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Purpose: A healthy conjunctiva secreting mucins is essential for maintaining the integrity of the ocular surface epithelium. We used Cu, Zn-superoxide dismutase 1-deficient mice (Sod1-/- mice) and investigated the effect of oxidative stress on the tear function, conjunctival phenotype, and ocular surface mucin expression., Methods: Fifty-week-old C57/B6 wild-type (WT) and Sod1-/- mice were used for evaluations of the tear film breakup time and periodic acid Schiff staining of the conjunctival specimens to detect goblet cell densities in the conjunctiva. Immunohistochemistry stainings with anti-Muc5AC, anti-Muc1, anti-4-hydroxy-2-nonenal, and anti-8-hydroxy-2'-deoxyguanosine antibodies were also performed. The mRNA expression levels of Muc1, Muc5AC, Spdef, involcurin, and transglutaminase 1 were quantified with real-time RT-PCR., Results: The mean goblet cell density in the aged Sod1-/- mice was significantly lower than the aged WT mice. The mean number of Muc5ac-positive cells was significantly lower in the aged Sod1-/- mice compared with the aged WT mice. The conjunctival epithelium in the aged Sod1-/- mice displayed marked staining with lipid and DNA oxidative stress markers. The mRNA expression of transglutaminase 1 and involcurin in the aged Sod1-/- mice was significantly higher than the aged WT mice. The Spdef mRNA expression in the aged Sod1-/- mice was also significantly lower than the aged WT mice., Conclusions: Elevated oxidative stress status appears to affect the conjunctival differentiation and alter the conjunctival epithelial phenotype with aging in the Sod1-/- mice.

An understanding of corneal optics is important to optimize the visual outcome after eye surgery. Recent advances in the surgical techniques of lamellar keratoplasty have changed the strategies used for corneal transplantation. Lamellar keratoplasty has the advantage of having a lower rate of graft rejection, superior biomechanical properties, and reduced higher-order aberrations (HOAs) compared with penetrating keratoplasty; thus, the use of lamellar keratoplasty has increased over the last 15 years. However, some patients have poor postoperative visual acuity despite a clear cornea, and the reasons for the poor visual outcome are poorly understood. By combining corneal imaging technologies and the latest optical software, we proposed the concept of "parallelism of anterior and posterior surfaces in lamellar keratoplasty." In physiologically normal eyes, in which the anterior and posterior surfaces are parallel to each other, the posterior surface of the cornea compensates the HOAs of the anterior surface, and this is also true in eyes after penetrating keratoplasty. However, after lamellar keratoplasty, in which the anterior and posterior surfaces are independent and not parallel, irregularities in the posterior surface increase the HOAs of the anterior surface. This article introduces this concept to enhance our understanding of visual optics in eyes after penetrating and lamellar keratoplasties and how to apply this concept to surgery to improve and optimize patient visual outcomes.

Objective: To evaluate the serial changes in anterior chamber depth (ACD) and angle parameters early after cataract surgery using anterior segment optical coherence tomography (ASOCT)., Methods: This was a retrospective chart review, case-control study; 150 eyes of 106 patients who underwent cataract surgery. Based on ACD and angle findings, the eyes were classified into two groups, open-angle eyes (87 eyes) and narrow-angle eyes (63 eyes). ASOCT was used to measure ACD and angle parameters (angle opening distance, angle recess area, trabecular iris space area, and trabecular iris angle (TIA [1]). Serial changes in each group were measured before and 1 day, 1 week, and 1 month after cataract surgery, and the differences between the two groups were compared., Results: ACD and all angle parameters in both groups at each examination time after cataract surgery were significantly different from the preoperative values (p < 0.01). In addition, all angle parameters significantly differed between the two groups at each examination time after cataract surgery (p < 0.001). However, ACD after surgery was not significantly different, irrespective of ACD before surgery. ACD and TIA500 both showed significantly greater changes from before surgery to 1 day after surgery in narrow-angle eyes compared to open-angle eyes (p < 0.001)., Conclusions: Cataract surgery increases ACD and all angle parameters early after the surgery. However, the degree of angle widening in narrow-angle eyes was not as much as that in open-angle eyes, suggesting that factors other than the lens influence the angle closure.

Objective: To determine the relationship between adiponectin levels and asthma control in non-obese asthmatic children., Methods: Eighty-two children with asthma who had been followed up in a single center were included. The control group included 28 children with no evidence of allergic disease. Adiponectin levels were analyzed in all children. Additionally, skin prick tests and pulmonary function tests were also performed in patients., Results: Three groups were designated with respect to asthma control as; well-controlled group (n = 28), partially controlled group (n = 34) and uncontrolled group (n = 20). There was no significant difference of gender, age, height, weight, BMI and adiponectin levels between study and control groups (p > 0.05). The duration of illness, presence of atopy and sensitivities to mite, pollens, dander and cockroaches were similar between the groups (p > 0.05). Adiponectin, FEV1, FVC, and FEV1/FVC levels were significantly lower in uncontrolled group (p < 0.05). Sensitivity to Alternaria alternata was significantly higher in the uncontrolled group (p < 0.05). In logistic regression analysis, as dependent parameter, adiponectin, FEV1, FVC and FEV1/FVC levels were found to be statistically significant for uncontrolled asthma., Conclusion: Adiponectin levels in non-obese asthmatics were not different from controls. Lower levels of adiponectin were associated with uncontrolled asthma. Low adiponectin level can therefore be used as an indicator of uncontrolled asthma.

Purpose: To report a novel "piggyback" penetrating keratoplasty technique performed in a patient with severe keratoconus., Methods: A 43-year-old man underwent cataract surgery and a new "piggyback" penetrating keratoplasty (PKP) technique in his right eye, as he suffered from severe keratoconus and mature cataract due to severe atopic dermatitis. Under general anesthesia, phacoemulsification and aspiration (PEA), intraocular lens (IOL) implantation, and "piggyback" PKP while avoiding open-sky surgery was performed to prevent serious complications including IOL and vitreous prolapse. This PKP technique had been completed as a totally closed surgery., Results: One year after "piggyback" PKP and cataract surgery, the grafted cornea remained clear and IOL was also well positioned. Best-corrected visual acuity improved from hand motions to 30/100., Conclusions: A novel "piggyback" PKP technique was successfully performed in a patient with severe keratoconus. The new "piggyback" corneal transplantation technique may become an indispensable tool for transplant surgeons who want to improve surgical safety and predictability.

