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Showing papers in "Current Eye Research in 2011"


Journal ArticleDOI
TL;DR: Blink rate, blink amplitude, and tear film stability were compromised during the most dynamic visual display terminal task, suggesting a negative influence of not only the cognitive aspects of the task, but also of the rate at which new visual information is presented.
Abstract: Purpose: The present study aimed at investigating the influence of the level of dynamism of two different visual display terminal tasks on spontaneous eyeblink rate, blink amplitude, and tear film integrity.Material and Methods: A total of 25 healthy, young volunteers participated in the study. Blink rate and blink amplitude were recorded in silent primary gaze conditions and while subjects were playing two computer games of similar cognitive demands but different rate of visual information presentation. For each experimental condition, tear volume was evaluated by measuring meniscus height and with the red phenol thread test. Fluorescein and non-invasive break-up time tests, as well as the observation of interference patterns and the estimation of the dry area extension, were employed to assess tear stability.Results: Statistically significant differences were revealed in blink rate (F = 595.85, p < 0.001) and blink amplitude (χ2 = 34.00, p < 0.001), with blink rate during fast- and slow-paced game play ...

188 citations


Journal ArticleDOI
TL;DR: The role of mitochondrial dysfunction originating from oxidative stress in the etiology of retinal diseases including diabetic retinopathy, glaucoma and age-related macular degeneration (AMD) is highlighted and mitochondria based drug targeting to diminish oxidative stress or promote repair of mtDNA damage may offer potential alternatives for the treatment of various retinal degenerative diseases.
Abstract: The mitochondrion is a vital intracellular organelle for retinal cell function and survival. There is growing confirmation to support an association between mitochondrial dysfunction and a number of retinal degenerations. Investigations have also unveiled mitochondrial genomic instability as one of the contributing factors for age-related retinal pathophysiology. This review highlights the role of mitochondrial dysfunction originating from oxidative stress in the etiology of retinal diseases including diabetic retinopathy, glaucoma and age-related macular degeneration (AMD). Moreover, mitochondrial DNA (mtDNA) damage associated with AMD due to susceptibility of mtDNA to oxidative damage and failure of mtDNA repair pathways is also highlighted in this review. The susceptibility of neural retina and retinal pigment epithelium (RPE) mitochondria to oxidative damage with ageing appears to be a major factor in retinal degeneration. It thus appears that the mitochondrion is a weak link in the antioxidant defens...

158 citations


Journal ArticleDOI
TL;DR: Anxiety and depression are correlated with dry eye syndrome, demonstrating that DES is an important public health problem that merits increased attention and research.
Abstract: Purpose: This study aimed to determine whether patients with dry eye syndrome [DES] have more symptoms of anxiety and depression than controls without DES.Methods: In this case-control study, the sample consisted of 89 DES subjects (13 diagnosed with Sjogren’s syndrome [SS]) and 73 control subjects. Each subject was diagnosed as having DES or was chosen as a control subject by an ophthalmologist. The Zung Self Rating Anxiety Scales (SAS), Zung Self Rating Depression Scales (SDS), and Ocular Surface Disease Index (OSDI) were administered to all subjects. Scores of SAS and SDS, measuring level of anxiety and depression symptoms, were compared between the DES group and the control group. Correlations with other health status measures were conducted.Results: The SAS and SDS scores of the DES group were significantly higher than the control group (P < 0.001, P < 0.001). The prevalence of DES subjects with anxiety or depression symptoms was significantly higher than in the control group (P = 0.003, P < 0.001). ...

154 citations


Journal ArticleDOI
TL;DR: OSD is common in treated glaucoma patients causing symptoms and signs that may impact on a patient’s quality of life and is directed towards any underlying disease process and the use of preservative-free or non-BAK-preserved glau coma preparations.
Abstract: Purpose: To review the prevalence, diagnosis, causes, and treatment of ocular surface disease (OSD) in patients with ocular hypertension or primary open-angle glaucoma.Methods: A review of the literature pertaining to OSD and glaucoma.Results: Recent studies indicate that OSD demonstrates an overall prevalence in glaucoma of 42% (range 20–59%) and is severe in 36% (range 14–66%). Further, the prevalence appears to increase with the greater the number of glaucoma drugs prescribed. Symptoms and signs are non-specific to the anterior surface of the eye and are thought to result from allergic, toxic, or pro-inflammatory conditions. However, the specific causes remain incompletely described, but may result from the benzalkonium chloride (BAK) preservative or occasionally the ocular hypotensive active molecule itself. Additionally, anterior segment ocular diseases might be causative, such as allergy, blepharitis, dry eye, and eyelid anatomical abnormalities. Treatment may consist of using preservative-free or n...

