Diagnosis of Glaucoma Based on Few-Shot Learning with Wide-Field Optical Coherence Tomography Angiography.

This study evaluated the utility of incorporating deep learning into the relatively novel imaging technique of wide-field optical coherence tomography angiography (WF-OCTA) for glaucoma diagnosis. To overcome the challenge of limited data associated with this emerging imaging, the application of few-shot learning (FSL) was explored, and the advantages observed during its implementation were examined. A total of 195 eyes, comprising 82 normal controls and 113 patients with glaucoma, were examined in this study. The system was trained using FSL instead of traditional supervised learning. Model training can be presented in two distinct ways. Glaucoma feature detection was performed using ResNet18 as a feature extractor. To implement FSL, the ProtoNet algorithm was utilized to perform task-independent classification. Using this trained model, the performance of WF-OCTA through the FSL technique was evaluated. We trained the WF-OCTA validation method with 10 normal and 10 glaucoma images and subsequently examined the glaucoma detection effectiveness. FSL using the WF-OCTA image achieved an area under the receiver operating characteristic curve (AUC) of 0.93 (95% confidence interval (CI): 0.912-0.954) and an accuracy of 81%. In contrast, supervised learning using WF-OCTA images produced worse results than FSL, with an AUC of 0.80 (95% CI: 0.778-0.823) and an accuracy of 50% (p-values < 0.05). Furthermore, the FSL method using WF-OCTA images demonstrated improvement over the conventional OCT parameter-based results (all p-values < 0.05). This study demonstrated the effectiveness of applying deep learning to WF-OCTA for glaucoma diagnosis, highlighting the potential of WF-OCTA images in glaucoma diagnostics. Additionally, it showed that FSL could overcome the limitations associated with a small dataset and is expected to be applicable in various clinical settings.

Ultra-Thin GaAs Single-Junction Solar Cells for Self-Powered Skin-Compatible Electrocardiogram Sensors.

GaAs thin-film solar cells have high efficiency, reliability, and operational stability, making them a promising solution for self-powered skin-conformal biosensors. However, inherent device thickness limits suitability for such applications, making them uncomfortable and unreliable in flexural environments. Therefore, reducing the flexural rigidity becomes crucial for integration with skin-compatible electronic devices. Herein, this study demonstrated a novel one-step surface modification bonding methodology, allowing a streamlined transfer process of ultra-thin (2.3 µm thick) GaAs solar cells on flexible polymer substrates. This reproducible technique enables strong bonding between dissimilar materials (GaAs-polydimethylsiloxane, PDMS) without high external pressures and temperatures. The fabricated solar cell showed exceptional performance with an open-circuit voltage of 1.018 V, short-circuit current density of 20.641 mA cm-2, fill factor of 79.83%, and power conversion efficiency of 16.77%. To prove the concept, the solar cell is integrated with a skin-compatible organic electrochemical transistor (OECT). Competitive electrical outputs of GaAs solar cells enabled high current levels of OECT under subtle light intensities lower than 50 mW cm-2, which demonstrates a self-powered electrocardiogram sensor with low noise (signal-to-noise ratio of 32.68 dB). Overall, this study presents a promising solution for the development of free-form and comfortable device structures that can continuously power wearable devices and biosensors.

Expression of microRNAs related to apoptosis in the aqueous humor and lens capsule of patients with glaucoma.