Objective: Adrenarche is a component of normal pubertal development. Recent decades have witnessed changes in the timing and tempo of puberty in different populations. We aimed to obtain normative data on dehydroepiandrosterone-sulphate (DHEA-S) secretion in healthy children and to evaluate the age of adrenarche, pubarche and the DHEA-S levels at which pubarche starts in both sexes., Methods: Serum DHEA-S concentrations were measured in 531 healthy (291 female) Turkish children aged 1 month-18 years by an automated chemiluminescence method. Pubic hair development was evaluated. DHEA-S concentrations >108·4 nmol/l (40 μg/dl) were regarded as adrenarche. Age-related normative data were constructed. Age at adrenarche and pubarche and the DHEA-S levels at pubarche were estimated using ROC analyses., Results: Serum DHEA-S levels were high in the first 6 months of life then declined below 108·4 nmol/l (40 μg/dl) with a cut-off age of 0·46 years for girls and 0·61 years for boys with 98% and 96% statistical sensitivity. Stable minimum levels were observed for the following 5 years. The cut-off age for DHEA-S levels rising above 108·4 nmol/l (40 μg/dl) was 8·0 and 7·0 years for girls for boys, respectively. DHEA-S levels at transition from Tanner stage P1 to P2 was 90·5 nmol/l (33·4 μg/dl) in girls and 118 nmol/l (43·6 μg/dl) in boys. Median (CI) DHEA-S levels were 170·7(94·8-336) and 244(119·2-357·7) nmo/l [63(35-124) and 90(44-132) μg/dl] in girls and boys, respectively, with Tanner stage P2 pubic hair., Conclusions: We established reference data of serum DHEA-S levels in a large group of children. Currently, adrenarche (DHEA-S>108·4 nmol/l) starts 1 year earlier in boys but higher DHEA-S levels are needed for transition from P1 to P2 in boys., (© 2014 John Wiley & Sons Ltd.)

Objectives: Adenoid hypertrophy (AH) may cause several comorbid conditions including sleep apnea, chronic serous otitis and sinusitis. Such conditions are more common among children with allergic diseases. In our study, we aimed to determine the patient profile associated with higher incidence of adenoid hypertrophy and the related influential factors., Methods: The study included 1322 children being treated and followed up for allergic conditions. 100 children with no allergic diseases presenting during the same period to the clinic were included as the control group. Skin prick test for the same allergens was performed for all patients. Adenoid tissue was analyzed by an ENT specialist and the diagnosis was confirmed based on the patient history, endoscopic physical examination and radiology., Results: Of the patients, 765 (57.9%) were males and 557 (42.1%) were females and their mean age was 5.9±3.3 years. In the control group, 56 (56%) children were males and 44 (44%) were females and their mean age was 6.3±4.1 years. Children with allergic disease and control subjects did not differ significantly by age and gender. Adenoid hypertrophy was identified in 164 (12.4%) of the patients with allergic disease and in 3 (3%) of the controls. Allergic children were divided into two groups, as children with and without AH, respectively. The groups did not differ statistically significantly by gender, age or familial history of atopic disease. However, cigarette smoke exposure at home and presence of allergic rhinitis was significantly more frequent in the group of patients with AH. In the logistic model investigating the effect of variables on AH presence (according to age, gender, cigarette smoke exposure, asthma, AR, AD presence, atopy presence, sensitivity to house dust, pollen, epithelium, Alternaria alternata and cockroach), AR presence and cigarette smoke exposure were statistically significant., Conlusions: AH frequency is higher in children with allergic disease compared to controls. The most common sensitivity to allergens among patients with AH was to house dust. Presence of allergic rhinitis and cigarette smoke exposure are risk factors for developing AH. Children with these risk factors should be questioned for AH during their routine examinations., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Importance: Dry eye disease has become an important health problem. A lack of concordance between self-reported symptoms and the outcome of dry eye examinations has raised questions about dry eye disease., Objective: To explore the association between subjective happiness and objective and subjective symptoms of dry eye disease., Design: The study adopted a cross-sectional design., Setting: All the employees of a company in Osaka, Japan., Participants: 672 Japanese office workers using Visual Display Terminals (age range: 26-64 years)., Methods: The dry eye measurement tools included the Schirmer test, conjunctivocorneal staining, the tear film break-up time, as well as the administration of a dry eye symptoms questionnaire. Happiness was measured by the Subjective Happiness Scale., Main Outcome Measures: Dry eye examination parameters, dry eye symptoms questionnaires, and the Subjective Happiness Scale score., Results: Of the 672 workers, 561 (83.5%) completed the questionnaires and examinations. The mean Subjective Happiness Scale score was 4.91 (SD = 1.01). This score was inversely correlated with the dry eye symptom score (r = -0.188, p < 0.001), but was not associated with objective findings which include conjunctivocorneal staining, low Schirmer test score, or low tear film break-up time. The level of subjective happiness was the lowest in the group without objective results, but reported subjective symptoms of dry eyes (p < 0.05)., Conclusions and Relevance: There is evidence of the relationship between subjective happiness and self-reported symptoms of dry eyes. Findings of this study revealed a new perspective on dry eye disease, including the potential for innovative treatments of a specific population with dry eye disease.

Purpose: To evaluate the relationship between subjective symptoms and clinical signs in dry eye disease (DED) in office workers using visual display terminals (VDTs)., Design: Cross-sectional study., Methods: This study involved 672 Japanese young and middle-aged office workers who use VDTs. The subjects completed questionnaires designed to detect subjective symptoms and risk factors for DED. Dry eye tests, including tear film break-up time (TBUT), corneal-conjunctival staining with fluorescein and lissamine green, and the Schirmer test, were performed. Based on the Japanese diagnostic criteria for DED, the subjects were classified into 3 groups: definite DED, probable DED, and non-DED. Between each group, subjective symptoms and clinical signs were compared., Results: Of the 672 subjects, 561 (374 male, 187 female) completed the questionnaire (response rate: 83.5%). Definite DED was diagnosed in 65 subjects (11.6%), probable DED in 303 subjects (54.0%), and non-DED in 193 subjects (34.4%). The mean subjective symptom score was significantly less in subjects with probable DED (2.05 ± 0.42) and non-DED (1.63 ± 0.38) than in those with definite DED (2.19 ± 0.40) (P < .05 and P < .01, respectively). In the subjects with probable DED, a subgroup with positive subjective symptoms and abnormal TBUT (≤5 seconds) was categorized as short TBUT-type DED, and it was found that they had a higher subjective symptom score (2.09 ± 0.40), equivalent to that of those with definite DED (P = .269)., Conclusions: Despite no or minor epithelial damage, the severity of subjective symptoms was greater in short TBUT-type DED, most likely attributable to tear film instability. Thus, it might prove important to evaluate TBUT to successfully treat those patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Ocular surface mucosa is the first-line ocular tissue to be exposed to environmental stress. We evaluated tear functions and keratoconjunctival epithelial alterations after sidestream cigarette smoke (SCS) exposure and tried to clarify the role of the transcription factor nuclear factor erythroid 2-related factor 2 (Nfe2l2, also known as Nrf2), on the ocular surface. In wild-type and Nrf2(-/-) mice, tear volume did not change after SCS exposure. Tear film breakup time (tear stability) in Nrf2(-/-) mice was significantly shorter than that in wild-type mice after SCS exposure. Vital staining scores, including fluorescein and Rose Bengal staining, showed significantly higher values in Nrf2(-/-) mice than in wild-type mice after SCS exposure. Excessive oxidative stress accumulation was detected in Nrf2(-/-) mice after SCS exposure using immunohistochemical analysis. Immunohistochemical analysis also revealed decreased mucin 1 (Muc1) and Muc5ac staining in Nrf2(-/-) mice after SCS exposure. mRNA expression levels of Muc1, Muc4, and Muc5ac and of SAM-pointed domain epithelial-specific transcription factor in Nrf2(-/-) mice were lower than those in wild-type mice after SCS exposure. Mean tear IL-6 concentrations increased significantly in Nrf2(-/-) mice after SCS exposure. In conclusion, SCS exposure induced decreased tear stability, ocular surface damage, and altered conjunctival phenotype in Nrf2(-/-) mice. Nrf2 could play an important role in protection of the ocular surface against SCS exposure., (Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background: Epidemiological and clinical studies suggest a relationship between rhinitis and asthma. Upper and lower airways may be influenced by a common inflammatory process., Objective: This study aimed to investigate the relationships between rhinitis symptom scores, and both nasal and bronchial airflow among children with seasonal allergic rhinitis (SAR) by means of spirometric and rhinomanometric measurement during and outside the pollen season., Methods: Twenty-nine children with both seasonal allergic rhinitis and asthma (AR+A), 30 children with SAR and no asthma (AR) and 36 non-allergic healthy children were evaluated prospectively during and outside the pollen season. Symptom severity was evaluated using both total symptom score and visual analog score (VAS). All participants also received rhinomanometric evaluation and pulmonary function testing., Results: In children with SAR the median total nasal flow, FEV1, FEF25-75 values were lower than control group during pollen season (p=0.01, p<0.001 and p<0.001 respectively). They had also higher total nasal resistance compared with control groups (p=0.01). Nasal symptom scores were higher among patients with concurrent asthma than patients who had only SAR out of pollen season (p<0.001). There was no significant difference between SAR participants with or without asthma and control group in terms of total nasal flow and total nasal resistance measured out of season (p=0.105 and p=0.19). FEF25-75 values of patients with and without asthma were significantly lower than those of controls out of season (p=0.022, p<0.001 respectively)., Conclusion: Our data suggests that as the presence of AR worsens asthma control, the presence of asthma may worsen symptoms of AR out of pollen season. We found that total nasal flow, FEV1, FEF25-75 values of patients with SAR were lower than those of controls out of season. FEF25-75 values of patients with asthma and without asthma were significantly lower than those of controls out of season. Thus, a careful evaluation of lower airways should be performed in even patients with seasonal allergic rhinitis alone., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

