Bacillus-Derived Manganese Superoxide Dismutase Relieves Ocular-Surface Inflammation and Damage by Reducing Oxidative Stress and Apoptosis in Dry Eye.

Purpose: We hypothesized that antioxidative enzymes supplementation could be a treatment option for dry eye. We investigated the efficacy of oral administration of Bacillus-derived superoxide dismutase (Bd-SOD) in a murine experimental dry eye (EDE). Methods: In part I, mice were randomly assigned to normal control, EDE, and mice groups that were treated with oral Bd-SOD after induction of EDE (EDE + Bd-SOD group; four mice in each group). Expression of SOD2, a major antioxidant enzyme with manganese as a cofactor, was assessed by immunofluorescence staining. In part II, mice were divided into seven groups (six mice in each group): normal control, EDE, vehicle-treated, topical 0.05% cyclosporin A (CsA)-treated, and oral Bd-SOD-treated (2.5, 5.0, and 10.0 mg/kg Bd-SOD) groups. Tear volume, tear-film break-up time (TBUT), and corneal fluorescein-staining scores (CFS) were measured at zero, five, and 10 days after treatment. Ten days after treatment, 2',7'-dichlorodihydrofluorescein diacetate for reactive oxygen species (ROS), enzyme-linked immunosorbent for malondialdehyde, and TUNEL assays for corneal apoptosis, flow cytometry inflammatory T cells, and histological assessment were performed. Results: Compared to the normal control group in part I, the EDE group showed significantly decreased SOD2 expression by immunofluorescence staining. However, the EDE + Bd-SOD group recovered similar to the normal control group. In part II, ROS, malondialdehyde, and corneal apoptosis were decreased in CsA and all Bd-SOD-treated groups. Corneal and conjunctival inflammatory T cells decreased, and conjunctival goblet cell density increased in CsA-treated and Bd-SOD-treated groups. Compared to the CsA-treated group, the 2.5 mg/kg Bd-SOD-treated group showed increased TBUT and decreased inflammatory T cells, and the 5.0 mg/kg Bd-SOD-treated group showed decreased CFS and increased conjunctival goblet cells. Conclusions: Oral Bd-SOD administration might increase autogenous SOD2 expression in ocular surface tissue in EDE and could be developed as a complementary treatment for DE in the future.

The Influence of Patent Foramen Ovale on the Clinical Features of Migraine without Aura: A Cross-Sectional Study.

Objective: To investigate the influence of patent foramen ovale (PFO) on the clinical features of migraine without aura (MoA). Methods: We consecutively enrolled 390 MoA patients and compared the frequency of headache, episode duration, and the Visual Analogue Scale (VAS), Headache Impact Test 6 (HIT-6), and European Health Interview Survey-Quality of Life 8-item index (EUROHIS-QOL8) scores of patients with and without PFO, those with the mild right-to-left shunt (RLS) and moderate to large RLS, and those with permanent RLS and latent RLS using a nonparametric Mann-Whitney U-test. In addition, we analyzed the clinical features of migraine in 39 MoA patients before and after PFO closure treatment using the paired Wilcoxon test. Results: The prevalence of PFO in the 390 MoA patients was 44.4%. Patients with PFO had significantly higher frequency of headaches, VAS scores, HIT-6 scores, and incidence of white matter lesions than those without PFO (all p< 0.05). Patients with moderate to large RLS had significantly higher VAS scores than those with mild RLS (p = 0.002). Additionally, 39 MoA patients underwent PFO closure, which remarkably decreased their frequency of headache, episode duration, VAS scores, and HIT-6 scores, and increased their EUROHIS-QOL8 scores. Conclusion: The migraine features in MoA patients could be influenced by PFO, especially in patients with moderate to large shunt, in whom PFO closure improved the symptoms.

Nomogram Prediction for Lower Extremity Deep Vein Thrombosis in Acute Ischemic Stroke Patients Receiving Thrombolytic Therapy.

