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Abstract Background Human induced pluripotent stem cells (hiPSCs) and their differentiated cell types have a great potential for tissue repair and regeneration. While the primary focus of using hiPSCs has historically been to regenerate damaged tissue, emerging studies have shown a more potent effect of hiPSC-derived paracrine factors on tissue regeneration. However, the precise contents of the transplanted hiPSC-derived cell secretome are ambiguous. This is mainly due to the lack of tools to distinguish cell-specific secretome from host-derived proteins in a complex tissue microenvironment in vivo. Methods In this study, we present the generation and characterization of a novel hiPSC line, L274G-hiPSC, expressing the murine mutant methionyl-tRNA synthetase, L274GMmMetRS, which can be used for tracking the cell specific proteome via biorthogonal non-canonical amino acid tagging (BONCAT). We assessed the trilineage differentiation potential of the L274G-hiPSCs in vitro and in vivo. Furthermore, we assessed the cell-specific proteome labelling in the L274G-hiPSC derived cardiomyocytes (L274G-hiPSC-CMs) in vitro following co-culture with wild type human umbilical vein derived endothelial cells and in vivo post transplantation in murine hearts. Results We demonstrated that the L274G-hiPSCs exhibit typical hiPSC characteristics and that we can efficiently track the cell-specific proteome in their differentiated progenies belonging to the three germ lineages, including L274G-hiPSC-CMs. Finally, we demonstrated cell-specific BONCAT in transplanted L274G-hiPSC-CMs. Conclusion The novel L274G-hiPSC line can be used to study the cell-specific proteome of hiPSCs in vitro and in vivo, to delineate mechanisms underlying hiPSC-based cell therapies for a variety of regenerative medicine applications.

Abstract This study investigated intraocular pressure (IOP) in Dutch belted rabbits using two different tonometers, rebound tonometry (TonoVet Plus; TVP) and a Tonopen (Tono-Pen AVIA Vet; TPA). Post-pubescent male Dutch belted rabbits aged 36 weeks (n = 10 animals) were used in the study. IOP measurements were conducted every 2 weeks for 22 weeks using TVP and TPA on both eyes of each rabbit. The average IOP measurements were compared by the paired Student’s t-test. Pairwise Pearson’s correlation coefficients and Bland–Altman statistics were used. The overall mean IOP measured with TPA was significantly higher than that with TVP (23.5 ± 4.9 vs. 21.8 ± 2.4 mmHg for the right eyes; P = 0.045, and 23.0 ± 4.7 vs. 21.5 ± 2.4 mmHg for the left eyes; P = 0.047). Both tonometers tended to show increased IOP readings with age, and positive correlations between IOP and age were observed with both TPA (r = 0.95, P

Abstract This prospective cross-sectional study investigated the visual function of preperimetric glaucoma (PPG) patients based on hemifield (HF) pattern electroretinogram (PERG) amplitudes. Thirty-two (32) normal subjects and 33 PPG patients were enrolled in control and PPG groups, respectively. All of the participants had undergone full ophthalmic examinations, including spectral-domain optical coherence tomography (SD-OCT), visual field (VF) examination and pattern electroretinography (PERG). The PERG parameters along with the HF ratios of SD-OCT and PERG were compared between the control and PPG groups. Pairwise Pearson's correlation coefficients and linear regression models were fitted to investigate the correlations. The PERG N95 amplitudes were significantly lower in the PPG group (P

Abstract This study focused on patients with advanced open-angle glaucoma (OAG) and aimed to identify key factors for monitoring them. We included 127 such patients who were followed for seven years or more, undergoing annual ophthalmic examinations. Glaucoma progression was defined as a deterioration in either structure or function. The progression rates and risk factors were evaluated. The patients were divided into upper- and lower-half subgroups based on the reduction in intraocular pressure (IOP) from the baseline. Over an 11-year period, glaucoma progression was detected in 59 eyes (46.5%). The rate of change in mean deviation (MD) was − 0.43 dB/year for the entire population; − 0.67 dB/year for progressors; and − 0.20 dB/year for non-progressors. Hypertension and disc hemorrhage (DH) were more common in progressors compared to non-progressors (45.8 vs. 23.5%, 11.9 vs. 1.5%; P = 0.008 and P = 0.016). Multivariate Cox’s proportional hazard model revealed that the presence of DH and a better baseline MD were associated with glaucoma progression. Additionally, patients with a higher percentage reduction in IOP (> 20.94%) had a lower risk of progression compared to those with less reduction. Inadequate IOP reduction, better baseline MD, presence of DH, and lower central corneal thickness were identified as risk factors for progression in advanced OAG patients.

Background In adult patients with high myopia (HM), progressive axial elongation poses a significant risk for the development of subsequent ocular complications that may lead to visual impairment. Effective strategies to reduce or prevent further axial elongation in highly myopic adult patients have not been available so far. Recent studies suggested that medically lowering intraocular pressure (IOP) may reduce axial elongation.Objective This clinical randomised controlled trial (RCT) aims to evaluate the efficacy of medical IOP reduction in adult patients with progressive HM (PHM).Trial design Single-centre, open-label, prospective RCT.Methods This RCT will recruit 152 participants with PHM at the Zhongshan Ophthalmic Center (ZOC). Randomised in a ratio of 1:1, participants will receive IOP-lowering eyedrops (intervention group) or will be followed without treatment (control group) for 12 months. Follow-up visits will be conducted at 1, 6 and 12 months after baseline. Only one eye per eligible participant will be included for analysis. The primary outcome is the change in axial length (AL) within the study period of 12 months. Secondary outcomes include the incidence and progression of visual field (VF) defects, changes in optic disc morphology and incidence and progression of myopic maculopathy. Difference in AL changes between the two groups will be analysed using linear regression analysis. For the secondary outcomes, a multifactor Poisson regression within a generalised linear model will be used to estimate the relative risk of progression in VF defects and myopic maculopathy, and the rate of thinning in retinal nerve fibre layer and ganglion cell-inner plexiform will be assessed through Kaplan-Meier curves and log-rank tests.Ethics and dissemination Full ethics approval for this trial has been obtained from the Ethics Committee of ZOC, Sun Yat-sen University, China (ID: 2023KYPJ110). Results of this trial will be disseminated through peer-reviewed journals and conference presentations.Trial registration number NCT05850936.

Abstract Little is known about the papillomacular bundle defect (PMBD) in glaucoma. As such, we investigated the frequency of PMBD in glaucoma patients with high myopia, and its risk factors. In this retrospective, cross-sectional study, retinal nerve fiber layer (RNFL) defect was analyzed in 92 glaucomatous eyes with high myopia (axial length of 26.0 mm or more or an average spherical value of − 6.0 diopters or less). After dividing them into two groups with and without PMBD, the clinical characteristics of the groups were compared and analyzed. The mean age of the patients was 52.1 ± 10.5 years, and there were 53 males and 39 females. PMBD were observed in 55 eyes (59.8%). There was no significant intergroup difference in baseline or follow-up intraocular pressure (IOP). Parapapillary atrophy (PPA)-to-disc-area ratio (OR 3.83, CI: 1.58–10.27, p = 0.010), lamina cribrosa defect (LCD; OR 2.92, CI: 1.14–8.13, p = 0.031) and central visual field defect (CVFD; OR 3.56, CI: 1.38–9.58, p = 0.010) were significantly associated with the PMBD. .