We describe the facile synthesis of several two-dimensional covalent-organic frameworks (2D COFs) as films by vapor-assisted conversion at room temperature. High-quality films of benzodithiophene-containing BDT-COF and COF-5 with tunable thickness were synthesized under different conditions on various substrates. BDT-COF films of several micrometer thickness exhibit mesoporosity as well as textural porosity, whereas thinner BDT-COF films materialize as a cohesive dense layer. In addition, we studied the formation of COF-5 films with different solvent mixture compositions serving as vapor source. Room temperature vapor-assisted conversion is an excellent method to form COF films of fragile precursors and on sensitive substrates.

Background and Objective: Although potato is greatly consumed all over the world, adverse reactions to potato are uncommon. Our aim is to describe the clinical features of potato sensitivity in allergic children., Materials and Methods: Forty children with sensitivity to potato were followed up in the Pediatric Immunology and Allergy Clinic of our hospital were included in the study. These patients were retrospectively evaluated from January 2012 to December 2013., Results: Forty children aged between 6 months and 10 years (mean 2.9±3.2, median:1.5 years) were enrolled of whom 26 were male (65%). Thirty three of these children had presented eczema, nine wheezing, seven urticaria and/or angioedema, six rhinitis, four subjects had experienced anaphylaxis, and two vomiting or other gastrointestinal complaints. In 38 (95%) patients, skin prick tests detected sensitivity to other allergens besides potato. The most frequently identified sensitivities were to food sensitivities (82.5%). In addition sensitivity to house dust mite, cat dander, pollens, A. Alternata and cockroaches in skin prick tests were documented in nine, six, five, four and four patients, respectively. Latex sensitivity was not detected in any patient. Five (38.5%) out of 13 patients over the age of three showed sensitivity to pollen., Conclusions: Potatoes sensitivity is mostly seen in children with atopic dermatitis. In children with atopic eczema should be asked whether the increase in complaints with potatoes. Mostly potato sensitivity is combined with other food allergies. Therefore potato should be included in the test in patients with atopic eczema and food allergy.

Covalent organic frameworks (COFs) offer a strategy to position molecular semiconductors within a rigid network in a highly controlled and predictable manner. The π-stacked columns of layered two-dimensional COFs enable electronic interactions between the COF sheets, thereby providing a path for exciton and charge carrier migration. Frameworks comprising two electronically separated subunits can form highly defined interdigitated donor-acceptor heterojunctions, which can drive the photogeneration of free charge carriers. Here we report the first example of a photovoltaic device that utilizes exclusively a crystalline organic framework with an inherent type II heterojunction as the active layer. The newly developed triphenylene-porphyrin COF was grown as an oriented thin film with the donor and acceptor units forming one-dimensional stacks that extend along the substrate normal, thus providing an optimal geometry for charge carrier transport. As a result of the degree of morphological precision that can be achieved with COFs and the enormous diversity of functional molecular building blocks that can be used to construct the frameworks, these materials show great potential as model systems for organic heterojunctions and might ultimately provide an alternative to the current disordered bulk heterojunctions.

Purpose: To evaluate changes in functional visual acuity (FVA) measurements before and after treatment with 0.1% cyclosporine ophthalmic solution for 3 months in patients with severe atopic keratoconjunctivitis (AKC)., Methods: Pairs of eyes were analyzed from 3 boys (mean age 9 ± 3.6 years) who complained of having severe AKC and were recruited for the study. Conventional Landolt visual acuity, FVA, and visual maintenance ratio (VMR) measurements were conducted before and after 3 months of 0.1% cyclosporine eye drop treatment. Tear film lipid layer interferometry, tear film break-up time, fluorescein and rose bengal vital stainings, and the Schirmer test were also performed before and after treatment., Results: Eye drop treatment was associated not only with improvement of tear function and ocular surface status but also with better quality of visual function. The mean logarithm of the minimum angle of resolution FVA and Landolt visual acuity values improved from 0.45 ± 0.26 and 0.13 ± 0.17 before treatment to 0.16 ± 0.03 and -0.06 ± 0.05 after treatment, respectively. Similarly, the mean VMR values were markedly improved from 0.88 ± 0.06 to 0.95 ± 0.03 after treatment., Conclusions: FVA and VMR are promising parameters in the assessment of dynamic visual acuity changes in AKC-affected patients and evaluation of treatment outcome.

Recent advances in ocular surface reconstruction for patients with severe ocular surface diseases have significantly improved the prognosis of patients with vision-impairing corneal abnormalities. The history of cultivated epithelial sheet transplantation is short, and debate on the current approaches for these procedures is continuing. Limbal stem cell transplantation, including conjunctivolimbal autograft and keratolimbal allograft, has brought opportunities for vision improvement. In addition, the use of cultivated limbal epithelial transplantation from both allogeneic and autologous sources has provided further options for immediate postoperative epithelialization of the corneal surface. Finally, cultivated oral mucosal epithelial transplantation, which allows autologous transplantation for patients with bilateral limbal stem cell deficiency, has provided the best overall midterm and long-term results. Its biggest advantages are the absence of rejection reactions and the reduction of postoperative complications associated with steroid therapy. However, a solitary surgical approach is not sufficient for obtaining a good clinical outcome. To maximize the possibility of success using these procedures, it is important to preoperatively enhance aggressive treatment of the ocular surface, especially with factors that facilitate moisture retention. In this review article, we also discuss our clinical experience in relation to these surgical procedures.

