AC volume (ACV), ACA from four quadrants, and intraocular pressure (IOP) were also obtained. For comparison of the results, the linear mixed-effects model was employed. RESULTS: ACD significantly increased from 2.09 ± 0.25 mm to 2.10 ± 0.23 mm at 1 year after laser (all p < 0.05). ACV and ACA increased significantly after laser at 1 year (all p < 0.05). IOP significantly decreased from 15.97 ± 4.20 mmHg to 13.73 ± 2.63 mmHg at 1 year (all p < 0.0001). No significant changes were found in the coma, trefoil, total corneal aberration, pachymetry from three zones, corneal volume, central corneal thickness, and SE after LI and PI until 1 year (all p > 0.05). CONCLUSIONS: LI plus PI ameliorated parameters of ACA efficiently and significantly reduced IOP in eyes with shallow AC until 1 year of long-term follow-up. However, parameters of the cornea and SE were not influenced by LI with PI until after 1 year.

Deep learning classification of early normal-tension glaucoma and glaucoma suspect eyes using Bruch's membrane opening-based disc photography.

Purpose: We aimed to investigate the performance of a deep learning model to discriminate early normal-tension glaucoma (NTG) from glaucoma suspect (GS) eyes using Bruch's membrane opening (BMO)-based optic disc photography. Methods: 501 subjects in total were included in this cross-sectional study, including 255 GS eyes and 246 eyes of early NTG patients. BMO-based optic disc photography (BMO overview) was obtained from spectral-domain optical coherence tomography (OCT). The convolutional neural networks (CNN) model built from scratch was used to classify between early NTG and GS. For diagnostic performances of the model, the accuracy and the area under the curve (AUC) of the receiver operating characteristic curve (ROC) were evaluated in the test set. Results: The baseline demographics were age, 48.01 ± 13.03 years in GS, 54.48 ± 11.28 years in NTG (p = 0.000); mean deviation, -0.73 ± 2.10 dB in GS, -2.80 ± 2.40 dB in NTG (p = 0.000); and intraocular pressure, 14.92 ± 2.62 mmHg in GS, 14.79 ± 2.61 mmHg in NTG (p = 0.624). Our CNN model showed the mean AUC of 0.94 (0.83-1.00) and the mean accuracy of 0.91 (0.82-0.98) with 10-fold cross validation for discriminating between early NTG and GS. Conclusion: The performance of the CNN model using BMO-based optic disc photography was considerably good in classifying early NTG from GS. This new disc photography of BMO overview can aid in the diagnosis of early glaucoma.

Quantitative analysis of exosomes in the aqueous humor of Korean patients with pseudoexfoliation glaucoma.

We aimed to quantitatively analyze the exosome and its cargo in individual aqueous humor (AH) samples from pseudoexfoliation (PEX) glaucoma patients compared to controls using a novel detection platform. We investigated the size distribution and measured the quantitative exosome particle counts in each AH sample. AH (80-120 µL) was obtained during cataract surgery or glaucoma filtering surgery from 12 Korean subjects (six with PEX glaucoma and six age-matched controls). The mean size of the exosomes was 58.9 ± 18.5 nm measured by a tangential flow filtration system using single-particle interferometric reflectance imaging sensor. Exosome particle count in each CD 63, CD 81, and CD9 spot was significantly greater in PEX glaucoma than in controls in total, CD 63, CD9, syntenin, and scattering(all p < 0.003). The CD63 spot showed a particle count of 8319.1 ± 797.7 in PEX glaucoma patients and 4786.8 ± 1302.1 in controls (p = 1.88E-11). Individual fluorescent capture spot images also revealed denser exosome particles in PEX patients than in controls. Syntenin, indicating exosomal origin, was detected in all AH samples. Exosomes differentially detected in AH suggest the possible role of exosomes in the pathogenesis of PEX glaucoma.

MicroRNA profiles in aqueous humor between pseudoexfoliation glaucoma and normal tension glaucoma patients in a Korean population.