Abstract Little is known about the diagnostic utility of three-dimensional neuroretinal rim thickness (3D-NRRT) for differentiating patients with superior segmental optic nerve hypoplasia (SSOH) from normal-tension glaucoma (NTG). Since SSOH is defined by characteristic optic nerve head features, investigation of diagnostic usefulness of 3D-NRRT is necessary. In this cross-sectional study, 49 SSOH eyes, 52 NTG eyes, and 41 normal eyes were enrolled. Retinal nerve fiber layer thickness (RNFLT) and 3D-NRRT values, as obtained in the right-eye orientation by optical coherence tomography (OCT), were recorded. On RNFLT clock-hour comparison, the 11–3 clock-hour sectors were significantly thinner for SSOH than for NTG (all P

In recent years, there has been increasing interest in exploring the potential therapeutic advantages of Citrullus mucosospermus extracts (CME) for nonalcoholic steatohepatitis (NASH). In this study, we investigated the therapeutic effects of CME on NASH using a mice model. High-performance liquid chromatography (HPLC) was employed to identify cucurbitacin E and cucurbitacin E-2-O-glucoside from the CME. Although CME did not significantly alter the serum lipid levels in methionine- and choline-deficient (MCD) mice, it demonstrated a protective effect against MCD diet-induced liver damage. CME reduced histological markers, reduced alanine transaminase (ALT) and aspartame transaminase (AST) levels, and modulated key NASH-related genes, including C/EBPα, PPARγ, Fas, and aP2. In addition, CME was found to restore hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) activity, both crucial for fat catabolism, and reduced the levels of pro-inflammatory cytokines. Furthermore, CME demonstrated the potential to mitigate oxidative stress by maintaining or enhancing the activation and expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and superoxide dismutase (SOD), both pivotal players in antioxidant defense mechanisms. These findings underscore the promising therapeutic potential of CME in ameliorating liver damage, inflammation, and oxidative stress associated with NASH.

Abstract This study undertook to investigate the diurnal variation of optical coherence tomography angiography (OCTA) -derived retinal vessel density (RVD) in glaucoma patients with low baseline intraocular pressure (IOP). A prospective evaluation was performed on low-teens normal-tension glaucoma (low-teens NTG) patients with pre-treatment IOP

Abstract The rates, patterns and associated factors for false-positive classification of deviation maps by Cirrus optical coherence tomography (OCT) have been reported. However, research on OCT layer-by-layer deviation maps is lacking. We aimed to determine the rates and associated factors for false-positive classification of segmented macular layers and retinal nerve fiber layer (RNFL) deviation maps of Spectralis OCT, and to identify false-positive patterns on segmented macular layers deviation maps. 118 healthy eyes of 118 normal participants who had undergone Spectralis OCT imaging were included. False-positive classification was determined by the area and location of yellow or red color-coded regions on the deviation map. The false-positive rates on the deviation maps were the highest on the ganglion cell layer map, followed by the inner plexiform layer, retinal layer, and RNFL maps. More myopic/less hyperopic refractive error was a factor significantly associated with higher false-positive classification on the RNFL deviation map, and three false-positive patterns were found on the segmented macular layers deviation maps. Spectralis OCT deviation maps should be interpreted carefully to avoid misdiagnosis, especially for eyes with higher degrees of myopic refractive error on the RNFL map, for which purpose, recognizing the characteristic false-positive patterns would be helpful in clinical practice.

Abstract Macular OCT angiography (OCTA) measurements have been reported to be useful for glaucoma diagnostics. However, research on highly myopic glaucoma is lacking, and the diagnostic value of macular OCTA measurements versus OCT parameters remains inconclusive. We aimed to evaluate the diagnostic ability of the macular microvasculature assessed with OCTA for highly myopic glaucoma and to compare it with that of macular thickness parameters, using deep learning (DL). A DL model was trained, validated and tested using 260 pairs of macular OCTA and OCT images from 260 eyes (203 eyes with highly myopic glaucoma, 57 eyes with healthy high myopia). The DL model achieved an AUC of 0.946 with the OCTA superficial capillary plexus (SCP) images, which was comparable to that with the OCT GCL+ (ganglion cell layer + inner plexiform layer; AUC, 0.982; P = 0.268) or OCT GCL++ (retinal nerve fiber layer + ganglion cell layer + inner plexiform layer) images (AUC, 0.997; P = 0.101), and significantly superior to that with the OCTA deep capillary plexus images (AUC, 0.779; P = 0.028). The DL model with macular OCTA SCP images demonstrated excellent and comparable diagnostic ability to that with macular OCT images in highly myopic glaucoma, which suggests macular OCTA microvasculature could serve as a potential biomarker for glaucoma diagnosis in high myopia.

Abstract Little is known about the myopic characteristics of lamina cribrosa (LC) curvature. As such, we investigated nasal and temporal LC curvatures in myopia. In this retrospective, cross-sectional study, 144 myopic eyes (refraction − 0.5D) underwent swept-source optical coherence tomography scanning of the LC. The anterior border of LC curvature was delineated with 17 points and interpolated with the “cardinal spline” curve-fitting method. The average curvature indices of the temporal and nasal sides were presented as the temporal and nasal curvatures. Myopic eyes had a mean refraction of − 6.7 ± 2.8D, while for non-myopic eyes, the value was 0.3 ± 1.0D. Nasal LC curvature was visible in 54 myopia (37.5%) and 42 non-myopia (47.7%) cases (P = 0.126), and temporal LC curvature was visible in 142 myopia (98.6%) and 68 non-myopia (77.3%) cases (P = 0.001). The nasal LC curvature was significantly larger in myopia than in non-myopia (P

We investigated the internal morphology of filtration blebs after XEN gel stent implantation using anterior segment optical coherence tomography (AS-OCT) and identified factors related to intraocular pressure (IOP) postoperatively. Eighteen eyes of 18 patients who had undergone XEN gel stent implantation were analyzed. Blebs were imaged using Visante OCT (Carl Zeiss Meditec AG, Germany) at 6 months and 1 year after surgery and evaluated for quantitative parameters including bleb height, maximum height of internal cavity, maximum bleb wall thickness, and maximum bleb epithelial thickness. Subjects were classified into two groups according to the presence or absence of a definite internal cavity between the conjunctiva and sclera using AS-OCT imaging. Nine eyes (50%) were assigned to the internal cavity group and 9 (50%) to the uniform group. Postoperative IOP was significantly lower in the internal cavity group than in the uniform group both at 6 months and 1 year after surgery (p = 0.024 and p = 0.040). Postoperative IOP showed statistically significant negative correlations with bleb height and the height of the internal cavity (Spearman correlation coefficient r = −0.518, p = 0.028 and r = −0.453, p = 0.034, respectively). AS-OCT facilitates analysis of bleb morphology after XEN gel stent implantation. A larger height of the internal cavity of the bleb appeared to correlate with lower IOP after XEN implantation.

Summary: Evaluation of autophagy flux could be challenging for muscle fibers due to the baseline expression of mCherry-EGFP-LC3 along the Z-line. We established a protocol to overcome this difficulty. We overexpress mChery-EGFP-LC3 in the FDB muscle of an adult mouse via electroporation. Then, we enzymatically digest FDB muscle to yield individual fibers for live cell imaging. Finally, we develop an ImageJ-based program to eliminate the baseline striation pattern and semi-automatically quantify autophagosomes (APs) and autolysosomes (ALs) for autophagy flux analysis. : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract GLH8NDE, a derivative of eupatilin, is currently under development to treat dry eye disease. We conducted a randomized, double‐masked, placebo‐controlled, single‐ and multiple‐day study to evaluate safety, tolerability, pharmacodynamics, and pharmacokinetics of ocular GLH8NDE in healthy male adults. Subjects randomly received topical ocular dosing of GLH8NDE or its matching placebo for a day, then for 7 consecutive days with a 62‐h washout at one of the following daily doses: 9, 18, 36 (Koreans), and 36 mg (Whites). The study drug was administered in divided doses over 10 h with 2‐ or 5‐h intervals. Thirty‐nine (97.5%) out of 40 subjects completed the study. A total of 17 subjects experienced 31 treatment‐emergent adverse events, all of which were mild in severity and recovered without sequelae. Neither pathological changes in eye compartments nor clinically significant systemic effects were observed. GLH8NDE was rapidly absorbed reaching the peak concentration within 0.25–0.75 h postdose. The systemic exposure as measured by area under the concentration‐time curve from time of administration up to the time of the last quantifiable concentration (AUClast) after single‐day administration of the same dose was 109% higher in Koreans than in Whites. In conclusion, GLH8NDE was safe and well‐tolerated in healthy Korean and White male adults at 9–36 mg/day after single‐ and multiple‐day administrations.