Objective: In this study, we aimed to compare vitamin D levels of children with recurrent tonsillopharingitis and healthy controls, and investigate the relationship between sociodemographic characteristics and serum vitamin D levels., Methods: Children with recurrent tonsillopharingitis and healthy controls aged between 2, and 12 years who consulted to the outpatient clinics of Zeynep Kamil Maternity and Children's Diseases Training and Research Hospital from January to October 2012 were included in this study. Serum 25 (OH) vitamin D levels were studied by tandem mass spectroscopy (tandem ms) method. Risk factors which might be associated with vitamin D levels were questioned. Ethical aproval was obtained from the Ethics Committee of Zeynep Kamil Maternity and Children's Diseases Training and Research Hospital and informed consent from the parents of the children., Results: A total of 147 children; 74 (50.3%) patients and 73 (49.7%) controls were included in our study. Age, gender and demographic characteristics did not differ significantly between the two groups. Vitamin D levels in patients with recurrent tonsillopharingitis and controls were 19.7±8.7 ng/ml and 23.6±9.2 ng/ml, respectively (p<0.01). Although duration of vitamin D usage was shorter in children with recurrent tonsillopharingitis, this difference was not statistically significant (p>0.05)., Conclusion: Vitamin D levels in children with ≥7 recurrent episodes of tonsillophargitis within the preceeding year were significantly lower compared to the control group. We believe that serum vitamin D levels should be checked in children with recurrent tonsillopharingitis and deficiencies should be treated., Competing Interests: No conflict of interest was declared by the authors.

Importance: There are limited reports on the relationship between mucin 5AC (MUC5AC) concentrations in tears, working hours, and the frequency of ocular symptoms in visual display terminal (VDT) users. This investigation evaluated these relationships among patients with dry eye disease (DED) and individuals serving as controls., Objective: To determine the relationship between MUC5AC concentration in the tears of VDT users based on the diagnosis of DED and frequency of ocular symptoms., Design, Setting, and Participants: An institutional, cross-sectional study was conducted. Participants included 96 young and middle-aged Japanese office workers. Both eyes of 96 volunteers (60 men and 36 women) were studied. Participants working in a company that used VDTs completed questionnaires about their working hours and the frequency of ocular symptoms. Dry eye disease was diagnosed as definite or probable, or it was not present. Tear fluid was collected from the inferior fornix after instillation of 50 μL of sterilized saline. The MUC5AC concentration was normalized to tear protein content and expressed as MUC5AC (nanograms) per tear protein (milligrams). The differences in MUC5AC concentration between DED groups, between VDT working hours (short, intermediate, and long), and between symptomatic and asymptomatic groups were evaluated with 95% CIs based on nonparametric Hodges-Lehmann determination., Main Outcomes and Measures: Ocular surface evaluation, prevalence of DED, and MUC5AC concentration., Results: The prevalence of definite and probable DED was 9% (n = 9) and 57% (n = 55), respectively. The mean MUC5AC concentration was lower in the tears of VDT users with definite DED than in those with no DED (P = .02; Hodges-Lehmann estimator, -2.17; 95% CI, -4.67 to -0.30). The mean MUC5AC concentration in tears was lower in the group that worked longer hours than in the group that worked shorter hours (P = .049; estimated difference, -1.65; 95% CI, -3.12 to 0.00). Furthermore, MUC5AC concentration was lower in participants with symptomatic eye strain than in asymptomatic individuals (P = .001; estimated difference, -1.71; 95% CI, -2.86 to -0.63)., Conclusions and Relevance: The data obtained in the present study suggest that office workers with prolonged VDT use, as well as those with an increased frequency of eye strain, have a low MUC5AC concentration in their tears. Furthermore, MUC5AC concentration in the tears of patients with DED may be lower than that in individuals without DED.

Purpose: The purpose of our study was to investigate alterations in the meibomian gland (MG) in Cu, Zn-Superoxide Dismutase-1 knockout (Sod1-/-) mouse., Methods: Tear function tests [Break up time (BUT) and cotton thread] and ocular vital staining test were performed on Sod1-/- male mice (n = 24) aged 10 and 50 weeks, and age and sex matched wild-type (+/+) mice (n = 25). Tear and serum samples were collected at sacrifice for inflammatory cytokine assays. MG specimens underwent Hematoxylin and Eosin staining, Mallory staining for fibrosis, Oil Red O lipid staining, TUNEL staining, immunohistochemistry stainings for 4HNE, 8-OHdG and CD45. Transmission electron microscopic examination (TEM) was also performed., Results: Corneal vital staining scores in the Sod1-/- mice were significantly higher compared with the wild type mice throughout the follow-up. Tear and serum IL-6 and TNF-α levels also showed significant elevations in the 10 to 50 week Sod1-/- mice. Oil Red O staining showed an accumulation of large lipid droplets in the Sod1-/- mice at 50 weeks. Immunohistochemistry revealed both increased TUNEL and oxidative stress marker stainings of the MG acinar epithelium in the Sod1-/- mice compared to the wild type mice. Immunohistochemistry staining for CD45 showed increasing inflammatory cell infiltrates from 10 to 50 weeks in the Sod1-/- mice compared to the wild type mice. TEM revealed prominent mitochondrial changes in 50 week Sod1-/- mice., Conclusions: Our results suggest that reactive oxygen species might play a vital role in the pathogensis of meibomian gland dysfunction. The Sod1-/- mouse appears to be a promising model for the study of reactive oxygen species associated MG alterations.

Purpose: To investigate the role of a water and mucin secretagogue (3% diquafosol sodium eye drops) on the tear function and conjunctival ocular surface changes in Sod1(-/-) in comparison to the wild-type (WT) mice., Methods: Fourteen eyes of 7 Sod1(-/-) male mice with C57BL/background and 14 eyes of 7 C57BL6 strain wild-type male mice were examined at 40 weeks in this study. All mice had application of 3% diquafosol ophthalmic solution six times a day for 2 weeks. Tear film stability and corneal epithelial damage was evaluated by fluorescein and Rose Bengal stainings. Anterior segment photography was performed before and after eye drop instillations. Aqueous tear quantity was measured with phenol red-impregnated cotton threads without anesthesia. Animals were sacrificed at 42 weeks after diquafosol treatment and the whole globe specimens were subjected to periodic acid Schiff staining. Goblet cell density was quantified by J Image software. Quantitative real-time PCR for conjunctival muc 5AC messenger RNA expression was also performed., Results: Sod1(-/-) mice had significantly higher fluorescein staining scores compared to the WT mice before eye drop instillation. The mean tear film breakup time, Rose Bengal staining scores, and muc5 messenger RNA expression improved significantly with diquafosol treatment in both the WT and the knockout mice. The mean fluorescein staining score and aqueous tear quantity significantly improved in the Sod1(-/-) mice with treatment. A notable and consistent increase in goblet cells and decrease in inflammatory cell infiltrates could be confirmed in all specimens after 2 weeks of diquafosol eye drop application., Conclusions: Three percent diquafosol ophthalmic solution appears to be effective in the treatment of ocular surface disease in this age-related dry eye disease mouse model.

