Analysis of the performance of the CorneAI for iOS in the classification of corneal diseases and cataracts based on journal photographs.

CorneAI for iOS is an artificial intelligence (AI) application to classify the condition of the cornea and cataract into nine categories: normal, infectious keratitis, non-infection keratitis, scar, tumor, deposit, acute primary angle closure, lens opacity, and bullous keratopathy. We evaluated its performance to classify multiple conditions of the cornea and cataract of various races in images published in the Cornea journal. The positive predictive value (PPV) of the top classification with the highest predictive score was 0.75, and the PPV for the top three classifications exceeded 0.80. For individual diseases, the highest PPVs were 0.91, 0.73, 0.42, 0.72, 0.77, and 0.55 for infectious keratitis, normal, non-infection keratitis, scar, tumor, and deposit, respectively. CorneAI for iOS achieved an area under the receiver operating characteristic curve of 0.78 (95% confidence interval [CI] 0.5-1.0) for normal, 0.76 (95% CI 0.67-0.85) for infectious keratitis, 0.81 (95% CI 0.64-0.97) for non-infection keratitis, 0.55 (95% CI 0.41-0.69) for scar, 0.62 (95% CI 0.27-0.97) for tumor, and 0.71 (95% CI 0.53-0.89) for deposit. CorneAI performed well in classifying various conditions of the cornea and cataract when used to diagnose journal images, including those with variable imaging conditions, ethnicities, and rare cases.

A Possible Reciprocal Relationship Between Myopia and Dry Eye Disease in Japanese Teenagers.

Purpose: To investigate the relationship between dry eye disease (DED) and myopia in Japanese teenagers. Methods: This clinic-based, retrospective, cross-sectional study assessed DED condition in 10- to 19-year-old teenagers presenting at Japanese eye clinics. They included 106 high myopic patients (HM; mean age, 16.4 ± 2.2 years), 494 mild myopic patients (15.0 ± 2.6 years) and 82 non-myopic teenagers (NM; 13.8 ± 2.6 years). Subjective refraction and anisometropia were measured. Myopia grade was classified as HM (≤ -6.00 D), MM (> -6.00 D, < -0.50 D), or NM (≥ -0.5 D). The presence of DED-related symptoms including dryness, irritation, pain, fatigue, blurring and photophobia were assessed through a questionnaire. Tear film break-up time (BUT) and fluorescein corneal staining were investigated. Comparison among three groups and regression analysis of myopic error and other variables were conducted. Results: Anisometropia and astigmatic error were greatest in the HM group compared with the other groups (p < 0.001). The HM group reported less photophobia (p < 0.001) and less pain (p = 0.039) compared with the NM group. Regression analysis revealed that myopic error was correlated with astigmatic error (ß = -0.231, p <0.001), anisometropia (ß = -0.191, p <0.001), short BUT (ß = -0.086, p = 0.028) and the presence of diagnosed DED (ß = -0.112, p = 0.003). Dryness (ß = -0.127 p = 0.004), photophobia (ß = 0.117, p = 0.002) and pain (ß = 0.084, p = 0.034) correlated with myopic error. Conclusion: This study associated clinical findings of DED in HM teenagers. The present results suggest DED might be associated with myopia, possibly in a reciprocal relationship.

Role of telepharmacy in pharmacist counselling to coronavirus disease 2019 patients and medication dispensing errors.