Background: The aim of this study is to investigate the expression profiles of microRNAs (miRNAs) related to apoptosis in the aqueous humor (AH) and lens capsule (LC) of patients with glaucoma. Methods: AH and LC samples were collected from patients with open-angle glaucoma and control participants who were scheduled for cataract surgery. A miRNA PCR array comprising 84 miRNAs was used to analyze the AH (glaucoma, n = 3; control, n = 3) and LC samples (glaucoma, n = 3; control, n = 4). Additionally, the AH and LC samples (glaucoma, n = 3; control, n = 4) were subjected to quantitative real-time PCR to validate the differentially expressed miRNAs determined using the PCR array. Bioinformatics analysis was performed to identify the interactions between miRNAs and diseases. Additionally, the differential expression of these miRNAs and the target gene was validated through in vitro experiments using a retinal ganglion cell (RGC) model. Results: Expression levels of 19 and 3 miRNAs were significantly upregulated in the AH and LC samples of the glaucoma group, respectively (p < 0.05). Of these, the expression levels of hsa-miR-193a-5p and hsa-miR-222-3p showed significant differences in both AH and LC samples. Bioinformatics analysis showed experimentally validated 8 miRNA:gene pairs. Among them, PTEN was selected to analyze the expression level in AH and LC from separate cohort (glaucoma, n = 5; control, n = 4). The result showed downregulation of PTEN concurrent with upregulation of the two miRNAs in LC samples of glaucoma group. In vitro experiments validated that the expression levels of hsa-miR-193a-5p and hsa-miR-222-3p were significantly upregulated, and that of PTEN was significantly downregulated in the H2O2-treated RGC, while the level of PTEN was recovered through co-treatment with miR-193a inhibitor or miR-222 inhibitor. Conclusion: This is the first study to investigate the differential expression of apoptosis-related miRNAs in the AH and LC of patients with glaucoma. Hsa-miR-193a-5p and hsa-miR-222-3p, which were upregulated in both AH and LC, may be considered potential biomarkers for glaucoma.

Wide-range and selective detection of SARS-CoV-2 DNA via surface modification of electrolyte-gated IGZO thin-film transistors.

The 2019 coronavirus pandemic resulted in a massive global healthcare crisis, highlighting the necessity to develop effective and reproducible platforms capable of rapidly and accurately detecting SARS-CoV-2. In this study, we developed an electrolyte-gated indium-gallium-zinc-oxide (IGZO) thin-film transistor with sequential surface modification to realize the low limit of detection (LoD <50 fM) and a wide detection range from 50 fM to 5 µM with good linearity (R2 = 0.9965), and recyclability. The surface chemical modification was achieved to anchor the single strand of SARS-CoV-2 DNA via selective hybridization. Moreover, the minute electrical signal change following the chemical modification was investigated by in-depth physicochemical analytical techniques. Finally, we demonstrate fully recyclable biosensors based on oxygen plasma treatment. Owing to its cost-effective fabrication, rapid detection at the single-molecule level, and low detection limit, the proposed biosensor can be used as a point-of-care platform to perform timely and effective SARS-CoV-2 detection.

Diagnostic performance of wide-field optical coherence tomography angiography for high myopic glaucoma.

Diagnosing and monitoring glaucoma in high myopic (HM) eyes are becoming very important; however, it is challenging to diagnose this condition. This study aimed to evaluate the diagnostic ability of wide-field optical coherence tomography angiography (WF-OCTA) maps for the detection of glaucomatous damage in eyes with HM and to compare the diagnostic ability of WF-OCTA maps with that of conventional imaging approaches, including swept-source optical coherence tomography (SS-OCT) wide-field maps. In this retrospective observational study, a total 62 HM-healthy eyes and 140 HM eyes with open-angle glaucoma were included. Patients underwent a comprehensive ocular examination, including SS-OCT wide-field and 12 × 12 WF-OCTA scans. The WF-OCTA map represents the peripapillary and macular superficial vascular density maps. Glaucoma specialists determined the presence of glaucomatous damage in HM eyes by reading the WF-OCTA map and comparing its sensitivity and specificity with those of conventional SS-OCT images. The sensitivity and specificity of 12 × 12 WF-OCTA scans for HM-glaucoma diagnosis were 87.28% and 86.94%, respectively, while, the sensitivity and specificity of SS-OCT wide-field maps for HM-glaucoma diagnosis were 87.49% and 80.51%, respectively. The specificity of the WF-OCTA map was significantly higher than that of the SS-OCT wide-field map (p < 0.05). The sensitivity of the WF-OCTA map was comparable with that of the SS-OCT wide-field map (p = 0.078). The WF-OCTA map showed good diagnostic ability for discriminating HM-glaucomatous eyes from HM-healthy eyes. As a complementary method to an alternative imaging modality, WF-OCTA mapping can be a useful tool for the detection of HM glaucoma.