Aim: To evaluate the central corneal thickness (CCT) measurements of premature infants., Methods: The premature infants who were born between 25-34wk of gestational age (GA) were retrieved for the study. All CCT measurements were performed within the first 2d of their life under topical anesthesia by using an ultrasonic pachymeter., Results: The mean CCT of 200 eyes was 647.79±63.94 µm. The mean CCT of the right and left eyes were similar (647.30±64.72 µm and 648.29±63.47 µm consecutively). The mean CCT of the girls was 642.08±54.89 µm and the boys was 653.07±71.14 µm, with no statistically significant difference (P>0.05). But there was a negative correlation of the CCT with GA and birth weight (BW) (P<0.01)., Conclusion: The CCT values of premature babies were negatively correlated with GA and BW.

Background: Skin prick tests are widely used to determine sensitivity in allergic diseases. There is limited information about the natural history of skin sensitization tests and factors that affect them. It was aimed to determine the changes in skin test results and the factors affecting the reactivity of skin tests after a period of approximately four years in children with allergic disease., Methods: SPT of 170 patients among 2485 children with asthma and/or allergic rhinitis and/or atopic dermatitis, who underwent SPT between 2005 and 2007, were repeated after an interval of at least 3 years., Results: The mean age was 10.7 ± 3.1 (5-18) years and 70% of the patients were male. In total 66 (39.0% of the study population) had a different skin tests result in follow-up. Alterations: loss of sensitivity in 18 (11%) patients, the formation of a new sensitivity in 37 (22%) patients, and 11 (6%) both gained and lost sensitization. The presence of atopy in the family, the presence of allergic rhinitis and IgE elevation significantly predicted the incidence of new sensitization. The presence of sensitization to multiple allergens significantly predicted the incidence of loss of sensitization., Conclusions: It is found that there was an alteration of sensitization in 4/10 children at the end of the average 4-year period. The presence of family atopy, the presence of allergic rhinitis and serum total IgE elevation were risk factors for the development of new sensitization. On the other hand sensitization to multiple allergens was risk factors for the loss of sensitization.

Purpose: To investigate the differences of functional visual acuity (FVA) and high order aberrations (HOAs) in relation to tinted and clear hydrogel soft contact lens (SCL) wear., Methods: A prospective comparative study was performed in 16 eyes of 16 healthy volunteers. Dynamic visual acuity (using a FVA measurement system) and higher-order aberrations (using a wavefront sensor) were compared in subjects wearing two types of soft contact lenses: 1-day Acuvue(®) (Vistakon, Jacksonville, FL) clear and the 1-day Acuvue(®) Define(TM) (Vistakon, Jacksonville, FL) tinted lens. The blink rates were recorded during FVA testing. The correlation between the difference of HOAs and differences in FVA values was analyzed., Results: The mean LogMAR FVA scores with clear and tinted SCLs were 0.07 ± 0.13 and 0.14 ± 0.17 (P<0.05). The mean blink frequencies with clear and tinted SCL wear were 18.4 ± 8.3 and 25.3 ± 4.7 blinks/min (P<0.05). Both 3rd-order aberrations and total HOAs showed statistically significant differences between the two types of soft contact lenses for 6mm pupil measurements (P<0.05). A significant positive linear correlation was observed between ΔHOAs and ΔLogMAR FVA for 6mm pupil measurements (R=0.53, P=0.04)., Conclusions: Tinted contact lens wear appears to induce a reduction in optical quality. Functional visual acuity measurement is a useful procedure to study the changes of visual performance and quality in tinted contact lens wear., (Copyright © 2013 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)

Covalent organic frameworks (COFs) are a novel class of porous crystalline organic materials assembled from molecular building blocks. The construction principles of these materials allow for the design of precisely controllable structures since their chemical and physical properties can be easily tuned through the selection of the building blocks and the linkage motif. Their extraordinary and versatile properties impart functionality that is of great interest in areas such as gas storage, separation, catalysis and optoelectronics. This feature article discusses key aspects of the design of covalent organic frameworks with a focus on electroactive COFs for potential optoelectronic and photovoltaic applications.

Purpose: We determined whether functional visual acuity (VA) parameters and a dry eyes (DEs) symptoms questionnaire could predict DEs in a population of visual terminal display (VDT) users., Methods: This prospective study included 491 VDT users from the Osaka Study. Subjects with definite DE, diagnosed with the presence of DE symptoms, tear abnormality (Schirmer test ≤ 5 mm or tear breakup time [TBUT] ≤ 5 seconds), and conjunctivocorneal epithelial damage (total staining score of ≥3 points), or probable DE, diagnosed with the presence of two of them, were assigned to a DE group, and the remainder to a non-DE group. Functional VA was assessed, and DE questionnaires were administered. We assessed whether univariate and discriminant analyses could determine to which group a subject belonged. Sensitivity and specificity were assessed., Results: Of 491 subjects, 320 and 171 were assigned to the DE and non-DE groups, respectively. No significant differences were observed between DE and non-DE groups in Schirmer test value and epithelial damage, but TBUT value (3.1 ± 1.5 vs. 5.9 ± 3.0 seconds). The sensitivity and specificity of single test using functional VA parameters were 59% and 49% in functional VA, 60% and 50% in visual maintenance ratio, and 83% and 30% in frequency of blinking, respectively. According to a discriminant analysis using a combination of functional VA parameters and a DE questionnaire, six variables were selected for the discriminant equation, of which area under the curve (AUC) was 0.735. Sensitivity and specificity of diagnoses predicted by the discriminant equation were 85.9% and 45.6%, respectively., Conclusions: The discriminant equation obtained using functional VA measurement combined with a symptoms questionnaire may suggest the possibility for the first step screening of DE with unstable tear film. Since the questionnaire has an overall poor sensitivity and specificity, further amelioration may be necessary for the actual utilization of this screening tool., (Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.)

The aim of the present study was to define some novel radiological clues that may aid in the ultrasonographic diagnosis of gastroesophageal reflux in pregnant women. A total of 84 pregnant women, consisting of 42 reflux patients and 42 controls were included in the study. Reflux and control groups were compared in terms of age and our novel ultrasonographic landmarks related to oesophageal structure. While the two groups did not differ in terms of age, they were significantly different from each other with respect to: single layer, single wall oesophageal thickness; double layer, double wall oesophageal thickness; oesophageal hiatal diameter; perioesophageal fat pad thickness; hypoechogenic single wall muscularis mucosa and lamina propria thickness. Owing to our newly defined radiological clues, ultrasonography may have a 'greater than expected' role in the diagnosis of gastroesophageal reflux in pregnant women. However, further studies must be performed to document the actual diagnostic potential of these radiological tips.

Purpose: To evaluate the accuracy of intraocular lens (IOL) power calculations using ray tracing software in eyes after myopic laser in situ keratomileusis (LASIK)., Methods: Twenty-four eyes of 17 cataract patients who underwent phacoemulsification and IOL implantation after myopic LASIK were analyzed retrospectively. The IOL power calculation was performed using OKULIX ray tracing software. The axial length was measured using the IOLMaster and keratometry data using TMS2N. The accuracy of the IOL power calculation using OKULIX was compared with those using the Camellin-Calossi, Shammas-PL, Haigis-L formulas and the double-K SRK/T formula using 43.5 diopters (D) for the Kpre., Results: The mean values of the arithmetic and absolute prediction errors were 0.63 ± 0.85 and 0.80 ± 0.68 D, respectively. The arithmetic prediction error by OKULIX was a significant hyperopic shift of the distribution of the postoperative refractive errors compared to the Camellin-Calossi, Shammas-PL and Haigis-L formulas (P < 0.05), and the absolute prediction error showed no significant difference with other formulas. The prediction errors using OKULIX were within ± 0.5 D in 10 eyes (41.7 %) and within ± 1.0 D in 18 eyes (75.0 %). The percentages of eyes within ± 1.0 D using OKULIX were comparable to those obtained using the Camellin-Calossi, the Shammas-PL formulas and the double-K SRK/T formula using 43.5 D for the Kpre, and significantly (P < 0.05) higher than that obtained using the Haigis-L formula., Conclusions: IOL power calculations using OKULIX provided predictable outcomes in eyes that had undergone a previous myopic LASIK.