97 citations


Journal ArticleDOI
TL;DR: The findings of the present study are potentially of significance and add to the growing body of evidence for oxidative stress in POAG and PEG.
Abstract: Purpose: The aim of this study was to establish the antioxidant status and oxidative stress in patients with primary open-angle glaucoma (POAG) and pseudoexfoliative glaucoma (PEG).Methods: Serum levels of total antioxidant capacity (TAC) and superoxide dismutase (SOD) as indicators of antioxidant status; and total oxidant status (TOS), nitric oxide (NO), protein carbonyl (PC), and malondialdehyde (MDA) as indicators of oxidative stress were measured from the blood samples of patients with POAG (n = 23), PEG (n = 24) and healthy control subjects (n = 19) by spectrophotometry.Results: Mean TAC level was 0.6 ± 0.1 mmol/L in the POAG group; 0.5 ± 0.1 mmol/L in the PEG group and 1.2 ± 0.3 mmol/L in the control group (p = 0.001). Mean SOD level was 13 ± 0.5 mg/L in the POAG group, 11.6 ± 0.2 mg/L in the PEG group and 9.4 ± 0.6 mg/L in the control group (p = 0.001). Mean TOS level was 19.6 ± 2.6 μmol/L in the POAG group, 21.2 ± 4.2 μmol/L in the PEG group and 15.1 ± 7 μmol/L in the control group (p = 0.001). Me...

91 citations


Journal ArticleDOI
TL;DR: The combination of heat applied to the palpebral surface, while simultaneously expressing MGs during a single 12-minute treatment, was effective in treating obstructive MG dysfunction and dry eye signs and symptoms for the 3-month study period.
Abstract: Purpose: To evaluate a novel thermodynamic treatment for obstructive meibomian gland dysfunction (MGD).Materials and Methods: Fourteen adult subjects (10 females, 4 males, mean age = 54.2 ± 9.6 yr) were recruited in a multi-center, feasibility clinical trial in Durham and Cary, North Carolina and Boston, Massachusetts. Inclusion criteria included: previous diagnosis of moderate to severe dry eye; dry eye symptoms for at least three months prior; daily topical lubricant use; and evidence of meibomian gland (MG) obstruction in the central five glands of both eyes lower eyelids. Exclusion criteria included: history of recent acute or chronic ocular inflammation or infection and lid surface abnormalities affecting lid function. The treatment: the device heats the palpebral surface of upper and lower eyelids while simultaneously applying graded pulsatile pressure to the outer eyelid for 12 min, thereby expressing the MGs during heating. One eye was randomly selected to undergo additional manual heated expressi...

81 citations


Journal ArticleDOI
TL;DR: This finding provides evidence for the first time that the thickened vascular basement membrane contributes to the development of excess permeability seen in diabetic retinopathy.
Abstract: Purpose: The following study was designed to investigate early biosynthetic and ultrastructural changes that alter functional properties of the basement membrane (BM) and affect vascular permeability in diabetic retinopathy.Materials and Methods: To determine whether altered matrix synthesis affects cell monolayer permeability, rat retinal endothelial cells (RRECs) were grown for 4 days to confluency in normal (N, 5 mM) or high glucose (HG, 30 mM) medium on transwell inserts and subjected to an in vitro cell monolayer permeability assay. Inserts were cut out and viewed under a transmission electron microscope to assess extracellular matrix (ECM) accumulation and cell morphology. In parallel cell cultures, fibronectin and collagen IV protein expression were determined using Western Blot analysis.Results: Electron microscopic analysis of cells exposed to short-term HG showed no difference in inter-endothelial cell tight junctions (TJs) or in the number of vesicles or coated pits compared to those of normal ...

76 citations


Journal ArticleDOI
TL;DR: Dry eye findings and the ocular surface damage in Graves’ disease patients either with or without thyroid associated orbitopathy (TAO) were most likely associated with the Ocular surface inflammation.
Abstract: Purpose: To evaluate the tear function tests and the ocular surface damage in Graves’ disease (GD) patients either with or without thyroid associated orbitopathy (TAO).Methods: Forty-two eyes of 21 randomly selected patients with GD, and 30 eyes of 15 healthy subjects were included in this prospective study. The presence of TAO was evaluated clinically. The palpebral fissure height, degree of proptosis, ocular surface disease index (OSDI), Schirmer tear test, tear break-up time (TBUT), and conjunctival impression cytology were assessed. The results were first compared between the patient and the control groups. Results were then compared between the patients with TAO (group I) and without TAO (group II).Results: The mean OSDI score in the patient group was 44.79 ± 11.83 and it was 21.17 ± 9.89 in the control group (p = 0.001). The mean Schirmer tear test score was 14.4 ± 8.32 mm and 24.9 ± 3.57 mm in the patient and control group, respectively (p = 0.001). The mean TBUT in the patient group was 7.1 se...

