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Purpose: To derive the optimized intraocular lens (IOL) constants from automated and manifest refraction after cataract surgery in Korean patients, and to evaluate whether there is a difference in optimized IOL constants according to the refraction method.Methods: This retrospective multicenter cohort study enrolled 4,103 eyes of 4,103 patients who underwent phacoemulsification and in-the-bag IOL implantation at 18 institutes. Optimized IOL constants for the SRK/T, Holladay, Hoffer Q, and Haigis formulas were calculated via autorefraction or manifest refraction of samples using the same biometry and IOL. The IOL constants derived from autorefraction and manifest refraction were compared.Results: Of the 4,103 eyes, the majority (62.9%) were measured with an IOLMaster 500 followed by an IOLMaster 700 (15.2%). A total of 33 types of IOLs were used, and the Tecnis ZCB00 was the most frequently used (53.0%). There was no statistically significant difference in IOL constants derived from autorefraction and manifest refraction when IOL constants were optimized with a large number of study subjects. On the other hand, optimized IOL constants derived from autorefraction were significantly smaller than those from manifest refraction when the number of subjects was small.Conclusions: It became possible to use the IOL constants optimized from Koreans to calculate the IOL power. However, if the IOL constant is optimized using autorefraction in a small sample group, the IOL constant tends to be small, which may lead to refractive error after surgery.

Conjunctival goblet cells (CGCs) are mucin-secreting cells in the eye and play essential roles for ocular surface homeostasis. Since various ocular surface pathologies are related to CGC dysfunction, CGC examination is important for the evaluation of ocular surface conditions. Recently we introduced moxifloxacin-based fluorescence microscopy (MBFM) for non-invasive CGC imaging. However, the imaging speed was up to 1 frame per second (fps) and needed to be improved for clinical applications. In this study, we developed a high-speed moxifloxacin-based, extended depth-of-field (EDOF) microscopy system that operates at a maximum imaging speed of 15 fps. The system used a deformable mirror for the high-speed axial sweeping of focal plane during single-frame acquisitions. The acquired images contained both in-focus and out-of-focus information, and deconvolution was used to filter the in-focus information. The system had a DOF of 800 [Formula: see text], field-of-view of 1.2 mm ×1.2 mm, and resolution of [Formula: see text]. Its performance was demonstrated by real-time, breathing-motion-insensitive CGC imaging of mouse and rabbit models, in vivo. High-speed EDOF microscopy has potentials for non-invasive, real-time CGC examinations of human subjects.

Purpose: To report the effect of removal of a central descemet membrane on the endothelial function, morphology, and clinical symptoms of eyes with Fuch’s endothelial dystrophy.Methods: From August 2019 to January 2021, patients with Fuch’s endothelial dystrophy, i.e., with confluent, central corneal guttae and cataracts that required surgery, underwent phacoemulsification, intraocular lens implantation, and central descemet membrane stripping. To evaluate the effect of descemet stripping only (DSO), visual acuity and intraocular pressure were measured, and corneal pachymetry, slit-lamp and specular microscopy, and anterior segment optical coherence tomography performed, before surgery and at 1, 7, and 30 days and 3 and 6 months after surgery.Results: Seven patients (10 eyes) were included. Visual acuity improved from 1.01 ± 0.40 logarithm of the minimum angle of resolution (logMAR) preoperatively to 0.33 ± 0.22 logMAR 6 months after surgery (p = 0.008). The mean central corneal thickness decreased from 578.50 ± 36.88 μm preoperatively to 568.50 ± 48.61 μm 6 months after surgery; the difference was not significant (p = 0.507). The endothelial cell count increased significantly from 663.80 ± 356.40/mm2 preoperatively to 1,082.00 ± 274.46/mm2 6 months after surgery (p = 0.043).Conclusions: DSO can serve as a useful alternative when corneal transplantation is not possible in patients with Fuch’s endothelial dystrophy, but treatment efficacy and safety require further evaluation.

Purpose: To analyze the change in the weekly incidence of epidemic keratoconjunctivitis (EKC) per 1,000 outpatients during the coronavirus disease 2019 (COVID-19) pandemic by comparing the mean weekly proportion of EKC of 2020 with that from 2016 to 2019.Methods: Using data from the Korea Disease Control and Prevention Agency for 2016-2020, we analyzed the weekly proportion of EKC per 1,000 outpatients. The data were also analyzed according to age, semester and vacation periods, region, and social distancing stages. For the Daegu data, we also analyzed the effects of social distancing in an area.Results: The mean weekly proportion of EKC per 1,000 outpatients in 2020 was lower than in previous years for all ages (2016-2019 19.77 ± 7.17‰, 2020 7.28 ± 2.97‰; p < 0.001). During the semester, the mean difference between 2016-2019 and 2020 was significant, particularly for preschool children. In Daegu, the weekly proportion of EKC per 1,000 outpatients during the extra 12-18 weeks of social distancing was significantly lower (2016-2019, 18.78 ± 6.61‰; 2020, 8.94 ± 2.92‰; p < 0.001).Conclusions: The public health interventions implemented during the COVID-19 outbreak not only reduced the prevalence of COVID-19 but also reduced the prevalence of EKC. Therefore, maintaining hygiene principles and standard precautions may help prevent EKC.

Background/aims We evaluate the clinical characteristics of intermittent exotropia with controllability and compare surgical outcomes between patients with and without controllability. Methods We reviewed the medical records of patients aged 6–18 years with intermittent exotropia who underwent surgery between September 2015 and September 2021. Controllability was defined as the patient’s subjective awareness of exotropia or diplopia associated with the presence of exotropia and ability to instinctively correct the ocular exodeviation. Surgical outcomes were compared between patients with and without controllability, with a favorable surgical outcome defined as an ocular deviation between ≤ 10 PD of exotropia and ≤ 4 PD of esotropia at distance and near. Results Among 521 patients, 130 (25%, 130/521) had controllability. The mean age of onset (7.7 years) and surgery (9.9 years) were higher in patients with controllability than in those without controllability (p Conclusions Patients with controllability showed better surgical outcomes, later exotropia onset, and better level of control than patients without controllability. Preoperative ocular exodeviation was a significant factor influencing favorable outcomes in patients with controllable exotropia.