Purpose: To investigate the short-term adverse effects of using rebamipide for the treatment of dry eye by assessing visual function and optical quality., Methods: This interventional noncomparative study included 14 right eyes of 14 healthy volunteers. Serial measurements of visual acuity (VA) and higher-order aberrations were obtained prior to instillation of the rebamipide suspension (baseline) and immediately after and at 5, 10, 20, and 30 min after instillation. Functional VA measurement was performed over a 60-s period with the subject blinking naturally. Ocular aberrations were measured for 10 s while the subject was told not to blink, but no topical anesthesia was applied. Each patient also filled out a questionnaire exploring the rebamipide-associated adverse effects., Results: There was no significant difference between functional VA measured at baseline and at each time point after the instillation of rebamipide. In contrast, the root mean square of third-order and total higher-order aberrations increased significantly immediately after drug instillation (P<0.05). The severity of higher-order aberrations at baseline was similar to that observed at 5, 10, 20, and 30 min after instillation (P>0.05)., Conclusions: The transient reduction in optical quality immediately after administration of rebamipide is corrected by the patient's natural blink reflex. The adverse effects observed in this study do not outweigh the benefits of rebamipide treatment.

A mesoporous electron-donor covalent organic framework based on a benzodithiophene core, BDT-COF, was obtained through condensation of a benzodithiophene-containing diboronic acid and hexahydroxytriphenylene (HHTP). BDT-COF is a highly porous, crystalline, and thermally stable material, which can be handled in air. Highly porous, crystalline oriented thin BDT-COF films were synthesized from solution on different polycrystalline surfaces, indicating the generality of the synthetic strategy. The favorable orientation, crystallinity, porosity, and the growth mode of the thin BDT-COF films were studied by means of X-ray diffraction (XRD), 2D grazing incidence diffraction (GID), transmission and scanning electron microscopy (TEM, SEM), and krypton sorption. The highly porous thin BDT-COF films were infiltrated with soluble fullerene derivatives, such as [6,6]-phenyl C61 butyric acid methyl ester (PCBM), to obtain an interpenetrated electron-donor/acceptor host-guest system. Light-induced charge transfer from the BDT-framework to PCBM acceptor molecules was indicated by efficient photoluminescence quenching. Moreover, we monitored the dynamics of photogenerated hole-polarons via transient absorption spectroscopy. This work represents a combined study of the structural and optical properties of highly oriented mesoporous thin COF films serving as host for the generation of periodic interpenetrated electron-donor and electron-acceptor systems.

The aim of the present study was to investigate the diagnostic significance of visualization of periesophageal fat pad in ultrasonography or computed tomography for sliding hiatal hernias. Forty-six controls and 21 esophageal hiatal hernia patients were compared in terms of sonographic and tomographic esophageal diameters. We suggest that absence of periesophageal fat pad sign in ultrasonography or computerized tomography is a noteworthy finding that calls for further investigation for the diagnosis of sliding hiatal hernias., (© 2013.)

In vivo confocal microscopy (IVCM) is an emerging technology that provides minimally invasive, high resolution, steady-state assessment of the ocular surface at the cellular level. Several challenges still remain but, at present, IVCM may be considered a promising technique for clinical diagnosis and management. This mini-review summarizes some key findings in IVCM of the ocular surface, focusing on recent and promising attempts to move "from bench to bedside". IVCM allows prompt diagnosis, disease course follow-up, and management of potentially blinding atypical forms of infectious processes, such as acanthamoeba and fungal keratitis. This technology has improved our knowledge of corneal alterations and some of the processes that affect the visual outcome after lamellar keratoplasty and excimer keratorefractive surgery. In dry eye disease, IVCM has provided new information on the whole-ocular surface morphofunctional unit. It has also improved understanding of pathophysiologic mechanisms and helped in the assessment of prognosis and treatment. IVCM is particularly useful in the study of corneal nerves, enabling description of the morphology, density, and disease- or surgically induced alterations of nerves, particularly the subbasal nerve plexus. In glaucoma, IVCM constitutes an important aid to evaluate filtering blebs, to better understand the conjunctival wound healing process, and to assess corneal changes induced by topical antiglaucoma medications and their preservatives. IVCM has significantly enhanced our understanding of the ocular response to contact lens wear. It has provided new perspectives at a cellular level on a wide range of contact lens complications, revealing findings that were not previously possible to image in the living human eye. The final section of this mini-review provides a focus on advances in confocal microscopy imaging. These include 2D wide-field mapping, 3D reconstruction of the cornea and automated image analysis.

