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Showing papers in "Current Eye Research in 2014"


Journal ArticleDOI
TL;DR: In vivo confocal microscopy 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.
Abstract: 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 minireview 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.

167 citations


Journal ArticleDOI
TL;DR: This review focuses on the molecular basis of mechanical strain transduction as a primary mechanism that can damage RGCs and molecules that mediate these mechanosensory and immune responses represent plausible targets for protecting ganglion cells in glaucoma, optic neuritis and retinal ischemia.
Abstract: Purpose of the study: Many blinding diseases of the inner retina are associated with degeneration and loss of retinal ganglion cells (RGCs). Recent evidence implicates several new signaling mechanisms as causal agents associated with RGC injury and remodeling of the optic nerve head. Ion channels such as Transient receptor potential vanilloid isoform 4 (TRPV4), pannexin-1 (Panx1) and P2X7 receptor are localized to RGCs and act as potential sensors and effectors of mechanical strain, ischemia and inflammatory responses. Under normal conditions, TRPV4 may function as an osmosensor and a polymodal molecular integrator of diverse mechanical and chemical stimuli, whereas P2X7R and Panx1 respond to stretch- and/or swelling-induced adenosine triphosphate release from neurons and glia. Ca 2þ influx, induced by stimulation of mechanosensitive ion channels in glaucoma, is proposed to influence dendritic and axonal remodeling that may lead to RGC death while (at least initially) sparing other classes of retinal neuron. The secondary phase of the retinal glaucoma response is associated with microglial activation and an inflammatory response involving Toll-like receptors (TLRs), cluster of differentiation 3 (CD3) immune recognition molecules associated with the T-cell antigen receptor, complement molecules and cell type-specific release of neuroactive cytokines such as tumor necrosis factor-a (TNF-a) and interleukin-1b (IL-1b). The retinal response to mechanical stress thus involves a diversity of signaling pathways that sense and transduce mechanical strain and orchestrate both protective and destructive secondary responses. Conclusions: Mechanistic understanding of the interaction between pressure-dependent and independent pathways is only beginning to emerge. This review focuses on the molecular basis of mechanical strain transduction as a primary mechanism that can damage RGCs. The damage occurs through Ca 2þ -dependent

131 citations


Journal ArticleDOI
TL;DR: Determination of oxidative stress in aqueous humor may help in understanding the course of this disease, and oxidative damage might be a relevant target for both prevention and therapy.
Abstract: Purpose: The present study was designed to determine the levels of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) and non-enzymatic antioxidants (vitamins C and E) in aqueous humor of primary open angle glaucoma (POAG) and primary angle closure glaucoma (PACG) patients.Materials and Methods: In this study, aqueous humor of POAG (n = 30) and PACG (n = 30) patients was obtained. For control, aqueous humor of 30 age-matched cataract patients (n = 30) was collected. Activities of antioxidant enzymes and non-enzymatic antioxidants levels were measured spectrophotometrically.Results: A significant increase in superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities was found in aqueous humor of POAG and PACG patients as compared to cataract patients (p < 0.001). No significant changes were observed in catalase activity. The levels of vitamins C and E were significantly lower in the aqueous humor of POAG and PACG as compared to cataract patients (p < 0.001)...

128 citations


Journal ArticleDOI
TL;DR: Results indicated that K-115 ophthalmic solution, a selective and potent ROCK inhibitor, is a novel and potent antiglaucoma agent.
Abstract: Purpose: To evaluate the topical instillation of K-115, a selective Rho-associated coiled coil-containing protein kinase (ROCK) inhibitor, on intraocular pressure (IOP), ocular distribution, and aqueous humor dynamics in experimental animals.Methods: Kinase inhibition by K-115 was measured by biochemical assay. IOP was monitored using a pneumatonometer in albino rabbits and monkeys after topical instillation of K-115. The ocular distribution of [14C]K-115 was determined by whole-head autoradiography. The aqueous flow rate was determined by fluorophotometry. The total outflow facility and uveoscleral outflow were measured by two-level constant pressure perfusion and perfusion technique using fluorescein isothiocyanate-dextran, respectively.Results: Biochemical assay showed that K-115 had selective and potent inhibitory effects on ROCKs. In rabbits, topical instillation of K-115 significantly reduced IOP in a dose-dependent manner. Maximum IOP reduction was observed 1 h after topical instillation, w...