INTRODUCTION: Remote pharmacist interventions have achieved much more attention during the coronavirus disease 2019 (COVID-19) outbreak, since they reduce the risk of transmission and can potentially increase the access of vulnerable populations, such as patients with COVID-19, to pharmaceutical care. This study aimed to examine differences in rates and types of pharmacist interventions related to COVID-19 and medication dispensing errors (MDEs) across community pharmacies with and without telepharmacy services. METHODS: This was a prospective, disguised, observational study conducted over four months (from March 2020 to July 2020) in 52 community pharmacies (26 with and 26 without telepharmacy) across all seven states of the United Arab Emirates using proportionate random sampling. A standardised data-collection form was developed to include information about patient status, pharmacist interventions and MDEs. RESULTS: The test (telepharmacy) group pharmacies provided pharmaceutical care to 19,974 patients, of whom 6371 (31.90%) and 1213 (6.07%) were probable and confirmed cases of COVID-19, respectively. The control group pharmacies provided care to 9151 patients, of whom 1074 (11.74%) and 33 (0.36%) were probable and confirmed cases of COVID-19, respectively. Rates of MDEs and their subcategories, prescription-related errors and pharmacist counselling errors across pharmacies with telepharmacy versus those without remote services were 15.81% versus 19.43% (p < 0.05), 5.38% versus 10.08% (p < 0.05) and 10.42% versus 9.35% (p > 0.05), respectively. DISCUSSION: This is one of the first studies to provide high-quality evidence of the impact of telepharmacy on COVID-19 patients' access to pharmaceutical care and on medication dispensing safety.

The Microstructure Formation of a Protective Oxide-Scale Layer on Small-Diameter FeCrAl Fibers.

FeCrAl fibers, at high temperatures, form a protective oxide-scale layer dominated by aluminum oxide on the surface to prevent further oxidation of the base metal alloy. This study investigates the effects of heat treatment on the microstructure formation of the oxide-scale layer on small-diameter FeCrAl fibers, 12 and 17 µm, produced using a bundle drawing process. The morphology examination and chemical analyses of the small-diameter fibers exhibit the microstructure and chemical compositions of the surface and cross-section areas, revealing a distinctive interface layer with a high aluminum concentration between the base metal and the oxide-scale layer. Furthermore, thermogravimetric analysis results show that the 12 µm fibers have about a 60% higher oxidation rate than the 17 µm fibers-caused by the high outward diffusion of aluminum to the surface of the fibers due to their high surface-area-to-weight ratio. Consequently, the high growth rate of the nonuniform oxide-scale layer and the limited aluminum reservoir of the 12 and 17 µm diameter fibers lead to faster depletion of aluminum from the base metal alloy-limiting the lifetime and durability of the smaller-diameter fibers in high-temperature applications.

Efficacy and Safety of Neostigmine Adjunctive Therapy in Patients With Sepsis or Septic Shock: A Randomized Controlled Trial.

Background: Neostigmine has been found to improve survival in animal models of sepsis. However, its feasibility, efficacy, and safety in patients with sepsis or septic shock have not been investigated. Aim: This parallel randomized controlled double-blinded design aimed to investigate the efficacy and safety of neostigmine as an adjunctive therapy in patients with sepsis or septic shock. Patients and Methods: A total of 167 adult patients with sepsis or septic shock were assessed for eligibility; 50 patients were randomized to receive a continuous infusion of neostigmine (0.2 mg/h for 120 h; neostigmine arm) or 0.9% saline (control arm) in addition to standard therapy. The primary outcome was the change in Sequential Organ Failure Assessment (SOFA) scores 120 h after therapy initiation. Secondary outcomes included mortality rates and changes in procalcitonin level. Results: The median (interquartile range) change in SOFA scores improved significantly in the neostigmine arm [-2 (-5, 1)] as compared with the control arm [1.5 (0, 2.8); p = 0.007]. Progression from sepsis to septic shock was more frequent in the control arm (p = 0.01). The incidence of shock reversal in patients with septic shock was significantly lower in the control arm than in the neostigmine arm (p = 0.04). Differences in 28-days mortality rates did not reach statistical significance between the control and neostigmine arms (p = 0.36). Percentage change in procalcitonin levels was similar in both arms (p = 0.74). Conclusion: Neostigmine adjunctive therapy may be safe and effective when administered in patients with sepsis or septic shock. Clinical Trial Registration: NCT04130230.

Multistage heat treatment and the development of a protective oxide-scale layer on the surface of FeCrAl sintered-metal-fibers.

