Optical Assessment of Tear Glucose by Smart Biosensor Based on Nanoparticle Embedded Contact Lens.

Diabetes is a disease condition characterized by a prolonged, high blood glucose level, which may lead to devastating outcomes unless properly managed. Here, we introduce a simple camera-based optical monitoring system (OMS) utilizing the nanoparticle embedded contact lens that produces color changes matching the tear glucose level without any complicated electronic components. Additionally, we propose an image processing algorithm that automatically optimizes the measurement accuracy even in the presence of image blurring, possibly caused by breathing, subtle movements, and eye blinking. As a result, using in vivo mouse models and human tear samples we successfully demonstrated robust correlations across the glucose concentrations measured by three different independent techniques, validating the quantitative efficacy of the proposed OMS. For its methodological simplicity and accessibility, our findings strongly support that the innovation offered by the OMS and processing algorithm would greatly facilitate the glucose monitoring procedure and improve the overall welfare of diabetes patients.

Comparison of cytokine expression and ultrastructural alterations in fresh-frozen and dried electron beam-irradiated human amniotic membrane and chorion.

The purpose of the current study was to compare the effects of drying and fresh-freezing on human amniotic membrane (HAM) and amnion/chorion membrane (HACM) in terms of histological and structural characteristics and cytokine levels. HAM and HACM samples, obtained from six placentae, were investigated. HAM and HACM were dried, electron beam-irradiated (dehydration group; d-HAM/d-HACM), or fresh-frozen (freezing group; f-HAM/f-HACM). Luminex assay was used to assay the levels of 15 cytokines. The ultrastructural characteristics of HAM and HACM were evaluated using light and transmission electron microscopies. Total cytokine contents did not show the statistical difference between dehydration and fresh-freezing process. Significantly higher levels of total cytokines were observed in HACM than in HAM. Epidermal growth factor (EGF) level was significantly higher in d-HAM than in the other samples. The levels of most of the other growth factors were higher in HACM than in HAM, but there was no statistical difference between the dehydration process and the fresh-freezing process. The levels of the cytokines, other than the growth factors, were higher in HACM than in HAM, and higher concentrations of cytokines were observed in the freezing group than in the dehydration group. Histological examination revealed that the dehydration group had thinner tissues than the freezing group, but the structural stability, including the basement membrane, did not differ between the two groups. Microscopic structures such as microvilli and nuclei were well-preserved in the freezing group, based on the results of the transmission electron microscopy. Our dehydration process maintained the histological structure of HAM/HACM and a variety of growth factors and cytokines were identified. Especially, the HAM, processed with the dehydration method, had a higher EGF level than that processed with the fresh-freezing method. Therefore, dehydration method can be used to effectively promote wound repair.

Clinical characteristics and ophthalmologic findings of pituitary adenoma in Korean patients.

PURPOSE: To investigate the clinical characteristics of and ophthalmic findings in Korean patients diagnosed with a pituitary adenoma. METHODS: The medical records of 534 patients diagnosed with a pituitary adenoma at Kyung Hee University Hospital between January 2007 and December 2016 were retrospectively reviewed. RESULTS: Mean patient age was 47.9 ± 16.2 years. The most common symptoms at the time of presentation were headache (26.2%) and visual disturbance (12.4%). The referral rate to the ophthalmology department was 18.44% and patients most often presented to the neurosurgery department. Optic chiasm compression was identified in 23.4% of patients (54.4% of patients referred to ophthalmology, 15.0% of patients not referred to ophthalmology). Normal visual field (57%) was the most common visual field feature followed by bitemporal hemianopsia (17.8%). Optic chiasmal compression without visual field defects was found in 36.1% of patients. Tumor volume was positively correlated with visual field pattern standard deviation (PSD, p = 0.020) and best-corrected logMAR visual acuity (p = 0.000) and negatively associated with tumor volume and visual field mean deviation (MD, p = 0.000). Best-corrected visual acuity (p = 0.000), MD (p = 0.001), and PSD (p = 0.028) significantly improved after surgery. CONCLUSIONS: Pituitary adenoma patients do not always have ocular symptoms at their first presentation, even when optic chiasm compression and visual field deficits are present. Therefore, collaboration with an ophthalmologist is important when evaluating pituitary adenoma patients.