85 citations


Journal ArticleDOI
TL;DR: This article reviews the advantages and disadvantages of the established carrier materials for limbal stem cell transplantation, as well as discussing emerging alternatives, including carriers based on collagen, fibrin, siloxane hydrogel contact lenses, poly(ε-caprolactone), gelatin–chitosan, silk fibroin, human anterior lens capsule and poly(lactide-co-glycolide).
Abstract: Severe ocular surface disorders can result in deficiency of limbal stem cells that is potentially associated with chronic inflammation, impaired vision and even blindness. Advanced stem cells deficiency requires reconstruction of the OS with autologous or allogeneic limbal stem cells. To address such deficiency, a limbal tissue biopsy is taken and limbal cells are expanded on a carrier, which then can be used for OS reconstruction. Human amniotic membrane - currently the most common carrier for transplantation of limbal epithelial stem cells - has the downsides of carrying the risk of disease transmission, limited transparency, variable and unstable quality and low mechanical strength. This article reviews the advantages and disadvantages of the established carrier materials for limbal stem cell transplantation, as well as discussing emerging alternatives, including carriers based on collagen, fibrin, siloxane hydrogel contact lenses, poly(e-caprolactone), gelatin-chitosan, silk fibroin, human anterior lens capsule, keratin, poly(lactide-co-glycolide), polymethacrylate, hydroxyethylmethacrylate and poly(ethylene glycol) for their potential use in the treatment of limbal stem cell deficiency.

62 citations


Journal ArticleDOI
TL;DR: The choroidal and retinal thicknesses did not differ significantly between the healthy young smokers and non-smokers, and smoking caused acute, significant increase in choroid thickness that returned to baseline levels after 1 h.
Abstract: Purpose: To evaluate the acute and chronic effects of cigarette smoking on the choroidal thickness of young male smokers with smoking histories exceeding 10 years using spectral domain optical coherence tomography (SD OCT).Materials and methods: The right eyes of 40 never-smoking and 30 smoking healthy subjects were included in this study. We measured the choroidal thicknesses of the never-smoking subjects as a control group. The choroidal thicknesses of the smoking subjects were measured before, 5, 30 and 60 min after smoking. Choroidal thickness measurements were taken at the fovea and at two points that were 1500 µm nasal and temporal to the fovea.Results: No significant difference was found for the retinal thickness, choroidal thicknesses, spherical equivalent, intraocular pressure and central corneal thickness of the smokers and non-smokers (p > 0.05 for all). In the measurements that were taken after smoking, a statistically significant increase was found in choroidal thickness that was obse...

60 citations


Journal ArticleDOI
TL;DR: The significant correlation of LSFG-measured tissue area falling rate with age suggests that it may be a new candidate biomarker for age-dependent microcirculation.
Abstract: Purpose: Laser speckle flowgraphy (LSFG), a new, non-invasive method of measuring the mean blur rate (MBR) of ocular blood flow, allows for the analysis of the pulse waveform of a heartbeat as it changes dynamically. Here, we investigated the relationship between the pulse waveform and clinical parameters, particularly age.Materials and methods: Sixty eyes of 60 healthy subjects without diabetes were enrolled from among patients undergoing annual health examinations. LSFG, and its analysis software, were used to determine pulse waveform parameters including MBR, skew, blowout score (BOS), blowout time (BOT), rising rate and falling rate in the optic nerve head (ONH), both specifically in the tissue area and in the ONH overall. Fifteen clinical parameters were also recorded, including age and blood pressure, as well as triglyceride and creatinine levels.Results: Skew, BOT and falling rate had a strong correlation (|r| > 0.60) with age, but not with the other clinical parameters. This correlation wi...

57 citations


Journal ArticleDOI
TL;DR: Trainable segmentation in Fiji software using CAM is a novel approach to measuring ECL that captured a statistically significantly higher percentage of ECL comparable to Adobe and was more accurate in standardized testing.
Abstract: Purpose: To improve accuracy and efficiency in quantifying the endothelial cell loss (ECL) in eye bank preparation of corneal endothelial grafts.Methods: Eight cadaveric corneas were subjected to Descemet Membrane Endothelial Keratoplasty (DMEK) preparation. The endothelial surfaces were stained with a viability stain, calcein AM dye (CAM) and then captured by a digital camera. The ECL rates were quantified in these images by three separate readers using trainable segmentation, a plug-in feature from the imaging software, Fiji. Images were also analyzed by Adobe Photoshop for comparison. Mean times required to process the images were measured between the two modalities.Results: The mean ECL (with standard deviation) as analyzed by Fiji was 22.5% (6.5%) and Adobe was 18.7% (7.0%; p = 0.04). The mean time required to process the images through the two different imaging methods was 19.9 min (7.5) for Fiji and 23.4 min (12.9) for Adobe (p = 0.17).Conclusions: Establishing an accurate, efficient and re...