This study investigates the effects of Multistage Heat Treatment (MSHT) on the development of an oxide-scale layer on the surface of FeCrAl sintered-metal-fibers. The oxide-scale layer was developed using an MSHT cycle at 930 °C for 1 h, followed by 960 °C for 1 h, and finally at 990 °C for 2 h. In this study, three samples were considered: Sample 1 was kept without thermal oxidation, while Samples 2 and 3 were exposed to one and eighteen MSHT cycles. Thermo-gravimetric analyses show that the weight gain of the heat-treated sample slows with time, confirming the growth of the protective oxide-scale layer. Scanning electron microscope images, after one MSHT cycle, reveal nonuniform oxide-scale growth with platelet-like on the surface. After eighteen MSHT cycles, however, clumped particles formed on the surface of the fibers. Atomic force microscopy was utilized to study the surface topography of the fibers. The results show that MSHT increases the surface roughness, where the surface roughness of one and eighteen MSHT cycles are the same. The x-ray diffraction analyses of the baseline sample and the sample with one MSHT cycle show pattern peaks of crystalline Fe2CrAl. In contrast, the results of eighteen MSHT cycles displayed diffraction pattern peaks of crystalline Cr and stable α-Al2O3. In summary, the results of this study reveal the changing nature of the oxide-scale layer. The findings of this study form the foundation for new techniques to protect and prepare the FeCrAl fibers as a support for catalysts.

Corneal In Vivo Laser-Scanning Confocal Microscopy Findings in Dry Eye Patients with Sjögren's Syndrome.

PURPOSE: To evaluate the changes in cornea in Sjögren's syndrome (SS) with a novel confocal microscopy device. METHODS: Twenty-three right eyes of patients with SS (23 women; mean age, 65.4 ± 11.4 years) and 13 right eyes of 13 age- and sex-matched control subjects (13 women; mean age, 68.8 ± 9.8 years) were studied. Furthermore, eight right eyes of patients with SS (8 women; mean age, 66.9 ± 9.6 years) were studied to evaluate the corneal microscopic alterations after the treatment with topical 3% diquafosol sodium eye drops. All cases had tear quantity, tear breakup time (BUT), ocular surface staining measurements, and corneal in vivo laser-scanning confocal microscopy examinations. The density and area of corneal epithelial cells (superficial, wing, and basal), density of corneal stromal cells (anterior, intermediate, and posterior), density and area of corneal endothelial cells, density and morphology of corneal sub-basal nerve plexus, density of corneal sub-basal inflammatory cells were also assessed. RESULTS: The tear quantity, stability, and vital staining scores were significantly worse in patients with SS than in control subjects (p < 0.0001). Corneal superficial epithelial cell density was significantly lower in SS compared with control subjects (p < 0.0001). Corneal superficial epithelial cell area was significantly larger in SS compared with control subjects (p = 0.007). Corneal sub-basal nerve fiber density was lower in SS compared with control subjects (p < 0.0001). Morphological abnormality of nerve fibers was observed in SS patients. Corneal sub-basal inflammatory cell density was significantly higher in SS patients compared with control subjects (p < 0.0001). Furthermore, the mean corneal superficial epithelial cell density and area, inflammatory cell density, corneal sub-basal nerve fiber density, and morphological abnormality of nerve fibers, were improved with topical 3% diquafosol sodium treatment in the dry eye patients with SS (p < 0.05). CONCLUSIONS: The diagnostic modality using in vivo laser-scanning confocal microscopy was a useful method for the evaluation of the corneal cell density and area, nerve fiber density and morphology, and inflammatory cell density in patients with SS and also a useful tool in the assessment of treatment effect with topical 3% diquafosol sodium in the SS patients.

Two regimens of dexamethasone versus prednisolone for acute exacerbations in asthmatic Egyptian children.