This study developed and evaluated a tailored nomogram to predict the potential occurrence of early lower extremity deep vein thrombosis (LDVT) in patients receiving thrombolytic therapy. We performed several logistic analyses on the training cohort and created a corresponding nomogram to forecast early LDVT. The classification accuracy and the accuracy of predicted probabilities of the multiple logistic regression model were evaluated using area under the curve (AUC) and the calibration graph method. According to the multivariate logistic regression model homocysteine, previous history of hypertension and atrial fibrillation, indirect bilirubin, age, and sex was identified as independent determinants of early LDVT. The nomogram was constructed using these variables. The calibration plots showed a good agreement between the predicted and observed LDVT possibilities in the training and validation cohorts with AUCs being 0.833 (95% CI: 0.774-0.892) and 0.907 (95% CI: 0.801-1.000), respectively. Our nomogram offers clinicians a tool for predicting the individual risk of LDVT in the early stage of acute ischemic stroke in patients receiving thrombolytic therapy, which could lead to early intervention.

Cellulose Acetate Phthalate-Based pH-Responsive Cyclosporine A-Loaded Contact Lens for the Treatment of Dry Eye.

Cyclosporine A (CsA) as an eye drop is an effective treatment for dry eye. However, it has potential side effects and a short ocular residence time. To overcome these obstacles, we developed a cellulose acetate phthalate-based pH-responsive contact lens (CL) loaded with CsA (CsA-CL). The CsA was continuously released from the CsA-CL at physiological conditions (37 °C, pH 7.4) without an initial burst. CsA was well-contained in the selected storage condition (4 °C, pH 5.4) for as long as 90 days. In safety assays, cytotoxicity, ocular irritation, visible light transmittance, and oxygen permeability were in a normal range. CsA concentrations in the conjunctiva, cornea, and lens increased over time until 12 h. When comparing the therapeutic efficacy between the normal control, experimental dry eye (EDE), and treatment groups (CsA eye drop, naïve CL, and CsA-CL groups), the tear volume, TBUT, corneal fluorescein staining at 7 and 14 days, conjunctival goblet cell density, and corneal apoptotic cell counts at 14 days improved in all treatment groups compared to EDE, with a significantly better result in the CsA-CL group compared with other groups (all p < 0.05). The CsA-CL could be an effective, stable, and safe option for inflammatory dry eye.

Melatonin Type 2 Receptor Activation Regulates Blue Light Exposure-Induced Mouse Corneal Epithelial Damage by Modulating Impaired Autophagy and Apoptosis.

The MT1/2 receptors, members of the melatonin receptor, belong to G protein-coupled receptors and mainly regulate circadian rhythms and sleep in the brain. Previous studies have shown that in many other cells and tissues, such as HEK293T cells and the retina, MT1/2 receptors can be involved in mitochondrial homeostasis, antioxidant, and anti-inflammatory responses. In our study, we aimed to investigate the effects of blue light (BL) exposure on the expression of melatonin and its receptors in the mouse cornea and to evaluate their functional role in corneal epithelial damage. After exposing 8-week-old C57BL/6 mice to BL at 25 and 100 J/cm2 twice a day for 14 days, a significant increase in the expression of 4-HNE and MT2 was observed in the cornea. MT2 antagonist-treated mice exposed to BL showed an increased expression of p62 and decreased expression of BAX and cleaved caspase 3 compared with mice exposed only to BL. In addition, MT2 antagonist-treated mice showed more enhanced MDA and corneal damage. In conclusion, BL exposure can induce MT2 expression in the mouse cornea. MT2 activation can modulate impaired autophagy and apoptosis by increasing the expression of BAX, an apoptosis activator, thereby regulating the progression of corneal epithelial damage induced by BL exposure.

TRIM22 actives PI3K/Akt/mTOR pathway to promote psoriasis through enhancing cell proliferation and inflammation and inhibiting autophagy.