75 citations


Journal ArticleDOI
TL;DR: The flush method allows much faster collection than basal secretion sampling but returns essentially the same spectrum of proteins in similar proportions, confirming that the flush technique has utility as a more convenient alternative to basal tear sampling in studies involving composition analysis.
Abstract: Purpose: To validate the more easily applicable “flush” tear collection technique as a viable alternative to basal and reflex tear collection.Materials and Methods: Total protein content (TPC) and immunoglobulin A (IgA) concentrations were determined in the basal, reflex, and flush tears of 16 healthy non-contact lens wearers. The overall protein profile was established using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and mass spectrometry (MS).Results: Collection-rates were 4.6 ± 6.7 μl/min, 13.9 ± 11.1 μl/min, and 25.7 ± 12.4 μl/min for the basal, reflex, and flush tears, respectively. TPC was 7.14 ± 2.22 mg/mL, 6.01 ± 2.11 mg/mL, and 3.79 ± 1.51mg/ mL for basal, reflex, and flush tears, respectively, with flush tears being significantly less concentrated than basal (p = 0.001) and reflex (p = 0.008). IgA concentration was 1.04 ± 0.29 mg/ mL, 0.64 ± 0.26 mg/mL, and 0.65 ± 0.23 mg/mL for basal, reflex, and flush tears, respectively, with basal tears being significantly more conc...

68 citations


Journal ArticleDOI
TL;DR: The aromatase inhibitor (AI) anastrozole affects perception similarly, but in an age-dependent manner suggesting that the change of estrogen activity towards lower levels is more important than the low estrogen activity itself.
Abstract: This review concerns the effects on vision and the eye of medications prescribed at three phases of treatment for women with early-stage breast cancer (BC): (1) adjuvant cytotoxic chemotherapy, (2) adjuvant endocrine therapy, and (3) symptomatic relief. The most common side effects of cytotoxic chemotherapy are epiphora and ocular surface irritation, which can be caused by any of several different regimens. Most notably, the taxane docetaxel can lead to epiphora by inducing canalicular stenosis. The selective-estrogen-receptor-modulator (SERM) tamoxifen, long the gold-standard adjuvant-endocrine-therapy for women with hormone-receptor-positive BC, increases the risk of posterior subcapsular cataract. Tamoxifen also affects the optic nerve head more often than previously thought, apparently by causing subclinical swelling within the first 2 years of use for women older than ~50 years. Tamoxifen retinopathy is rare, but it can cause foveal cystoid spaces that are revealed with spectral-domain optical coherence tomography (OCT) and that may increase the risk for macular holes. Tamoxifen often alters the perceived color of flashed lights detected via short-wavelength-sensitive (SWS) cone response isolated psychophysically; these altered perceptions may reflect a neural-response sluggishness that becomes evident at ~2 years of use. The aromatase inhibitor (AI) anastrozole affects perception similarly, but in an age-dependent manner suggesting that the change of estrogen activity towards lower levels is more important than the low estrogen activity itself. Based on analysis of OCT retinal thickness data, it is likely that anastrozole increases the tractional force between the vitreous and retina. Consequently, AI users, myopic AI users particularly, might be at increased risk for traction-related vision loss. Because bisphosphonates are sometimes prescribed to redress AI-induced bone loss, clinicians should be aware of their potential to cause scleritis and uveitis occasionally. We conclude by suggesting some avenues for future research into the visual and ocular effects of AIs, particularly as relates to assessment of cognitive function.

67 citations


Journal ArticleDOI
TL;DR: Overnight orthokeratology induces structural and optical changes particularly in the central corneal epithelium during myopia treatment, and irreversible changes detected indicate a need for further investigation.
Abstract: Purpose: To assess long-term morphological and biometric corneal changes produced by overnight orthokeratology and to examine their recovery after cessation of contact lens wear. Methods: Prospective, single-center, longitudinal trial. Fifteen right eyes with low to moderate myopia underwent overnight orthokeratology for 1 year. The central cornea was examined using a confocal microscope and changes determined in visual acuity, refractive error and corneal topography. Cell counts were performed using both the confocal microscope’s software and the image analysis software of the USA Health Institute. All measurements were made during orthokeratology treatment and 1 month after discontinuing treatment. Results: No significant changes in endothelial cell density were observed over time but polymegethism increased significantly and baseline values were not recovered (p < 0.01). Stromal cell density remained unchanged though numbers of activated keratocytes increased during the study and returned to baseline when lens wear ceased. Basal epithelium cell densities significantly fell (p < 0.01) and epithelial wing and superficial cells showed enhanced visibility (p < 0.05). Superficial cells increased in height and width; this width increase being significant after 1 year of orthokeratology (p < 0.01). All epithelial cell changes returned to baseline. Corneal thickness, Bowman layer thickness, subbasal plexus thickness and epithelial thickness were reduced in the central cornea but the stroma was thickened. Of these changes, the decrease in epithelium thickness reached statistical significance (p < 0.01) and baseline values were not recovered. Conclusion: Overnight orthokeratology induces structural and optical changes particularly in the central corneal epithelium during myopia treatment. If confirmed, the irreversible changes detected indicate a need for further investigation.

