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Artificial Intelligence (AI) is transforming healthcare, notably in ophthalmology, where its ability to interpret images and data can significantly enhance disease diagnosis and patient care. Recent developments in oculomics, the integration of ophthalmic features to develop biomarkers for systemic diseases, have demonstrated the potential for providing rapid, non-invasive methods of screening leading to enhance in early detection and improve healthcare quality, particularly in underserved areas. However, the widespread adoption of such AI-based technologies faces challenges primarily related to the trustworthiness of the system. We demonstrate the potential and considerations needed to develop trustworthy AI in oculomics through a pilot study for HbA1c assessment using an AI-based approach. We then discuss various challenges, considerations, and solutions that have been developed for powerful AI technologies in the past in healthcare and subsequently apply these considerations to the oculomics pilot study. Building upon the observations in the study we highlight the challenges and opportunities for advancing trustworthy AI in oculomics. Ultimately, oculomics presents as a powerful and emerging technology in ophthalmology and understanding how to optimize transparency prior to clinical adoption is of utmost importance.

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BACKGROUND: Retinal vascular occlusions, including retinal vein occlusion and retinal artery occlusion, are common causes of visual impairment. In order to evaluate the national medical burden and help improve ophthalmic health care policy planning, we investigated the incidence of retinal vascular occlusive diseases from 2011 to 2020 in Korea. METHODS: This study is a nationwide population-based retrospective study using data from the Korea national health claim database of the Health Insurance Review and Assessment (HIRA) service. We identified retinal vascular occlusive diseases registered from January 1, 2009, to December 31, 2020, according to the retinal vascular occlusion code (H34) and its sub-codes from international classification of disease, tenth revision diagnosis code. We used data from the entire Korean population based on the 2015 census of the population in Korea to calculate standardized incidence rates. RESULTS: We identified 348,775 individuals (male, 161,673 [46.4%]; female, 187,102 [53.6%]) with incident retinal vascular occlusion (H34), 10,451 individuals (males, 6,329 [60.6%]; females, 4,122 [39.4%]) with incident central retinal artery occlusion (H34.1), and 252,810 individuals (males, 114,717 [45.4%]; females, 138,093 [54.6%]) with incident retinal vein occlusion (H34.8) during the 10-year study period. The weighted mean incidence rate of retinal vascular occlusion was 70.41 (95% CI, 70.18-70.65) cases/100,000 person-years. The weighted mean incidence rate of central retinal artery occlusion was 2.10 (95% CI, 2.06-2.14) cases/100,000 person-years. The weighted mean incidence rate of retinal vein occlusion was 50.99 (95% CI, 50.79-51.19) cases/100,000 person-years. CONCLUSION: The total retinal vascular occlusion and retinal vein occlusion showed a decreasing trend until 2020. However, the central retinal artery occlusion decreased until 2014 and remained stable without a significant further decline until 2020. The incidence of total retinal vascular occlusion and retinal vein occlusion was higher in females than in males, while the incidence of central retinal artery occlusion was higher in males. All retinal vascular occlusive diseases showed an increasing incidence with older age; the peak age incidence was 75-79 years for total retinal vascular occlusion and retinal vein occlusion, and 80-85 years for central retinal artery occlusion.

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Fluorescein angiography is a crucial examination in ophthalmology to identify retinal and choroidal pathologies. However, this examination modality is invasive and inconvenient, requiring intravenous injection of a fluorescent dye. In order to provide a more convenient option for high-risk patients, we propose a deep-learning-based method to translate fundus photography into fluorescein angiography using Energy-based Cycle-consistent Adversarial Networks (CycleEBGAN) We propose a deep-learning-based method to translate fundus photography into fluorescein angiography using CycleEBGAN. We collected fundus photographs and fluorescein angiographs taken at Changwon Gyeongsang National University Hospital between January 2016 and June 2021 and paired late-phase fluorescein angiographs and fundus photographs taken on the same day. We developed CycleEBGAN, a combination of cycle-consistent adversarial networks (CycleGAN) and Energy-based Generative Adversarial Networks (EBGAN), to translate the paired images. The simulated images were then interpreted by 2 retinal specialists to determine their clinical consistency with fluorescein angiography. A retrospective study. A total of 2605 image pairs were obtained, with 2555 used as the training set and the remaining 50 used as the test set. Both CycleGAN and CycleEBGAN effectively translated fundus photographs into fluorescein angiographs. However, CycleEBGAN showed superior results to CycleGAN in translating subtle abnormal features. We propose CycleEBGAN as a method for generating fluorescein angiography using cheap and convenient fundus photography. Synthetic fluorescein angiography with CycleEBGAN was more accurate than fundus photography, making it a helpful option for high-risk patients requiring fluorescein angiography, such as diabetic retinopathy patients with nephropathy.