Development of an LCD-Based Visual Field System.

BACKGROUND: The present study investigated the diagnostic effectiveness of an LCD-based visual field testing system (LVF) in comparison with the standard automated perimetry Humphrey Field Analyzer II-750i (HFA). METHODS: A randomized controlled crossover study was conducted with 202 normal and 128 glaucomatous eyes using both LVF and HFA. The visual field testing systems were compared in terms of mean deviation (MD), pattern standard deviation (PSD), and area under the receiver operating characteristics curve (AUC) of MD and PSD differentiating the normal and glaucomatous eyes. RESULTS: Significant correlations were found between MD measurements from LVF and those from HFA for normal eyes (r = 0.342) and glaucomatous eyes (r = 0.796); slightly higher significant correlations were identified between PSD measurements from LVF and those from HFA for normal eyes (r = 0.363) and glaucomatous eyes (r = 0.828). Furthermore, high AUCs of MD were found as 0.786 for LVF and 0.868 for HFA and AUCs of PSD as 0.913 for LVF and 0.932 for HFA. CONCLUSION: The comparison results of the present study support the competence of LVF compared with HFA in visual field testing for early detection of glaucoma.

TGFbeta mediates activation of transglutaminase 2 in response to oxidative stress that leads to protein aggregation.

Transglutaminase 2 (TGase2) is a ubiquitously expressed enzyme that catalyzes irreversible post-translational modification of protein, forming cross-linked protein aggregates. We previously reported that intracellular TGase2 is activated by oxidative stress. To elucidate the functional role of TGase2 activation in cells under the oxidatively stressed condition, we identified the mediator that activates TGase2. In this study, we showed that low levels of oxidative stress trigger the release of TGFbeta, which subsequently activates TGase2 through the nuclear translocation of Smad3. Analysis of substrate proteins reveals that TGase2-mediated protein modification results in a decrease of protein solubility and a collapse of intermediate filament network, which leads to aggregation of proteins. We confirm these results using lens tissues from TGase2-deficient mice. Among several antioxidants tried, only N-acetylcysteine effectively inhibits TGFbeta-mediated activation of TGase2. These results indicate that TGFbeta mediates oxidative stress-induced protein aggregation through activation of TGase2 and suggest that the formation of protein aggregation may not be a passive process of self-assembly of oxidatively damaged proteins but may be an active cellular response to oxidative stress. Therefore, TGFbeta-TGase2 pathway may have implications for both the pathogenesis of age-related degenerative diseases and the development of pharmaceutics.

Machine learning models based on the dimensionality reduction of standard automated perimetry data for glaucoma diagnosis.