Abstract The purpose of this study was to evaluate longitudinal changes of circumpapillary retinal nerve fiber layer thickness (cpRNFLT) profile arising in the course of childhood myopia progression. Thirty-six eyes of 36 healthy children who showed myopia progression (spherical equivalent [SE] decrease of ≥ 2.0 diopters [D]) were included. To account for the axial-elongation-induced magnification effect on spectral-domain optical coherence tomography (SD-OCT) measurements, we calculated the proportion of quadrant-cpRNFLT distribution (i.e., the percentage of cpRNFLT within a single quadrant of total cpRNFLT). During 4.1 ± 1.1 years, the mean SE changed from -1.3 ± 0.9 to -4.3 ± 0.8D, and both the optic disc tilt ratio and the torsional angle increased (both P 0.05). For longitudinal evaluations of patients with myopia progression, scan-circle alteration should be given due consideration.

BackgroundMany artificial intelligence (AI) studies have focused on development of AI models, novel techniques, and reporting guidelines. However, little is understood about clinicians' perspectives of AI applications in medical fields including ophthalmology, particularly in light of recent regulatory guidelines. The aim for this study was to evaluate the perspectives of ophthalmologists regarding AI in 4 major eye conditions: diabetic retinopathy (DR), glaucoma, age-related macular degeneration (AMD) and cataract.MethodsThis was a multi-national survey of ophthalmologists between March 1st, 2020 to February 29th, 2021 disseminated via the major global ophthalmology societies. The survey was designed based on microsystem, mesosystem and macrosystem questions, and the software as a medical device (SaMD) regulatory framework chaired by the Food and Drug Administration (FDA). Factors associated with AI adoption for ophthalmology analyzed with multivariable logistic regression random forest machine learning.ResultsOne thousand one hundred seventy-six ophthalmologists from 70 countries participated with a response rate ranging from 78.8 to 85.8% per question. Ophthalmologists were more willing to use AI as clinical assistive tools (88.1%, n = 890/1,010) especially those with over 20 years' experience (OR 3.70, 95% CI: 1.10–12.5, p = 0.035), as compared to clinical decision support tools (78.8%, n = 796/1,010) or diagnostic tools (64.5%, n = 651). A majority of Ophthalmologists felt that AI is most relevant to DR (78.2%), followed by glaucoma (70.7%), AMD (66.8%), and cataract (51.4%) detection. Many participants were confident their roles will not be replaced (68.2%, n = 632/927), and felt COVID-19 catalyzed willingness to adopt AI (80.9%, n = 750/927). Common barriers to implementation include medical liability from errors (72.5%, n = 672/927) whereas enablers include improving access (94.5%, n = 876/927). Machine learning modeling predicted acceptance from participant demographics with moderate to high accuracy, and area under the receiver operating curves of 0.63–0.83.ConclusionOphthalmologists are receptive to adopting AI as assistive tools for DR, glaucoma, and AMD. Furthermore, ML is a useful method that can be applied to evaluate predictive factors on clinical qualitative questionnaires. This study outlines actionable insights for future research and facilitation interventions to drive adoption and operationalization of AI tools for Ophthalmology.

Ischemic injury to the heart induces mitochondrial dysfunction due to increasing oxidative stress. MG53, also known as TRIM72, is highly expressed in striated muscle, is secreted as a myokine after exercise, and is essential for repairing damaged plasma membrane of many tissues by interacting with the membrane lipid phosphatidylserine (PS). We hypothesized MG53 could preserve mitochondrial integrity after an ischemic event by binding to the mitochondrial-specific lipid, cardiolipin (CL), for mitochondria protection to prevent mitophagy. Fluorescent imaging and Western blotting experiments showed recombinant human MG53 (rhMG53) translocated to the mitochondria after ischemic injury in vivo and in vitro. Fluorescent imaging indicated rhMG53 treatment reduced superoxide generation in ex vivo and in vitro models. Lipid-binding assay indicated MG53 binds to CL. Transfecting cardiomyocytes with the mitochondria-targeted mt-mKeima showed inhibition of mitophagy after MG53 treatment. Overall, we show that rhMG53 treatment may preserve cardiac function by preserving mitochondria in cardiomyocytes. These findings suggest MG53's interactions with mitochondria could be an attractive avenue for developing MG53 as a targeted protein therapy for cardioprotection.

Abstract Glaucoma shares common risk factors with chronic kidney disease (CKD) but previous cross-sectional studies have demonstrated discrepancies in the risk of glaucoma in CKD patients. This study enrolled kidney transplantation recipients (KTRs) (n = 10,955), end stage renal disease (ESRD) patients (n = 10,955) and healthy controls (n = 10,955) from National Health Insurance Service database of the Republic of Korea. A Cox proportional hazard regression model was used to calculate the hazard ratios (HR) for primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG) incidences. The incidence of POAG was higher in ESRD patients (3.36/1,000 person-years, P

Ubiquitin carboxyl-terminal esterase L1 (UCHL1) has been thought to be a neuron specific protein and shown to play critical roles in Parkinson's Disease and stroke via de-ubiquiting and stabilizing key pathological proteins, such as α-synuclein. In the present study, we found that UCHL1 was significantly increased in both mouse and human cardiomyocytes following myocardial infarction (MI). When LDN-57444, a pharmacological inhibitor of UCHL1, was used to treat mice subjected to MI surgery, we found that administration of LDN-57444 compromised cardiac function when compared with vehicle treated hearts, suggesting a potential protective role of UCHL1 in response to MI. When UCHL1 was knockout by CRISPR/Cas 9 gene editing technique in human induced pluripotent stem cells (hiPSCs), we found that cardiomyocytes derived from UCHL1−/− hiPSCs were more susceptible to hypoxia/re-oxygenation induced injury as compared to wild type cardiomyocytes. To study the potential targets of UCHL1, a BioID based proximity labeling approach followed by mass spectrum analysis was performed. The result suggested that UCHL1 could bind to and stabilize HIF-1α following MI. Indeed, expression of HIF-1α was lower in UCHL1−/− cells as determined by Western blotting and HIF-1α target genes were also suppressed in UCHL1−/− cells as quantified by real time RT-PCR. Recombinant UCHL1 (rUCHL1) protein was purified by E. Coli fermentation and intraperitoneally (I.P.) delivered to mice. We found that administration of rUCHL1 could significantly preserve cardiac function following MI as compared to control group. Finally, adeno associated virus mediated cardiac specific UCHL1 delivery (AAV9-cTNT-m-UCHL1) was performed in neonatal mice. UCHL1 overexpressing hearts were more resistant to MI injury as compare to the hearts infected with control virus. In summary, our data revealed a novel protective role of UCHL1 on MI via stabilizing HIF-1α and promoting HIF-1α signaling.