Herein, a wireless and soft smart contact lens that enables real-time quantitative recording of cholesterol in tear fluids for the monitoring of patients with hyperlipidemia using a smartphone is reported. This contact lens incorporates an electrochemical biosensor for the continuous detection of cholesterol concentrations, stretchable antenna, and integrated circuits for wireless communication, which makes a smartphone the only device required to operate this lens remotely without obstructing the wearer's vision. The hyperlipidemia rabbit model is utilized to confirm the correlation between cholesterol levels in tear fluid and blood and to confirm the feasibility of this smart contact lens for diagnostic application of cholesterol-related diseases. Further in vivo tests with human subjects demonstrated its good biocompatibility, wearability, and reliability as a non-invasive healthcare device.

In corneal transplantation, 16 submillimeter-sized sutures are generated around the circular-shaped graft cornea. A major challenge in corneal transplantation is the generation of uniformly shaped sutures, where the suture shapes need to be changed depending on the patient. In this study, a corneal suturing robot that can produce sutures of the desired shape with high uniformity is described. The proposed robot manipulates the corneal tissue deformation before inserting the needle for suture shape control. A simulation using the finite element method was proposed to predict the suture shape. The suturing experiment was conducted on a porcine model, and the result was compared with the simulation. As a result, the proposed robot was able to generate sutures with a standard deviation of 108 $\mu$ m in length and 36 $\mu$ m in depth. The mean absolute error between the simulation and the experiment was 95 $\mu$ m in length and 31 $\mu$ m in depth. This is the first study to suggest a method for controlling the suture shape and quantitatively analyzing it in ophthalmic surgery.

본 연구에서는 경력정체의 결과 경력만족과 이직의도에 미치는 영향관계와 경력정체에 따라 자원상실이 예상되며, 상실된 자원을 줄일 수 있는 개인 내부자원으로서 긍정심리자본을 제시하여 긍정심리자본이 경력정체가 이직의도에 미치는 영향에 있어 조절효과를 검증하고자 한다. 실증분석 결과 다음과 같은 결과가 도출되었다. 첫째, 경력정체에 있어 내용적 경력정체, 구조적 경력정체 순으로 높게 지각할수록 경력만족이 낮아지는 것으로 나타났다. 이에 호텔기업에서는 종사원들이 경력정체를 지각하지 않도록 노력을 해야 할 것이다. 특히 조직차원에 대한 지원도 중요하지만 가장 중요한 것은 개인적으로 경력정체를 지각하지 않도록 노력을 해야 할 것이다. 둘째, 경력정체에 있어 내용적 경력정체, 구조적 경력정체 순으로 높게 지각할수록 이직의도가 높아지는 것으로 나타났다. 이에 개인차원에서 경력계획을 세우는 것이 중요하며, 조직차원에서는 조직에서는 직무체계의 개선, 교육훈련, 평가, 보상체계의 개선 등 인사관리시스템 전반의 개선이 필요하다. 셋째, 경력만족에 대해 높게 지각할수록 이직의도가 낮아지는 것으로 나타났다. 이에 조직 내부의 직무 관련 교육훈련 프로그램뿐만 아니라, 조직 외부의 전문 기관을 통한 직무 또는 비 직무 관련 교육 기회를 제공하여 개인의 경력에 대한 만족도를 높일 수 있도록 하여야 할 것이다. 넷째, 구조적 경력정체에 대해 높게 지각하더라도 낙관주의와 희망이 높으면 이직의도가 낮아지는 것으로 나타났다. 따라서 우수한 인적자원을 관리해야 하는 기업입장에서는 종사원들의 이직의도를 낮추기 위해 종사원들의 희망과 낙관주의를 높이기 위한 노력을 해야 할 것이다. 마지막으로 경력정체와 이직의도를 낮추기 위해서는 유연근무제, 재택근무제, 원격 근무 및 안식년 등의 제도 도입을 통하여 구성원들이 학습을 위한 시간을 할애하고 궁극적으로 일과 삶의 균형을 꾀할 수 있도록 돕는 것이 중요하다. 이는 점차 개인들은 자신의 직업을 통한 흥미 및 일과 삶의 균형을 추구하고 있기 때문이다.

Significance Multimodal imaging based on optics and ultrasound can provide guide images and complementary structural and functional information, thus improving the accuracy of medical diagnosis and treatment monitoring. However, because conventional ultrasound transducers are opaque, in multimodal imaging with optics, the optical devices must be placed off-axis from the ultrasound transducer. This off-axis arrangement is prone to misalignment, adds complexity and bulk to the system, and can result in a low signal-to-noise-ratio. Here, we present a transparent ultrasound transducer at the heart of a quadruple fusion imaging system that seamlessly integrates ultrasound imaging, photoacoustic imaging, optical coherence tomography, and fluorescence imaging, and we demonstrate the system’s use in imaging responses to both ophthalmologic injuries and oncologic diseases., Ultrasound and optical imagers are used widely in a variety of biological and medical applications. In particular, multimodal implementations combining light and sound have been actively investigated to improve imaging quality. However, the integration of optical sensors with opaque ultrasound transducers suffers from low signal-to-noise ratios, high complexity, and bulky form factors, significantly limiting its applications. Here, we demonstrate a quadruple fusion imaging system using a spherically focused transparent ultrasound transducer that enables seamless integration of ultrasound imaging with photoacoustic imaging, optical coherence tomography, and fluorescence imaging. As a first application, we comprehensively monitored multiparametric responses to chemical and suture injuries in rats’ eyes in vivo, such as corneal neovascularization, structural changes, cataracts, and inflammation. As a second application, we successfully performed multimodal imaging of tumors in vivo, visualizing melanomas without using labels and visualizing 4T1 mammary carcinomas using PEGylated gold nanorods. We strongly believe that the seamlessly integrated multimodal system can be used not only in ophthalmology and oncology but also in other healthcare applications with broad impact and interest.