Synthesis of Superabsorbent Hydrogels with Predefined Geometries and Controlled Swelling Properties for Versatile 3D Cell Culture Scaffolds.

This research presents a simple but general method to prepare water-soluble-polymer-based superabsorbent hydrogels with predefined microscale geometries and controlled swelling properties. Unlike conventional hydrogel preparation methods based on bulk solution-phase cross-linking, poly(vinyl alcohol) is homogeneously mixed with polymer-based cross-linkers in the solution phase and thermally cross-linked in the solid phase after drying; the degree of cross-linking is modulated by controlling the cross-linker concentration, pH, and/or thermal annealing conditions. After the shape definition process, cross-linked films or electrospun nanofibers are treated with sulfuric acid to weaken hydrogen bonds and introduce sulfate functionality in polymer crystallites. The resultant superabsorbent hydrogels exhibit an isotropic expansion of the predefined geometry and tunable swelling properties. Particularly, hydrogel microfibers exhibit excellent optical transparency, good biocompatibility, large porosity, and controlled cell adhesion, leading to versatile 3D cell culture scaffolds that not only support immortalized cell lines and primary neurons but also enable stiffness-modulated cell adhesion studies.

Chiroptical Switching of Electrochromic Polymer Thin Films.

The interaction between light and chiroptical polymers plays a crucial role in chiroptics, spintronics, and chiral-spin selectivity. Despite considerable successes in creating dissymmetric polymer films, the elucidation of chiroptical activities under electrochemical switching remains unexplored. Here homogeneous chiral electrochromics is reported using chiral assembly of conjugated polymers through a transient solidification process with molecular chiral templates. In their neutral state, the chiral electrochromic polymers directly produce a remarkably dissymmetric polarization-dependent transmittance. The circular dichroism (CD) and dissymmetric transmission can be tuned by adjusting the doping level of the electrochemically active polymer films. Under high levels of oxidation, the chiroptical activities are reversed with strong bleaching in the visible, leading to formation of monosignate CD spectra over the infrared region. The matching between circular polarization handedness and chirality of chiroptical polymers makes a distinct impact on optical contrast and color switching dynamics due to the flipped chiroptical activities through polymer redox reactions. The differential circularly polarized transmission in the chiral see-through display can make a well-resolved color change in human eyes, demonstrating proof-of-concept devices for 3D imaging and information encryption. This work serves as a foundation to develop advanced on-chip fabrication of circular polarization-multiplexed display in flexible and highly integrated platforms.

Fully Automated Segmentation of Human Eyeball Using Three-Dimensional U-Net in T2 Magnetic Resonance Imaging.

Purpose: To develop and validate a fully automated deep-learning-based tool for segmentation of the human eyeball using a three-dimensional (3D) U-Net, compare its performance to semiautomatic segmentation ground truth and a two-dimensional (2D) U-Net, and analyze age and sex differences in eyeball volume, as well as gaze-dependent volume consistency in normal subjects. Methods: We retrospectively collected 474 magnetic resonance imaging (MRI) scans, including different gazing scans, from 119 patients. A 10-fold cross-validation was applied to separate the dataset into training, test, and validation sets for both the 3D U-Net and 2D U-Net. Performance accuracy was measured using four quantitative metrics compared to the ground truth, and Bland-Altman plot analysis was conducted. Age and sex differences in eyeball volume and variability in eyeball volume differences across gazing directions were analyzed. Results: The 3D U-Net outperformed the 2D U-Net with mean accuracy scores >0.95, showing acceptable agreement in the Bland-Altman plot analysis despite a tendency for slight overestimation (mean difference = -0.172 cm³). Significant sex differences and age effects on eyeball volume were observed for both methods (P < 0.05). No significant volume differences were found between the segmentation methods or within each method for the different gazing directions. Significant differences in performance accuracy were identified among the five gazing directions, with the upward direction showing a notably lower performance. Conclusions: Our study demonstrated the effectiveness of 3D U-Net human eyeball volume segmentation using T2-weighted MRI. The robustness and reliability of 3D U-Net across diverse populations and gaze directions support enhanced ophthalmic diagnosis and treatment strategies. Translational Relevance: Our findings demonstrate the feasibility of using the proposed 3D U-Net model for the automatic segmentation of the human eyeball, with potential applications in various ophthalmic research fields that require the analysis of 3D geometric eye globe shapes or eye movement detection.