We aimed to obtain microRNA (miRNA) profiles of patients with pseudoexfoliation (PEX) glaucoma or normal-tension glaucoma (NTG) compared to normal controls using individual aqueous humor (AH) samples and investigate the role of miRNAs in the pathogenesis of PEX glaucoma compared to NTG in Korean. AH (80-120 µl) was collected before cataract surgery or trabeculectomy from 26 Korean subjects (eleven with PEX glaucoma, age-matched eight NTG, and seven controls). RNA sequencing was conducted for RNA samples extracted from 26 AH samples. Bioinformatics analysis was performed for targets and related pathways. A total of 334 and 291 discrete miRNAs were detected in AH samples of PEX glaucoma and NTG patients, respectively. Two significantly upregulated miRNAs (hsa-miR-30d-5p and hsa-miR-320a) and ten significantly downregulated miRNAs (hsa-miR-3156-5p, hsa-miR-4458, hsa-miR-6717-5p, hsa-miR-6728-5p, hsa-miR-6834-5p, hsa-miR-6864-5p, hsa-miR-6879-5p, hsa-miR-877-3p, hsa-miR-548e-3p, and hsa-miR-6777-5p) in PEX glaucoma patients compared to control (fold-change > 2, p < 0.05) were found. In NTG patients, ten significantly upregulated and two downregulated miRNAs compared to control were found. Only hsa-miR-6777-5p was commonly downregulated in both PEX glaucoma and NTG patients. Related pathways were proteoglycans in cancer, glioma, and TGF-beta signaling pathway in PEX glaucoma. These differentially expressed miRNAs between PEX glaucoma and NTG samples suggest the possible role of miRNA in the pathogenesis of glaucoma, further implying that pathogenic mechanisms may differ between different types of glaucoma.

Resveratrol prevents hypoxia-induced retinal ganglion cell death related with ErbB2.

AIM: To confirm the changes in proteins related with hypoxia-induced retinal cell death and to assess the effects of resveratrol (Res). METHODS: The therapeutic effect of Res was verified using an ischemic/reperfusion (I/R) model in vivo and a hypoxia modelin retinal ganglion cells (RGCs) in vitro. Death of RGCs were confirmed by TUNEL assay. Protein expression was confirmed by Western blotting and immunohistochemistry. In addition, flow cytometric analysis was used to confirm the response in the cell unit to obtain more accurate data. RESULTS: ErbB2 expression and apoptosis in the ganglion cell layer (GCL) increased after I/R injury. Treatment of Res rescued I/R-induced ganglion cell death, downregulated apoptosis and ErbB2 protein expression in the retina. In subsequent in vitro models, Res affects apoptosis by regulating the phosphorylation and expression of mouse double minute 2 homolog (MDM2), along with those of ErbB2. These results suggest that Res reverses GCL-specific apoptosis via downregulation of ErbB2 in ischemic injury. CONCLUSION: In light of Res favorable properties, it should be evaluated in the treatment of RGC death and related retinal disease characterized by ErbB2 and MDM2 expression. Therefore, Res is appropriate therapeutic agent for treating ischemic injury-related eye diseases by targeting the expression of ErbB2 and MDM2.

Long noncoding RNAs associated with nonalcoholic fatty liver disease in a high cholesterol diet adult zebrafish model.

The mechanism of nonalcoholic fatty liver disease (NAFLD) has not been completely revealed. In this study, we investigated the association of liver histological changes and long noncoding RNAs (lncRNAs) in the NAFLD zebrafish model. Forty zebrafish were fed a high-cholesterol diet (1.5 g per day) for 8 weeks. We measured fatty liver changes in the zebrafish liver using oil red O staining and divided them into two groups based on high and low scores. We pooled each group of zebrafish livers and identified lncRNAs, miRNAs, and mRNAs using Next-generation sequencing. Human homologs of lncRNAs were identified using ZFLNC, Ensembl, and NONCODE. We found several significant genes, including 32 lncRNAs, 5 miRNA genes, and 8 protein-coding genes, that were associated with liver metabolism and NAFLD-related functions in zebrafish. In particular, eight conserved human homologs of lncRNAs were found. We discovered the human homologs of eight lncRNA candidates from fatty liver zebrafish for the first time. The spectrum of biological mechanisms by which lncRNAs mediate their functional roles in NAFLD in a high cholesterol diet adult zebrafish model remains to be uncovered.

Association Between Chronic Renal Disease and the Risk of Glaucoma Development: A 12-year Nationwide Cohort Study.

Purpose: The purpose of this study was to present the results of our investigation into the risk of glaucoma development in patients with chronic renal disease (CRD). Methods: The present retrospective cohort study used the Korean National Health Insurance Service data, which consisted of 1,025,340 random subjects who were tracked from 2002 to 2013. Newly diagnosed glaucoma and CRD were included on the basis of the Korean Classification of Disease codes. The CRD group consisted of patients who received an initial CRD diagnosis between January 2003 and December 2007 as an index period (n = 3640). The control group (n = 17,971) was selected using 1:5 propensity-score matching using social and demographic factors, along with the year of enrollment. Each group subject was followed until 2013. We used multivariate Cox proportional hazard regression analysis to compare the risk of glaucoma development between the two groups. Results: Glaucoma consecutively developed in 4.3% in the CRD group and 2.8% in the control group (P < 0.0001). CRD increased the risk of glaucoma development (hazard ratio [HR] = 1.63, 95% confidence interval [CI] = 1.34-1.98] after adjusting for age, sex, comorbidities, residence, household income, and the year of enrollment. In multivariate Cox regression analysis, patients with comorbidity of hypertension, diabetes mellitus, or aged ≥ 50 years showed a significantly higher risk of glaucoma development (all P < 0.008). Conclusions: A significant association between CRD and following development of glaucoma was revealed after adjusting the potential confounding factors.