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In this study, we investigated a convolutional neural network (CNN)-based framework for the estimation of the best-corrected visual acuity (BCVA) from fundus images. First, we collected 53,318 fundus photographs from the Gyeongsang National University Changwon Hospital, where each fundus photograph is categorized into 11 levels by retrospective medical chart review. Then, we designed 4 BCVA estimation schemes using transfer learning with pre-trained ResNet-18 and EfficientNet-B0 models where both regression and classification-based prediction are taken into account. According to the results of the study, the predicted BCVA by CNN-based schemes is close to the actual value such that 94.37% of prediction accuracy can be achieved when 3 levels of difference can be tolerated during prediction. The mean squared error and [Formula: see text] score were measured as 0.028 and 0.654, respectively. These results indicate that the BCVA can be predicted accurately for extreme cases, i.e., the level of BCVA is close to either 0.0 or 1.0. Moreover, using the Guided Grad-CAM, we confirmed that the macula and the blood vessel surrounding the macula are mainly utilized in the prediction of BCVA, which validates the rationality of the CNN-based BCVA estimation schemes since the same area is also exploited during the retrospective medical chart review. Finally, we applied the t-distributed stochastic neighbor embedding to examine the characteristics of CNN-based BCVA estimation schemes. The developed BCVA estimation schemes can be employed to obtain the objective measurement of BVCA as well as the medical screening of people with poor access to medical care through smartphone-based fundus imaging.

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In a previous study, we identified biocular asymmetries in fundus photographs, and macula was discriminative area to distinguish left and right fundus images with > 99.9% accuracy. The purposes of this study were to investigate whether optical coherence tomography (OCT) images of the left and right eyes could be discriminated by convolutional neural networks (CNNs) and to support the previous result. We used a total of 129,546 OCT images. CNNs identified right and left horizontal images with high accuracy (99.50%). Even after flipping the left images, all of the CNNs were capable of discriminating them (DenseNet121: 90.33%, ResNet50: 88.20%, VGG19: 92.68%). The classification accuracy results were similar for the right and left flipped images (90.24% vs. 90.33%, respectively; p = 0.756). The CNNs also differentiated right and left vertical images (86.57%). In all cases, the discriminatory ability of the CNNs yielded a significant p value (< 0.001). However, the CNNs could not well-discriminate right horizontal images (50.82%, p = 0.548). There was a significant difference in identification accuracy between right and left horizontal and vertical OCT images and between flipped and non-flipped images. As this could result in bias in machine learning, care should be taken when flipping images.

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Patients with weak or no symptoms accelerate the spread of COVID-19 through various mutations and require more aggressive and active means of validating the COVID-19 infection. More than 30% of patients are reported as asymptomatic infection after the delta mutation spread in Korea. It means that there is a need for a means to more actively and accurately validate the infection of the epidemic via pre-symptomatic detection, besides confirming the infection via the symptoms. Mishara et al. (Nat Biomed Eng 4, 1208-1220, 2020) reported that physiological data collected from smartwatches could be an indicator to suspect COVID-19 infection. It shows that it is possible to identify an abnormal state suspected of COVID-19 by applying an anomaly detection method for the smartwatch's physiological data and identifying the subject's abnormal state to be observed. This paper proposes to apply the One Class-Support Vector Machine (OC-SVM) for pre-symptomatic COVID-19 detection. We show that OC-SVM can provide better performance than the Mahalanobis distance-based method used by Mishara et al. (Nat Biomed Eng 4, 1208-1220, 2020) in three aspects: earlier (23.5-40% earlier) and more detection (13.2-19.1% relative better) and fewer false positives. As a result, we could conclude that OC-SVM using Resting Heart Rate (RHR) with 350 and 300 moving average size is the most recommended technique for COVID-19 pre-symptomatic detection based on physiological data from the smartwatch.

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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.