Structural Engineering Three-Dimensional Nano-Heterojunction Networks for High-Performance Photochemical Sensing.

Nanoscale heterojunction networks are increasingly regarded as promising functional materials for a variety of optoelectronic and photocatalytic devices. Despite their superior charge-carrier separation efficiency, a major challenge remains in the optimization of their surface properties, with surface defects playing a major role in charge trapping and recombination. Here, we report the effective engineering of the photocatalytic properties of nanoscale heterojunction networks via deep ultraviolet photoactivation throughout their cross-section. For the first time, in-depth XPS analysis of very thick (∼10 µm) NixOy-ZnO films reveals localized p-n nanoheterojunctions with tunable oxygen vacancies (Vo) originating from both NixOy and ZnO nanocrystals. Optimizing the amount of oxygen vacancies leads to a 30-fold increase in the photochemoresistive response of these networks, enabling the detection of representative analyte concentrations down to 2 and 20 ppb at an optimal temperature of 150 °C and room temperature, respectively. Density functional theory calculations reveal that this performance enhancement is presumably due to an 80% increase in the analyte adsorption energy. This flexible nanofabrication approach in conjunction with straightforward vacancy control via photoactivation provides an effective strategy for engineering the photocatalytic activity of porous metal oxide semiconductor networks with applications in chemical sensors, photodetectors, and photoelectrochemical cells.

Trends in the Prevalence of Blindness and Correlation With Health Status in Korean Adults: A 10-Year Nationwide Population-Based Study.

BACKGROUND: Contemporary data on vision impairment form an important basis for public health policies. However, most data on the clinical epidemiology of blindness are limited by small sample sizes and focused not on systemic conditions but ophthalmic diseases only. In this study, we examined the ten-year trends of blindness prevalence and its correlation with systemic health status in Korean adults. METHODS: This study investigated 10,000,000 participants randomly extracted from the entire Korean population (aged ≥ 20 years) who underwent a National Health Insurance Service health checkup between 2009 and 2018. Participants with blindness, defined as visual acuity in the better-seeing eye of ≤ 20/200, were identified. The prevalence of blindness was assessed, and the systemic health status was compared between participants with blindness and without blindness. RESULTS: The mean prevalence of blindness was 0.473% (47,115 blindness cases) and tended to decrease over ten years (0.586% in 2009 and 0.348% in 2018; P < 0.001). The following factors were significantly associated with blindness: female sex, underweight (body mass index < 18.5), high serum creatinine (> 1.5 mg/dL), and bilateral hearing loss. In addition, except for those aged 30-39 and 40-49 years, high fasting glucose (≥ 126 mg/dL) and low hemoglobin (male: < 12 g/dL, female: < 10 g/dL) were significantly correlated with prevalent blindness. CONCLUSION: Our ten-year Korean nationwide population-based study suggested a gradual decrease in the prevalence of blindness and its association with specific systemic health status. These conditions might be the cause or consequence of blindness and can be used as a reference for the prevention and/or rehabilitation of blindness to establish public health policies.

Aqueous electrolyte-gated solution-processed metal oxide transistors for direct cellular interfaces.