OBJECTIVE: To reveal the function and underlying mechanism of Tri-domain protein 22 (TRIM22) in psoriasis. METHODS: M5 cytokines were applied in HaCat cells to mimic psoriasis in vitro. The TRIM22-silencing viruses were established to knockdown TRIM22 in HaCat cells. Western blot and/or real-time PCR were used to detect the expression of TRIM22, KRT1, KRT6, p-P65, P65, LC3, Beclin 1, P62, p-PI3K, PI3K, p-Akt, Akt, p-mTOR, and mTOR. ELISA kits were applied to assess levels of TNF-α, IL-1ß, IL-18, and HMGB1. RESULTS: TRIM22 expression levels were upregulated in M5-treated HaCat cells. M5 treatment enhanced cell proliferation and inflammation, and inhibited autophagy in HaCat cells which were effectively reversed by TRIM22 deficiency. Activation of PI3K/Akt/mTOR pathway is an essential promoter of cell proliferation and inflammation, and inhibitor of autophagy in psoriasis. TRIM22 deficiency blocked M5-induced activation of PI3K/Akt/mTOR pathway in HaCat cells. CONCLUSIONS: TRIM22 facilitates cell proliferation and inflammation, and suppresses autophagy in M5-treated HaCat cells through activating PI3K/Akt/mTOR pathway, and inhibition of TRIM22 can be a novel potential treatment for psoriasis.

Comparative analysis of 0.1% cyclosporin A cationic emulsion and 0.05% cyclosporin A emulsion in murine dry eye cases with different severities.

Dry eye (DE), especially severe DE (SDE), can cause ocular surface defects and reduce the patient's quality of life. Several clinical studies have shown that 0.1% cyclosporin A cationic emulsion (CsA CE) could decrease corneal damage. However, no experimental study has reported the effect of 0.1% CsA CE on SDE. The present study aimed to compare the efficacy of 0.1% CsA CE with that of 0.05% CsA emulsion for ocular surface damage and inflammation in the cases of murine DE with different severities. Following exposure to desiccating stress and subcutaneous injection of scopolamine for 5 days, C57BL/6 female mice were divided into SDE and non-SDE (NSDE) groups based on corneal fluorescein staining scores (CFSs). Mice from both groups were topically treated with 0.05% CsA emulsion or 0.1% CsA CE for 10 days. The results demonstrated that 0.1% CsA CE-treated mice in the SDE and NSDE groups exhibited significant improvements in all the clinical and experimental parameters. Furthermore, the CFS of 0.1% CsA CE-treated mice in the SDE group was lower compared with that of the 0.05% CsA-treated mice. In addition, in the SDE group, 0.1% CsA CE-treated mice had significantly lower levels of nuclear factor-κB activation, inflammatory infiltrations and apoptosis on the ocular surface, and they also exhibited higher conjunctival goblet cell density compared with the 0.05% CsA-treated mice. In summary, these findings indicated that 0.1% CsA CE was more effective than topical 0.05% CsA emulsion at improving corneal epithelial injury and decreasing the levels of inflammatory cytokines and T cells in mice with SDE.

Effects of eye drops containing a mixture of 3% diquafosol sodium and tocopherol acetate (vitamin E) on the ocular surface of murine dry eye.

PURPOSE: To investigate the efficacy of topical application of 3% diquafosol sodium (DQS) and tocopherol (TCP) acetate mixtures in a mouse model of experimental dry eye (EDE). METHODS: After exposure to desiccating stress for 5 days, eye drops consisting of 3% DQS alone, 0.01% TCP alone, or 3% DQS and 0.005% or 0.01% TCP mixture were applied for the treatment of EDE. Tear volume, tear film break-up time (TBUT), corneal fluorescein staining scores (CFSS), and tear film lipid layer grades (TFLLG) were measured at 0, 5 and 10 days after treatment. The 2',7'-dichlorodihydrofluorescein diacetate assay (DCFDA) for reactive oxygen species (ROS) production, enzyme-linked immunosorbent assay (ELISA) for malondialdehyde (MDA), and flow cytometry for CD4 + interferon (IFN)-γ+ T cells were evaluated on the ocular surface at 10 days after treatment. In addition, levels of tumour necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and chemokine CC motif ligand 4 (CCL4) in the conjunctiva were measured using a multiplex immunobead assay, and conjunctival goblet cells were counted by periodic acid-Schiff staining at 10 days after treatment. RESULTS: Both the TCP mixture groups indicated a significant improvement in TBUT, ROS production, and MDA concentrations compared to those in the DQS alone group. Furthermore, the 0.01% TCP mixture group also showed higher tear film lipid layer grades and conjunctival goblet cell density and lower corneal fluorescein staining scores, number of CD4 + IFN-γ+ T cells, and levels of TNF-α, IL-1ß, and CCL4 than the DQS alone group (P < 0.05). CONCLUSIONS: Application of eye drops containing the mixture of DQS and TCP could stabilize the tear film lipid layer, improve TBUT and corneal epithelial damages, decrease ROS production, inflammatory molecules, and T cells, and increase conjunctival goblet cell density on the ocular surface. Topical DQS and TCP mixtures may have a greater therapeutic effect on clinical signs, oxidative damage, and inflammation of dry eye than DQS eye drops.