Journal ArticleDOI
TL;DR: Y-39983 may be a candidate drug not only for lowering of IOP but also for increasing of blood flow in ONH in the treatment of glaucoma, although improvements of formulation or route of administration are needed in order to reach an effective concentration in retina.
Abstract: Purpose: To investigate the effects of Y-39983, a selective Rho-associated coiled coil-forming protein kinase inhibitor, on blood flow in the optic nerve head (ONH) in rabbits and axonal regeneration of retinal ganglion cells (RGCs) in rats.Methods: Blood flow in ONH was measured by the laser speckle method after topical administration of 0.05% Y-39983 solution or its vehicle in rabbit eyes. To investigate the effects of Y-39983 on axonal regeneration of RGCs, RGCs purified from rat eyes were cultured with or without 10 μM Y-39983 and morphologically observed by phase-contrast microscopy. Moreover, the effects of intravitreal administration of Y-39983 were evaluated using an in vivo model of axotomized RGCs in peripheral nerve-grafted rats.Results: Topical administration of 0.05% Y-39983 solution significantly increased blood flow in ONH compared with the vehicle group in rabbits. Maximum increase in blood flow in the 0.05% Y-39983 group was 122.84 ± 5.98 % (Mean ± S.E.) at 90 minutes after administration...

Journal ArticleDOI
TL;DR: The data suggest that the continuous IOP fluctuation monitoring device is sensitive to individual IOP rhythms and to differences in such rhythms due to anti-glaucomatous drug therapy.
Abstract: Background: Intraocular pressure (IOP) remains the only treatable risk factor of progressive glaucoma. Recently a device became available to continuously record IOP fluctuation in contrast to classical, discreet IOP measurements.Objectives: To perform 24-h IOP fluctuation monitoring using a CE-marked silicone lens-embedded strain gauge sensor (SENSIMED Triggerfish) in five normal tension glaucoma patients in the presence and absence of anti-glaucomatous treatment and to show the clinical importance of this diagnostic tool.Methods: 24-h continuous IOP fluctuation monitoring was performed on two occasions separated by at least 6 weeks in each patient. In the control session patients were untreated or previous IOP-lowering medication was washed-out for at least 6 weeks. In the treatment session patients received IOP-lowering medication for at least 6 weeks. The continuous recordings were analyzed for differences between daytime and nighttime data and for repeatability over time. Furthermore, profiles recorde...

Journal ArticleDOI
TL;DR: Tear osmolarity values were found to be greater in patients with dry eye syndrome related to primary SS compared to control subjects, and positively correlated with the severity of dry eye.
Abstract: Background: To evaluate the tear osmolarity in patients with dry eye syndrome related to primary Sjogren’s Syndrome (SS).Materials and Methods: Twenty eyes of 10 patients with dry eye and primary SS (Group 1) and 20 eyes of 20 subjects who do not have dry eye syndrome (Group 2) were included in this cross-sectional study. In all eyes, ophthalmic examination was performed in the same order: International Ocular Surface Disease Index survey, visual acuity assessment, conjunctival hyperemia scoring, tear osmolarity measurement with TearLab™ Osmolarity System, tear film break-up time assessment, corneal fluorescein staining scoring, ocular surface Lissamine Green staining scoring, anesthetized Schirmer test. Dry eye severity was graded according to Dry Eye Workshop (DEWS) classification system.Results: Four eyes with grade 1, four eyes with grade 2, seven eyes with grade 3, and five eyes with grade 4 dryness, according to DEWS system, were included. The mean tear osmolarity value was 301.9 ± 11.40 mOsm/L (ran...