Biocompatible field-effect-transistor-based biosensors have drawn attention for the development of next-generation human-friendly electronics. High-performance electronic devices must achieve low-voltage operation, long-term operational stability, and biocompatibility. Herein, we propose an electrolyte-gated thin-film transistor made of large-area solution-processed indium-gallium-zinc oxide (IGZO) semiconductors capable of directly interacting with live cells at physiological conditions. The fabricated transistors exhibit good electrical performance operating under sub-0.5 V conditions with high on-/off-current ratios (>107) and transconductance (>1.0 mS) over an extended operational lifetime. Furthermore, we verified the biocompatibility of the IGZO surface to various types of mammalian cells in terms of cell viability, proliferation, morphology, and drug responsiveness. Finally, the prolonged stable operation of electrolyte-gated transistor devices directly integrated with live cells provides the proof-of-concept for solution-processed metal oxide material-based direct cellular interfaces.

Instant formation of horizontally ordered nanofibrous hydrogel films and direct investigation of peculiar neuronal cell behaviors atop.

BACKGROUND: Hydrogels have been widely used in many research fields owing to optical transparency, good biocompatibility, tunable mechanical properties, etc. Unlike typical hydrogels in the form of an unstructured bulk material, we developed aqueous dispersions of fiber-shaped hydrogel structures with high stability under ambient conditions and their application to various types of transparent soft cell culture interfaces with anisotropic nanoscale topography. METHOD: Nanofibers based on the polyvinyl alcohol and polyacrylic acid mixture were prepared by electrospinning and hydrogelified to nano-fibrous hydrogels (nFHs) after thermal crosslinking and sulfuric acid treatment. By modifying various material surfaces with positively-charged polymers, negatively-charged superabsorbent nFHs could be selectively patterned by employing micro-contact printing or horizontally aligned by applying shear force with a wired bar coater. RESULTS: The angular distribution of bar-coated nFHs was dramatically reduced to ± 20° along the applied shear direction unlike the drop-coated nFHs which exhibit random orientations. Next, various types of cells were cultured on top of transparent soft nFHs which showed good viability and attachment while their behaviors could be easily monitored by both upright and inverted optical microscopy. Particularly, neuronal lineage cells such as PC 12 cells and embryonic hippocampal neurons showed highly stretched morphology along the overall fiber orientation with aspect ratios ranging from 1 to 14. Furthermore, the resultant neurite outgrowth and migration behaviors could be effectively controlled by the horizontal orientation and the three-dimensional arrangement of underlying nFHs, respectively. CONCLUSION: We expect that surface modifications with transparent soft nFHs will be beneficial for various biological/biomedical studies such as fundamental cellular studies, neuronal/stem cell and/or organoid cultures, implantable probe/device coatings, etc.

Wide-field optical coherence tomography deviation map for early glaucoma detection.

BACKGROUND/AIMS: This study aimed to establish a wide-field optical coherence tomography (OCT) deviation map obtained from swept-source OCT (SS-OCT) scans. Moreover, it also aimed to compare the diagnostic ability of this wide-field deviation map with that of the peripapillary and macular deviation maps currently being used for the detection of early glaucoma (EG). METHODS: Four hundred eyes, including 200 healthy eyes and 200 eyes with EG were enrolled in this retrospective observational study. Patients underwent a comprehensive ocular examination, including wide-field SS-OCT (DRI-OCT Triton; Topcon, Tokyo, Japan). The individual wide-field scan was converted into a uniform template using the fovea and optic disc centres as fixed landmarks. Subsequently, the wide-field deviation map was obtained via the comparison between individual wide-field data and a normative wide-field database that had been created by combining images of healthy eyes into a uniform template in a previous study. The ability of the new wide-field deviation map to distinguish between EG and healthy eyes was assessed by comparing it with conventional deviation maps based on the area under the receiver operating characteristic curve (AUC). RESULTS: The wide-field deviation map obtained using the normative wide-field database showed the highest diagnostic ability for the diagnosis of EG (AUC=0.980 and 961 for colour-coded pixels presenting <5% and <1%, respectively) among various deviation maps. Its AUC was significantly superior to that of most conventional deviation maps (p<0.05). The wide-field deviation map demonstrated early structural glaucomatous damage well over a wider area. CONCLUSION: The wide-field SS-OCT deviation map exhibited good performance for distinguishing between eyes with EG and healthy eyes. The visualisation of the wider damaged area on the wide-field deviation map could be useful for the diagnosis of EG in clinical settings.