Blue Light Induces Impaired Autophagy through Nucleotide-Binding Oligomerization Domain 2 Activation on the Mouse Ocular Surface.

In this study, we investigated the effects of blue light exposure on nucleotide-binding oligomerization domain 2 (NOD2) expression on the mouse ocular surface and evaluated the role of NOD2 activation in light-induced cell death. Mice were divided into wild-type (WT), NOD2-knock out (KO), WT + blue light (WT + BL), and NOD2-KO + blue light (NOD2-KO + BL) groups, and the mice in the WT+BL and NOD2-KO + BL groups were exposed to blue light for 10 days. After 10 days of blue light exposure, increased reactive oxygen species and malondialdehyde were observed in the WT + BL and NOD2-KO + BL groups, and the WT + BL group showed a higher expression of NOD2 and autophagy related 16 like 1. Although both WT+BL and NOD2-KO + BL groups showed an increase in the expression of light chain 3-II, NOD2-KO + BL mice had a significantly lower p62 expression than WT + BL mice. In addition, NOD2-KO+BL mice had significantly lower corneal epithelial damage and apoptosis than WT + BL mice. In conclusion, blue light exposure can induce impaired autophagy by activation of NOD2 on the ocular surface. In addition, the reactive oxygen species (ROS)-NOD2-autophagy related 16 like 1 (ATG16L) signaling pathway may be involved in the blue-light-induced autophagy responses, resulting in corneal epithelial apoptosis.

Effects of Eurya japonica extracts on human corneal epithelial cells and experimental dry eye.

Eurya japonica (EJ) leaves have been indicated to exert anti-oxidative and anti-inflammatory effects. Dry eye disease (DED) is a chronic inflammatory disease and oxidative stress is closely associated with DED. The aim of the present study was to analyze the therapeutic efficacy of EJ in DED using human corneal epithelial (HCE) cells and a mouse model of experimental dry eye (EDE). EJ extracts (0.001, 0.01 and 0.1%) were used to treat HCE cells. Cell viability and mitochondrial function were detected using a EZ-Cytox cell viability assay kit and mitochondrial membrane potential assays. Dichlorofluorescein diacetate (DCF-DA) assay was used to measure cellular reactive oxygen species (ROS) levels. Subsequently, eye drops consisting of BSS or 0.001%, 0.01 and 0.1% EJ extracts were applied for treatment of EDE. At 7 days, conjunctival ROS production was measured using a DCF-DA assay. Tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, 10 kDa interferon gamma-induced protein 10 (IP-10) and monokine induced by interferon-γ (MIG) levels in the conjunctiva were analyzed using a multiplex immunobead assay. Tear film and ocular surface parameters were measured. Treatment with EJ extracts in HCE cells effectively improved cell viability, ROS levels and mitochondrial function. Mice treated with 0.01 and 0.1% EJ extracts indicated a significant decrease in ROS, TNF-α, IL-1ß, IP-10 and MIG levels compared with the EDE or BSS groups. Furthermore, a significant improvement in all clinical parameters was observed in the 0.01 and 0.1% EJ extract groups. EJ extracts could decrease cytotoxicity and ROS production in HCE cells. Additionally, topical EJ extracts reduced oxidative damage and inflammation and improved clinical signs of EDE, suggesting that EJ extracts may be used as an adjunctive therapy for DED.

Tear Osmolarity and Matrix Metallopeptidase-9 in Dry Eye Associated with Sjögren's Syndrome.