Introduction: Asthma is one of the most prevalent chronic respiratory diseases, which often leads to an emergency department visit. Prednisolone is the most commonly used corticosteroid in treatment of asthma exacerbation. Oral dexamethasone demonstrates bioavailability similar to that of oral prednisolone but has a longer half-life. Objective: To evaluate in adouble-blind, randomised clinical trial the efficacy of different doses of dexamethasone versus prednisolone in controlling asthma exacerbations in children. Methods: We recruited 60 patients with asthma exacerbation, aged 2-11 years. Participants were randomly divided into three groups (20 patients each). Group I received a single dose of oral dexamethasone 0.3 mg/kg (maximum 12 mg), group II received 0.6 mg/kg/day of oral dexamethasone for 2 days (maximum 16 mg/day) and group III received 1.5 mg/kg/day oral prednisolone for 5 days (maximum 60 mg/day). Our primary outcomes were changes in Paediatric Respiratory Assessment Measure (PRAM), eosinophilic count and serum immunoglobulin E on day 5. Secondary endpoints were reporting any adverse effects and relapse rate during the 5 days. After 30 days, the Asthma Therapy Assessment Questionnaire (ATAQ) was given to the parents of the recruited patients. Results: Among the three study groups, there was a highly statistically significant difference in IgE level, saturated oxygen, peak expiratory flow, forced expiratory volume in 1 s/forced vital capacity, PRAM and Modified Pulmonary Index Score; however, the eosinophilic count was significantly lower within the same group. Vomiting, gastrointestinal tract cramps, ATAQ and relapse rate showed a non-statistically significant difference. Conclusion: Single-dose dexamethasone was at least as effective as 5-day course of prednisolone in controlling asthma, while dexamethasone for 2 days was non-inferior to 5 days of prednisolone in children with asthma exacerbation.

Efficacy and Cost-effectiveness Comparison of 10-Day, 14-Day Sequential Versus 14-Day Triple Therapies for Treating Helicobacter pylori Infection in Egyptian Patients.

GOALS: The aim of this study was to clarify whether 10-day or 14-day sequential therapy (ST) can replace conventional triple therapy (TT) as a first-line treatment in Egypt. BACKGROUND: Antimicrobial resistance has decreased the eradication rates for Helicobacter pylori infection worldwide. MATERIALS AND METHODS: Patients who tested positive for H. pylori infection were randomly assigned to the 14-day triple-therapy group (n=34), 10-day ST group (n=34), or 14-day ST group (n=35). Sequential treatment includes lansoprazole 30 mg and amoxicillin 1000 mg, both twice for 5 or 7 days, followed by lansoprazole 30 mg, clarithromycin 500 mg, and tinidazole 500 mg, each twice for 5 or 7 days. Triple treatment consists of lansoprazole 30 mg, clarithromycin 500 mg, and amoxicillin 1000 mg, each twice for 14 days. Six weeks after treatment discontinuation, patients were examined by the urea breath test. Eradication rates, the incidence of adverse effects, compliance, and cost-effectiveness were evaluated. RESULTS: The eradication rate was 90% with 10-day ST, 96.7% with 14-day ST, and 63.3% for TT (P=0.001). Mild tolerated adverse effects occurred in the 3 groups. The cost-effectiveness ratio was 2194 LE, 1241 LE, 1157 LE for standard triple therapy, 10-day, and 14-day ST, respectively. CONCLUSIONS: Sequential therapies for 10 or 14 days are more cost-effective than standard TT, with 14-day ST being the most cost-effective. Accordingly, ST might replace TT as a first-line treatment for H. pylori infection in Egyptian patients.

Corneal higher-order aberrations in Stevens-Johnson syndrome and toxic epidermal necrolysis.