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We analyzed fundus images to identify whether convolutional neural networks (CNNs) can discriminate between right and left fundus images. We gathered 98,038 fundus photographs from the Gyeongsang National University Changwon Hospital, South Korea, and augmented these with the Ocular Disease Intelligent Recognition dataset. We created eight combinations of image sets to train CNNs. Class activation mapping was used to identify the discriminative image regions used by the CNNs. CNNs identified right and left fundus images with high accuracy (more than 99.3% in the Gyeongsang National University Changwon Hospital dataset and 91.1% in the Ocular Disease Intelligent Recognition dataset) regardless of whether the images were flipped horizontally. The depth and complexity of the CNN affected the accuracy (DenseNet121: 99.91%, ResNet50: 99.86%, and VGG19: 99.37%). DenseNet121 did not discriminate images composed of only left eyes (55.1%, p = 0.548). Class activation mapping identified the macula as the discriminative region used by the CNNs. Several previous studies used the flipping method to augment data in fundus photographs. However, such photographs are distinct from non-flipped images. This asymmetry could result in undesired bias in machine learning. Therefore, when developing a CNN with fundus photographs, care should be taken when applying data augmentation with flipping.

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PURPOSE: Acute and chronic hypertension may have different pathophysiological mechanisms in the retina. Here, we compared the retinal nerve fibre layer (RNFL)/ganglion cell-inner plexiform layer (GC-IPL) thickness ratios of patients with 'relieved' severe hypertensive retinopathy (relieved HTNR) and chronic hypertension without retinopathy (chronic HTN) to those of normal controls. METHODS: We performed cross-sectional study. The eyes were divided into the following groups: normal controls (Group A, age ≥50 years; Group D, age <50 years); chronic HTN (Group B, <10 years of HTN; TNHT; Group C, ≥10 years of HTN); and relieved HTNR (previously diagnosed with grade IV HTNR and relieved retinopathy for >1 year; Group E), and the RNFL/GC-IPL thickness ratio was compared among Groups A-C and between Groups D and E. RESULTS: A total of 379 eyes were included in this study. Groups A-E consisted of 145, 59, 63, 60 and 52 eyes, respectively. The RNFL/GC-IPL thickness ratios were 1.161 ± 0.093, 1.158 ± 0.082 and 1.162 ± 0.089 in groups A-C, respectively, and did not showed a statistically difference (p = 0.966). The RNFL/GC-IPL thickness ratio of groups D and E were 1.169 ± 0.080 and 1.221 ± 0.080, respectively, and showed a statistically difference (p = 0.001). CONCLUSIONS: The RNFL/GC-IPL thickness ratios of the chronic HTN group did not show a difference compared with the normal controls. However, relieved HTNR patients showed a higher ratio than the normal controls. Physicians should be aware that acute hypertensive injury could affect the RNFL/GC-IPL thickness ratio.

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RATIONALE: Several reports have described retinal pigment epithelial (RPE) tears in central serous chorioretinopathy (CSC). However, there have been no reports of spontaneously large RPE tears in acute CSC without bullous retinal detachment (RD). Herein, we report and provide sequential images of a case of bilateral spontaneous large RPE tears in patient with acute CSC without bullous RD. PATIENT CONCERNS: An 88-year-old female patient was admitted with impaired vision in both eyes, which began 10 days prior. The visual acuity was 0.4 and 0.5 in the right and left eye, respectively. She had started taking oral steroids 2 weeks prior for polymyalgia. DIAGNOSIS: Ophthalmologic examinations, including fundus photography, optical coherence tomography, and fluorescence angiography, were performed, and she was diagnosed with steroid-induced acute CSC in both eyes with large pigment epithelial detachment (PED) of approximately 4-disc diameter. Discontinuation of steroids and follow-up ophthalmic examinations were performed. However, a spontaneous large RPE tear occurred in the right eye. INTERVENTIONS: We performed follow-ups more frequently and CSC treatment such as laser photocoagulation, photodynamic therapy, and anti-vascular endothelial growth factor injections were not performed. OUTCOMES: Nine months later, a spontaneous large RPE tear occurred sequentially in the left eye. Her final visual acuity was 0.3 and 0.15 in the right and left eye, respectively. LESSONS: Patients may spontaneously develop large RPE tears in both eyes, despite no treatment for acute CSC with non-bullous RD. Large PED and old age may affect this. Therefore, for a CSC patient with a large PED and advanced age, attention must be paid when determining treatment.