Integration of a smart contact lens and a heat patch realizes personal management of ocular surface diseases wirelessly., Wearable electronic devices that can monitor physiological signals of the human body to provide biomedical information have been drawing extensive interests for sustainable personal health management. Here, we report a human pilot trial of a soft, smart contact lens and a skin-attachable therapeutic device for wireless monitoring and therapy of chronic ocular surface inflammation (OSI). As a diagnostic device, this smart contact lens enables real-time measurement of the concentration of matrix metalloproteinase-9, a biomarker for OSI, in tears using a graphene field-effect transistor. As a therapeutic device, we also fabricated a stretchable and transparent heat patch attachable on the human eyelid conformably. Both diagnostic and therapeutic devices can be incorporated using a smartphone for their wireless communications, thereby achieving instantaneous diagnosis of OSI and automated hyperthermia treatments. Furthermore, in vivo tests using live animals and human subjects confirm their good biocompatibility and reliability as a noninvasive, mobile health care solution.

Purpose To measure needle insertion force and change in intraocular pressure (IOP) in real-time during intravitreal injection (IVI). The effects of needle size, insertion speed, and injection rate to IOP change were investigated. Methods Needle insertion and fluid injection were performed on 90 porcine eyeballs using an automatic IVI device. The IVI conditions were divided according to needle sizes of 27-gauge (G), 30G, and 33G; insertion speeds of 1, 2, and 5 mm/s; and injection rates of 0.01, 0.02, and 0.05 mL/s. Insertion force and IOP were measured in real-time using a force sensor and a pressure transducer. Results The peak IOP was observed when the needle penetrated the sclera; the average IOP elevation was 96.3, 67.1, and 59.4 mmHg for 27G, 30G, and 33G needles, respectively. An increase in insertion speed caused IOP elevation at the moment of penetration, but this effect was reduced as needle size decreased: 109.8–85.9 mmHg in 27G for 5–1 mm/s (p = 0.0149) and 61.8–60.7 mmHg in 33G for 5–1 mm/s (p = 0.8979). Injection speed was also related to IOP elevation during the stage of drug injection: 16.65 and 11.78 mmHg for injection rates of 0.05 and 0.01 mL/s (p < 0.001). Conclusion The presented data offers an understanding of IOP changes during each step of IVI. Slow needle insertion can reduce IOP elevation when using a 27G needle. Further, the injection rate must be kept low to avoid IOP elevations during the injection stage.

To compare the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) and steroidal eyedrops for inflammation management after cataract surgery using slitlamp indicators.11 eye centers in South Korea.Randomized prospective multicenter study with a blinded evaluator.In 125 (250 eyes) patients who underwent cataract surgery, bromfenac sodium hydrate 0.1% (NSAID group) was applied twice a day in 1 eye, whereas the other eye was treated with fluorometholone 0.1% (steroid group), 4 times a day for 4 weeks postoperatively. The primary efficacy outcome was the presence of anterior chamber cells and flare at 1 week postoperatively. Anterior chamber cells and flare at 4 to 8 weeks, corrected distance visual acuity, central corneal thickness, conjunctival hyperemia, dry eye parameters, foveal thickness, and ocular and visual discomfort were evaluated as secondary outcomes.At week 1, residual anterior chamber inflammation was not statistically significantly different between the groups (-1.03 ± 1.27 vs -0.95 ± 1.24, P = .4850). However, the NSAID group recovered from conjunctival hyperemia more rapidly than the steroid group (0.30 ± 0.52 vs 0.44 ± 0.81, P = .0144 at week 1). The increase in central corneal thickness in the NSAID group was less than that in the steroid group 1 week postoperatively (7.87 ± 22.46 vs 29.47 ± 46.60 μm, P.0001). The change in foveal thickness in the NSAID group was significantly less than that in the steroid group (18.11 ± 68.19 vs 22.25 ± 42.37 μm, P = .0002). Lower levels of postoperative ocular and visual discomfort were reported in the NSAID group than in the steroid group under treatment.Preservative-free bromfenac was as effective as preservative-free fluorometholone eyedrops in anterior chamber inflammation control and showed better signs and symptoms after cataract surgery.

Skin grafts are required in numerous clinical procedures, such as reconstruction after skin removal and correction of contracture or scarring after severe skin loss caused by burns, accidents, and trauma. The current standard for skin defect replacement procedures is the use of autologous skin grafts. However, donor-site tissue availability remains a major obstacle for the successful replacement of skin defects and often limits this option. The aim of this study is to effectively expand full thickness skin to clinically useful size using an automated skin reactor and evaluate auto grafting efficiency of the expanded skin using Yucatan female pigs. We developed an automated bioreactor system with the functions of real-time monitoring and remote-control, optimization of grip, and induction of skin porosity for effective tissue expansion. We evaluated the morphological, ultra-structural, and mechanical properties of the expanded skin before and after expansion using histology, immunohistochemistry, and tensile testing. We further carried out in vivo grafting study using Yucatan pigs to investigate the feasibility of this method in clinical application. The results showed an average expansion rate of 180%. The histological findings indicated that external expansion stimulated cellular activity in the isolated skin and resulted in successful grafting to the transplanted site. Specifically, hyperplasia did not appear at the auto-grafted site, and grafted skin appeared similar to normal skin. Furthermore, mechanical stimuli resulted in an increase in COL1A2 expression in a suitable environment. These findings provided insight on the potential of this expansion system in promoting dermal extracellular matrix synthesis in vitro. Conclusively, this newly developed smart skin bioreactor enabled effective skin expansion ex vivo and successful grafting in vivo in a pig model.