PURPOSE: To characterize the topography patterns and quantify corneal higher-order aberrations (HOAs) in the chronic phase of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). METHODS: This retrospective, consecutive case series included 84 eyes of 49 patients in the chronic phase of SJS/TEN. HOAs of the total cornea, and of the anterior and posterior surfaces were measured using anterior segment optical coherence tomography (AS-OCT). Corneal topography patterns were classified into one of the 4 types: ectasia-, asymmetric-, flattening- and minimal change- patterns. RESULTS: Mean logarithm of the minimal angle of resolution (logMAR) was 0.93 ±â€¯0.95. AS-OCT showed ectasia pattern in 16 eyes (19.0%), asymmetric pattern in 28 eyes (33.3%), flattening pattern in 11 eyes (13.0%) and minimal change pattern in 29 eyes (34.5%). The HOAs of the total cornea were 1.23 ±â€¯1.04 µm within a 4-mm diameter, which were significantly larger than those in normal controls (P < 0.0001). LogMAR visual acuity was significantly correlated with corneal HOAs (4-mm: r = 0.793, P < 0.0001, 6-mm: r = 0.798, P < 0.0001) and corneal astigmatism (r = 0.508, P < 0.0001), but not with average keratometric value (r = 0.198, P = 0.065). When the participants were stratified based on corneal opacity, logMAR was significantly correlated with corneal HOAs within a 4-mm diameter in opacity grades 0 (35 eyes, r = 0.649, P < 0.0001), 1 (23 eyes, r = 0.678, P = 0.0004), and 2-3 (26 eyes, r = 0.570, P = 0.0024). Ectasia pattern was derived from either corneal thinning (68.7%) or epithelial hyperplasia (31.3%). CONCLUSIONS: The most common topographic patterns for SJS/TEN were minimal change pattern and asymmetric pattern. Corneal HOAs were associated with decreased visual acuity in SJS/TEN.

Exergy Analysis of Directional Solvent Extraction Desalination Process.

This paper presents an exergy analysis to evaluate the performance of a continuous directional solvent extraction (DSE) desalination process using octanoic acid. The flow of exergy was calculated for each thermodynamic state and balanced for different components of the system to quantify the inefficiencies in the process. A parametric study was performed to evaluate the impact of three critical design variables on exergy consumption. The parametric study reveals that the total exergy input decreases significantly with an increase in heat exchanger effectiveness. The results also indicate that the heat exchangers account for the highest exergy destruction. The total exergy consumption, however, has a slightly declining trend as the recovery-ratio increases. There is a small variation in the total exergy consumption, within the uncertainty of the calculation, as the highest process temperature increases. When compared to conventional desalination processes, the exergy consumption of the DSE, with heat recovery of 90%, is comparable to those of multi-stage flashing (MSF), but much higher than reverse osmosis (RO). Octanoic acid, which has low product water yield, is identified as the primary factor negatively impacting the exergy consumptions. To exploit the low-grade and low-temperature heat source feature of the DSE process, directional solvents with higher yield should be identified or designed to enable its full implementation.

Application of In Vivo Confocal Microscopy in Dry Eye Disease.

Confocal microscopy is a new, emerging, noninvasive technology that can aid in the in vivo assessment of structural changes in several ocular surface diseases at the cellular level. In the dry eye field, in vivo confocal microscopy has been applied to the examination of the cornea, bulbar and palpebral conjunctiva, Meibomian gland, and lacrimal gland. The device can assess the morphology, including superficial/wing/basal epithelial cell density, stromal keratocyte density, endothelial cell density, nerve fiber density, the number of beadings, nerve tortuosity, nerve reflectivity, and inflammatory cell density in the cornea. Furthermore, the device can not only assess epithelial cell density and area, goblet cell, microcyst, and inflammatory cell density but also the cellular architecture, including nucleocytoplasmic ratio in conjunctiva. The device also can disclose acinar unit density, acinar unit longest diameter, acinar unit shortest diameter, and inflammatory cell density in the Meibomian gland and lacrimal gland by other potential applications. Relevant research in Europe and the United States focused on the morphologic changes in the cornea in the dry eye field, while Japanese research focused on the conjunctival, Meibomian gland, and lacrimal gland alterations. The application of in vivo confocal microscopy in dry eye disease will be a powerful method to evaluate the morphologic change of the ocular surface around the world in the future.

Eyelid cleansing with ointment for obstructive meibomian gland dysfunction.