Journal ArticleDOI
TL;DR: While the majority of ocular MRSA strains in this study fit the classical profile of HA- and CA- MRSA, some CA-MRSA isolates exhibited higher levels of antimicrobial resistance, which should be of particular concern to eye-care professionals.
Abstract: Purpose: Methicillin-resistant Staphylococcus aureus (MRSA) strains are commonly classified as hospital-acquired (HA) or community-acquired (CA). Typical HA-MRSA isolates are characterized by multidrug resistance and the SCCmec type II cassette, while CA-MRSA isolates are generally susceptible to more drug classes, are often of SCCmec type IV, and frequently carry the PantonValentine leukocidin (PVL) genes. This study determined the presence of traits characteristic for CA and HA strains in ocular MRSA isolates. Materials and Methods: Fifty-six recent ocular isolates, consisting of 40 MRSA and 16 methicillinsusceptible Staphylococcus aureus (MSSA) comparator strains, were characterized. Minimum inhibitory concentration (MIC) testing was done according to current Clinical and Laboratory Standards Institute guidelines. Detection of the PVL encoding genes and determination of the SCCmec type was done by polymerase chain reaction (PCR), while spa typing and cluster analysis was performed following DNA sequencing. Results: Of the 38 typeable MRSA isolates, 22 were of SCCmec type II and 16 were of SCCmec type IV. All SCCmec type II isolates were multidrug-resistant, lacked the PVL genes, and were of spa type t002 or closely related spa types. In contrast, the SCCmec type IV isolates were resistant to fewer classes of antimicrobial agents, often possessed the PVL genes (75.0%), and were of spa type t008 or closely related spa types. Conclusions: While the majority of ocular MRSA strains in this study fit the classical profile of HAand CA-MRSA, some CA-MRSA isolates exhibited higher levels of antimicrobial resistance, which should be of particular concern to eye-care professionals. Furthermore, the apparent association of spa types and SCCmec types observed here warrants further investigation and suggests that spa typing may be useful in future HA- and CA-MRSA characterization studies.

Journal ArticleDOI
TL;DR: Long-term storage of amniotic membrane in cell culture media with 50% glycerol does not significantly impair sterility, histology, or biological properties of AM.
Abstract: Purpose: Cryopreserved amniotic membrane (AM) is widely used in ophthalmology because of its anti-angiogenic, anti-inflammatory, and wound healing promoting capabilities. A common method to conserve the tissue is the storage in cryo-medium containing 50% glycerol at −80°C. The aim of this study was to examine the influence of storage time on the sterility as well as the histological and biological properties of cryopreserved AM.Methods: Amniotic membrane from different donors was stored in cell culture media containing 50% glycerol for different time periods, on average 4 months (group 1), 15 months (group 2), and 24 months (group 3), at −80°C. Samples of the tissue and cryo-medium were examined for bacterial and fungal contamination. Tissue samples were incubated in 0.5 ml/cm2 serum-free medium at 37°C. The medium was changed after 1, 2, and 3 days. The proteins released by AM were TCA-precipitated and the presence of the proteins TIMP-1 and IL-1ra was analyzed using Western blotting and semi quantified ...

Journal ArticleDOI
Tianyu Zheng1, Yi Lu1
TL;DR: The expression of SIRT1 increased in ARC in humans, and its downstream p53 was inhibited, and FOXO pathway was activated, indicating that Sirt1 may play a protective role in ARC formation.
Abstract: Purpose: SIRT1, the most well-known sirtuin family (class III histone deacetylases) member, is involved in many age-related diseases. However, no study has demonstrated its relationship with age-related cataract (ARC). This study was to investigate the expression of SIRT1 in human lens epithelial cells, and to observe the changes in SIRT1 expression and its downstream P53 and forkhead box class O (FOXO) proteins at the onset of ARC.Methods: The anterior lens capsule specimens from 360 normal human donor eyes (age 19–91 years) were divided into three groups: group A of young lens (younger than age 49 without cataract), group B of old but normal lens (older than age 50 without cataract), and group C of ARC lens (older than age 50 with ARC). Real-time quantitative reverse transcription of SIRT1 mRNA; Western blot analysis by anti-SIRT1, anti-p53, anti-p53 (acetyl K379), anti-FOXO3a, anti-FOXO4, anti-p27kip1, anti-p130, and anti-Bim; immunofluorescence of SIRT1; and TUNEL assay were performed in each group.Re...

Journal ArticleDOI
TL;DR: Bvacizumab, ranibizumAB, pegaptanib, and trastuzumab were found effective for the inhibition of corneal NV and it was detected that the most effective agent was bevaczumab.
Abstract: Aim and scope: To investigate the inhibitory effect of subconjunctival application of VEGF antibodies bevacizumab, ranibizumab, pegaptanib, and HER2 antibody trastuzumab on corneal neovascularization in a rat model of experimental corneal neovascularization.Material and method: Thirty male Wistar albino rats were included in the study. A chemical burn was induced in central cornea of one eye of the rats by a 75% silver nitrate and 25% potassium nitrate stick. Rats were randomly divided into five groups so that each group contained 6 subjects. Right after the chemical burn, 0.1 ml serum physiologic was injected subconjuctivally in control group (group 1). 1.25 mg/0.05 ml bevacizumab was injected in group 2; 1.2 mg/0.1 ml trastuzumab was injected in group 3; 0.5 mg/0.05 ml ranibizumab was injected in group-4; and 0.3 mg/0.1 ml pegaptanib was injected in group 5. On the 8th day of the experiment, rat corneas were photographed by digital photo-camera. Later, eyes of the sacrificed rats were enucleated and cor...