PURPOSE: To evaluate the correlations between tear osmolarity and matrix metallopeptidase-9 (MMP-9) and dry eye (DE) indices in patients with DE associated with Sjögren's syndrome (SS). METHODS: Sixty-three patients with DE associated with SS who underwent tear analysis were included. DE tests performed were ocular surface disease index, tear break-up time, Schirmer's test, ocular staining score, and tear osmolarity and MMP-9 tests. Correlations between tear osmolarity and DE indices, differences between patients with abnormal and normal tear osmolarity, and those between positive and negative MMP-9 patients were analyzed. Patients were classified into four groups according to tear osmolarity and MMP-9 results, and between-group differences were analyzed (group 1: abnormal tear osmolarity, MMP-9 positive; group 2: abnormal tear osmolarity, MMP-9 negative; group 3: normal tear osmolarity, MMP-9 positive; group 4: normal tear osmolarity, MMP-9 negative). RESULTS: Mean age of patients was 54.2 ± 13.9 years, and 96.2% were female. Thirty-five patients had abnormal tear osmolarity and 40 patients were MMP-9 positive. DE indices differed between groups with abnormal and normal tear osmolarity (p < 0.01), but not between positive and negative MMP-9 groups. There were 22 patients in group 1, 13 in group 2, 18 in group 3, and 10 in group 4. Compared to group 4, tear break-up time was shorter in groups 1 (p < 0.01) and 2 (p = 0.02). Schirmer's test values in group 1 were lower than those in group 4 (p = 0.03). Ocular staining score was higher in groups 1 (p < 0.01) and 2 (p < 0.05) than in group 4. CONCLUSIONS: Tear osmolarity was correlated with ocular surface indices in DE associated with SS. Combination of tear osmolarity and MMP-9 test results may be helpful to determine the severity of DE associated with SS.

Anti-inflammatory effects of glycine thymosin ß4 eye drops in experimental dry eye.

The aim of the present study was to investigate the anti-inflammatory effects of glycine thymosin ß4 (Gly-Tß4) eye drops, and to compare the efficacy of topical Gly-Tß4 with Cyclosporine A (CsA) in a mouse model of experimental dry eye (EDE). Eye drops consisting of balanced salt solution (BSS), 0.1% Gly-Tß4 or 0.05% CsA were used for treatment of EDE. Tear volume, tear film break-up time and corneal staining scores were measured after 7 and 14 days. Periodic acid-Schiff staining for conjunctival gobleT cells, TUNEL assay for corneal apoptotic positive cells, multiplex immunobead assay for interleukin (IL)-1ß, IL-6, tumor necrosis factor-α and interferon-γ levels, and flow cytometry for CD4+/CCR5+ T cells were performed after 14 days. All clinical parameters showed improvement in the Gly-Tß4 and CsA groups (all P<0.05). Significantly increased conjunctival gobleT cells and decreased corneal TUNEL positive cells were observed in the Gly-Tß4 and CsA groups. The Gly-Tß4 and CsA treated groups showed significantly reduced inflammatory cytokine levels and T cells in the conjunctiva compared with the EDE and BSS groups (all P<0.05). However, there were no significant differences observed in the inflammatory and clinical parameters between the Gly-Tß4 and CsA treatment groups. Topical application of 0.1% Gly-Tß4 significantly reduced inflammation on the ocular surface, as well as clinical parameters of EDE, with a similar efficacy to that of 0.05% CsA emulsions, suggesting that Gly-Tß4 eye drops may be used as a therapeutic agent for treatment of dry eye disease.

Therapeutic Effect of Topical Adiponectin-Derived Short Peptides Compared with Globular Adiponectin in Experimental Dry Eye and Alkali Burn.