The endothelialization on the poly (ε-caprolactone) nanofiber has been limited due to its low hydrophilicity. The aim of this study was to immobilize collagen on an ultra-thin poly (ε-caprolactone) nanofiber membrane without altering the nanofiber structure and maintaining the endothelial cell homeostasis on it. We immobilized collagen on the poly (ε-caprolactone) nanofiber using hydrolysis by NaOH treatment and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/sulfo- N-hydroxysulfosuccinimide reaction as a cost-effective and stable approach. NaOH was first applied to render the poly (ε-caprolactone) nanofiber hydrophilic. Subsequently, collagen was immobilized on the surface of the poly (ε-caprolactone) nanofibers using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/sulfo- N-hydroxysulfosuccinimide. Scanning electron microscopy, Fourier transform infrared spectroscopy, transmission electron microscopy, and fluorescence microscopy were used to verify stable collagen immobilization on the surface of the poly (ε-caprolactone) nanofibers and the maintenance of the original structure of poly (ε-caprolactone) nanofibers. Furthermore, human endothelial cells were cultured on the collagen-immobilized poly (ε-caprolactone) nanofiber membrane and expressed tight junction proteins with the increase in transendothelial electrical resistance, which demonstrated the maintenance of the endothelial cell homeostasis on the collagen-immobilized-poly (ε-caprolactone) nanofiber membrane. Thus, we expected that this process would be promising for maintaining cell homeostasis on the ultra-thin poly (ε-caprolactone) nanofiber scaffolds.

Purpose To develop a new method of manufacturing contact lens-shaped crosslinked amniotic membranes (AMs) using glutaraldehyde (GA) and dialdehyde starch (DAS) as crosslinking agents. Methods Amniotic membranes were placed on a curved plastic mold and crosslinked with either 4.5% DAS or 1% GA, after which their physical properties and biological safety were evaluated. Results The tensile strength of the GA- and DAS-crosslinked samples was much increased compared with that of normal AMs. Neither crosslinking process affected AM transparency. Although the GA-crosslinked AM showed better enzymatic resistance, its physiological structure was severely damaged after the crosslinking process. On the other hand, compared with the GA-crosslinked AM, the DAS-crosslinked AM showed higher growth factor concentrations and better biocompatibility, similar to normal AMs. In addition, the DAS-crosslinked AM was effective in the recovery of corneal epithelial wounds and was well maintained over 3 days without decentration or degradation on the ocular surface in human subjects. Conclusions Contact lens-shaped AMs were successfully prepared with crosslinking agents. Crosslinking with DAS did not affect the structural properties or biological activity of the AMs, and the improved mechanical properties helped the AM to maintain its curved shape. This crosslinking method allowed us to transplant AMs into patients' eyes without sutures. Translational relevance Sutureless fixation of contact lens-shaped AMs would be very convenient and safe for the treatment of corneal surface disease.

Corneal transplantation by full‐thickness penetrating keratoplasty with human donor tissue is a widely accepted treatment for damaged or diseased corneas. Although corneal transplantation has a high success rate, a shortage of high‐quality donor tissue is a considerable limitation. Therefore, bioengineered corneas could be an effective solution for this limitation, and a decellularized extracellular matrix comprises a promising scaffold for their fabrication. In this study, three‐dimensional bioprinted decellularized collagen sheets were implanted into the stromal layer of the cornea of five rabbits. We performed in vivo noninvasive monitoring of the rabbit corneas using swept‐source optical coherence tomography (OCT) after implanting the collagen sheets. Anterior segment OCT images and averaged amplitude‐scans were acquired biweekly to monitor corneal thickness after implantation for 1 month. The averaged cornea thickness in the control images was 430.3 ± 5.9 μm, while the averaged thickness after corneal implantation was 598.5 ± 11.8 μm and 564.5 ± 12.5 μm at 2 and 4 weeks, respectively. The corneal thickness reduction of 34 μm confirmed the biocompatibility through the image analysis of the depth‐intensity profile base. Moreover, hematoxylin and eosin staining supported the biocompatibility evaluation of the bioprinted decellularized collagen sheet implantation. Hence, the developed bioprinted decellularized collagen sheets could become an alternative solution to human corneal donor tissue, and the proposed image analysis procedure could be beneficial to confirm the success of the surgery., Three‐dimensional bioprinted decellularized collagen sheets were implanted into the stromal layer of the cornea of five rabbits. After implanting the collagen sheets, the rabbit corneas were monitored biweekly in vivo with a swept‐source optical coherence tomography system to assess the biocompatibility of the bioprinted implantation for 1 month through corneal thickness measurements. The small variation in the averaged corneal thickness along with evidence from hematoxylin and eosin‐stained histology images shows the potential use of the biocompatible collagen sheet.

This study is aim to compare the clinical effectiveness between the two most prominent dry eye disease (DED)-specific eye drops, 0.05% cyclosporine (CN) and 3% diquafosol (DQ). This is a multi-centered, randomized, masked, prospective clinical study. A total of 153 DED patients were randomly allocated to use CN twice per day or DQ six times daily. Cornea and conjunctival staining scores (NEI scale), tear break-up time (TBUT), Schirmer test scores, and ocular surface disease index (OSDI) score were measured at baseline, 4 and 12 weeks after treatment. At 12 weeks after treatment, NEI scaled scores were significantly reduced from the baseline by − 6.60 for CN and − 6.63 for DQ group (all P

Background This study is aim to compare the clinical effectiveness between the two most prominent dry eye disease (DED)-specific eye drops, 0.05% cyclosporine (CN) and 3% diquafosol (DQ). Methods This is a multi-centered, randomized, masked, prospective clinical study. A total of 153 DED patients were randomly allocated to use CN twice per day or DQ six times daily. Cornea and conjunctival staining scores (NEI scale), tear break-up time (TBUT), Schirmer test scores, and ocular surface disease index (OSDI) score were measured at baseline, 4 and 12 weeks after treatment. Results At 12 weeks after treatment, NEI scaled scores were significantly reduced from the baseline by − 6.60 for CN and − 6.63 for DQ group (all P

This study is aim to compare the clinical effectiveness between the two most prominent dry eye disease (DED)-specific eye drops, 0.05% cyclosporine (CN) and 3% diquafosol (DQ). This is a multi-centered, randomized, masked, prospective clinical study. A total of 153 DED patients were randomly allocated to use CN twice per day or DQ six times daily. Cornea and conjunctival staining scores (NEI scale), tear break-up time (TBUT), Schirmer test scores, and ocular surface disease index (OSDI) score were measured at baseline, 4 and 12 weeks after treatment. At 12 weeks after treatment, NEI scaled scores were significantly reduced from the baseline by − 6.60 for CN and − 6.63 for DQ group (all P