INTRODUCTION: Visual field testing via standard automated perimetry (SAP) is a commonly used glaucoma diagnosis method. Applying machine learning techniques to the visual field test results, a valid clinical diagnosis of glaucoma solely based on the SAP data is provided. In order to reflect structural-functional patterns of glaucoma on the automated diagnostic models, we propose composite variables derived from anatomically grouped visual field clusters to improve the prediction performance. A set of machine learning-based diagnostic models are designed that implement different input data manipulation, dimensionality reduction, and classification methods. METHODS: Visual field testing data of 375 healthy and 257 glaucomatous eyes were used to build the diagnostic models. Three kinds of composite variables derived from the Garway-Heath map and the glaucoma hemifield test (GHT) sector map were included in the input variables in addition to the 52 SAP visual filed locations. Dimensionality reduction was conducted to select important variables so as to alleviate high-dimensionality problems. To validate the proposed methods, we applied four classifiers-linear discriminant analysis, naïve Bayes classifier, support vector machines, and artificial neural networks-and four dimensionality reduction methods-Pearson correlation coefficient-based variable selection, Markov blanket variable selection, the minimum redundancy maximum relevance algorithm, and principal component analysis- and compared their classification performances. RESULTS: For all tested combinations, the classification performance improved when the proposed composite variables and dimensionality reduction techniques were implemented. The combination of total deviation values, the GHT sector map, support vector machines, and Markov blanket variable selection obtains the best performance: an area under the receiver operating characteristic curve (AUC) of 0.912. CONCLUSION: A glaucoma diagnosis model giving an AUC of 0.912 was constructed by applying machine learning techniques to SAP data. The results show that dimensionality reduction not only reduces dimensions of the input space but also enhances the classification performance. The variable selection results show that the proposed composite variables from visual field clustering play a key role in the diagnosis model.

Three-Dimensionally Printed Interconnects for Smart Contact Lenses.

One of the ultimate wearable heath-monitoring gears, smart contact lens, requires miniaturized devices compounded and interconnected with each other on the lens for a successful system functioning. Because of the different device thickness, the interconnect patterns need to be three-dimensional (3D) conforming the steps given by the diversified on-lens devices. Also, the patterns should be low-temperature processed and flexible considering the mechanical and thermal property of the lens material. We demonstrate the 3D interconnects electrosprayed on a contact lens platform with Ag-Ag nanowire (NWs) composite ink conforming the steps. Quantitative and informative analysis on the interconnects is presented. Thick polyimide film (12.5 µm) in C-shape is employed as a primary substrate to form the 3D patterns that is to be transferred onto the contact lens. The AgNWs act as frames to support the Ag ion inks printed across the steps. The resultant interconnects realized with the Ag/AgNW composite ink with 0.3 wt % AgNW have the sheet resistance ( Rs) of 0.396 Ω/□ spanning the height difference of 300 µm. AgNWs also provide durability to the patterns against crack formation and propagation under significant device deformation. Unlike pure Ag pattern which shows the Rs changes of 86.1% in the bending condition, the optimally formulated composite pattern shows the suppressed Rs change of only 15.2% with a bending radius of 3 mm.

An atypical presentation of functional visual loss: A case report.

RATIONALE: Functional visual loss (FVL) can manifest as various symptoms. Decreased distant visual acuity is the most common symptom and visual field defect is the second most common symptom. Hemianopsia is rarely reported. In an atypical situation of FVL, it is important to prove that no organic pathology exists, through detailed history taking and appropriate examinations. PATIENT CONCERNS: This review presents the case of a 48-year-old male patient presented with decreased bilateral visual acuity and visual field defect after a traffic accident 3 weeks ago. Visual field test showed atypical features of FVL in which visual field change from binasal hemianopsia to left homonymous hemianopsia. DIAGNOSIS: The best corrected visual acuities (BCVA) were 20/63 in both eyes and binasal hemianopsia was observed on a Humphrey visual field test. Brain computed tomography (CT) scan and magnetic resonance imaging (MRI) showed no abnormalities in the brain and optic chiasm. Two weeks after presentation, however, the patient's visual field defect changed from binasal hemianopsia to left homonymous hemianopsia. We diagnosed it as FVL due to conversion disorder. INTERVENTION AND OUTCOMES: We decided to cooperate with a psychiatrist for cognitive behavioral therapy and the patient is under observation. LESSONS: Binasal hemianopsia and homonymous hemianopsia are rare; however, it may occur simultaneously in 1 patient with FVL. The possibility of FVL should be considered when there is atypical visual field defect and no organic abnormalities are observed. Repeated Humphrey field test and VEP may be helpful in diagnosis of FVL.

Spontaneous corneal perforation in Terrien's marginal degeneration in childhood: A case report.