Purpose: To evaluate the efficacy of adiponectin (APN)-derived short peptides (ADPs) 355 compared with globular APN in a mouse model of experimental dry eye (EDE) and corneal alkali burn. Methods: EDE and chemical burn were induced in C57BL/6 mice by desiccating stress and application of NaOH, respectively. Eye drops consisting of 0.01% globular APN, 0.01% ADPs, 0.1% ADPs, or balanced salt solution (BSS) were applied. Tear volume, tear film break-up time, and corneal staining scores were measured. Concentrations of interleukin (IL)-1ß, interferon (IFN)-γ, IL-6, CXCL-9, and CXCL-10 using multiplex immunobead assay were evaluated, and flow cytometry were performed. Corneal epithelial defects and haze degree were analyzed, and enzyme-linked immunosorbent assay for IL-1ß and transforming growth factor (TGF)-ß levels were observed. Results: All treatment groups showed an improvement in clinical parameters and CD4+CCR5+ T cell and CD11b+ cell infiltrations in the conjunctiva (all P < 0.05). Both ADPs groups had significantly decreased concentrations of IL-1ß, IFN-γ, IL-6, CXCL-9, and CXCL-10 in the conjunctiva than the EDE or BSS group. Significantly improved parameters of epithelial defect, degree of haze, and concentrations of IL-1ß and TGF-ß were observed in all treatment groups. However, no significant differences were noted in clinical or experimental parameters among treatment groups. Conclusion: Topical ADPs could effectively improve clinical signs and inflammation of ocular surface in the EDE or alkali burn, and its efficacy and potency were similar to those of globular APN.

Expression and Role of Nucleotide-Binding Oligomerization Domain 2 (NOD2) in the Ocular Surface of Murine Dry Eye.

Purpose: To investigate expression and role of nucleotide-binding oligomerization domain 2 (NOD2) in the ocular surface of experimental dry eye (EDE), which is a nod-like receptor member and is involved in innate immune response. Methods: C57/BL6 female mice were divided into the groups: untreated (UT), EDE, and NOD2 knockout (KO) mice exposed to desiccating stress for 14 days. Clinical parameters and levels of inflammatory cytokine were measured at 3,5,7, and 14 days. Immunofluorescent staining for NOD2 and Western blot for RIP2 and NF-κB were performed at 14 days. Flow cytometry, PAS staining and TUNEL staining were performed. Results: After EDE induction, NOD2 was expressed in the corneal epithelium of the EDE group. The EDE group showed a significantly increased RIP2 expression compared to the UT and NOD2-KO groups. A significantly lower expression of NF-κB and lower levels of IL-1ß, IL-6, IFN-γ, and TNF-α were noted in the NOD2-KO group than in the EDE group. The NOD2-KO group had lower CD11b+ and CD4+CCR5+ T cells, TUNEL-positive cells and corneal staining score and higher density of conjunctival goblet cell density, tear volume, and tear film break-up time than the EDE group. The UT group showed significant differences in inflammatory and clinical parameters compared to the EDE and NOD2-KO groups. Conclusions: The NOD2 receptor pathway induced inflammation and apoptosis by activation of RIP2 and NF-κB on the ocular surface of EDE, thereby reducing tear secretion. Therefore, NOD2 pathway may be involved in the pathogenesis of dry eye.

The Efficiency of Cyclosporine A-Eluting Contact Lenses for the Treatment of Dry Eye.

PURPOSE: To investigate the efficacy and safety of a new cyclosporine A (CsA) delivery system using contact lenses (CLs) for the treatment of experimental dry eye (EDE). METHODS: CsA-laden porous carriers and CsA-eluting CLs were fabricated using the supercritical fluid technique. The release of CsA from carriers and CLs was investigated using high-performance liquid chromatography. The CsA concentrations in the cornea, conjunctiva, and crystalline lens of rabbits were measured. Dry eye was induced using 0.1% benzalkonium chloride in rabbits, which were subdivided into the normal, EDE, balanced salt solution (BSS), 0.05% CsA, hydrogel CL, or CsA-CL groups. Tear volume, tear film break-up time (TBUT), and corneal staining scores were measured at 1 and 2 weeks after treatment. Periodic acid-Schiff staining for the evaluation of conjunctival goblet cell density was performed at 2 weeks. Interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, and interferon-γ levels in the conjunctiva were measured using enzyme-linked immune-sorbent assay. RESULTS: The porous carrier showed the release of drug. CsA-eluting CLs showed initial burst and sustained release of CsA until 48 h. The concentration of CsA elevated in the cornea, conjunctiva, and lens until 48 h after application of CsA-CLs. The CsA-CL group showed significantly higher tear volume, TBUT, and lower corneal staining scores compared to the other groups (p < 0.05). Goblet cell density was significantly higher in the CsA-CL group compared to the other groups. The CsA-CLs group showed a lower level of IL-1ß than the BSS and soft CL groups (p < 0.01), and a lower level of IFN-γ than the other groups (all p < 0.01). CONCLUSIONS: The newly designed CsA-eluting CLs released drug continuously and showed good penetration in the eye. In addition, the use of CsA-eluting CLs improved clinical parameters and conjunctival goblet cell density and decreased inflammatory cytokines.