56 citations


Journal ArticleDOI
TL;DR: Topically applied eye drops containing a mixture of omega-3 EFAs and HA could improve corneal irregularity and corNEal epithelial barrier disruption, and decrease inflammatory cytokines and oxidative stress markers on the ocular surface.
Abstract: Purpose: To investigate the efficacy of the topical application of omega-3 essential fatty acids (EFAs) and hyaluronic acid (HA) mixtures in a mouse model of experimental dry eye (EDE).Methods: Eye drops consisting of 0.1% HA, 0.02%, or 0.2% omega-3 EFAs alone and mixture of 0.02%, or 0.2% omega-3 EFAs and 0.1% HA were applied in desiccating stress-induced murine dry eye. Corneal irregularity scores and fluorescein staining scores were measured 5 and 10 days after treatment. Levels of interleukin (IL)-1β, -17, and interferon gamma-induced protein (IP)-10 were measured in the conjunctiva at 10 days using a multiplex immunobead assay. The concentrations of hexanoyl-lys (HEL) and 4-hydroxynonenal (4-HNE) in conjunctiva tissue were measured with enzyme-linked immunosorbent assays.Results: Mice treated with the mixture containing 0.2% omega-3 EFAs showed a significant improvement in corneal irregularity scores and corneal fluorescein staining scores compared with EDE, HA, 0.02% or 0.2% omega-3 EFAs alo...

55 citations


Journal ArticleDOI
TL;DR: A combination of ssOCT with autokeratometry yielded the best predictive quality for planning of toric IOL implantation and OCT as well as hybrid topography had better predictive precision due to posterior curvature data.
Abstract: Purpose: To compare corneal measurements obtained by a swept source fourier domain OCT (CASIA SS-1000), an autokeratometer (Haag-Streit Lenstar), a hybrid topographer (Tomey TMS-5), a Placido topographer (Tomey TMS-5 in Placido mode) and a Scheimpflug tomographer (Oculus Pentacam) to manifest subjective refraction.Methods: One hundred and four pseudophacic patients with non-toric IOLs were measured at least 6 months after surgery. Corneal astigmatism as measured on the anterior corneal surface as well as total corneal astigmatism including posterior surface data was compared to manifest refractive cylinder (cross-cylinder strategy) by computing difference vectors and correlation analysis of power vectors.Results: The OCT (0.43 ± 0.25 D) and the hybrid topographer (0.44 ± 0.25 D) yielded the smallest difference vector to subjective cylinder and by far the lowest percentage of outliers >0.75 D (≈10%). The rotating Scheimpflug camera showed the largest (0.70 ± 0.41 D) difference vector. The best pred...

54 citations


Journal ArticleDOI
TL;DR: The preoperative integrity of foveal photoreceptors may be a clinically significant prognostic factor for visual recovery in patients with idiopathic ERM and can be restored after ERM surgery.
Abstract: Purpose: To evaluate the correlation of foveal photoreceptor integrity with visual outcome in patients undergoing idiopathic epiretinal membrane (ERM) surgery using spectral domain optical coherence tomography (SD-OCT).Materials and methods: Forty-three eyes of 43 patients were examined by SD-OCT before and at 1 and 6 months after vitrectomy for idiopathic ERM. Patients were divided into two groups based on the preoperative integrity of photoreceptor inner and outer segment junction (IS/OS) – Group I, intact IS/OS and Group D, disrupted IS/OS. Where present, disrupted length of IS/OS was measured, and the association between disrupted length of IS/OS and foveal thickness with best corrected visual acuity (BCVA) was evaluated.Results: There were 27 eyes with an intact IS/OS (Group I) and 16 eyes with a disrupted IS/OS (Group D). Patients in Group I had significantly better postoperative BCVA and greater improvement than those in Group D at 6 months after surgery (p = 0.001 and p = 0.030, respective...

Journal ArticleDOI
TL;DR: The choroidal thickness decreased after all treatments, suggesting that IVB or PRP rapidly reduced choroid vascular permeability.
Abstract: Purpose: To investigate the choroidal thickness changes after intravitreal bevacizumab injection (IVB), panretinal photocoagulation (PRP) or both for diabetic retinopathy treatment.Materials and Methods: The study included 31 eyes (31 patients) in the IVB group, 35 eyes (35 patients) in the PRP group and 35 eyes (35 patients) in the IVB–PRP group. Enhanced depth imaging optical coherence tomography (EDI-OCT) was performed before and 1 month after each treatment to measure subfoveal and extrafoveal (500 and 1000 μm) choroidal thicknesses. The best-corrected visual acuity (BCVA) and central macular thickness (CMT) were also measured.Results: The choroidal thickness at all locations significantly decreased after treatment in all groups, but there was no significant difference in the amount of change among the three groups. The subfoveal choroidal thickness and CMT significantly decreased after treatment in the IVB and IVB–PRP groups. In the PRP group, the CMT significantly increased, while the choroi...