Journal ArticleDOI
TL;DR: The decrease in corneal volume in moderate and severe keratoconus as detected by the Pentacam tomographer, may be explained by loss of cornea tissue.
Abstract: Purpose: To compare the corneal volume in keratoconic and normal eyes to improve our understanding of the tissue distribution associated with the disease.Materials and Method: The Oculus Pentacam tomographer (Oculus Inc., Wetzlar, Germany) was used to analyze the corneal volume contained within discs with diameters of 3, 5, 7, and 10 mm in 21 patients with keratoconus and 21 matched healthy control subjects.Results: Corneal volume was significantly decreased in the keratoconus group (keratoconus vs. control group: 3.44 ± 0.39 vs. 4.05 ± 0.29 mm3, 10.34 ± 0.95 vs. 11.79 ± 0.84 mm3, 22.80 ± 1.73 vs. 25.26 ± 1.74 mm3, and 57.17 ± 3.94 vs. 61.90 ± 4.12 mm3 for the 3-, 5-, 7-, and 10-mm diameter discs, respectively; p < 0.001). As the corneal disc diameter analyzed increased, fewer differences were found between the control corneas and keratoconic corneas at different stages of the disease. Within the 3-mm and 5-mm diameter discs, significant differences were detected between the control group, moderate kerato...

Journal ArticleDOI
TL;DR: The developed HP-β-CD-based mucoadhesive system is a viable alternative to conventional eye drops of DXN due to its ability to enhance bioavailability through its longer precorneal residence time and ability to sustain the release of the drug.
Abstract: Purpose: Dexamethasone (DXN) is an effective anti-inflammatory drug in the treatment of acute and chronic eye disease such as uveitis. It is relatively lipophilic and permeates biological membranes quite easily. However, its low aqueous solubility limits its clinical usefulness. To circumvent this problem Hydroxypropyl-β-cyclodextrin (HP-β-CD) was used as solubilizer and penetration enhancer for DXN. The purpose of this study was to develop HP-β-CD based pH-induced mucoadhesive hydrogel for ophthalmic delivery of DXN to treat uveitis.Materials and methods: The formation of inclusion complex of DXN with HP-β-CD was characterized in solution and solid states by phase solubility, X-ray diffractometry and IR spectrum analyses. To improve ocular retention and sustained action Carbopol 980 NF and sodium carboxymethylcellulose (NaCMC) were added to the formulations as phase transition and mucoadhesive agents, respectively.Results: The HP-β-CD-based hydrogel system enhanced the solubility of DXN and the apparent ...

Journal ArticleDOI
TL;DR: Green light appears to suppress induction of melatonin production and in the guinea pig, MT1 receptor and melanopsin appear to play roles in the development of myopia induced by 530 nm of light.
Abstract: Purpose: To investigate (i) the effect of monochromatic light on inhibiting induction of light-induced melatonin and (ii) the roles of melanopsin and MT1 receptor in light-induced myopia in the guinea pig.Methods: Forty-eight guinea pigs were randomly distributed into three treatment groups: white-light (control), green-light (530 nm), and blue-light (480 nm) groups. Levels of pineal gland melatonin were measured twice daily—10:00 a.m. and 10:00 p.m.—10 days after initial light treatment. Thirty additional guinea pigs were also assigned to these groups and treated similarly. For these latter animals, refractive status, ocular length, and vitreous depth were measured before and after light treatment. Eight weeks after light treatment, retinal and sceral levels of melanopsin, melatonin receptor type (MT) 1, and mRNA protein were determined by Western blotting, real-time polymerase chain reaction (RT-PCR), and immunohistochemistry.Results: The level of pineal gland melatonin in the green-light group was sign...

Journal ArticleDOI
TL;DR: The findings show that coldCataract development is temperature dependent and that cataract formation starts between 10 and 20 min after exposure to low temperature, relevant for those experimental settings in which clear ocular media are required.
Abstract: Purpose: The aim of the present study was to study the time-course development of cold cataract in mice under general anesthesia.Methods: We anesthetized five groups of 10 mice (12 weeks old) with 400 mg/Kg intraperitoneal injections of chloral hydrate and exposed them to 0, 7, 15, 23, and 37°C for 1 hr. Cataract development was assessed and graded as no cataract, mild, medium, or severe at 10, 20, 30, 45, and 60 min after the exposure started. For quantification purposes, a value from 0 to 3 was assigned to each cataract grade, and the median value was calculated for each group and time point (cataract index, CI).Results: The CI for each temperature fitted a negative exponential equation. We found that four mice of the 37°C group, nine of the 23°C group, and all animals of the 15, 7, and 0°C groups developed cataract. The cataract started at 10 min after exposure to 0°C and at 20 min when exposed to 7, 15, and 23°C. The speed of development and CI significantly increased with lower temperatures. Similar ...