RationaleWhile reactive oxygen species (ROS) has been recognized as one of the main causes of cardiac injury following myocardial infarction, the clinical application of antioxidants has shown limited effects on protecting hearts against ischemia–reperfusion (I/R) injury. Thus, the precise role of ROS following cardiac injury remains to be fully elucidated.ObjectiveWe investigated the role of mitsugumin 53 (MG53) in regulating necroptosis following I/R injury to the hearts and the involvement of ROS in MG53-mediated cardioprotection.Methods and ResultsAntioxidants were used to test the role of ROS in MG53-mediated cardioprotection in the mouse model of I/R injury and induced human pluripotent stem cells (hiPSCs)-derived cardiomyocytes subjected to hypoxia or re-oxygenation (H/R) injury. Western blotting and co-immunoprecipitation were used to identify potential cell death pathways that MG53 was involved in. CRISPR/Cas 9-mediated genome editing and mutagenesis assays were performed to further identify specific interaction amino acids between MG53 and its ubiquitin E3 ligase substrate. We found that MG53 could protect myocardial injury via inhibiting the necroptosis pathway. Upon injury, the generation of ROS in the infarct zone of the hearts promoted interaction between MG53 and receptor-interacting protein kinase 1 (RIPK1). As an E3 ubiquitin ligase, MG53 added multiple ubiquitin chains to RIPK1 at the sites of K316, K604, and K627 for proteasome-mediated RIPK1 degradation and inhibited necroptosis. The application of N-acetyl cysteine (NAC) disrupted the interaction between MG53 and RIPK1 and abolished MG53-mediated cardioprotective effects.ConclusionsTaken together, this study provided a molecular mechanism of a potential beneficial role of ROS following acute myocardial infarction. Thus, fine-tuning ROS levels might be critical for cardioprotection.

Background: COVID-19 has been shown to affect the onset and severity of various diseases. We examined whether the clinical characteristics of Bell’s palsy differed between before and during the COVID-19 pandemic. Methods: From January 2005 to December 2021, 1839 patients were diagnosed and treated for Bell’s palsy at Kyung Hee University Hospital. These patients were divided into a pre-COVID period group and COVID-19 period group, and the clinical characteristics of the two groups were compared. Results: There were 1719 patients in the pre-COVID period group and 120 patients in the COVID-19 period group. There were no between-group differences in sex (p = 0.103) or in the presence of underlying hypertension (p = 0.632) or diabetes (p = 0.807). Regarding symptoms, there were no significant between-group differences in otalgia, dizziness, tinnitus, hyperacusis, or hearing loss (p = 0.304, p = 0.59, p = 0.351, p = 0.605, and p = 0.949). There were also no significant between-group differences in electroneurography results (p = 0.398), electromyography results (p = 0.331), House–Brackmann Grade at visit (p = 0.634), or recovery rate after treatment (p = 0.525). Conclusions: Contrary to our expectation that Bell’s palsy cases during the COVID-19 pandemic would show different clinical features than those occurring before COVID-19, the present study found no differences in clinical features or prognosis.

Abstract We developed a hybrid deep learning model (HDLM) algorithm that quantitatively predicts macular ganglion cell-inner plexiform layer (mGCIPL) thickness from red-free retinal nerve fiber layer photographs (RNFLPs). A total of 789 pairs of RNFLPs and spectral domain-optical coherence tomography (SD-OCT) scans for 431 eyes of 259 participants (183 eyes of 114 healthy controls, 68 eyes of 46 glaucoma suspects, and 180 eyes of 99 glaucoma patients) were enrolled. An HDLM was built by combining a pre-trained deep learning network and support vector machine. The correlation coefficient and mean absolute error (MAE) between the predicted and measured mGCIPL thicknesses were calculated. The measured (OCT-based) and predicted (HDLM-based) average mGCIPL thicknesses were 73.96 ± 8.81 µm and 73.92 ± 7.36 µm, respectively (P = 0.844). The predicted mGCIPL thickness showed a strong correlation and good agreement with the measured mGCIPL thickness (Correlation coefficient r = 0.739; P

MG53 is a protein that regulates the cell membrane repair process, and it’s been suggested that it might play a role in diabetes. Here, the authors demonstrate that circulating MG53 functions as a myokine to facilitate tissue injury-repair and regeneration without impacting glucose handling.

Aging is associated with chronic oxidative stress and inflammation that affect tissue repair and regeneration capacity. MG53 is a TRIM family protein that facilitates repair of cell membrane injury in a redox-dependent manner. Here, we demonstrate that the expression of MG53 was reduced in failing human hearts and aged mouse hearts, concomitant with elevated NF-κB activation. We evaluated the safety and efficacy of longitudinal, systemic administration of recombinant human MG53 (rhMG53) protein in aged mice. Echocardiography and pressure-volume loop measurements revealed beneficial effects of rhMG53 treatment in improving heart function of aged mice. Biochemical and histological studies demonstrated that the cardioprotective effects of rhMG53 are linked to suppression of NF-κB–mediated inflammation, reducing apoptotic cell death and oxidative stress in the aged heart. Repetitive administration of rhMG53 in aged mice did not have adverse effects on major vital organ functions. These findings support the therapeutic value of rhMG53 in treating age-related decline in cardiac function.

We sought to investigate the association between consumption of coffee, tea, or soft drinks and risk of open-angle glaucoma (OAG) among Koreans using nationwide population-based data. This cross-sectional survey was performed through the Korea National Health and Nutrition Examination Survey 2010 to 2011. Participants older than 19 years were included in the sample for analysis after excluding those with any missing data. The diagnosis of OAG was based on the International Society of Geographical and Epidemiological Ophthalmology criteria, and participants without glaucomatous optic neuropathy served as controls. The frequency of beverage consumption during the past 12 months was obtained through a questionnaire. Multivariate logistic regression models were used to determine the relationship between consumption of each type of beverage and prevalence of OAG. A total of 6,681 participants was included in the analysis. The prevalence of OAG was 4.4% (n = 323), including 5.4% (n = 169) among men and 3.5% (n = 154) among women. After adjusting for multiple covariates, coffee consumption was significantly associated with OAG, while no significant association was found between consumption of tea or soft drinks and OAG. Participants who drank coffee had a higher risk of having OAG compared with those who did not drink coffee (odds ratio [OR], 2.40; 95% confidence interval [CI], 1.22-4.72; p = 0.011). In sex-stratified analyses, the robust association of coffee consumption with OAG was observed in men (OR, 3.98; 95% CI, 1.71-9.25; p = 0.001) but not in women. Our results suggest that coffee consumption may affect the risk of OAG, particularly in men.

Optic-disc photography (ODP) has proven to be very useful for optic nerve evaluation in glaucoma. In real clinical practice, however, limited patient cooperation, small pupils, or media opacities can limit the performance of ODP. The purpose of this study was to propose a deep-learning approach for increased resolution and improved legibility of ODP by contrast, color, and brightness compensation. Each high-resolution original ODP was transformed into two counterparts: (1) down-scaled 'low-resolution ODPs', and (2) 'compensated high-resolution ODPs' produced via enhancement of the visibility of the optic disc margin and surrounding retinal vessels using a customized image post-processing algorithm. Then, the differences between these two counterparts were directly learned through a super-resolution generative adversarial network (SR-GAN). Finally, by inputting the high-resolution ODPs into SR-GAN, 4-times-up-scaled and overall-color-and-brightness-transformed 'enhanced ODPs' could be obtained. General ophthalmologists were instructed (1) to assess each ODP's image quality, and (2) to note any abnormal findings, at 1-month intervals. The image quality score for the enhanced ODPs was significantly higher than that for the original ODP, and the overall optic disc hemorrhage (DH)-detection accuracy was significantly higher with the enhanced ODPs. We expect that this novel deep-learning approach will be applied to various types of ophthalmic images.