Recent Advances in Biosensor Technologies for Point-of-Care Urinalysis.

Human urine samples are non-invasive, readily available, and contain several components that can provide useful indicators of the health status of patients. Hence, urine is a desirable and important template to aid in the diagnosis of common clinical conditions. Conventional methods such as dipstick tests, urine culture, and urine microscopy are commonly used for urinalysis. Among them, the dipstick test is undoubtedly the most popular owing to its ease of use, low cost, and quick response. Despite these advantages, the dipstick test has limitations in terms of sensitivity, selectivity, reusability, and quantitative evaluation of diseases. Various biosensor technologies give it the potential for being developed into point-of-care (POC) applications by overcoming these limitations of the dipstick test. Here, we present a review of the biosensor technologies available to identify urine-based biomarkers that are typically detected by the dipstick test and discuss the present limitations and challenges that future development for their translation into POC applications for urinalysis.

Immediate and Quantitative Changes in Tear Film Parameters and Meibomian Gland Structures after Warm Compression and Meibomian Gland Squeezing in Meibomian Gland Dysfunction Patients and Normal Subjects.

Meibomian gland dysfunction (MGD), a chronic abnormality of meibomian glands, causes various dry eye symptoms. Principal treatments for MGD are warm compression and mechanical squeezing of the eyelids. In this study, the immediate impact of this treatment on tear film lipid layer thickness (TFLLT) and the meibomian gland (MG) structure in MGD and normal groups was investigated to establish its efficacy and potential side effects. Nineteen MGD patients and seven normal subjects were enrolled. TFLLT and blinking parameters were evaluated before and after warm compression. Morphological changes of MG structures after mechanical squeezing were analyzed using Image J and Fiji. Differential analysis of the MGD and the normal groups of TFLLT changes after warm compression showed a significant increase in the normal group. In normal eyes, the average, maximum, and minimum TFLLT were significantly increased, and in the MGD group, only the minimum TFLLT was improved. Blinking parameters showed no significant change in either group. Morphometric analysis showed no damages of the MG after MG squeezing. A significant increase in MG length was observed in normal eyes. Warm compression immediately increased TFLLT more significantly in the normal group than in the MGD patients. Mechanical expression is a safe therapeutic option without remarkable structural MG damages.

Quantitative evaluation of intraorbital optic nerve in optic atrophy using diffusion tensor imaging.

The aim of this study is to quantitatively investigate the microstructural properties of the optic nerve (ON) in vivo using diffusion tensor imaging (DTI) in patients with unilateral optic atrophy (OA) and to determine their association with retinal nerve fiber layer (RNFL) thickness of the optic nerve head (ONH). Six patients with unilateral OA and 11 control subjects underwent DTI. ONs from ONH to the orbital apex were tracked. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were computed in both ONs and their correlation with RNFL thickness measured using optical coherence tomography was also analyzed. FA of atrophic ON was lower than that of non-affected and control ONs (atrophic [A], 0.136 ± 0.059; non-affected [N], 0.384 ± 0.048; control [C], 0.389 ± 0.053). MD and RD of atrophic ONs were higher than those of non-affected and control ONs (MD, A, 0.988 ± 0.247; N, 0.658 ± 0.058; C, 0.687 ± 0.079; RD, A, 0.920 ± 0.247; N, 0.510 ± 0.054; C, 0.532 ± 0.078). All DTI measures of atrophic ON except for AD showed a significant correlation with RNFL thickness of ONH; FA showed the strongest correlation, followed by RD and MD (FA, R2 = 0.936, P < 0.001; RD, R2 = 0.795, P < 0.001; MD, R2 = 0.655, P = 0.001). This study reports quantitative analysis of the ON using DTI and differences in DTI measures between atrophic and normal ONs. The significant correlation between DTI measures and RNFL thickness suggests the applicability of DTI as a clinical tool to evaluate the ON.