Journal ArticleDOI
TL;DR: Serum VEGF increased significantly after metastases developed, however, the wide inter-patient variance precludes the use of any cut-off level to determine the metastatic status of an individual patient based on a single V EGF serum level.
Abstract: Purpose: High levels of serum VEGF have been reported in many types of cancers, especially in the metastatic stage. The aim of this study was to examine the potential of VEGF serum level as a tumor marker for metastases in uveal melanoma (UM) patients.Materials and Methods: Levels of serum VEGF were analyzed by ELISA for 23 UM patients (none of whom developed metastases within 5 years from diagnosis) at the time of diagnosis, soon after treatment, and 3 years later, and compared with serum VEGF levels of 39 metastatic patients, 58 10-year disease-free (10yDF) patients, and 23 healthy subjects. VEGF ratios were calculated per patient between diagnosis and after treatment, and between diagnosis and 3 years later. Matched pairs univariate analysis was performed for 17 metastatic patients for whom sera were available from before and after the diagnosis of metastases. Patients were followed biannually with liver ultrasonography and liver function tests for the presence of metastases.Results: The inter-patient ...

Journal ArticleDOI
TL;DR: The idea that tear film instability is associated with the quantity of lid margin lipid is not supported by this study because the quantity did not change with MGD.
Abstract: Purpose: The purpose of this study was to determine if the variability in the amount of lid margin meibum is from donor-to-donor or from day-to-day variations and to determine if meibum from donors with meibomian gland dysfunction (MGD) had altered levels of casual eyelid meibum or skin sebum.Methods: Lipid absorbent Sebutape® was used to collect sebum or meibum. Samples were collected from six donors without dry eye and 21 donors with MGD. Lipid absorbed to Sebutape® was quantified using infrared and visible absorbance spectroscopy.Results: The amount of sebum from donors with MGD and donors without MGD was not significantly different. The amount of casual meibum from normal donors was 50% lower than that for donors with MGD using the spectroscopic assay, but was not significantly different using the chemical assay. The frequency and bandwidth of the infrared carbonyl band from sebum samples was significantly higher than that for meibum samples which indicates the carbonyls are in a different “dielectric...

Journal ArticleDOI
TL;DR: Taprenepag isopropyl significantly reduces IOP in POAG and ocular hypertension and is additive to that of latanoprost 0.005% in reducing IOP.
Abstract: Purpose: To evaluate the safety of escalating doses of taprenepag isopropyl (PF-04217329), a selective EP2 receptor agonist administered as a topical ophthalmic solution, versus its vehicle (Stage I), and dose-response of taprenepag isopropyl alone and in unfixed combination with latanoprost ophthalmic solution 0.005% versus latanoprost alone (Stage II).Subjects and Methods: Randomized, vehicle- and active-controlled, double-masked, two-stage, dose-finding trial in primary open-angle glaucoma (POAG) or ocular hypertension; first taprenepag isopropyl study in patients (NCT00572455). Study eye: 26 mmHg ≤ intraocular pressure (IOP) <36 mmHg at 8 am and 22 mmHg ≤ IOP <36 mmHg at 10 am, 1 pm, 4 pm. Stage I: 3 cohorts (total n = 67) received 1 drop of taprenepag isopropyl unit dose formulation qPM/eye for 14 days: low dose: 0.0025%, 0.005%, vehicle; middle dose: 0.01%, 0.015%, vehicle; high dose: 0.02%, 0.03%, vehicle. Stage II: 7 groups (total n = 250) received 1 drop of taprenepag isopropyl multidose formulat...

Journal ArticleDOI
TL;DR: In this paper, the authors investigated the effect of rapamycin on the cell death of human corneal endothelial cells (HCECs) using an oxidation-sensitive fluorescent probe.
Abstract: Purpose: To investigate the protective effect of rapamycin on oxidative stress-induced cell death of human corneal endothelial cells (HCECs).Methods: HCECs were cultured according to previously published methods. With treatment of 0 mM or 5 mM of tert-butyl hydroperoxide (tBHP) with various concentrations (0, 25 and 50 nM) of rapamycin, reactive oxygen species (ROS) production was measured using an oxidation-sensitive fluorescent probe, 2′7′-dichlorofluorescin diacetate (DCFH-DA, USA) methods. Cell viability was assayed by the method of Cell Counting Kit-8 (CCK-8, Wako). The levels of cellular glutathione were also assessed enzymatically with glutathione reductase by using a commercial glutathione (GSH) assay kit (Cayman Chemical, USA).Results: Rapamycin reduced 2′7′-dihydrodichlorofluorescein oxidation and increased GSH in HCECs. Rapamycin significantly inhibited tBHP-induced ROS production. Cells treated with rapamycin showed higher viability compared to control at 5 mM tBHP. Rapamycin effectively prote...