Journal ArticleDOI
TL;DR: The compartmental periodic-steady tear-dynamics model accurately predicts tear behavior in normal and dry eyes and is readily extended to predict the dynamics of aqueous solutes such as drugs or fluorescent tags.
Abstract: Purpose: Dry-eye disease, an increasingly prevalent ocular-surface disorder, significantly alters tear physiology. Understanding the basic physics of tear dynamics in healthy and dry eyes benefits both diagnosis and treatment of dry eye. We present a physiological-based model to describe tear dynamics during blinking.Materials and methods: Tears are compartmentalized over the ocular surface; the blink cycle is divided into three repeating phases. Conservation laws quantify the tear volume and tear osmolarity of each compartment during each blink phase. Lacrimal-supply and tear-evaporation rates are varied to reveal the dependence of tear dynamics on dry-eye conditions, specifically tear osmolarity, tear volume, tear-turnover rate (TTR), and osmotic water flow.Results: Predicted periodic-steady tear-meniscus osmolarity is 309 and 321 mOsM in normal and dry eyes, respectively. Tear osmolarity, volume, and TTR all match available clinical measurements. Osmotic water flow through the cornea and conjun...

Journal ArticleDOI
TL;DR: Subfoveal choroidal thickness increases in pregnant women compared with age-matched nonpregnant women, and no significant correlation was found with spherical refraction, IOP, AL, CCT, OPP, gestational age, maternal weight gain, or fetal weight.
Abstract: Purpose: To evaluate the subfoveal choroidal thickness (SFCT) measured by enhanced depth imaging optical coherence tomography (EDI-OCT) in pregnant women.Methods: In this prospective and cross-sectional study, 100 pregnant women and 100 age-matched nonpregnant women were enrolled. The SFCT was measured by EDI-OCT. The refractive error, intraocular pressure (IOP), axial length (AL), central corneal thickness (CCT), systolic and diastolic blood pressure, and ocular perfusion pressure (OPP) were also measured. Pregnancy-related factors including gestational age, maternal weight gain, and fetal weight were noted.Results: Mean SFCT was 371.1 ± 61.8 µm in the study group and 337.2 ± 62.4 µm in the control group (p < 0.001). No significant correlation was found between SFCT and spherical refraction, IOP, AL, CCT, OPP, gestational age, maternal weight gain, or fetal weight.Conclusion: Our results suggest that subfoveal choroidal thickness increases in pregnant women compared with age-matched nonpregnant w...

Journal ArticleDOI
TL;DR: The results suggest that SFCT is lower in eyes of CHF patients compared to age- and gender-matched healthy individuals.
Abstract: Purpose: To evaluate the subfoveal choroidal thickness (SFCT) measured by enhanced depth imaging optical coherence tomography (EDI-OCT) in eyes of chronic heart failure (CHF) patients.Methods: Fifty-six patients with CHF and 56 age- and gender-matched healthy individuals were enrolled. The SFCT was measured by EDI-OCT. The ejection fraction of left ventricle (EFLV), age, intraocular pressure (IOP), axial length (AL), systolic and diastolic blood pressure, and ocular perfusion pressure (OPP) were also measured.Results: Mean SFCT was 181.2 ± 80.23 μm in the study group and 283.6 ± 52.4 μm in the control group (p = 0.000). There was a statistically significant correlation between the SFCT and each of EFLV and age. SFCT value was not statistically significantly associated with AL, IOP and OPP.Conclusion: Our results suggest that SFCT is lower in eyes of CHF patients compared to age- and gender-matched healthy individuals.

Journal ArticleDOI
TL;DR: This in vivo study showed the involvement of M MP-9 and MMP-2 during different phases of the SM-induced ocular injury, and the potential of doxycycline treatment as a post exposure measure for reducing the acute injury and as a preventive therapy for ameliorating the delayed pathology.
Abstract: Purpose: Sulfur mustard (SM) induces acute ocular lesions, including erosions and inflammation that may be followed by delayed injuries expressed by epithelial defects and neovascularization (NV). Based on the matrix metalloproteinases (MMPs) activity, we evaluated the clinical and biochemical effects of topical treatment with doxycycline, an MMP inhibitor, targeted to the various injury stages.Methods: Rabbit eyes were exposed to SM vapor. A clinical follow-up was carried out up to 2 months. Tear fluid and cornea samples were collected at different time points for measurements of MMPs activity by zymography. Efficacy of a post-exposure topical doxycycline (2 mg/ml in phosphate buffer saline, ×4/d), targeted to the different phases of the clinical injury, was evaluated.Results: Elevated MMP-9 and MMP-2 activities were found in all corneas during the acute injury and in vascularized corneas during the delayed pathology. In the tear fluid, high MMP-9 activity and negligible MMP-2 activity were found...