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The Bruch's membrane opening-minimum rim width (BMO-MRW) is a recently introduced parameter of the neuroretinal rim. We analyzed the repeatability of spectral-domain optical coherence tomography (SD-OCT) measurements of BMO-MRW in epiretinal membrane (ERM) patients with peripapillary involvement, since the surface around the optic disc is distorted in such patients. BMO-MRW and retinal nerve fiber layer (RNFL) thickness measurements were performed using SD-OCT in prospectively enrolled ERM patients and age-matched healthy control individuals. After two consecutive measurements with a 5 min interval, repeatability was analyzed using the intraclass correlation coefficient (ICC), repeatability coefficient (RC), and coefficient of variation (CV). Fifty-two eyes of 52 ERM patients and 62 eyes of 62 healthy controls were included in the study. The ICCs of the mean BMO-MRW/RNFL thickness measurements were 0.999/0.985 in ERM eyes and 0.999/0.999 in normal eyes, respectively. The RC values of mean BMO-MRW/RNFL thickness measurements were 9.0/6.25 µm in ERM eyes and 4.61/0.92 µm in normal eyes, respectively. The CV values were 0.91% and 1.45% for BMO-MRW and RNFL thickness in ERM eyes, and 0.63% and 0.33% in normal eyes, respectively. In ERM eyes, the RC, CV of average BMO-MRW were 1.9 and 1.4 times greater than those of normal eyes, but 6.8 and 4.4 times greater for average RNFL thickness. BMO-MRW and RNFL thickness showed good repeatability in the diseased eyes with peripapillary involvement and healthy control eyes. Based on the ICC, RC, and CV values, the repeatability of BMO-MRW measurements in peripapillary membrane patients was better than that of RNFL thickness.

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Optical coherence tomography (OCT) is a noninvasive method that can quickly and accurately examine the eye at the cellular level. Several studies have used OCT for analysis of anterior chamber cells. However, these studies have several limitations. This study was performed to supplement existing reports of automated analysis of anterior chamber cell images using spectral domain OCT (SD-OCT) and to compare this method with the Standardization of Uveitis Nomenclature (SUN) grading system. We analyzed 2398 anterior segment SD-OCT images from 34 patients using code written in Python. Cell density, size, and eccentricity were measured automatically. Increases in SUN grade were associated with significant cell density increases at all stages (p < 0.001). Significant differences were observed in eccentricity in uveitis, post-surgical inflammation, and vitreous hemorrhage (p < 0.001). Anterior segment SD-OCT is reliable, fast, and accurate means of anterior chamber cell analysis. This method showed a strong correlation with the SUN grade system. Also, eccentricity could be helpful as a supplementary evaluation tool.

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Aim of the study is to report the clinical characteristics and prognostic factors in hypertensive anterior uveitis (AU) diagnosed with multiplex polymerase chain reaction (PCR). Eighty-eight eyes of 88 patients with hypertensive AU were enrolled from 2015 to 2019 in a tertiary center in South Korea. All patients underwent multiplex PCR that was performed using aqueous humor samples collected at first visit to detect the DNA of six herpesviruses. Twenty-eight (31.8%) eyes were PCR positive. Herpes simplex virus was found in 6 (6.8%) eyes, varicella-zoster virus in 7 (8.0%) eyes, cytomegalovirus in 14 (15.9%) eyes, and Epstein-Barr virus in 1 (1.1%) eye. On multivariate regression analysis, PCR positivity was significantly associated with coin-shaped keratic precipitates (odds ratio (OR) = 6.01, P = 0.044). Recurrence and final visual acuity were significantly associated with a presumed diagnosis of viral endotheliitis (OR = 21.69, P = 0.04 and OR = 6.3, P = 0.004, respectively). This study showed the importance of PCR positivity, suggesting that identification of the virus through active PCR testing could affect the course, treatment, and prognosis of hypertensive AU.

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PURPOSE: To compare visual improvements between initial intravitreal t-PA with gas injection before anti-vascular endothelial growth factor (VEGF) and anti-VEGF injection monotherapy for submacular haemorrhage (SMH) associated with age-related macular degeneration (AMD). METHODS: We retrospectively reviewed medical records of naive patients treated with intravitreal t-PA with gas injection before anti-VEGF (Group 1) or only with intravitreal anti-VEGF injection (Group 2) for SMH [disc area (DA) ≥ 2] associated with AMD from two institutions. Both groups received 3 monthly loads of anti-VEGF injections followed by injections as needed for AMD treatment. Changes in best-corrected visual acuity (BCVA, logMAR) between the initial visit and after 6 months of treatment were compared between two groups. RESULTS: A total of 82 patients were enroled. Of these, 32 patients and 50 patients were grouped in Groups 1 and 2, respectively. The mean change in BCVA over 6 months for Group 1 was -0.52 ± 0.88, which was significantly larger (p = 0.044) than the mean change for Group 2 (-0.15 ± 0.58). We compared visual improvements between the two groups based on the following SMH size categories: ≤5, >5, and ≤15, and >15 DA. When the SMH size was ≤5, or >5 and ≤15 DA, the mean change in BCVA was larger for Group 1 than for Group 2, but this difference was not significant. When SMH size was >15 DA, Group 1 patients exhibited a mean visual improvement of -0.79 ± 0.80, which was significantly greater (p = 0.029) than that of Group 2 (-0.06 ± 0.67). CONCLUSIONS: Patients that were primarily treated for SMH associated with AMD using t-PA and gas injection (followed by anti-VEGF injection) exhibited better visual improvement than those treated with anti-VEGF monotherapy, especially in patients exhibiting larger SMH sizes (>15 DA) at the initial visit.