Corneal transplantation is a typical surgical procedure for severe corneal diseases. However, the waiting time for a donor cornea has gradually increased due to a decrease in supply caused by an aging population and increased cases of laser-based surgeries. Artificial corneas were developed to meet the increase in demand; however, these approaches have suffered from material deterioration resulted by the limited tissue integration. Here, we introduce a cornea-derived decellularized extracellular matrix (Co-dECM) as a bioink for corneal regeneration. The developed Co-dECM bioink had similar quantitative measurement results for collagen and GAGs compared with that of the native cornea and also had the proper transparency for vision. The differentiation potential of human turbinate-derived mesenchymal stem cells (hTMSCs) to a keratocyte lineage was only observed in the Co-dECM group. Moreover, the developed bioink did not have any cytotoxic effect on encapsulated cells for three-dimensional (3D) culture and has great biocompatibility evident by the xeno-implantation of the Co-dECM gel into mice and rabbits for two and one month, respectively. An in vivo safety similar to clinical-grade collagen was seen with the Co-dECM, which helped to maintain the keratocyte-specific characteristics in vivo, compared with collagen. Taken together, the Co-dECM bioink has the potential to be used in various types of corneal diseases based on its corneal-specific ability and design flexibility through 3D cell printing technology.

Age-related macular degeneration (AMD) is the main cause of irreversible blindness among the elderly and require early diagnosis to prevent vision loss, and careful treatment is essential. Optical coherence tomography (OCT), the most commonly used imaging method in the retinal area for the diagnosis of AMD, is usually interpreted by a clinician, and OCT can help diagnose disease on the basis of the relevant diagnostic criteria, but these judgments can be somewhat subjective. We propose an algorithm for the detection of AMD based on a weakly supervised convolutional neural network (CNN) model to support computer-aided diagnosis (CAD) system. Our main contributions are the following three things. (1) We propose a concise CNN model for OCT images, which outperforms the existing large CNN models using VGG16 and GoogLeNet architectures. (2) We propose an algorithm called Expressive Gradients (EG) that extends the existing Integrated Gradients (IG) algorithm so as to exploit not only the input-level attribution map, but also the high-level attribution maps. Due to enriched gradients, EG can highlight suspicious regions for diagnosis of AMD better than the guided-backpropagation method and IG. (3) Our method provides two visualization options: overlay and top-k bounding boxes, which would be useful for CAD. Through experimental evaluation using 10,100 clinical OCT images from AMD patients, we demonstrate that our EG algorithm outperforms the IG algorithm in terms of localization accuracy and also outperforms the existing object detection methods in terms of class accuracy.

BACKGROUND: Skin grafts are required in numerous clinical procedures, such as reconstruction after skin removal and correction of contracture or scarring after severe skin loss caused by burns, accidents, and trauma. The current standard for skin defect replacement procedures is the use of autologous skin grafts. However, donor-site tissue availability remains a major obstacle for the successful replacement of skin defects and often limits this option. The aim of this study is to effectively expand full thickness skin to clinically useful size using an automated skin reactor and evaluate auto grafting efficiency of the expanded skin using Yucatan female pigs. METHODS: We developed an automated bioreactor system with the functions of real-time monitoring and remote-control, optimization of grip, and induction of skin porosity for effective tissue expansion. We evaluated the morphological, ultra-structural, and mechanical properties of the expanded skin before and after expansion using histology, immunohistochemistry, and tensile testing. We further carried out in vivo grafting study using Yucatan pigs to investigate the feasibility of this method in clinical application. RESULTS: The results showed an average expansion rate of 180%. The histological findings indicated that external expansion stimulated cellular activity in the isolated skin and resulted in successful grafting to the transplanted site. Specifically, hyperplasia did not appear at the auto-grafted site, and grafted skin appeared similar to normal skin. Furthermore, mechanical stimuli resulted in an increase in COL1A2 expression in a suitable environment. CONCLUSIONS: These findings provided insight on the potential of this expansion system in promoting dermal extracellular matrix synthesis in vitro. Conclusively, this newly developed smart skin bioreactor enabled effective skin expansion ex vivo and successful grafting in vivo in a pig model.

To compare the conjunctival epithelial toxicities of three newer-generation fluoroquinolones without preservatives. In a prospective, randomized, double blind comparative study, 47 eyes of 47 patients with a primary pterygium were enrolled, and divided randomly into three groups (levofloxacin 0.5%, gatifloxacin 0.3%, and moxifloxacin 0.5%). After pterygium surgery with the same conjunctival autograft technique, each patient maintained a regimen with a randomly assigned fluoroquinolone eye drop. Patients were examined every other day after surgery until the epithelium had completely healed. Photos were taken and used to measure the area of residual epithelial defects. Conjunctival healing time and speed (initial defect area/healing time (mm2/d) compared in each group using Kruskal-Wallis tests. There were no significant differences in mean age, gender, and conjunctival defect size of the donor site between these groups. However, the mean of conjunctival healing time and speed were statistically different in each group. The mean of conjunctival epithelial healing time was 8.93±2.69d (levofloxacin group), 10.31±2.96d (gatifloxacin group), and 13.50±4.10d (moxifloxacin group), P=0.006. The mean conjuctival epithelial healing speed was 6.18±1.39 mm2/d (levofloxacin group), 5.52±1.68 mm2/d (gatifloxacin group), and 4.40±1.30 mm2/d (moxifloxacin group), P=0 .003. Without the influence of preservatives, levofloxacin and gatifloxacin might be less toxic to the regeneration of conjunctival epithelial cells and cause a faster conjunctival wound healing relative to moxifloxacin.