Purpose: To estimate the impact of dry eye disease (DED) on work performance and productivity in office workers using visual display terminals (VDTs)., Design: Cross-sectional study., Methods: Six hundred seventy-two Japanese young and middle-aged office workers using VDTs completed a questionnaire that was designed to measured at-work performance deficits and productivity losses using the Japanese version of the Work Limitations Questionnaire, completed by e-mail. Using the Japanese dry eye diagnostic criteria, respondents were classified into 3 groups: definite DED, probable DED, and non DED., Results: Of the 672 office workers, 553 subjects (82.3%), including 366 men and 187 women, completed the questionnaire and underwent clinical evaluation. As for the total workplace productivity loss, the non DED group demonstrated a loss of 3.56%, those with probable DED demonstrated a loss of 4.06%, and those with definite DED demonstrated a loss of 4.82%, indicating significantly worse performance and productivity (P = .014, trend test). For the 4 subscales, DED was associated with significantly lower on-the-job time management (P = .009, trend test) and combined mental performance and interpersonal functioning (P = .011, trend test). After controlling for age, sex, VDT working hours, and diagnosis of DED, time management, physical demands, and mental and interpersonal functioning showed a significant relationship to DED (each P > .05). Annual DED productivity losses were estimated to be $6160 per employee when measured by total production and $1178 per employee calculated by wage., Conclusions: This study indicated that there is a significant impact of DED on the total productivity of Japanese VDT users., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the efficacy of a thermosensitive atelocollagen punctal plug in the treatment of dry eye disease., Design: Prospective observational case series., Methods: The thermosensitive atelocollagen punctal plug was warmed at 37 C, 39 C, 41 C, and 43 C to evaluate the appropriate temperature and time for solidification. Dry eye patients were divided into 2 groups according to the preparation method of the atelocollagen punctal plug. In the conventional implantation group, atelocollagen gel was kept at room temperature for 15 minutes before implantation (27 eyes of 14 patients). In the preheating group, atelocollagen was warmed at 41 C for 8 minutes before implantation (23 eyes of 13 dry eye patients). Strip meniscometry, vital stainings, tear film break-up time (BUT), and symptom scores were evaluated before and 1 month after plug implantation., Results: In vitro experiments revealed that heating at 41 C for 8 minutes was sufficient to solidify the gel. The mean fluorescein score in the conventional implantation group significantly improved after treatment (before, 3.5 ± 2.3 points; after, 2.5 ± 0.9 points, P < .05). In the preheating group, the mean fluorescein score (before, 3.7 ± 1.7 points; after, 1.5 ± 1.2 points), strip meniscometry (before, 0.6 ± 0.7 mm; after, 1.1 ± 0.3 mm), BUT (before, 3.2 ± 0.7 seconds; after, 4.8 ± 1.0 seconds), and visual analog scale scores (before, 6.6 ± 1.5 points; after, 4.1 ± 0.9 points) significantly improved after treatment (P < .05)., Conclusion: The thermosensitive atelocollagen punctal plug was effective for dry eye treatment. The preheating method was found to be useful to strengthen the efficacy of the thermosensitive atelocollagen punctal plug., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The purpose of this study was to evaluate whether 50 Hz extremely low frequency electromagnetic fields (ELF-EMFs) affect the amount of orthodontic tooth movement in rats. The experiments were performed on 18 male Sprague-Dawley rats. The rats were randomly divided into three groups ( n = 6): cage-control (Cg-Cnt) group ( n = 6); sinusoidal electromagnetic field (SEMF) group ( n = 6); and pulsed electromagnetic field (PEMF) group ( n = 6). In SEMF and PEMF groups, rats were subjected to 1.5 mT EMF exposure eight hours per day for eight days. In order to obtain tooth movement, holes were drilled on the right and left maxillary central incisors of the rats at a distance 1.5-2 mm away from the gingiva and 20 g of orthodontic forces were applied to the teeth. Generated linear model for repeated measures and Bonferroni tests were used to evaluate the differences between the groups. Interactions among groups by days were found by using Pillai's trace multivariate test. The results showed that significant differences were present among the groups ( F = 5.035; p = 0.03) according to the extent of tooth movement. Significant differences between the amount of tooth movements were determined especially after the fifth day and the following days six, seven and eight ( p < 0.001). Within the limitations, according to the results of the present study, the application of ELF-EMF accelerated the orthodontic tooth movement in rats.

Objective: Both asthma and vitamin D deficiency are common among children. The results from studies examining the relationship between them are contradictory. The aim of this study is to determine the relationship between the clinical parameters of asthma and vitamin D status in children., Methods: One hundred and twenty children diagnosed with asthma and followed-up in our hospital were included in the study. The control group included 74 children with no evidence of allergic disease. The eosinophil counts, IgE levels and serum 25 OH cholecalciferol [25(OH)D] levels were measured., Results: The patient group consisted of 73 (60.8%) males and 47 (39.2%) females with a mean age of 4.4 ± 1.2 years. There was no significant difference between the patient and control groups with respect to gender and age. The mean 25(OH)D level was 21.49 ± 7.74 ng/ml in the study group and 23.94 ± 8.97 ng/ml in the control group, and this difference was not significant (p = 0.094). The patients with asthma were grouped according to their vitamin D status as 'deficient' (group 1), 'insufficient' (group 2) and 'normal' (group 3). The sociodemographic features, duration of illness, number of hospitalizations, number of sensitivities to allergens, eosinophil count and serum IgE levels were not found to be different between the groups. However, the total number of exacerbations, asthma severity and systemic glucocorticoid need in the previous year were significantly higher in the deficiency group (p < 0.05)., Conclusion: Vitamin D levels were not significantly different in patients with asthma. Vitamin D deficiency was common in the study group as well as in the control group. The clinical severity of disease, the number of exacerbations and the systemic glucocorticoid need were related to vitamin D level., (© 2014 S. Karger AG, Basel.)

Purpose: To identify genetic mutations and study the corneal epithelium in Japanese patients with Meesmann corneal dystrophy., Design: Laboratory investigation and prospective observational case series., Methods: Slit-lamp biomicroscopy with fluorescein vital staining and in vivo confocal microscopy were performed. Mutation screening of the KRT3 and KRT12 genes was performed via polymerase chain reaction and direct sequencing for 5 patients in 2 families., Results: Slit-lamp biomicroscopy revealed multiple corneal intraepithelial microcysts in all patients. A clear zone was seen in the younger generation, whereas mild subepithelial opacity was seen in the older generation. In the in vivo confocal microscopy, numerous corneal intraepithelial microcysts and hyperreflective materials, which were believed to be degenerative cells, were detected closer to the basal layer of the corneal epithelium in older patients. The superficial layer contained more enlarged microcysts, and the hyperreflective materials showed atrophic changes, as compared to the basal layer. The demarcation line between the microcysts and normal epithelial cells was clearly visualized by in vivo confocal microscopy and corresponded to the demarcation line of the clear zone observed by the slit-lamp examination. Two heterozygous mutations (Q130P, L140Q) in the KRT12 gene, one of which (L140Q) was novel, were identified only in the affected patients of the families., Conclusions: We identified a novel missense mutation of the KRT12 gene in Meesmann corneal dystrophy. The in vivo confocal microscopy examinations revealed previously unreported depth-dependent ultrastructural changes in the living cornea of Meesmann corneal dystrophy patients., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose. To assess the association of dry eye disease (DED) with physical activity and sedentary behavior. Methods. The cross-sectional survey conducted included Japanese office workers who use visual display terminals (n = 672). DED was assessed according to the Japanese Dry Eye Diagnostic Criteria, and participants were categorized into "definite DED," "probable DED," or "non-DED" groups based on the results of DED examinations. Physical activity and sedentary behavior of participants were assessed using the International Physical Activity Questionnaire (IPAQ), and physical activity level was calculated in metabolic equivalent units per week (MET, min/week). Participants were classified as having a high, moderate, or low level of physical activity. Results. Participants with abnormal tear break-up time (BUT) (≤5 s) were involved in sedentary behavior for significantly longer duration than those with normal BUT (P = 0.035). Non-DED participants (14.5%) tended to have higher levels of physical activity than definite DED participants (2.5%). Participants with definite DED had significantly lower MET scores than those with non-DED (P = 0.025). Conclusions. Our findings suggest that a lower level of physical activity and sedentary behavior are associated with DED; however, longitudinal/intervention studies with large groups of participants are needed to validate these findings.

Introduction: Dry eye is a visually disabling disease encountered in many countries with a wide variation of treatment practices all over the world. On that front, the 2007 Report of the International Dry Eye WorkShop (DEWS) reviewed the current knowledge on all aspects of dry-eye disease (DED), in an evidence-based manner, and outlined the trends and recommendations in the treatment of DED on the basis of disease severity., Areas Covered: This review mainly focuses on treatments for DED based on severity as recommended in the DEWS report, particularly artificial eye drops, hyaluronate sodium eye drops, autologous serum, anti-inflammatory eye drops including cyclosporine and steroids, and mucin secretagogues. New dry-eye treatment modalities in current trials outlined on the clinicaltrial.gov site are also outlined., Expert Opinion: Further investigations into the mechanism of action of the new mucin and tear secretagogues which have been suggested to have anti-inflammatory properties will enrich our understanding in relation to relevant ocular surface responses after treatment with these new agents.