Journal ArticleDOI
TL;DR: The macula-off status was associated with a lower success rate in the SB group, although break location and lens status had no significant effect on success rates in either group.
Abstract: Purpose: To investigate the anatomical success rates of scleral buckling (SB) and pars plana vitrectomy (PPV) performed for rhegmatogenous retinal detachment (RRD) in a large case series and to identify prognostic factors for the primary anatomical success rates of surgical techniques.Methods: We reviewed 542 consecutive eyes for primary RRD in this retrospective study. Follow-ups were performed for at least six months. In each of the two groups, 271 eyes were examined. The main outcome measure was the primary anatomical success rate. Multivariate analysis was also performed to determine whether independent risk factors of the preoperative parameters for redetachment exist.Results: The primary anatomical success rates were 93.7% and 96.3% in the SB and PPV groups; and the final anatomical success rates were 100% in both groups (each with 271 eyes). In the SB group, eyes with macula-off had significantly lower primary anatomical success rates than those with macula-on (p = 0.002). Preoperative brea...

Journal ArticleDOI
TL;DR: Thrombospondins influence many cellular interactions in the eye such as angiogenesis, cell migration, wound healing, TGF-β activation and regulation of inflammatory immune responses, and these processes are known to contribute to the immune privilege status of the eye.
Abstract: Thrombospondins are a family of large multi-domain glycoproteins described as matricelluar proteins based on their ability to interact with a broad range of receptors, matrix molecules, growth factors or proteases, and to modulate array of cellular functions including intracellular signaling, proliferation and migration. Two members of the thrombospondin family, thrombospondin 1 (TSP-1) and thrombospondin 2 (TSP-2) are studied extensively to determine their structure and function. While expressed at low levels in normal adult tissues, their increased expression is seen predominantly in response to cellular perturbations. Despite structural similarities, a notable functional difference between TSP-1 and TSP-2 includes the ability of former to activate of latent TGF-β and its competitive inhibition by the latter. Both these thrombospondins are reported to play important roles in TGF-β rich ocular environment with most reports related to TSP-1. They are expressed by many ocular cell types and detectable in the aqueous and vitreous humor. TSP-1 and TSP-2 influence many cellular interactions in the eye such as angiogenesis, cell migration, wound healing, TGF-β activation and regulation of inflammatory immune responses. Together, these processes are known to contribute to the immune privilege status of the eye. Emerging roles of TSP-1 and TSP-2 in ocular functions and pathology are reviewed here.

Journal ArticleDOI
TL;DR: It is suggested that rebamipide increased MUC1, MUC4 and MUC16 expression levels through signals involved in EGF receptor activation in the human corneal epithelia by upregulating MAM expression.
Abstract: Purpose Membrane-associated mucins (MAMs) play important roles in barrier function and tear stability, and their expression on the ocular surface is altered in dry eye disease. Rebamipide is a mucin secretagogue that promotes the production of mucin-like glycoproteins in human corneal epithelial (HCE) cells. However, the expression of MAMs on the corneal epithelia (MUC1, MUC4, MUC16), which is induced by rebamipide, is poorly understood. In this study, we investigated the effect of rebamipide on the regulation of MAM expression in HCE cells. Materials and methods MUC16, Ki67 and PCNA expression levels in HCE cells isolated at confluence and at 24 hours after confluence were examined by Western blotting to assess cell proliferation. HCE cells isolated at 24 hours after confluence were cultured in medium supplemented with 1-10 µM rebamipide or 0.3-30 nM of epidermal growth factor (EGF). Real-time PCR (RT-PCR) and Western blot analysis of MAMs were performed to evaluate the effect of rebamipide. Western blot analysis of cells treated with an EGF receptor inhibitor (AG1478) or MEK1/2 inhibitor (U0126) was performed to reveal the relationship between EGF receptor activation and rebamipide-induced MAM expression. Results HCE cells isolated at 24 hours after confluence had lower cell proliferation activity and increased MUC16 expression compared with cells isolated at confluence. RT-PCR and Western blot analysis revealed that rebamipide increased MAM gene expression for 2 hours and protein expression for 24 hours in HCE cells. EGF inhibitor treatment led to reduced levels of all three MAMs that are normally induced by rebamipide, whereas EGF induced the expression of all three MAMs. Conclusions We suggested that rebamipide increased MUC1, MUC4 and MUC16 expression levels through signals involved in EGF receptor activation in the human corneal epithelia. These data suggest that rebamipide may improve subjective symptoms of dry eye disease by upregulating MAM expression.