Purpose. To establish an optimized and standardized protocol for the development of optimal scaffold for bioengineering corneal substitutes, we used femtosecond laser to process human corneal tissue into stromal lenticules and studied to find the most efficient decellularization method among various reagents with different tonicities. Methods. The decellularization efficacy of several agents (0.1%, 0.25%, and 0.5% of Triton X-100, SDS, and trypsin-EDTA (TE), resp.) with different tonicities was evaluated. Of all protocols, the decellularization methods, which efficiently removed nuclear materials examined as detected by immunofluorescent staining, were quantitatively tested for sample DNA and glycosaminoglycan (GAG) contents, recellularization efficacy, and biocompatibilities. Results. 0.5% SDS in hypertonic and isotonic buffer, 0.25% TE in hypotonic buffer, and 0.5% TE in all tonicities completely decellularized the corneal lenticules. Of the protocols, decellularization with hypotonic 0.25 and 0.5% TE showed the lowest DNA contents, while the GAG content was the highest. Furthermore, the recellularization efficacy of the hypotonic TE method was better than that of the SDS-based method. Hypotonic TE-treated decellularized corneal lenticules (DCLs) were sufficiently transparent and biocompatible. Conclusion. We generated an ideal protocol for DCLs using a novel method. Furthermore, it is possible to create a scaffold using a bioengineered corneal substitute.

Background: Pilocarpine hydrochloride is commonly prescribed to patients with dry mouth and eye using a frequent dosing schedule. The aim of this study was to evaluate the sustained effects of this highly soluble drug carried by a gelatin hydrogel, which was administered by an implant mediated drug delivery system (IMDDS). Methods: The IMDDS was installed in a total of 24 rabbits. After complete healing, pilocarpine hydrochloride was administered as 30 mg as raw powder (Group 1; n = 8), 30 mg in gelatin hydrogel (Group 2; n = 8), and 60 mg in gelatin hydrogel (Group 3; n = 8). The effects were evaluated by tear volume measured using the Schirmer tear test for 2 weeks after administration. Results: All 3 groups showed an increase in tear volume from the initial measurement at 1 hour. Group 1 exhibited this increase for 24 hours, while Groups 2 and 3 sustained this increase for 5 days and 7.5 days, respectively. Conclusion: When provided in gelatin hydrogel, highly water-soluble pilocarpine hydrochloride administered through IMDDS resulted in sustained effects with increased tear volume in normal rabbits.

Wearable contact lenses which can monitor physiological parameters have attracted substantial interests due to the capability of direct detection of biomarkers contained in body fluids. However, previously reported contact lens sensors can only monitor a single analyte at a time. Furthermore, such ocular contact lenses generally obstruct the field of vision of the subject. Here, we developed a multifunctional contact lens sensor that alleviates some of these limitations since it was developed on an actual ocular contact lens. It was also designed to monitor glucose within tears, as well as intraocular pressure using the resistance and capacitance of the electronic device. Furthermore, in-vivo and in-vitro tests using a live rabbit and bovine eyeball demonstrated its reliable operation. Our developed contact lens sensor can measure the glucose level in tear fluid and intraocular pressure simultaneously but yet independently based on different electrical responses., Wearable electronics have been utilized for a number of applications including for ocular use, although their use has been limited to a single function. Here, the authors developed a multifunctional contact lens with wireless electronics for measurement of glucose and intraocular pressure.

Purpose. To study the correlation between ocular parameters and subjective pain that patients perceived during phacoemulsification.Methods. Medical records of 142 patients who underwent standard phacoemulsification under topical anesthesia between March and August 2016 were retrospectively reviewed. The pain during phacoemulsification and 1 h after surgery was assessed and compared using a visual analog scale. In addition, demographic data, preoperative biometric parameters, and intraoperative surgical parameters were recorded.Results. Mean age of patients was 67.49 ± 12.50 years. The mean pain score was 2.26 ± 0.85 during phacoemulsification and 0.40 ± 0.69 postoperatively. Intraoperative pain was significantly associated with higher preoperative intraocular pressure (β = 0.220,P=0.016), greater anterior chamber depth (β = 0.210,P=0.028), and greater axial length (β = 0.181,P=0.043).Conclusions. To reduce the subjective pain when patients have high preoperative intraocular pressure, large anterior chamber depth, or great axial length, supplementary procedures may be required.

Background: Osseogate is a novel drug delivery route through bone marrow involving a modified implant used as the drug delivery system. The purpose of this study was to evaluate the effects of individual drug physicochemical characteristics on the pharmacokinetic behavior when using the Osseogate as administration route. Methods: Implant-mediated drug delivery systems (IMDDS) were installed in a total of 18 rabbits. After complete healing, water-soluble metformin hydrochloride was administered to one group (n = 9) while poorly soluble dexamethasone was administered to the other group (n = 9). The release patterns of each group were monitored for two weeks by measuring the plasma concentration of each drug. Results: Both groups showed relative sustained release. However, metformin hydrochloride showed more rapid diffusion and early termination of drug release compared with dexamethasone. Conclusions: The physicochemical properties of drugs significantly affected the release pattern through Osseogate. Further research is required to achieve controlled delivery using this route.

In this paper we evaluate the performance of voluntary environmental agreements in South Korea, called as the 30/50 program. We constructed establishment- and chemical substance-level panel data from 2004 to 2010 by using the Pollutant Release and Transfer Registers (PRTR) Information System. Although firms voluntarily participate in the program and the agreement is not binding, we find that the chemical materials released by the participating firms is substantially reduced by 1.2 to 2.7 tons. Although the abatement effect is more salient for those listed chemical substances in the agreements, the reductions in other substances are also significant. This implies that participating firms adopted new technologies that could reduce environmental hazards.