Comparison between Deep-Learning-Based Ultra-Wide-Field Fundus Imaging and True-Colour Confocal Scanning for Diagnosing Glaucoma.

In this retrospective, comparative study, we evaluated and compared the performance of two confocal imaging modalities in detecting glaucoma based on a deep learning (DL) classifier: ultra-wide-field (UWF) fundus imaging and true-colour confocal scanning. A total of 777 eyes, including 273 normal control eyes and 504 glaucomatous eyes, were tested. A convolutional neural network was used for each true-colour confocal scan (Eidon AF™, CenterVue, Padova, Italy) and UWF fundus image (Optomap™, Optos PLC, Dunfermline, UK) to detect glaucoma. The diagnostic model was trained using 545 training and 232 test images. The presence of glaucoma was determined, and the accuracy and area under the receiver operating characteristic curve (AUC) metrics were assessed for diagnostic power comparison. DL-based UWF fundus imaging achieved an AUC of 0.904 (95% confidence interval (CI): 0.861−0.937) and accuracy of 83.62%. In contrast, DL-based true-colour confocal scanning achieved an AUC of 0.868 (95% CI: 0.824−0.912) and accuracy of 81.46%. Both DL-based confocal imaging modalities showed no significant differences in their ability to diagnose glaucoma (p = 0.135) and were comparable to the traditional optical coherence tomography parameter-based methods (all p > 0.005). Therefore, using a DL-based algorithm on true-colour confocal scanning and UWF fundus imaging, we confirmed that both confocal fundus imaging techniques had high value in diagnosing glaucoma.

Analysis of MicroRNA Expression in Tears of Patients with Herpes Epithelial Keratitis: A Preliminary Study.

Purpose: Herpes epithelial keratitis (HEK) is the most common form of herpes simplex virus (HSV) eye involvement, and understanding the molecular mechanisms underlying HEK is important. We investigated the expression of microRNAs (miRNAs) in the tears of patients with HEK. Methods: Tear samples from eight patients with HEK and seven age-matched controls were evaluated. Clinical ophthalmologic evaluation was performed, and an anterior segment photograph was obtained after fluorescence staining. Dendritic or geographic ulcer areas were measured using ImageJ software. The expression of 43 different miRNAs in tears was measured using real-time polymerase chain reaction and compared between patients with HEK and controls. Differences in miRNA expression between the dendritic and geographic ulcer groups and correlations involving miRNA expression and ulcer area were evaluated. Results: Of the 43 miRNAs, 23 were upregulated in patients with HEK compared to normal controls. MiR-15b-5p, miR-16-5p, miR-20b-5p, miR-21-5p, miR-23b-3p, miR-25-3p, miR-29a-3p, miR-30a-3p, miR-30d-5p, miR-92a-3p, miR-124-3p, miR-127-3p, miR-132-3p, miR-142-3p, miR-145-5p, miR-146a-5p, miR-146b-5p, miR-155-5p, miR-182-5p, miR-183-5p, miR-221-3p, miR-223-3p, and miR-338-5p were significantly upregulated in patients with HEK. MiR-29a-3p exhibited significant differences between the dendritic and geographic ulcer groups. All 23 miRNAs with significant differences between patients with HEK and the control group were not significantly correlated with ulcer area. Conclusions: Twenty-three miRNAs were significantly upregulated in the tears of patients with HEK, and the expression of miRNAs may play important roles in herpes infection in relation to host immunity.