Journal ArticleDOI
TL;DR: VEGF was involved in corneal angiogenesis in SM-induced ocular injury and bevacizumab was beneficial in reducing CNV by both, topical or subconjunctival injection, when given as a symptomatic therapy with or without dexamethasone, however with no effect on SC deficiency.
Abstract: Purpose: To investigate the involvement of VEGF in corneal neovascularization (CNV) following sulfur mustard (SM) exposure and to test the therapeutic effects of bevacizumab (Avastin) in respect to dose, route of administration and timing.Materials and methods: Topical bevacizumab (6 or 25 mg/ml, ×2/day) was applied to rabbit eyes, before or after appearance of NV, following SM vapor exposure, and was compared with subconjunctival injection (25 mg/ml, ×2/week) and topical dexamethasone (1%, ×4/day). Treatments were given for 3 weeks. VEGF levels were monitored by immunohistochemistry and ELISA assay. Clinical evaluations included slit-lamp examination, impression cytology for diagnosis of Limbal Stem Cell Deficiency (LSCD), pachymetry, measurement of NV length and histology.Results: Corneal NV was developed, as early as 2 weeks after exposure, in 50–70% of the eyes, associated with increased levels of VEGF. Topical bevacizumab treatment with both doses, starting at 4 weeks, reduced vascularization...

Journal ArticleDOI
TL;DR: Despite the fact that AMD is essentially a choroidal disease, retinal vessels show a functional abnormality, which may suggest that the vascular abnormality in this disease is more generalized.
Abstract: Purpose/Aim of the study: To study changes in retinal blood flow velocity in patients with early and neovascular age-related macular degeneration (AMD). We used the Retinal Function Imager (RFI, Optical Imaging Ltd., Rehovot, Israel), a noninvasive diagnostic approach for measuring blood flow velocity.Materials and Methods: Sixty eyes of 43 AMD patients and 53 eyes of 35 healthy individuals over the age of 50 were recruited for this study. All patients were scanned by the RFI with analysis of blood flow velocity of secondary and tertiary branches of arteries and veins. Differences among groups were assessed by mixed linear models.Results: The average velocity in AMD patients was significantly lower compared to controls in arteries (3.6 ± 1.4 versus 4.3 ± 1.0 mm/sec, p = 0.009) but not in veins (2.6 ± 0.9 versus 3.1 ± 0.6 mm/sec, p = 0.08). When comparing the velocity between low- and high-grade AMD eyes, venous velocity was slower in the high grade AMD eyes only in the “narrow” group of vessels.Co...

Journal ArticleDOI
TL;DR: It was found that three-month AS treatment led especially to the improvement of ocular surface dryness and damage of the epithelium.
Abstract: Aim: To assess the impact of autologous serum (AS) eye drops on the ocular surface of patients with bilateral severe dry eye and to draw a comparison between the clinical and laboratory examinations and the degree of subjective symptoms before and after serum treatment.Materials and methods: A three-month prospective study was conducted on 17 patients with severe dry eye. AS eye drops were applied a maximum of 12 times a day together with regular therapy. Dry eye status was evaluated by clinical examination (visual acuity, Schirmer test, tear film breakup time, vital staining, tear film debris and meniscus), conjunctival impression cytology (epithelial and goblet cell density, snake-like chromatin, HLA-DR-positive and apoptotic cells) and subjectively by the patients.Results: The application of AS eye drops led to a significant improvement in the Schirmer test (p < 0.01) and tear film debris (p < 0.05). The densities of goblet (p < 0.0001) and epithelial cells (p < 0.05) were significantly increas...

Journal ArticleDOI
TL;DR: The results show that the amino terminus of gK is essential for neuroinvasiveness and acute herpes keratitis in the mouse eye model, and it is likely thatgK is involved in efficient infection of axonal termini, since mouse eye scarification provided a direct access to the high density of neurons innervating mouse corneas.
Abstract: Purpose: To determine the role of the amino terminus of herpes simplex virus-1 (HSV-1) glycoprotein K (gK) in corneal infection, neuroinvasion, and establishment of virus latency in trigeminal ganglia of mice.Methods: The recombinant virus HSV-1 (McKΔgK31-68) was constructed by engineering gK genes encoding gK lacking 38 amino acids immediately after the gK signal sequence. A rescued virus was also produced. Mouse eyes were scarified and infected with 105 plaque forming units (PFU) in each eye. Clinical signs of ocular disease were monitored daily. Thirty days postinfection trigeminal ganglia were collected and processed for quantitative PCR (qPCR) analysis of viral DNA and recovery of infectious virions by cell culture of ganglionic tissues.Results: Deletion of the amino terminus of gK encoded by the McKΔgK31-68 mutant virus did not substantially affect its replication kinetics on African green monkey kidney cells (Vero), while it reduced cell-to-cell spread. McK viral infection of scarified mous...