The influences of smartphone use on the status of the tear film and ocular surface.

PURPOSE: To investigate the influences of smartphone use on ocular symptoms, status of the tear film, and oxidative stress indices in the tears and at the ocular surface. METHODS: Eighty healthy volunteers were enrolled in the study. Subjective symptoms and asthenopia were evaluated using the ocular surface disease index (OSDI), visual analogue scale (VAS), and computer vision syndrome (CVS) score before and after smartphone or computer display (control) use. The status of the tear film was evaluated using fluorescein film break-up time (FBUT), non-invasive keratograph break up time (NIKBUT), Schirmer score, keratoepitheliopathy (KEP), and tear meniscus height (TMH). Oxidative stress markers in the tear film including hexanoyl lysine (HEL), 4-hydroxy-2-nonenal (4-HNE), malondialdehyde (MDA), and 8-oxo-2'-deoxyguanosine (8-OHdG) in the tear film were measured using ELISA. Reactive oxygen species (ROS) at the ocular surface were measured through 2',7'-dichloro-dihydrofluorescein diacetate. All measurements were conducted at baseline, and after use for 1 and 4 h. RESULTS: All parameters showed no significant group-wise differences at baseline. Scores of OSDI, VAS, fatigue, burning sensation, and dryness showed significant increases after 1 and 4 h of smartphone use compared with those at baseline (all P < 0.05). The smartphone group showed higher OSDI, fatigue, burning, and dryness scores than the control group at 4 h. Smartphone use showed significantly decreased FBUT and NIBUT at 4 h than those at baseline (P < 0.01). In the smartphone group, the concentration of HEL significantly increased at 4 h compared with that at baseline and 1 h (P < 0.01). Both groups showed increased ROS with higher value in the smartphone group versus the control group at 4 h (P < 0.01). CONCLUSIONS: Smartphone use could not only aggravate subjective symptom indices such as the OSDI, VAS, and CVS but also induce tear film instability and oxidative stress indices in the tears and at the ocular surface.

Comparison of 0.1%, 0.18%, and 0.3% Hyaluronic Acid Eye Drops in the Treatment of Experimental Dry Eye.

PURPOSE: To compare the efficacy of 0.1%, 0.18%, and 0.3% hyaluronic acid (HA) artificial tear in the treatment of experimental dry eye (EDE). METHODS: EDE was established in female C57BL/6 mice through an air draft and subcutaneous scopolamine injection. The mice were divided into 5 groups according to topical treatment regimens (n = 5 each): EDE control, balanced salt solution (BSS), preservative-free 0.1% HA, 0.18% HA, and 0.3% HA. The tear film break-up time (TBUT) and corneal fluorescein staining scores were measured 5, 10, 14, 21, and 28 days after treatment. The corneal smoothness scores were measured. In addition, periodic acid-Schiff (PAS) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were performed. RESULTS: The values for TBUT and corneal fluorescein staining showed greater improvements in all the HA groups (P < 0.05) than in the EDE and BSS groups after 10 days of treatment. Mice treated with 0.3% HA showed a more significant improvement in all clinical parameters than did those in the EDE control, BSS, 0.1% HA, and 0.18% HA groups (all P < 0.05) after 28 days of treatment. The goblet cell counts were higher in the 0.3% and 0.18% HA groups than in the 0.1% HA group. The number of TUNEL-positive cells was the lowest in the 0.3% HA group. CONCLUSIONS: In EDE, 0.3% HA artificial tears are more effective than the 0.1% and 0.18% HA in improving tear film instability and ocular surface staining and irregularity, in increasing the number of conjunctival goblet cells, and in decreasing corneal epithelial apoptosis.