Amoebic keratitis (AK) caused by Acanthamoeba is one of the most serious corneal infections. AK is frequently misdiagnosed initially as viral, bacterial, or fungal keratitis, thus ensuring treatment delays. Accordingly, the early detection of Acanthamoeba would contribute significantly to disease management and selection of an appropriate anti-amoebic therapy. Recently, the loop-mediated isothermal amplification (LAMP) method has been applied to the clinical diagnosis of a range of infectious diseases. Here, we describe a rapid and efficient LAMP-based method targeting Acanthamoeba 18S rDNA gene for the detection of Acanthamoeba using clinical ocular specimens in the diagnosis of AK. Acanthamoeba LAMP assays detected 11 different strains including all AK-associated species. The copy number detection limit for a positive signal was 10 DNA copies of 18S rDNA per reaction. No cross-reactivity with the DNA of fungi or other protozoa was observed. The sensitivity of LAMP assay was higher than those of Nelson primer PCR and JDP primer PCR. In the present study, LAMP assay based on directly heat-treated samples was found to be as efficient at detecting Acanthamoeba as DNA extracted using a commercial kit, whereas PCR was only effective when commercial kit-extracted DNA was used. This study showed that the devised Acanthamoeba LAMP assay could be used to diagnose AK in a simple, sensitive, and specific manner.

Bialveolar protrusion and dental crowding seems to have common features in terms of aetiology and treatment method, although they result in different facial profiles and tooth alignment. The aim of this longitudinal study is to determine when children begin to show bialveolar protrusive traits in order to get more clue about the aetiology of bialveolar protrusion. Longitudinal lateral cephalometric data of children followed from 6 to 14 years of age were used. A total of 155 children (81 girls and 74 boys) with showing Class molar relationships at the age of 14 were assigned to either the protrusive group (PG) or the non-protrusive group (NPG), based on 5 cephalometric measurements. The cephalometric measurements of these 2 groups were compared at each age separately in both sexes by independent t-tests. Throughout the entire observation period, there were differences between PG and NPG in both sexes in measurements which were used for classification at 14 years of age. There were differences between sexes in both PG and NPG in several measurements of at several different ages. Individuals with bialveolar protrusive traits at the age of 14 exhibited the signs early in life, at least from the early mixed dentition.

Horse health has become a major concern with the expansion of horse-related industries and sports; the importance of healthy muscles for horse performance and daily activities is undisputed. Here we generated equine-induced pluripotent stem cells (E-iPSCs) by reprogramming equine adipose-derived stem cells (E-ADSCs) into iPSCs using a polycistronic lentiviral vector encoding four transcription factors (i.e., Oct4, Sox2, Klf4, and c-Myc) and then examined their pluripotent characteristics. Subsequently, established E-iPSCs were transplanted into muscle-injured Rag/ mdx mice. The histopathology results showed that E-iPSC-transplanted mice exhibited enhanced muscle regeneration compared to controls. In addition, E-iPSC-derived myofibers were observed in the injured muscles. In conclusion, we show that E-iPSCs could be successfully generated from equine ADSCs and transplanted into injured muscles and that E-iPSCs have the capacity to induce regeneration of injured muscles.

Inhibition of osteoclast differentiation and bone resorption is a therapeutic strategy for the management of postmenopausal bone loss. This study investigated the effects ofRhus javanica(R. javanica) extracts on bone marrow cultures to develop agents from natural sources that may prevent osteoclastogenesis. Extracts ofR. javanica(eGr) cocoons spun byRhus javanica(Bell.) Baker inhibited the osteoclast differentiation and bone resorption. The effects of aqueous extract (aeGr) or 100% ethanolic extract (eeGr) on ovariectomy- (OVX-) induced bone loss were investigated by various biochemical assays. Furthermore, microcomputed tomography (µCT) was performed to study bone remodeling. Oral administration of eGr (30 mg or 100 mg/kg/day for 6 weeks) augmented the inhibition of femoral bone mineral density (BMD), bone mineral content (BMC), and other factors involved in bone remodeling when compared to OVX controls. Additionally, eGr slightly decreased bone turnover markers that were increased by OVX. Therefore, it may be suggested that the protective effects of eGr could have originated from the suppression of OVX-induced increase in bone turnover. Collectively, the findings of this study indicate that eGr has potential to activate bone remodeling by inhibiting osteoclast differentiation and bone loss.

Intraoperative surgical microscope is an essential surgical equipment. However, it has a restriction to classify the retina layers because of the contrast differences. To solve this problem, operators use surgical instrument such as an intraocular mirror. In this case, it has to amputate the patient`s eye. In this study, we developed a probe the intraoperative surgical optical coherence tomography. We expect that the developed OCT probe can overcome the limit of OCT and be applied as a real-time surgical tool. In this paper, we demonstrate applicability of the probe through rabbit`s experimentation.

PURPOSE To describe current cataract surgery practice patterns and trends among Korean ophthalmologists. METHODS A survey was conducted among members of the Korean Society of Cataract and Refractive Surgery in October 2020. Of the 998 questionnaires, 262 (26.3%) were received for analysis. Data were analyzed using descriptive statistics and compared with those of previous surveys. RESULTS The largest percentage of respondents (39%) had 11 years of practical experience. The average, median, and mode monthly volumes of cataract surgeries performed by the Korean Society of Cataract and Refractive Surgery members were 31, 20, and 10 cases, respectively. Topical anesthesia was administered by 85% of the respondents. For intraocular lens (IOL) calculations, 96% of the respondents used optical biometry. The proportion of surgeons providing femtosecond laser-assisted cataract surgery increased significantly from 5% in 2018 to 29% in 2020. This increase was accompanied by an increase in the multifocal IOLs. Those who implant multifocal IOL for >10% of their cases increased from 16% (2018) to 29% (2020). Topical nonsteroidal anti-inflammatory drugs were prescribed postoperatively by 76% of the respondents. Most respondents (70%) prescribed these anti-inflammatory drugs for 4 weeks. CONCLUSIONS This survey provided a comprehensive update on current cataract surgery practice in the Republic of Korea. The results highlighted the increasing use of premium IOLs, femtosecond laser-assisted cataract surgery, optical biometry, and topical anesthesia to better meet the patients' needs.