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PURPOSE: The innate immune system is strongly implicated in the pathogenesis of uveitis. This study was designed to clarify the responses of the innate immune system in uveal tissues. MATERIALS AND METHODS: We utilized quantitative, real-time RT-PCR to measure mRNA of innate immune system receptors from porcine iris, choroid, and retina tissues. We used RT-PCR for cytokines to evaluate the responses of these tissues to specific ligands or extracts of whole bacteria that activate the innate immune system. We used ELISA for IL-6 on selected choroidal supernatants to confirm that the mRNA measurement correlated with protein levels. RESULTS: In each of the studied tissues, we detected the expression of important receptors belonging to the innate immune system including dectin-1, TLR4, TLR8, and NOD2. Relative mRNA expression was generally lower in the retina compared to iris or choroid. All three tissues demonstrated upregulation of cytokine mRNA in response to a range of ligands that activate the innate immune system. The measurement of IL-6 protein was consistent with results based on mRNA. Notably, the expression of mRNA for IL-23 was more pronounced than IL-12 in all three tissues after stimulation with various innate immune system ligands. CONCLUSIONS: These data provide evidence of a potent innate immune response intrinsic to uveal tissues. Specific innate immune system ligands as well as bacterial extracts enhanced the production of several inflammatory cytokines. Furthermore, the observation of higher upregulation of IL-23 mRNA, compared to IL-12 in response to innate immune stimuli, suggested that a local TH17 response might be more robust than a local TH1 response in uveal tissues. Our results expand the understanding as to how the innate immune system may contribute to uveitis.

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PURPOSE: We investigated risk factors for breakthrough vitreous hemorrhage (VH) after an intravitreal tissue plasminogen activator (tPA) and gas injection in patients with submacular hemorrhage (SMH) associated with age-related macular degeneration (AMD). METHODS: The medical records of patients diagnosed with SMH associated with AMD who received an intravitreal tPA (50 µg/0.05 mL) and perfluoropropane gas (0.3 mL) injection were reviewed retrospectively. We analyzed the associations of breakthrough VH with age, sex, best-corrected visual acuity, intraocular pressure, AMD subtype, accompanying sub-retinal pigment epithelium (RPE) hemorrhage, history of cataract surgery, history of hypertension and diabetes mellitus, history of drinking and smoking, and history of antiplatelet or anticoagulant medication. We also examined the relationships between various parameters, including the area ratio of the SMH to the optic disc (AHD) and the height of the SMH obtained from optical coherence tomography. RESULTS: In total, 52 eyes from 52 patients were enrolled in this study; 16 eyes (30%) showed breakthrough VH. The proportions of patients with a current smoking history were 75.0% in the VH group and 22.2% in the non-VH group (p = 0.010). Other factors did not differ significantly between the two groups. The proportion of cases with accompanying sub-RPE hemorrhage was 50.0% and 58.3% in the VH and non-VH groups, respectively (p = 0.763). The AHD (p = 0.001) and SMH height (p < 0.001) were significantly greater in the VH group. In a receiver operating characteristic curve analysis, the cut-off values of AHD and SMH height were 20.1 and 1208 µm, respectively. According to logistic regression analysis, when the AHD and SMH height were greater than the individual cut-off values, the odds ratio of VH increased by 10.286 fold (95% confidence interval [CI], 2.452-43.148; p = 0.001) and 75.400 fold (95% CI, 7.991-711.441; p < 0.001), respectively, with respect to their respective reference groups (less than the cut-off value). Among the significant factors associated with VH occurrence, including current smoking, AHD, and SMH height, only current smoking and SMH height were found to be significant in multiple regression analysis (p = 0.040, 0.016). CONCLUSIONS: The incidence of breakthrough VH was significantly higher in those with current smoking status and for SMH with a larger AHD and greater height. The height of the SMH was more predictable of the possibility of VH than AHD.