RATIONALE: Terrien's marginal corneal degeneration (TMD) is characterized by progressive peripheral corneal thinning. It appears primarily above the age of 40 years and is rare at younger ages. Spontaneous corneal perforation in TMD is a rare, but serious complication that may occur in childhood. PATIENT CONCERNS: This review presents the case of a 16-year-old girl presented with blurred vision in the right eye on awakening in the morning. Slit-lamp examination revealed superior corneal thinning with a corneal perforation. DIAGNOSES: The best-corrected visual acuity (BCVA) was 20/50 in the right eye and 20/20 in the left eye. Intraocular pressures were 5 and 18 mm Hg in the right and left eyes, respectively, measured using a noncontact tonometer. Slit-lamp examination revealed superior corneal thinning with superficial pannus. A 1-mm corneal perforation was observed at the 11 o'clock position. The anterior chamber of the right eye was flat and the Seidel test result was positive. The left eye showed no apparent abnormality on slit-lamp examination. Corneal topography showed 4.3 D of against-the-rule astigmatism, and anterior segment optical coherence tomography revealed superior corneal thinning. We diagnosed it as childhood onset TMD. INTERVENTIONS: Multilayered amniotic membrane transplantation was performed over the perforation site and a bandage contact lens was placed. OUTCOMES: At 1 week postoperatively, the BCVA of the right eye improved to 20/32, the amniotic membrane graft was well-attached, and the anterior chamber remained deep. At 2 months postoperatively, the BCVA was 20/25 and the anterior chamber depth was maintained. LESSONS: Spontaneous corneal perforation due to TMD is rare, but may occur in childhood. The possibility of corneal perforation should be considered even in childhood and good surgical results can be obtained with amniotic membrane transplantation.

Regulation of SPARC by transforming growth factor ß2 in human trabecular meshwork.

PURPOSE: An increased aqueous level of TGF-ß2 has been found in many primary open-angle glaucoma patients. Secreted Protein, Acidic, and Rich in Cysteine (SPARC)-null mice have a lower intraocular pressure. The mechanistic relationship between SPARC and TGF-ß2 in trabecular meshwork (TM) is unknown. We hypothesized that TGF-ß2 upregulates SPARC expression in TM. METHODS: Cultured TM cells were incubated with selective inhibitors for p38 MAP kinase (p38), Smad3, p42, JNK, RhoA, PI3K, or TGF-ß2 receptor for 2 hours, and then TGF-ß2 was added for 24 hours in serum-free media. Quantitative polymerase chain reaction (qPCR) and immunoblot analysis were performed. Immunofluorescent microscopy was used to determine nuclear translocation of signaling proteins. Ad5.hSPARC and Lentiviral shRNA for p38 and Smad3 were constructed, and infected human TM cells. RESULTS: SPARC was upregulated by TGF-ß2 in the human TM cells (3.8 ± 1.7-fold, n = 6, P = 0.01 for protein and 7.1 ± 3.7-fold, n = 6, P = 0.01 for mRNA), while upregulation of SPARC had no effect on TGF-ß2. TGF-ß2-induced SPARC expression was suppressed by inhibitors against p38 (-40.3 ± 20.9%, n = 10, P = 0.0001), Smad3 (-56.2 ± 18.9%, n = 10, P = 0.0001), JNK (-49.1 ± 24.6%, n = 10, P = 0.0001), and TGF-ß2 receptor (-83.6 ± 14.4%, n = 6, P = 0.003). Phosphorylation and translocation of Smad3, p38, and MAPKAPK2 were detected at 30 minutes and 1 hour, respectively, following TGF-ß2 treatment. Phosphorylation of JNK and c-jun was detected before TGF-ß2 treatment. SPARC was suppressed 31 ± 13% (n = 5, P < 0.0001) by shRNA-p38 and 41 ± 3% (n = 5, P < 0.0001) by shRNA-Smad3. CONCLUSIONS: TGF-ß2 upregulates SPARC expression in human TM through Smad-dependent (Smad2/3) or -independent (p38) signaling pathways. SPARC may be a downstream regulatory node of TGF-ß2-mediated IOP elevation.