Journal ArticleDOI
TL;DR: Obstructive sleep apnea is seen nearly in 2/3 of patients with the diagnosis of CSR, and there are possible common pathophysiological mechanisms like oxidative stress, vasoconstriction, or blood coagulation abnormalities that should be considered in subjects with the diagnosed CSR.
Abstract: Purpose: In this study, we aimed to evaluate the relation between obstructive sleep apnea (OSA) and central serous retinopathy (CSR).Methods: Twenty-three consecutive subjects aged >18 years with the diagnosis of CSR were included in this prospective study. Overnight polysomnography was performed to all subjects. Desaturation index and apnea-hypopnea index (AHI) were recorded. Obstructive sleep apnea was classified according to AHI as mild, moderate, or severe. Statistical analysis was performed using chi-square test, Fisher’s exact test, and Mann–Whitney U test.Results: Fourteen of 23 CSR patients (60.9%) had OSA. Prevalence of OSA was significantly higher in male subjects with CSR compared to female subjects with CSR (p = 0.018). One (16.7%) female subject with CSR had OSA whereas thirteen (76.5%) male subjects were found to have OSA. Desaturation index was found to be 5.1 ± 4.2 in females and 12.9 ± 11.1 in males (p = 0.036).Conclusion: Obstructive sleep apnea is seen nearly in 2/3 of patients ...

Journal ArticleDOI
TL;DR: Combined orbital bone and fat decompression significantly reduced the IOP levels and increased the SOV-BFV in GO, which could be the confirmative finding of prediction that elevated IOP in GO is associated with increased episcleral venous pressure.
Abstract: Purpose: To investigate the effects of combined orbital bone and fat decompression on intraocular pressure (IOP) and superior ophthalmic vein blood flow velocity (SOV-BFV), and their association with the clinical features of Graves orbitopathy (GO).Methods: During the 2002–2008 period, 72 eyes of 36 GO cases demonstrating moderate to severe orbitopathy were evaluated according to their clinical features as: cases with or without dysthyroid optic neuropathy (DON), and underwent orbital decompression. A control group comprised 40 eyes of 20 healthy subjects. In both groups, a full ophthalmic examination including IOP and Hertel measurements was performed, and SOV-BFV was analyzed with color Doppler imaging. Examinations were repeated after orbital decompression in GO patients.Results: All the cases demonstrated clinical features of inactive disease. Among the patients 24 of 72 eyes (33.3%) showed clinical features of DON. After surgery, the mean decrease in Hertel values was 6.2 ± 1.8 mm (p = 0.001)...

Journal ArticleDOI
TL;DR: Vision-specific QoL is reduced, and the reduction in theQoL bears a positive association with severity of VI among older people living in nursing homes.
Abstract: Background: Visual impairment (VI) has a significant negative impact on quality of life (QoL) amongst older people living in nursing homes. The purpose of this study was to determine the prevalence of VI and blindness and to explore the association between severity of VI and vision-specific QoL among older people living in nursing homes of Kathmandu, Nepal.Methods: This cross-sectional study involved 158 residents aged 60 years or older residing in seven nursing homes of Kathmandu Valley, Nepal. Near acuity, presenting and the best corrected distance visual acuity (VA) were assessed in each eye and considered in the better eye after adequate refraction. A complete anterior and posterior segment examination was carried out. Face-to-face interviews were conducted using a 57-item Nursing Home Vision-Targeted Health-Related Quality of Life (NHVQoL) questionnaire.Results: The mean age of residents was 75.60 ± 7.12 years and the majority were female (66.46%). The prevalence of VI and blindness was 45.57...