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Neovascularization in the retina can cause loss of vision. Vascular endothelial growth factor (VEGF) serves an important role in the pathogenesis of retinal vascular diseases. Hypoxia is a notable cause of VEGF release and both STAT3 and ERBB2 are known to be associated with VEGF. In addition, STAT3 and ERBB2 interact with each other. In the present study, it was hypothesized that signal transducer and activator of transcription 3 (STAT3) and erbB­2 receptor tyrosine kinase 2 (ERBB2) may be involved in the regulation of hypoxia­induced VEGF in the retina. Cells of the retinal pigment epithelium (RPE) are an important source of VEGF. Therefore, the RPE­derived human cell line ARPE­19 was exposed to hypoxia. Hypoxia­induced phosphorylation of STAT3 and ERBB2 in ARPE­19 cells was decreased by AG490, an inhibitor of Janus kinase 2, as were hypoxia­induced VEGF release and tube formation in human umbilical vein endothelial cells. Thus, phosphorylation of ERBB2 and STAT3 regulates hypoxia­induced VEGF release in ARPE­19 cells. The results of the present study suggested that inhibition of ERBB2 and STAT3­mediated pathways under hypoxia may represent a new strategy for treating retinal vascular disease.

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RATIONALE: Macular hole (MH) formation after vitrectomy is rare and it may be due to several mechanisms associated with change of foveolar anatomy by vitrectomy. If a MH develops after vitrectomy, surgical treatments including internal limiting membrane peeling and intravitreal gas injection are usually needed for repair of hole. Spontaneous closure of MH is much rarer. PATIENT CONCERNS: A 66-year-old patient had a vitrectomy for rhegmatogenous retinal detachment not involving the macula of the right eye. Eight months after the vitrectomy, the visual acuity decreased and full-thickness defect of macula, epiretinal membrane progression, intraretinal cysts, and flame shape hemorrhage along with superior temporal vascular arcade were observed on fundus examination and optical coherence tomography. DIAGNOSES: MH and branch retinal vein occlusion (BRVO) accompanying cystoid macular edema (CME) were both present on her right eye. Thus, we planned a surgery for MH repair. INTERVENTIONS: The status of MH was observed while waiting the surgery schedule. At 2 weeks after detection of the MH, optical coherence tomography showed that intraretinal cysts had decreased in extent and the inner wall of the MH had contracted; 4 weeks later, the MH was closed with a subtle subretinal space. OUTCOMES: The fovea was well-maintained with a complete closure for 9 months. LESSONS: MH formation and spontaneous closure occurred in association with BRVO accompanying CME in a patient who had a vitrectomy. In vitrectomized eyes, physicians should consider the possibility of MH development in association with BRVO, and possible spontaneous closure of the MH in accordance with CME resolution.

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Postoperative endophthalmitis (PE) is the devastating complication that frequently results in vision loss. Recently, enterococcus have emerged as a major cause of PE in several countries and resulted in poor visual outcome. However, the reason remains elusive. We investigate whether selection pressure of fluoroquinolone exerts effects on microorganism profiles isolated from PE. Medical records of patients who were diagnosed with PE at eight resident training institutions between January 2004 and December 2015 were reviewed. The most common isolate was Enterococcus faecalis (28.0%), followed by Staphylococcus epidermidis (18.6%) and other coagulase negative Staphylococci (7.6%). However, the rates of E. faecalis isolated from conjunctival microbes were 6.2% (16/257) and their resistance to fluoroquinolones was higher than those of S. epidermidis. In vitro and in vivo co-culture models of E. faecalis and S. epidermidis were established for survival assays after administration of fourth-generation fluoroquinolone. In in vitro co-culture model, the survival assay of E. faecalis and S. epidermidis against the treatment of moxifloxacin showed that E. faecalis survived significantly better than S. epidermidis in the presence of moxifloxacin 1 µg/mL and more. In in vivo co-culture model, E. faecalis survived significantly better than S. epidermidis after topical treatment of moxifloxacin (5 mg/mL). E. faecalis has been the most common causative strain of PE in Korea. We suggest that the increase of E. faecalis in PE could be associated with the selection pressure of fourth-generation fluoroquinolone. Summary: Enterococcus spp. have emerged as a leading causative strain of postoperative endophthalmitis in 11-year clinical data. We suggest that the increase of Enterococcus spp. is associated with the selection pressure of fourth-generation fluoroquinolone.

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