Purpose To evaluate the efficacy and safety of cyclosporine nanoemulsion 0.05% compared to cyclosporine emulsion 0.05% and diquafosol sodium 3%. Methods This was a multicenter, randomized, evaluator-masked, active control, parallel, phase IV study. A total of 227 patients were randomly allocated to instill cyclosporine nanoemulsion 0.05% (CN) twice daily, cyclosporine emulsion 0.05% (CE) twice daily, or diquafosol sodium 3% (DQ) six times daily. Non-inferiority of CN was analyzed by primary endpoint (cornea and conjunctival staining scores at week 12). The secondary endpoints were scores of corneal staining, conjunctival staining, tear break-up time, Schirmer test, and Ocular Surface Disease Index at weeks 4 and 12. Results Primary endpoints showed statistically significant improvements in all groups. Primary endpoints were −6.60 for the CN group, −5.28 for the CE group, and −6.63 for the DQ group (National Eye Institute scale from 0 to 33), verifying the non-inferiority of CN compared to CE (95% confidence interval, −0.15 to 2.80, Δ>−2.88). In intergroup comparison between CN and CE groups, the CN group had significantly more decreased conjunctival staining score at week 12. Intergroup comparison between CN and DQ groups showed consistent statistically significant improvements in TBUT and Schirmer test in the CN group. In the DQ group, TBUT showed late statistically significant improvement at week 12 and Schirmer test showed relatively short-term statistically significant improvement at week 4. Conclusions Cyclosporine nanoemulsion 0.05% was equivalently efficient compared to cyclosporine emulsion 0.05% and diquafosol sodium 3%. In addition, CN showed significant improvements in several parameters for treatment of dry eyes.

Purpose: Too develop a flexible drill device that can be inserted into the shoulder joint so that arthroscopic transosseous suture repair for Bankart lesion is possible. Materials and Methods: We created a device composed of a flexible drill unit and a guide pipe unit. The flexible drill unit was made of flexible multifilament wires (1.2 mm in diameter) that was twisted into one cord so that it can flex in any direction and a drill bit (1.2 mm in diameter) that is attached onto one end of the flexible wire. The guide pipe unit was a 150 mm long metal pipe (2.0 mm in inner diameter and 3.0 mm in outer diameter), with one end bent to 30 degrees. The flexible drill set was inserted into the shoulder joint through the posterior portal of the joint. The guide pipe component was placed onto the medial wall of the glenoid so that the pipe was placed 5 mm posterior to the margin of the anterior glenoid rim. The flexible drill was driven through the glenoid by the power drill so that holes were made in the glenoid. A non- absorbable suture was passed through the hole. Tying of a sliding knot tying was accomplished over the capsule and labrum after making a stitch through the capsule and labrum with a suture hook loaded with suture passer. The same procedures were done at the 2 and 4 O`Clock positions of the glenoid. Results: Five cases with Bankart lesion received arthroscopic transosseous repair with our flexible drill device. There were no intraoperative problems. Neither redislocation nor subluxation was reported at final follow-up. Conclusion: Arthroscopic transosseous suture repair without suture anchors and easy tying of a sliding knot are possible with a flexible drill set.

Purpose. To evaluate surgical efficacy of in situ refixation technique for dislocated posterior chamber intraocular lens (PCIOL).Methods. This was a single-center retrospective case series. 34 patients (34 eyes) who underwent sclera fixation for dislocated IOLs combined with vitrectomy were studied. Of 34 eyes, 17 eyes underwent IOL exchange and the other 17 eyes underwent in situ refixation.Results. Mean follow-up period was 6 months. Mean logMAR best corrected visual acuity (BCVA) was not significantly different between the groups 6 months after surgery (0.10±0.03in the IOL exchange group and0.10±0.05in the refixation group;p=0.065). Surgically induced astigmatism (SIA) was significantly lower in the refixation group (0.79±0.41) than in the IOL exchange group (1.29±0.46) (p=0.004) at 3 months, which persisted to 6 months (1.13±0.18in the IOL exchange group and0.74±0.11in the refixation group;p=0.006). Postoperative complications occurred in 3 eyes in the IOL exchange group (17.6%) and 2 eyes in the refixation group (11.8%). However, all of the patients were well managed without additional surgery.Conclusion. The in situ refixation technique should be preferentially considered if surgery is indicated since it seemed to produce a sustained less SIA compared to IOL exchange.

62 year old female underwent closed reduction of subtrochanter fracture by the minor trauma. She was checked quantitative computerized tomography (QCT) for the bone mineral density. It showed highly elevated density above the normal range. She could easily take the bisphosphonate for 3 and half years without regular evaluation of the bone mineral density. The fracture was bilateral and atypical fracture pattern in the subtrochanter area. These kinds of fracture were occurred in the osteoporotic bones in the previous literature, so we hardly conclude the culprit of bisphosphonate related atypical fractures. The prevalence of these kinds of insufficiency fracture among the normal population and bisphosphonate medicated patients has been still debated but we can strongly suggest that our fractures were related to the bisphosphonate medication because she was a nonosteoporotic bone who took a bisphosphonate medication.

Purpose To evaluate the effect of platelet-rich plasma (PRP) eye drops in the treatment of recurrent corneal erosions (RCE). Methods A total of 47 eyes were included in this retrospective study. Clinical records of 20 consecutive patients with RCE who had been treated with conventional lubricant eye drops (conventional treatment group) from June 2006 to December 2008 and 27 consecutive patients treated with autologous PRP eye drops in addition to lubricant eye drops (PRP eye drops treated group) from January 2009 to September 2014 were reviewed. Major and minor recurrences were recorded and compared between two groups. Results This study included 31 men and 16 women. The mean age was 44.5 ± 14.5 years (range, 19 to 86 years), and the mean follow-up duration was 14.9 ± 14.4 months (range, 6 to 64 months). Of the 27 cases in the PRP eye drops treated group, there were seven major recurrences in six eyes (22.2%) and ten minor recurrences in seven eyes (25.9%). In contrast, 16 eyes (80.0%) from the 20 patients in the conventional lubricant eye drops treated group had major recurrences, and all patients in this group reported minor recurrences. The mean frequency of recurrence was 0.06 ± 0.08 per month in the PRP eye drops treated group and 0.39 ± 0.24 per month in the conventional treatment group (p = 0.003). No side effects were noted in any of the patients over the follow-up period. Conclusions The use of PRP eye drops for the treatment of RCE was shown to be effective in reducing the recurrence rate without any significant complications.