PURPOSE: To investigate the efficacy of eyelid margin cleansing with ofloxacin ophthalmic ointment in obstructive meibomian gland dysfunction (MGD) patients. METHODS: Thirty-one eyes of 31 patients diagnosed with obstructive MGD were enrolled. All subjects were instructed to rub the eyelid edge with ofloxacin eye ointment once daily prior to bathing. Lid margin abnormalities, meibum properties, and tear stability were observed before and 3 months after ointment treatment. A questionnaire relating to the severity of MGD symptoms was administered after the treatment. RESULTS: Vascular engorgement, meibum, dandruff-like debris, and fluorescein staining scores significantly decreased after the treatment, whereas tear break-up time significantly increased (p < 0.05). Symptoms related to MGD improved after the treatment in 86.2 % of cases. CONCLUSIONS: Cleansing treatment ofloxacin ophthalmic ointment at the eyelid margin may be effective for patients with obstructive MGD.

Microwave Irradiation as a Promising Method of Sterilization for Acanthamoeba polyphaga in Cultures.

PURPOSE: To determine the killing effect of microwave irradiation on Acanthamoeba polyphaga. METHODS: The trophozoites and cysts of A. polyphaga both in water and on agar were exposed to microwave irradiation with a capacity of 750 W for 0, 1, 3, 5, and 10 minutes, respectively. Furthermore, the trophozoites and cysts of A. polyphaga in water were exposed to microwave irradiation with a capacity of 100, 300, and 500 W for 1 minute, respectively. RESULTS: The trophozoites and cysts of A. polyphaga on agar were completely killed by 3 minutes of microwave irradiation with a capacity of 750 W. The trophozoites and cysts of A. polyphaga in water were completely killed by microwave irradiation with a capacity of 300 W for 1 minute. CONCLUSIONS: We demonstrate that microwave treatment is effective in killing A. polyphaga both in water and on agar and may be a helpful modality to prevent Acanthamoeba keratitis.

The effect of Nrf2 knockout on ocular surface protection from acute tobacco smoke exposure: evidence from Nrf2 knockout mice.

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.

Effects of Oxidative Stress on the Conjunctiva in Cu, Zn-Superoxide Dismutase-1 (Sod1)-Knockout Mice.

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.

Functional visual acuity assessment of severe atopic keratoconjunctivitis.

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.

Oxidative stress induced age dependent meibomian gland dysfunction in Cu, Zn-superoxide dismutase-1 (Sod1) knockout mice.

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.

The effects of 3% diquafosol sodium application on the tear functions and ocular surface of the Cu,Zn-superoxide dismutase-1 (Sod1)-knockout mice.

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.

Evaluation of the protective effect of Cystone against cisplatin-induced nephrotoxicity in cancer patients, and its influence on cisplatin antitumor activity.

PURPOSE: Evaluating the role of cystone, a polyherbal preparation, in protecting cancer patients against cisplatin-induced nephrotoxicity, and its impact on the cytotoxic activity of cisplatin. METHODS: A prospective open-label randomized controlled trial conducted on 49 cancer patients who received six cycles of 70 mg/m(2) cisplatin-based regimens. The study comprised two groups, a control group (A) in which 28 patients received cisplatin without cystone supplement, and an experimental group (B) in which 21 patients received cisplatin with cystone supplement. Renal function parameters including serum creatinine, creatinine clearance, blood urea, and serum cystatin C were compared between both groups throughout chemotherapy cycles. Patient response to treatment was evaluated in both groups after 3rd and 6th cycles. RESULTS: At the end of the study, mean levels of serum creatinine, blood urea, and serum cystatin C were significantly lower, whereas creatinine clearance was significantly higher in group (B) compared with group (A). In group (B), there was no significant difference between mean levels of renal markers at baseline and after completion of treatment; while significant changes were observed in group (A). Grading of acute kidney injury according to Common Terminology Criteria for Adverse Events revealed significantly better renal status among patients in group (B) "grades 0 and 1 in 76 and 24 % of the patients, respectively" compared with group (A) "grades 0, 1, and 2 in 36, 32, and 32 % of the patients, respectively". Based on Response Evaluation Criteria in Solid Tumors, there was no significant difference between both groups. CONCLUSIONS: Cystone can protect cancer patients from cisplatin nephrotoxicity without interfering with its antitumor activity.