Purpose: To investigate tear function and prevalence of dry eye disease (DED) in visual display terminal (VDT) users., Design: Cross-sectional study., Methods: Six hundred and seventy-two young and middle-aged Japanese office workers who used VDT completed questionnaires and underwent dry eye testing. We estimated the prevalence of DED using logistic regression analysis to examine associations between DED and possible risk factors. The ocular surface feature, prevalence of DED, and risk factors were evaluated., Results: Of the 672 workers, 561 (83.5%, mean age: 43.3 ± 9.1 years) completed the questionnaire. The percentage of women with a composite outcome of definite DED or probable DED was 76.5%, which was higher than that among men (60.2%; odds ratio [OR] = 2.00; 95% confidence interval [CI], 1.29-3.10, P = .002). Workers over 30 years of age had a higher risk of DED (OR = 2.22; 95% CI, 1.06-4.66), as did workers using a VDT >8 hours per day (OR = 1.94; 95% CI, 1.22-3.09). Average Schirmer value was 18.7 ± 11.7 mm and tear break-up time (TBUT) was 4.0 ± 2.5 seconds (78.6% of study participants had TBUT ≤5 seconds)., Conclusions: DED is prevalent among young to middle-aged Japanese VDT users. Ophthalmic findings revealed short TBUT and corneal staining accompanied by normal Schirmer test values. Increased risk for DED was noted for women aged over 30 years and prolonged VDT use. Measures to modify the adverse impact of VDT use on the ocular surface may provide a positive impact on public health and quality of life for office workers using VDTs., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Importance: A validated questionnaire that assesses symptoms and the effect of dry eye disease (DED) on the patient's daily life is needed to evaluate the condition., Objective: To develop and validate the Dry Eye-Related Quality-of-Life Score (DEQS) questionnaire in Japan., Design, Setting, and Participants: Development and evaluation of the DEQS questionnaire were conducted in 4 phases: (1) item generation, (2) pilot study to assess content and face validity, (3) preliminary psychometric validation study to examine factor structure and reduce the number of items, and (4) final psychometric validation with 224 participants (203 with DED and 21 serving as controls). Participants completed the DEQS questionnaire, the Short Form-8, and the National Eye Institute Visual Function Questionnaire-25. To evaluate reproducibility and responsiveness, individuals with DED completed the DEQS questionnaire twice., Main Outcomes and Measures: Internal consistency, reproducibility, discriminant validity, concurrent validity, and responsiveness., Results: Items were generated from a literature review, and 35 items were selected for the draft version. In the pilot study, 11 items were deleted; furthermore, 9 items were deleted based on the results of item analysis and factor analysis in the preliminary validation study. The final 15-item DEQS questionnaire consisted of an Overall Summary scale and 2 multi-item subscales: Impact on Daily Life and Bothersome Ocular Symptoms. The psychometric analysis revealed that the DEQS questionnaire has good internal consistency, test-retest reliability, discriminant validity, and responsiveness to change. The DEQS questionnaire correlated well with the mental component of the Short Form-8 and showed strong correlations with 4 subscales (Ocular Pain, Near Vision, Distance Vision, and Mental Health) of the National Eye Institute Visual Function Questionnaire-25., Conclusions and Relevance: The DEQS questionnaire is valid and reliable for evaluating the multifaceted effect of DED on the patient's daily life, including mental health, and it can be used easily in routine clinical practice.

Purpose: We examined symptoms, tear stability, visual function, and conjunctival cytology in eyes with an unstable tear film (UTF), expressed as a short tear film breakup time without epithelial damage or low tear secretion, and compared the results with those from eyes with aqueous deficiency (AD) associated with epithelial damage, and healthy eyes., Methods: We divided the patients with ocular discomfort into 2 groups according to the breakup time, Schirmer value, and epithelial staining score: UTF group (≤5 seconds, >5 mm, and <3 points; 21 eyes of 21 patients) and AD group (≤5 seconds, ≤5 mm, and ≥3 points; 21 eyes of 21 patients). We examined all patients and 17 healthy subjects for symptoms, tear functions, tear film stability by tear film lipid layer interferometry and tear film analysis system, and functional visual acuity. Conjunctival impression cytology was performed to investigate changes in goblet cell density, squamous metaplasia, and messenger RNA expression of MUC5AC and MUC16., Results: The symptom scores, tear film analysis system index, and functional visual acuity testing were significantly worse in the UTF and AD groups compared with those in the control group (P < 0.05). The messenger RNA expression levels of MUC5AC and MUC16 were significantly lower in UTF and AD eyes compared with those in the control eyes (P < 0.0001)., Conclusions: An UTF itself can cause dry eye symptoms and visual disturbance comparable with those of AD dry eyes.

The Jelly belly (Jeb)/Anaplastic Lymphoma Kinase (Alk) signalling pathway regulates myoblast fusion in the circular visceral mesoderm (VM) of Drosophila embryos via specification of founder cells. However, only a limited number of target molecules for this pathway are described. We have investigated the role of the Lame Duck (Lmd) transcription factor in VM development in relationship to Jeb/Alk signal transduction. We show that Alk signalling negatively regulates Lmd activity post-transcriptionally through the MEK/MAPK (ERK) cascade resulting in a relocalisation of Lmd protein from the nucleus to cytoplasm. It has previously been shown that downregulation of Lmd protein is necessary for the correct specification of founder cells. In the visceral mesoderm of lmd mutant embryos, fusion-competent myoblasts seem to be converted to 'founder-like' cells that are still able to build a gut musculature even in the absence of fusion. The ability of Alk signalling to downregulate Lmd protein requires the N-terminal 140 amino acids, as a Lmd(141-866) mutant remains nuclear in the presence of active ALK and is able to drive robust expression of the Lmd downstream target Vrp1 in the developing VM. Our results suggest that Lmd is a target of Jeb/Alk signalling in the VM of Drosophila embryos.

Purpose: To investigate the effects of diquafosol sodium (DQS) eye drops, a purinergic P2Y2 receptor agonist, on tear film stability in patients with unstable tear film (UTF)., Methods: Two prospective studies were conducted. One was an exploratory nonrandomized trial on 39 eyes with dry eye symptoms and short tear film break-up time (BUT), but without epithelial damage. Changes in symptoms, BUT, Schirmer value, and ocular surface fluorescein staining (FS) scores were studied for 3 months. The other was a randomized clinical trial of DQS and artificial tears (AT) in 17 eyes with short BUT. Eyes with decreased Schirmer values (≤ 5 mm) were excluded. Changes in symptoms, BUT, FS scores, and tear film stability using continuous corneal topographic analysis were studied for 4 weeks., Results: In the exploratory study, while Schirmer values were not significantly increased, significant improvements in symptoms and BUT were noted at both 1 and 3 months. In the randomized clinical trial, significant improvements in symptoms were noted in the DQS group, but not in the AT group, at 2 weeks. BUT was significantly prolonged in the DQS group at 4 weeks but not in the AT group. No significant changes were noted in FS scores or tear film stability., Conclusions: DQS improved subjective symptoms and prolonged BUT in eyes with UTF not associated with low tear secretion and ocular surface epithelial damage. Because many patients who have UTF are refractory to conventional treatments, DQS may offer benefits in the treatment of dry eyes.