Journal ArticleDOI
TL;DR: Non-invasive wide-field FAF detects more retinal or chorioretinal involvement in patients with posterior uveitis than seen in color imaging and thus is useful in diagnosis and follow-up of uveitic patients.
Abstract: Purpose: To evaluate wide-field fundus autofluorescence (FAF) in patients with uveitis with retinal or chorioretinal involvement. Materials and methods: We included 78 study eyes in this prospective study. Best-corrected visual acuity, a full clinical examination, wide-field green-light FAF and composite color, green and red laser separation fundus imaging with Optomap SLO were performed. In a systematic analysis, the number, extension and margins of central and peripheral retinal or chorioretinal alterations, scars and infiltrates in infectious and non-infectious uveitic study eyes were evaluated. Wide-field FAF and color fundus imaging results were compared regarding their diagnostic properties. Results: Nine out of 78 study eyes were diagnosed with infectious, 69 cases with non-infectious uveitis. Six infectious uveitic study eyes had changes of the peripheral fundus compared with 48 of 69 non-infectious uveitic eyes. In 33 (infectious versus non-infectious: 4 versus 29) cases, wide-field FAF images revealed more retinal or chorioretinal alterations or pathologies with a farther extended demarcation than wide-field composite color fundus imaging. Eleven out of 69 non-infectious study eyes were diagnosed with vasculitis which could be more precisely evaluated with wide-field FAF than wide-field composite color, green or red light filtered fundus imaging. Conclusions: Non-invasive wide-field FAF detects more retinal or chorioretinal involvement in patients with posterior uveitis than seen in color imaging and thus is useful in diagnosis and follow-up of uveitic patients.

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TL;DR: A visual fixation protocol with cued eye blinks achieves sufficient stability for magnetic resonance imaging (MRI) blood-flow measurements and to determine if choroidal blood flow (ChBF) changes with age in humans.
Abstract: Purpose: To verify that a visual fixation protocol with cued eye blinks achieves sufficient stability for magnetic resonance imaging (MRI) blood-flow measurements and to determine if choroidal blood flow (ChBF) changes with age in humans. Methods: The visual fixation stability achievable during an MRI scan was measured in five normal subjects using an eye-tracking camera outside the MRI scanner. Subjects were instructed to blink immediately after recorded MRI sound cues but to otherwise maintain stable visual fixation on a small target. Using this fixation protocol, ChBF was measured with MRI using a 3 Tesla clinical scanner in 17 normal subjects (24–68 years old). Arterial and intraocular pressures (IOP) were measured to calculate perfusion pressure in the same subjects. Results: The mean temporal fluctuations (standard deviation) of the horizontal and vertical displacements were 29 ± 9mm and 38 ± 11mm within individual fixation periods, and 50 ± 34mm and 48 ± 19mm across different fixation periods. The absolute displacements were 67 ± 31mm and 81 ± 26mm. ChBF was negatively correlated with age (R = � 0.7, p = 0.003), declining 2.7 ml/100 ml/min per year. There were no significant correlations between ChBF versus perfusion pressure, arterial pressure, or IOP. There were also no significant correlations between age versus perfusion pressure, arterial pressure, or IOP. Multiple regression analysis indicated that age was the only measured independent variable that was significantly correlated with ChBF (p = 0.03). Conclusions: The visual fixation protocol with cued eye blinks was effective in achieving sufficient stability for MRI measurements. ChBF had a significant negative correlation with age.

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TL;DR: Green tea polyphenol epigallocatechin gallate pretreatment can protect primary rat RPE cells from H2O2-induced death, suggesting potential effect of EGCG in the prevention of retinal diseases associated with H1N1-induced oxidative stress.
Abstract: Purpose: To determine whether the green tea polyphenol epigallocatechin gallate (EGCG) could prevent H2O2-induced oxidative stress in primary rat retinal pigment epithelial cells.Methods: Primary cultures of retinal pigment epithelium (RPE) cells were established from Long–Evans newborn rats. RPE cells were pretreated with various concentrations of EGCG for 24 h before being exposed to hydrogen peroxide (H2O2) for 2 h to induce oxidative stress. Cell metabolic activity was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell death was quantified by flow cytometry using propidium iodide (PI).Results: Treatment of RPE cells with EGCG alone does not affect the cell viability up to 50 µM. Exposure of RPE cells to 600 µM H2O2 caused a significant decrease in cell viability; whereas pretreatment with 10, 25, and 50 µM EGCG significantly reduced this decrease in a dose-dependent manner. The proportion of PI-positive cells increased significantly in cultures treate...

Journal ArticleDOI
Fen Xiong1, Xinhua Du1, Jianyan Hu1, Tingting Li1, Shanshan Du1, Qiang Wu1 
TL;DR: It is suggested that miRNAs perform critical regulatory functions during the early stages of DR evolution, based on both their target genes and signaling pathways.
Abstract: Purpose: MicroRNAs (miRNAs) – as negative regulators of target genes – are associated with various human diseases, but their precise role(s) in diabetic retinopathy (DR) remains to be elucidated. T...