ObjectivesTo investigate significant intraocular pressure (IOP) levels associated with the risk of open-angle glaucoma (OAG) in the treatment-naïve Korean population.MethodsParticipants ≥20 years of age in Korea National Health and Nutrition Examination Survey 2010-2011 were divided into two groups, those with higher and lower IOP values, compared with the reference IOP value. We compared the risk of OAG in each group using regression analyses. The IOP value that yielded the highest statistical significance was determined as an IOP significantly associated with the OAG risk.ResultsA total of 7,650 participants (7,292 control, 358 OAG) were included. The mean IOP was significantly higher in OAG group (14.4 ± 2.9 mmHg), compared to control group (13.9 ± 2.7 mmHg, P = 0.022). In association with an increased risk of OAG, the significant IOP value was 18 mmHg (Odds ratio [OR] = 1.79, 95% confidence interval [CI] 1.14-2.80, P = 0.011). Additionally, sex-difference was identified and they were 19 mmHg (OR = 2.79, 95% CI 1.27-6.16, P = 0.011) in men and 18 mmHg (OR = 2.65, 95% CI 1.32-5.33, P = 0.006) in women. The IOP values associated with significantly decreased risk of glaucoma were determined to be 14 mmHg in men (OR = 0.68, 95% CI 0.47-0.99, P = 0.042) and 16 mmHg in women (OR = 0.47, 95% CI 0.27-0.81, P = 0.007).ConclusionsIn consideration of the risk to benefit ratio, the reference IOP level for screening or setting the target IOP for treatment could be considered different from traditional 21 mmHg in Korean population.

Abstract Background To investigate the clinical features of corneal opacity and the surgical outcome of penetrating keratoplasty (PK) in eyes with congenital glaucoma. Methods A retrospective review was made of the records from 320 eyes of 193 patients who were diagnosed with congenital glaucoma between January 1981 and January 2016. Anterior segment photographs at disease presentation were examined for the presence and severity of corneal opacity. Data on patient demographics, intraocular pressure (IOP), ocular and systemic comorbidities, ocular surgery and its outcome were collected. Results Overall, corneal opacification was observed in 248 of 320 eyes (77.5%). Out of 248 eyes with corneal opacification, 53 eyes had Haab striae alone, and 195 eyes presented with either nebulomacular corneal opacity (128 eyes, iris details visible through opacity) or leukomatous corneal opacity (67 eyes, iris details invisible through opacity). In 12 eyes with severe leukomatous corneal opacity, PK was performed at the mean age of 18.6 months (range 4–57 months). The grafts failed in 6 eyes (50%) due to endothelial rejection (4 eyes) or graft infection (2 eyes) during the mean 80.6 months of follow-up (range 15–228 months). The median survival time was 36 months. The graft failure was significantly associated with smaller corneal diameter at the time of surgery, but not with the age, IOP, combined aniridia, simultaneous glaucoma or lens surgery. Conclusion Congenital glaucoma was combined with corneal opacity in 77.5%. The corneal transplant survival was 50% in eyes with congenital glaucoma and total corneal opacity.

Abstract Background Many studies have investigated the clinical benefits of Ologen for trabeculectomy. However, its benefits for Ahmed glaucoma valve (AGV) implantation have not been investigated as extensively. The aim of this study was to compare the 1-year outcomes of AGV implantation with and without Ologen adjuvant for the treatment of refractory glaucoma. Methods This retrospective study included a total of 20 eyes of 20 glaucoma patients, who were followed for at least 1-year after undergoing AGV implantation. In 12 eyes of 12 patients, conventional AGV (CAGV) surgery was performed, while in 8 eyes of 8 patients, Ologen-augmented AGV (OAGV) implantation was performed. The outcomes were evaluated according to intraocular pressure (IOP) and the number of IOP-lowering medications. Complete success was defined as IOP ≤ 21 mmHg without medications throughout the 1-year follow-up period, and qualified success was defined as IOP ≤ 21 mmHg with or without medications throughout the 1-year follow-up period. Results The rate of complete success was significantly higher in the OAGV group (50.0%) than in the CAGV group (8.3%) (p = 0.035). There were no significant differences between the two groups in terms of qualified success or incidence of the early hypertensive phase. The IOP changes were similar between the groups within 1-year postoperatively, though the number of IOP-lowering medications was significantly lower in the OAGV group during the early hypertensive phase (p = 0.031, 0.031, and 0.025 at postoperative months 1, 2, and 3, respectively). When subjects were divided into groups according to the occurrence of the early hypertensive phase, the group with early hypertensive phase was more likely to use IOP-lowering medications at postoperative 6 months and 1 year (p = 0.002 and 0.005, respectively). Conclusions OAGV surgery shows encouraging results for patients with refractory glaucoma, specifically with respect to the achievement of complete success and the reduction of the number of IOP-lowering medications during the early hypertensive phase. Furthermore, our results suggest that occurrence of the early hypertensive phase is predictive of which patients will require IOP-lowering medications at postoperative 6 months and 1 year.

Background The aortic valve of the heart experiences constant mechanical stress under physiological conditions. Maladaptive valve injury responses contribute to the development of valvular heart disease. Here, we test the hypothesis that MG53 (mitsugumin 53), an essential cell membrane repair protein, can protect valvular cells from injury and fibrocalcific remodeling processes associated with valvular heart disease. Methods and Results We found that MG53 is expressed in pig and human patient aortic valves and observed aortic valve disease in aged Mg53−/− mice. Aortic valves of Mg53−/− mice showed compromised cell membrane integrity. In vitro studies demonstrated that recombinant human MG53 protein protects primary valve interstitial cells from mechanical injury and that, in addition to mediating membrane repair, recombinant human MG53 can enter valve interstitial cells and suppress transforming growth factor‐β‐dependent activation of fibrocalcific signaling. Conclusions Together, our data characterize valve interstitial cell membrane repair as a novel mechanism of protection against valvular remodeling and assess potential in vivo roles of MG53 in preventing valvular heart disease.

PurposeTo evaluate the risk factors associated with recurrent disc hemorrhage (DH), defined for the present study as at least 3 occurrences of DH in primary open-angle glaucoma (POAG).MethodsA total of 178 POAG patients (89 eyes showing at least 3 occurrences of DH and 89 age-matched control eyes with a minimum of 10 years' follow-up without DH) were included in a retrospective, case-control study. Ocular factors were evaluated by a retrospective chart review, and systemic factors were evaluated by a telephone survey. Associations between factors and recurrent DH were investigated by logistic regression analysis. The Kaplan-Meier survival analysis and Cox proportional-hazards regression models were used to evaluate glaucoma progression and to identify the factors predictive of glaucoma progression.ResultsUnivariate regression analysis revealed the association of recurrent DH with low baseline intraocular pressure (IOP) [odds ratio (OR), 0.88; 95% confidential interval (CI), 0.80-0.98; P = 0.014], lower percentage reduction of IOP (OR, 0.96; 95% CI, 0.93-0.99; P = 0.020), cold extremities (OR, 2.80; 95% CI, 1.03-7.60; P = 0.043), prone or lateral decubitus sleeping position (OR, 2.14; 95% CI, 1.13-4.03; P = 0.019), and sleeping disorders (OR, 2.33; 95% CI, 1.05-5.15; P = 0.037). Multivariate regression analysis revealed that a lower percentage reduction in IOP (OR, 0.96; 95% CI, 0.93-1.00; P = 0.046) increased the risk of recurrent DH. The control group exhibited a greater cumulative probability of non-progression than the recurrent DH group (P = 0.01, by log-rank test). The Cox proportional-hazards regression model showed that recurrent DH was associated with glaucoma progression [hazard ratio (HR), 1.88; 95% CI; 1.66-3.05; P = 0.01.ConclusionsAmong the ocular and systemic factors, only lower-percentage reduction of IOP in POAG was associated with recurrent DH. DH recurrence is associated with glaucoma progression and may be dependent on IOP.