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TL;DR: Flap creation with the Intralase laser does produce a biomechanical consequence consistent with reduction of corneal stiffness, as measured by the reduced amplitude of Peak 1, but CH and CRF do not fully characterize this change.
Abstract: Purpose: This study aims to investigate the effect of both flap creation and laser ablation on corneal hysteresis (CH) and corneal resistance factor (CRF), as well as the inward applanation signal amplitude produced by the ocular response analyzer (ORA), immediately following each step of the LASIK procedure using the Intralase femtosecond laser for flap creation.Methods: A total of 66 eyes of 35 subjects who underwent Intra-LASIK surgery were prospectively enrolled in this study. Changes in the CH, CRF, and amplitude of the first applanation peak (Peak 1) of the infrared signal were measured preoperatively, immediately after flap elevation and repositioning, as well as subsequent to laser ablation in all eyes. Repeated measures analysis of variance (ANOVA) was performed with a post-test of contrast variable profiles to investigate changes following each step of the procedure.Results: The repeated measures ANOVA indicated a significant difference (p < 0.001) among the three time points for CH, CRF, and Pe...

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TL;DR: The results, and in particular the absence of a primary damage to the epithelial stem cells, indicate the presence of a therapeutic window for intervention to avoid the development of the delayed Limbal Stem Cell Deficiency.
Abstract: Purpose: Ocular injuries following exposure to the chemical agent sulfur mustard (SM) are characterized by acute corneal erosions and inflammation of the anterior segment that may be followed by delayed Partial Limbal Stem Cell Deficiency (LSCD), expressed clinically by corneal neovascularization and epithelial defects. LSCD may derive from direct destruction of limbal stem cells or indirectly from altered limbal stromal niche. The aim of this study was to investigate the mechanism underlying LSCD in SM injuries, focusing on the effects of the chemical on limbal epithelium.Methods: Rabbit eyes were exposed to SM vapor and were observed by slit lamp examinations and pachymetry. Eyes were taken for histological and molecular biology evaluations at different time points (4 h–4 weeks), to include acute and delayed injuries. Epithelial stem cells were identified by ABCG2, p63 and by in vivo BrdU labeling for slow cycling cells.Results: Limbal stem cells were not damaged during the acute phase following SM expo...

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TL;DR: The data suggest that experimental diabetic retinopathy is associated with a complex pattern of alteration in the retinal AQP expression that might be involved in the adaptation of retinal cells to hyperglycemic conditions and the development and/or resolution of Retinal edema.
Abstract: Purpose/Aim: The development of retinal edema is the main reason of impaired vision in non-proliferative diabetic retinopathy. Water transport through aquaporins (AQPs) has been suggested to facilitate the development of ischemic edema in the retina. Here, we investigated whether experimental diabetic retinopathy in rats results in alterations of the AQP expression in the neural retina and retinal pigment epithelium (RPE).Materials and Methods: Experimental diabetes in rats was induced by a single intravenous injection of streptozotocin (65 mg/kg body weight). The gene expression of AQPs in tissues from control and diabetic rats was examined by real-time RT-PCR. Retinal cryosections were immunostained against AQP5, 6, and 9.Results: The total RNAs extracted from the neural retina and RPE contained gene transcripts for AQP0, 1, 3, 4, 5, 6, 8, 9, 11, and 12. Experimental diabetes was associated with an upregulation of AQP1 in the neural retina, and of AQP5, 9, 11, and 12 in the RPE. Furthermore, diabetes wa...

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Na Rae Kim1, Chan Yun Kim1, Hyunjoong Kim1, Gong Je Seong1, Eun Suk Lee1 
TL;DR: IOP measurement differences between the three tonometers are affected by age, type of glaucoma, and especially CCT and IOP levels.
Abstract: Purpose: To compare intraocular pressure (IOP) measurements by Goldmann applanation tonometer (GAT), noncontact tonometer (NCT), and TonoPen XL in glaucomatous, ocular hypertensive (OHT), and normal eyes, all with various central corneal thickness (CCT).Methods: In 508 subjects, IOP was measured by three different tonometers: GAT, NCT, and TonoPen. CCT was also measured.Results: There was a statistically significant difference between IOP measurements made using the three different tonometers (RMANOVA, P < 0.0001). Both NCT/GAT and TonoPen/GAT differences were significantly associated with age, CCT, IOP, and glaucoma diagnosis (multiple regression analysis, all P ≤ 0.05). CCT and IOP had the greatest effect on IOP measurement variance by different tonometers. IOP measurements made by NCT were consistently higher than those made by GAT; this difference increased both with IOP and CCT levels, but decreased with age and OHT. In addition, TonoPen overestimated the GAT in the eyes of subjects with OHT.Conclusi...