Profiles of microRNA in aqueous humor of normal tension glaucoma patients using RNA sequencing.

We aimed to identify and compare microRNAs (miRNAs) from individual aqueous humor samples between normal-tension glaucoma (NTG) patients and normal controls. Aqueous humor (80 to 120 µl) was collected before cataract surgery. Six stable NTG patients and seven age-matched controls were included in the final analysis. RNA sequencing was conducted for RNA samples extracted from the 13 aqueous humor samples, and bioinformatics analysis was employed for the miRNA targets and related pathways. Two hundred and twenty-eight discrete miRNAs were detected in the aqueous humor and consistently expressed in all samples. Eight significantly upregulated miRNAs were found in the NTG patients compared to the controls (fold-change > 2, p < 0.05). They were hsa-let-7a-5p, hsa-let-7c-5p, hsa-let-7f-5p, hsa-miR-192-5p, hsa-miR-10a-5p, hsa-miR-10b-5p, hsa-miR-375, and hsa-miR-143-3p. These miRNAs were predicted to be associated with the biological processes of apoptosis, autophagy, neurogenesis, and aging in the gene ontology categories. The related Kyoto encyclopedia of genes and genomes pathways were extracellular matrix-receptor interaction, mucin-type O-glycan biosynthesis, biotin metabolism, and signaling pathways regulating the pluripotency of stem cells. The differentially expressed miRNA in the NTG samples compared to the controls suggest the possible roles of miRNA in the pathogenesis of NTG. The underlying miRNA-associated pathways further imply novel targets for the pathogenesis of NTG.

Does enhanced environmental cleaning reduce carbapenem-resistant Acinetobacter baumannii colonization in the intensive care unit?

OBJECTIVE: To evaluate the impact of enhanced environmental cleaning (two times per day) compared with conventional cleaning on the acquisition of carbapenem-resistant Acinetobacter baumannii (CRAB) in a highly endemic intensive care unit (ICU). METHODS: The intervention consisted of alternating environmental cleaning and conventional cleaning every 3 months during the study period from July 2018 to June 2019. CRAB acquisition was assessed using incidence and prevalence rates, and colonization pressure. RESULTS: The incidence rates of CRAB with and without enhanced cleaning were 16.3 and 13.9 cases per 1000 population, respectively; and the prevalence rates were 66.9 and 61.7 cases per 1000 population, respectively. Colonization pressure was 53.3% with enhanced cleaning and 51.3% without enhanced cleaning. No association was found between enhanced environmental cleaning and the incidence (P=0.156), prevalence (P=0.888) and colonization pressure (P=0.825) of CRAB acquisition. The ventilator utilization ratio increased the colonization pressure of CRAB acquisition (P=0.010, ß coefficient=0.37). The proportion of new nurses with <3 years of clinical practice experience was positively correlated with the incidence and prevalence of CRAB acquisition. CONCLUSION: Enhanced environmental cleaning alone failed to reduce CRAB acquisition in a highly endemic ICU. The ventilator utilization ratio may be of more importance than environmental cleaning. Inexperienced nurses may need to be monitored regarding infection control activities in addition to hand hygiene adherence.

Is the insertional anatomy of rectus extraocular muscles binocularly symmetrical?

PURPOSE: This study was performed to examine the location, width, and insertional shape of rectus extraocular muscles (EOMs), and to elucidate the symmetry of the insertional anatomy of rectus EOMs in the left and right eyes. METHODS: EOMs were dissected from their origin to the insertion point in 100 intact orbits of 50 cadavers. The width, location, and shape of 4 rectus EOMs insertions were measured. The insertional shapes were classified into 6 categories: straight, oblique, convex, oblique-convex, concave, and nonspecific types. RESULTS: The most common types of insertional shapes were superior rectus muscle, oblique type (34%); inferior rectus muscle, oblique type (7%); lateral rectus muscle, concave type (41%); and medial rectus muscle, straight type (37%). The distance from the limbus to insertion and the width of rectus EOMs were almost symmetrical between the left and right eyes of the paired specimens. However, the insertional shapes were different in 46% of the superior rectus, 56% of the inferior rectus, 58% of the lateral rectus, and 46% of the medial rectus muscles. In a given individual, 49 individuals demonstrated asymmetric insertional shapes in at least 1 rectus EOM in both eyes. CONCLUSIONS: Ocular surgeons should consider the possibility of differences in the insertional shape of rectus EOMs between the left and right eyes, especially when performing rectus EOM recession.