PurposeTo investigate, in primary open-angle glaucoma (POAG) and healthy subjects, the pattern and magnitude of diurnal variation in optical coherence tomography angiography (OCTA) retinal vessel density (RVD).DesignProspective, observational cross-sectional study.ParticipantsA prospective study was conducted on 20POAG patients and 19 healthy subjects.MethodsPeripapillary/macular RVD (using swept-source OCTA), intraocular pressure (IOP), and systemic blood pressure (BP) were measured five times a day (8 a.m., 11 a.m., 2 p.m.,5 p.m. and 8 p.m.). The magnitudes and patterns of diurnal changes in RVD, diastolic BP, and mean ocular-perfusion pressure (MOPP) were analyzed and compared between the POAG patients and the healthy subjects.Main outcome measuresThe patterns and magnitudes of diurnal RVD change in OCTA.ResultsIntra-visit repeatability (0.755-0.943) and inter-visit reproducibility (0.843-0.986) for the RVD measurements showed excellent reliability. In the POAG patients, the magnitude of diurnal change in peripapillary RVD (9.71±7.04%) and macular RVD (7.22±4.73%) were significantly greater than that in the healthy group (5.73±3.85%, P = 0.013 and 5.51±3.45%, P = 0.042, respectively). The magnitudes of diurnal variations of IOP and MOPP in the POAG group likewise were greater than those in the healthy group (P = 0.003 and 0.039). As for the patterns of diurnal RVD change, interestingly, at 8 p.m., the macular RVD of the healthy group increased to the highest level (44.12±2.95%) while that of the POAG group decreased to the lowest level (40.41±2.54%).ConclusionsIn POAG eyes, diurnal change of IOP, MOPP and RVD was significantly greater than in the healthy eyes. These findings suggest that diurnal RVD changes might reflect the hemodynamic variation of POAG.

PurposeTo investigate whether mass glaucoma screening relative to opportunistic case finding at a primary eye clinic is helpful for early detection of glaucoma.MethodsSubjects referred by glaucoma screening (by non-contact tonometry and non-mydriatic fundus photography; group A, n = 220) and from a primary eye clinic (group B, n = 327) were retrospectively recruited. The positive predictive value (PPV) for glaucoma and the rate of glaucoma awareness were compared. Also, for the newly diagnosed glaucoma ('definite glaucoma') patients, the demographics and structural and functional severities of glaucoma were compared.ResultsThe PPV for definite glaucoma was 25.5% for group A and 52.4% for group B. The rate of false-positive for 'glaucoma referral to tertiary hospital' was significantly higher for group A than for group B (38.6 vs. 18.3%, P < 0.001). Among the definite-glaucoma patients (group A: n = 56; group B: n = 182), the proportion of glaucoma awareness was significantly higher in group B (69.2%) than in group A (8.9%, P < 0.001). The mean deviation (MD) of visual field (VF) was significantly higher in group A than in group B (-3.08 ± 3.99 vs. -6.70 ± 7.29 dB, Padjusted = 0.040), and the inferior and inferotemporal ganglion cell-inner plexiform layer (GCIPL) thicknesses tended to be greater in group A than in group B, with marginal significance (Padjusted < 0.10).ConclusionsGlaucoma screening can be helpful for early detection of glaucoma. However, improvement of the screening strategy is needed in order to enhance its specificity for glaucoma.

(1) Background: Mitomycin C (MMC) is commonly used during trabeculectomy. However, there is no consensus on which concentration should be used. We aimed to compare the efficacy and safety of 0.2 mg/mL and 0.4 mg/mL of MMC in eyes undergoing trabeculectomy. (2) Methods: Thirty-six eyes (36 glaucoma patients) were randomized to undergo a trabeculectomy with 0.2 mg/mL or 0.4 mg/mL of MMC. The success rate was evaluated according to three criteria: (A) intraocular pressure (IOP) ≤ 18 mmHg and IOP reduction ≥ 20%; (B) IOP ≤ 15 mmHg and IOP reduction ≥ 25%; (C) IOP ≤ 12 mmHg and IOP reduction ≥ 30%. Cox’s proportional hazard model was used to identify the predictive factors for failure. Immunohistochemical procedures for matrix metalloproteinase (MMP) were performed on Tenon’s tissue. Bleb morphology was evaluated. Safety was assessed based on the incidence of complications. (3) Results: Of the 36 eyes, 19 underwent trabeculectomy with 0.2 mg/mL of MMC and 17 with 0.4 mg/mL. The success rates were 75%, 67%, and 47% at 6 months for criteria A, B, and C, respectively. There were no significant differences between the two groups. High MMP-9 staining and low preoperative IOP were associated with failure (hazard ratio (HR), 5.556; p = 0.033, and HR, 0.936; p = 0.033). Complications included hypotony in two eyes (6%), hyphema in one eye (3%), and choroidal detachment in one eye (3%). (4) Conclusions: Trabeculectomy with 0.2 mg/mL and 0.4 mg/mL of MMC showed similar IOP-control effects to those recorded in previous studies, along with a low rate of complications. There was no significant difference in efficacy or safety between the 0.2 mg/mL and 0.4 mg/mL MMC groups.

This study researched the association between alcohol consumption, intraocular pressure (IOP), and risk of open-angle glaucoma (OAG) using nationwide population-based cross-sectional data from the Korean population based survey. Information on alcohol intake was obtained by questionnaire and comprehensive ophthalmic examinations were performed. Among a total of 6057 participants, the prevalence of OAG was 4.4% (6.0% for men and 3.0% for women). Multivariate adjusted models showed that alcohol consumption showed significant relationship with changes in IOP. In sex-stratified analyses, alcohol consumption more than 2 times per week was associated with increased IOP in men without OAG, while in women with OAG drinking alcohol more than 4 times per week was associated with increased IOP. This study showed significant differences between men and women without glaucoma who consumed alcohol more than four times per week (p-value: 0.03). Our results suggest that alcohol consumption is associated with risk of elevated IOP depending on sex and presence of glaucoma in Koreans. Therefore, patients who need to control IOP should consider the effects of alcohol consumption.

To investigate the association between nutrient intake and primary open angle glaucoma (POAG) in Koreans, a population-based, cross-sectional survey, the Korean National Health and Nutrition Examination Survey, was analyzed. Glaucoma diagnosis was based on criteria established by the International Society of Geographic and Epidemiologic Ophthalmology. Multivariate regression analysis was used to assess the correlation between dietary intake and the prevalence of POAG in all enrolled subjects. In the low Body mass index(BMI) group (BMI p < 0.05). In females with a medium BMI (18.5 ≤ BMI < 23), POAG showed a significant association with lower food intake, energy, protein, calcium, phosphorus, potassium, thiamin and niacin. (all p < 0.05). Lower protein thiamine intake in medium BMI males was related to POAG. Low dietary intake of several nutrients showed an association with glaucoma in low BMI female subjects. An insufficient intake of certain nutrients may be associated with an increased risk of glaucoma in Koreans. Further large-scale cohort studies are needed to determine how specific nutrients alter the risk of glaucoma.

[This corrects the article DOI: 10.1371/journal.pone.0189706.].