Risk factors for the progression of intima-media thickness of carotid arteries: a 2-year follow-up study in patients with newly diagnosed type 2 diabetes.

BACKGROUND: Intima-media thickness (IMT) of the carotid arteries is known to have a positive correlation with the risk of cardiovascular disease. This study was designed to identify risk factors affecting the progression of carotid IMT in patients with type 2 diabetes mellitus (T2DM). METHODS: Patients with newly diagnosed T2DM with carotid IMT measurements were enrolled, and their clinical data and carotid IMT results at baseline and 2 years later were compared. RESULTS: Of the 171 patients, 67.2% of males and 50.8% of females had abnormal baseline IMT of the left common carotid artery. At baseline, systolic blood pressure, body mass index and smoking in male participants, and fasting plasma glucose and glycated hemoglobin levels in females were significantly higher in patients with abnormal IMT than in those with normal IMT. Low density lipoprotein cholesterol (LDL-C) levels in males and high density lipoprotein cholesterol (HDL-C) levels in females at the 2-year follow-up were significantly different between the nonprogression and the progression groups. Reduction of the United Kingdom Prospective Diabetes Study (UKPDS) 10-year coronary heart disease (CHD) risk score after 2 years was generally higher in the nonprogression group than the progression group. CONCLUSION: LDL-C levels in males and HDL-C levels in females at the 2-year follow-up were significantly different between participants with and without progression of carotid IMT. Furthermore, a reduction in the UKPDS 10-year CHD risk score appeared to delay the advancement of atherosclerosis. Therefore, the importance of establishing the therapeutic goal of lipid profiles should be emphasized to prevent the progression of carotid IMT in newly diagnosed T2DM patients.

Thrombospondin-1 (TSP1)-null and TSP2-null mice exhibit lower intraocular pressures.

PURPOSE: Thrombospondin-1 (TSP1) and TSP2 are matricellular proteins that have been shown to regulate cytoskeleton, cell adhesion, and extracellular matrix remodeling. Both TSP1 and TSP2 are found in the trabecular meshwork (TM). In cadaver eyes with primary open-angle glaucoma (POAG), TSP1 is increased in one third of patients. We hypothesized that TSP1 and TSP2 participate in the regulation of intraocular pressure (IOP). Methods. IOPs of TSP1-null, TSP2-null mice, and their corresponding wild-type (WT) mice were measured using a commercial rebound tonometer. Fluorophotometric measurements assessed aqueous turnover. Central corneal thickness (CCT) was measured by optical coherence tomography. Iridocorneal angles were examined using light microscopy (LM), immunofluorescence (IF), and transmission electron microscopy (TEM). RESULTS: Average IOPs of TSP1-null and TSP2-null mice were 10% and 7% less than that of the corresponding WT mice, respectively. CCTs were 6.5% less in TSP1-null mice (P < 0.05) and 1.1% less in TSP2-null mice (P > 0.05). Fluorophotometric measurements suggest that aqueous turnover rates in TSP1-null and TSP2-null mice are greater than those of WT mice. LM of the TSP1-null and TSP2-null iridocorneal angles reveals morphology, which is indistinguishable from that of their corresponding WTs. IF revealed possible concurrent underexpression of TSP2 in TSP1-null mice and of TSP1 in TSP2-null mice. TEM revealed larger collagen fibril diameters in TSP1-null and TSP2-null mice compared with WTs. CONCLUSIONS: TSP1-null and TSP2-null mice have lower IOPs than their WT counterparts. The rate of aqueous turnover suggests that the mechanism is enhanced outflow facility. An alteration in the extracellular matrix may contribute to this finding.