PURPOSE:To investigate the effect of reading or writing on a smartphone in terms of intraocular pressure (IOP) changes. DESIGN:Prospective, comparative case series. PARTICIPANTS:Thirty-nine (39) healthy young (age < 40) volunteers. METHODS:The participants were requested to conduct standardized work (i.e., read a sample text on single mobile device and subsequently type it on the same device) under daylight [300 lux] and low-light [100 lux] conditions independently on consecutive days. On each day, three sets of IOP measurements (total: 7) using a rebound tonometer (iCare PRO; Tiolat, Helsinki, Finland) were performed: (1) pre-work (baseline) [2 measurements], (2) during smartphone work [5, 15, and 25 minutes], and (3) post-work [5 and 15 minutes]. MAIN OUTCOME MEASURES:Changes in IOP at different check-out points. RESULTS:Under the daylight condition, the mean baseline IOP was 13.7 ± 1.8 mmHg, and the mean IOP increased after 5 minutes of work (14.1 ± 1.8 mmHg; +2.0 ± 1.9%; P < 0.001). When the smartphone work lasted for 15 minutes, the IOP showed a further significant increase (15.5 ± 1.7 mmHg; +12.9 ± 4.4%; P < 0.001), which persisted over the course of the 25 minutes of smartphone work (15.3 ± 1.8 mmHg; +11.1 ± 3.9%; P < 0.001); then, after stopping work for 5 minutes, the IOP was restored (13.9 ± 1.7 mmHg; +0.9 ± 2.1%; P = 0.220). Under the low-light condition, the mean IOP was significantly increased immediately after 5 minutes of smartphone work (from 13.9 ± 1.9 to 15.6 ± 1.8 mmHg; +12.1 ± 4.8%; P < 0.001); this IOP increase continued: 17.3 ± 1.9 [+24.7 ± 10.3%] at 15 minutes' work, and 17.0 ± 1.7 mmHg [+23.1 ± 9.5%] at 25 minutes' work (P < 0.001 at both check-out points). Five minutes after stopping the smartphone work, interestingly, the IOP significantly dropped, to a level even lower than that of the pre-work (12.8 ± 1.9 mmHg; -8.1 ± 3.0%; P < 0.001), and at post-work 15 minutes, the IOP returned to the baseline (13.9 ± 1.8 mmHg; -0.3 ± 2.6%; P = 0.360). CONCLUSIONS:In healthy young subjects, reading or writing on smartphone significantly increased IOP, and the changes of IOP were faster and greater under the low-light condition. Smartphone users who are concerned about IOP fluctuation are advised to (1) take a break if they read or write on smartphone for more than 5 minutes, and (2) avoid using smartphones wherever possible in dark places.

AIMS:To evaluate the relationships between open-angle glaucoma (OAG) and various anthropometric measurements. DESIGN:Korea National Health and Nutrition Examination Survey (KNHANES), a population-based cross-sectional study using a complex, stratified, multistage, probability-cluster survey. METHODS:A total of 5,255 participants including 247 glaucoma patients, aged ≥ 19 years were included from the KNHANES V database. Glaucoma diagnosis was based on International Society of Geographical and Epidemiological Ophthalmology criteria. Various anthropometric data regarding obesity were analyzed including body mass index (BMI), total body fat mass, total body muscle mass (lean body mass, non-bone lean body mass, and appendicular skeletal muscle (ASM) mass), and waist circumference (WC). The differences in OAG prevalence with respect to anthropometric parameter quartiles were examined. RESULTS:In males, the multivariate general linear model adjusted for age, alcohol, smoking, exercise, systemic hypertension, diabetes, and intraocular pressure (IOP) showed the quartiles for the anthropometric parameters BMI, fat mass/weight ratio and fat mass/muscle mass ratio were negatively associated with OAG. However, muscle mass parameter/BMI ratio was significantly positively associated with OAG (P for trend

PURPOSE:To evaluate whether defects in cervical lymphatic drainage influence the intraocular pressure (IOP)-lowering effect of latanoprost in patients with primary open-angle glaucoma (POAG) who have undergone unilateral radical neck dissection (uRND). METHODS:We enrolled (1) bilateral POAG patients who had started (bilateral) latanoprost (0.005%) monotherapy prior to their uRND and (2) treatment-naïve, bilateral glaucoma suspects (GSs) who had undergone the same surgery. We compared the eyes ipsilateral to the uRND with their fellow eyes in terms of the changes in IOP between the baseline (prior to the uRND) and the follow-up visits (1, 3, and 6 months after the uRND). RESULTS:The study involved 22 eyes of 11 POAG patients and 14 eyes of 7 GSs. In the POAG patients, IOP had increased significantly after surgery in the eyes ipsilateral to the uRND (from 14.7±1.4mmHg to 17.1±2.2mmHg; P = 0.007). Interestingly, in the eyes contralateral to the uRND, IOP had not changed significantly after surgery (from 14.2±1.8mmHg to 14.4±2.0mmHg; P = 0.826). In GSs, the eyes ipsilateral to the uRND did not differ significantly from their fellow eyes in terms of post-operative IOP change (ipsilateral value: 0.3±0.5mmHg, fellow eyes: -0.1±0.7mmHg; P = 0.242). CONCLUSION:In the POAG patients, IOP had increased significantly in the eyes ipsilateral to the uRND. However, it had not changed significantly in the eyes contralateral to the surgery or in the eyes of the GSs. These findings suggest that, latanoprost works, at least in part, by enhancing outflow from the aqueous humor via the uveolymphatic pathway.

To investigate the prevalence and associated factors of retinal nerve fiber layer defects (RNFLDs) in a Korean population.The Korea National Health and Nutrition Examination Survey (KNHANES) is a population-based study using a complex, stratified, multistage, probability-cluster survey. We performed a review of 2008-2012 data from the KNHANES. Two masked ophthalmologists evaluated fundus photography to detect RNFLDs. All participants underwent ocular and systemic evaluations.A total of 28,637 subjects aged ≥ 19 years with at least one evaluable fundus photograph were enrolled. The estimated prevalence of RNFLDs in this Korean population was 4.8% (95% confidence interval, 4.4%-5.3%). The estimated percentages of glaucomatous RNFLD and non-glaucomatous RNFLD subjects were 34.4% and 65.6%, respectively. In a multivariate analysis, the prevalence of RNFLDs was significantly associated with older age (P < 0.001), male gender (P = 0.047), glycosylated hemoglobin (P = 0.048), disc hemorrhage (P = 0.016), ISNT rule (P < 0.001), and vertical cup to disc ratio (P < 0.001).The prevalence of RNFLDs in a large Korean population-based sample with a minimum age of 19 years was 4.8%. RNFLD prevalence was associated with old age, male gender, glycosylated hemoglobin, disc hemorrhage, and glaucomatous optic disc.

To investigate optic disc hemorrhage (DH)'s clinical implications to subsequent progression of primary open-angle glaucoma (POAG) in cases of mild-to-moderate myopia.Retrospective comparative study.(1) Fifty-nine (59) myopic (26.5 mm > axial length [AXL] ≥ 24.0 mm) POAG patients with DH and (2) 59 age-, AXL-, and mean deviation (MD) of visual field (VF)-matched controls without DH were evaluated over the course of a minimum 3.5 years of follow up. For clear assessment of the effect of DH on progression of glaucoma, the patients selected for inclusion in the study were those with stable IOP (i.e., those showing an at least 20% reduction relative to the baseline IOP) whose IOP-lowering medication was not increased, supplemented or changed during the follow-up period.The patients' optic disc/retinal nerve fiber layer (RNFL) photographs were independently evaluated by three glaucoma specialists for structural progression of glaucoma. Event-based analysis with Guided Progression Analysis (GPA) software was used to determine their functional progression. The durations of structural and functional progression were compared by Kaplan-Meier life survival analyses.Optic disc/RNFL progression and VF progression.The mean follow-up periods between the DH and non-DH groups were not significantly different: in the DH group, 5.6±2.7 years; in the non-DH group, 5.4±2.6 years (P = 0.588). In the DH group, 30 (50.8%) of 59 eyes manifested optic disc/RNFL deterioration; in the non-DH group, however, only 17 (28.8%) of 59 eyes showed structural progression. For the DH group, the cumulative probability of structural glaucoma progression was significantly greater than for the non-DH group (P = 0.001; log rank test). Interestingly, the two groups did not significantly differ in the cumulative probability of functional progression (P = 0.79; log rank test): in the DH group, VF progression was observed in 14 eyes (23.7%); in the non-DH group, in 12 eyes (20.3%).DH was associated with a greater probability of structural progression in medically well-controlled-IOP POAG eyes with mild-to-moderate myopia. However, the relevance of DH to VF progression was not clear over the course of the average 5.5-year duration of the study.

Objective. To evaluate the efficacy and tolerability of travoprost 0.004%/timolol 0.5% fixed-dose combination (TTFC) in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT) inadequately controlled on beta-blocker monotherapy. Methods. In this phase IV, open-label study, 156 patients on beta-blocker monotherapy with mean intraocular pressure (IOP) between 18 and 32 mmHg were randomized (no washout period) to receive TTFC for 8 weeks (TTFC group) or to continue beta-blocker monotherapy for 4 weeks followed by TTFC for the remaining 4 weeks (beta-blocker group). Results. The mean IOP (±standard deviation) at baseline in the TTFC and beta-blocker groups was 22.5±2.5 mmHg and 22.2±2.3 mmHg, respectively, and at weeks 4 and 8, was 16.7±3.1 mmHg and 16.1±3.1 mmHg, respectively, in TTFC group and 21.1±3.1 mmHg and 16.1±2.8 mmHg, respectively, in the beta-blocker group. There was a significant least squares mean difference between TTFC and beta-blocker in 8 a.m. IOP at week 4 (−4.6 mmHg; one-sided 95% confidence interval [−inf, −3.9]; p

Quantitative evaluation of lamina cribrosa (LC) posterior bowing in primary open-angle glaucoma (POAG) eyes using swept-source optical coherence tomography.Patients with POAG (n = 123 eyes) and healthy individuals of a similar age (n = 92 eyes) were prospectively recruited. Anterior laminar insertion depth (ALID) was defined as the vertical distance between the anterior laminar insertion and a reference plane connecting the Bruch's membrane openings (BMO). The mean LC depth (mLCD) was approximated by dividing the area enclosed by the anterior LC, the BMO reference plane, and the two vertical lines for ALID measurement by the length between those two vertical lines. The LC curvature index was defined as the difference between the mLCD and the ALID. The factors influencing the LC curvature index were evaluated.The ALID and mLCD were significantly larger in POAG eyes than in healthy controls (P < 0.05). The LC curvature index was significantly larger in POAG eyes than in healthy controls on both the horizontal (85.8 ± 34.1 vs. 68.2 ± 32.3 μm) and vertical meridians (49.8 ± 38.5 vs. 32.2 ± 31.1 μm, all P < 0.001). Multivariate regression showed significant associations of greater disc area (P < 0.001), vertical C/D ratio (P < 0.001) and mLCD (P < 0.001), smaller rim area (P = 0.001), thinner average RNFLT (P < 0.001), and myopic refraction (P = 0.049) with increased LC curvature index. There was no difference in the LC curvature index between mild (MD > -6 dB) and moderate-to-advanced glaucoma (MD < -6 dB, P = 0.95).LC posterior bowing was increased in POAG eyes, and was significantly associated with structural optic nerve head (ONH) changes but not with functional glaucoma severity. Quantitative evaluation of LC curvature can facilitate assessment of glaucomatous ONH change.

To evaluate the effect of multiple covariates on the diagnostic performance of the Cirrus high-definition optical coherence tomography (HD-OCT) for glaucoma detection.A prospective case-control study was performed and included 173 recently diagnosed glaucoma patients and 63 unaffected individuals from the Macular Ganglion Cell Imaging Study. Regression analysis of receiver operating characteristic were conducted to evaluate the influence of age, spherical equivalent, axial length, optic disc size, and visual field index on the macular ganglion cell-inner plexiform layer (GCIPL) and peripapillary retinal nerve fiber layer (RNFL) measurements.Disease severity, as measured by visual field index, had a significant effect on the diagnostic performance of all Cirrus HD-OCT parameters. Age, axial length and optic disc size were significantly associated with diagnostic accuracy of average peripapillary RNFL thickness, whereas axial length had a significant effect on the diagnostic accuracy of average GCIPL thickness.Diagnostic performance of the Cirrus HD-OCT may be more accurate in the advanced stages of glaucoma than at earlier stages. A smaller optic disc size was significantly associated with improved the diagnostic ability of average RNFL thickness measurements; however, GCIPL thickness may be less affected by age and optic disc size.

To compare peripapillary and macular choroidal thickness (PCT and MCT) between open-angle glaucoma (OAG) and normal controls using swept-source optical coherence tomography (SS-OCT), and to evaluate global and localized relationships between choroidal thickness and various factors in OAG, also using SS-OCT.In this cross-sectional comparative study, 134 OAG patients and 73 normal controls were examined. PCT (global, 12 clock-hour sectors), MCT (global, six sectors) were measured by SS-OCT. The difference in choroidal thickness between the OAG patients and the normal controls was analyzed. The relationships between choroidal thickness and various factors including age, sex, spherical equivalent (SE), axial length (AXL), central corneal thickness (CCT), intraocular pressure (IOP), peripapillary retinal nerve fiber layer thickness (pRNFLT), visual field mean deviation (MD), ganglion cell-inner plexiform layer thickness (GCIPLT), and disc area were analyzed by univariate and multivariate linear regression. Global and regional analyses were performed in 12 segments of the peripapillary circle and in six sectors of the macula.There were significant differences in global PCT and MCT between the OAG patients and the normal controls (115.22±41.17 vs. 138.89±44.70, P

PURPOSE:To investigate the variation of lamina cribrosa (LC) structure based on the baseline intraocular pressure (IOP) in eyes with primary open-angle glaucoma (POAG) and healthy individuals using swept-source optical coherence tomography. METHODS:A total of 108 eyes with POAG and 61 healthy eyes were recruited. Based on the baseline IOP, the POAG eyes were divided into higher-baseline IOP (HTG; baseline IOP > 21 mmHg, n = 38 eyes) and lower-baseline IOP (NTG; baseline IOP ≤ 21 mmHg, n = 70 eyes). The anterior laminar insertion depth (ALID), mean LC depth (mLCD), and the LC curvature index (mLCD-ALID) were measured, and compared among the three groups. The regional variation of LC structure was evaluated by vertical-horizontal ALID difference. RESULTS:The mLCD and LC curvature index were greatest in HTG eyes (520.3 ± 123.0 and 80.9 ± 30.7 μm), followed by NTG (463.2 ± 110.5 and 64.5 ± 30.7 μm) and healthy eyes (382.9 ± 107.6 and 47.6 ± 25.7 μm, all P < 0.001). However, there were no significant difference in ALID between HTG and NTG eyes. The vertical-horizontal ALID difference was larger in NTG eyes (72.8 ± 56.2 μm) than in HTG (32.7 ± 61.4 μm, P = 0.004) and healthy eyes (25.5 ± 34.8 μm, P < 0.001). CONCLUSIONS:Lamina cribrosa position and curvature differed in POAG eyes with low and high IOP. This would support the theory that IOP induced biomechanical effects on the optic play a role on glaucoma.

To report an asymmetry analysis of macular inner retinal layers using swept-source optical coherence tomography (OCT) and to evaluate the utility for glaucoma diagnosis.Observational, cross-sectional study.Seventy normal healthy subjects and 62 glaucoma patients.Three-dimensional scans were acquired from 70 normal subjects and 62 open angle glaucoma patients by swept-source OCT. The thickness of the retinal nerve fiber layer, ganglion cell-inner plexiform layer (GCIPL), ganglion cell complex, and total retina were calculated within a 6.2×6.2 mm macular area divided into a 31×31 grid of 200×200 μm superpixels. For each of the corresponding superpixels, the thickness differences between the subject eyes and contra-lateral eyes and between the upper and lower macula halves of the subject eyes were determined. The negative differences were displayed on a gray-scale asymmetry map. Black superpixels were defined as thickness decreases over the cut-off values.The negative inter-ocular and inter-hemisphere differences in GCIPL thickness (mean ± standard deviation) were -2.78 ± 0.97 μm and -3.43 ± 0.71 μm in the normal group and -4.26 ± 2.23 μm and -4.88 ± 1.46 μm in the glaucoma group. The overall extent of the four layers' thickness decrease was larger in the glaucoma group than in the normal group (all Ps