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A 4-week, dose-ranging study comparing the efficacy, safety and tolerability of latanoprost 75, 100 and 125 micro g/mL to latanoprost 50 micro g/mL (Xalatan) in the treatment of primary open-angle glaucoma and ocular hypertension
Background:
Several studies have investigated the effect of latanoprost on intraocular pressure (IOP). We compared the IOP-lowering effects of three higher concentrations of latanoprost with the commercially available concentration of 0.005% (50 micro g/mL) in patients with primary open-angle glaucoma or ocular hypertension.
Methods:
Treatment-naive subjects or those receiving IOP-lowering medication with baseline IOP levels of ¿24 mmHg and ¿36 mmHg in at least one eye after washout were randomized to receive an evening dose of latanoprost 50, 75, 100, or 125 ¿g/mL for 4 weeks. At weeks 1, 2, 3, and 4, ocular examinations were performed and IOP was measured. Ocular symptoms and adverse events were monitored. The primary efficacy endpoint was the change in IOP from baseline to week 4 at 8 a.m. and 4 p.m. for the per protocol (PP) population using a "worse eye" analysis. Secondary efficacy endpoints were change in IOP at each time point from baseline across all visits, and percentage change in IOP from baseline to week 4 at 8 a.m.
Results:
In all, 282 patients were randomized and treated; 274 were included in the PP population. Treatment groups were similar at baseline; 68% were diagnosed with primary open-angle glaucoma. Mean baseline IOP levels were comparable across treatments. There were no statistically significant differences in IOP reductions from baseline to week 4 at either time point between those treated with higher concentrations of latanoprost versus those receiving 50 ¿g/mL. Least squares mean IOP changes at 8 a.m. were ¿10.13, -9.59, -10.02, and ¿9.06 mmHg for latanoprost 50, 75, 100, and 125 ¿g/mL, respectively, and at 4 p.m. were ¿8.90, -8.29, -8.81, and ¿8.34 mmHg, respectively. Results of secondary efficacy analyses supported those of the primary analysis. Conjunctival hyperemia, the most commonly reported adverse event, occurred in 16.9%, 18.6%, 20.8% and 15.9% of subjects receiving latanoprost 50, 75, 100, and 125 ¿g/mL, respectively.
Conclusions:
IOP reductions were observed in all treatment groups postbaseline, with no clinically relevant or statistically significant differences detected favoring any of the higher concentrations of latanoprost compared with latanoprost 50 micro g/mL. All doses of latanoprost were well tolerated. Clinical Trials.gov Identifier NCT01379144.
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Retro-mode imaging and fundus autofluorescence with
scanning laser ophthalmoscope of retinal dystrophies
Background:
Retinal dystrophies display a considerably wide range of phenotypic variability, which can make diagnosis and clinical staging difficult. The aim of the study is to analyze the contribution of retro-mode imaging (RMI) and fundus autofluorescence (FAF) to the characterization of retinal dystrophies.
Methods:
Eighteen consecutive patients affected by retinal dystrophies underwent a complete ophthalmological examination, including best corrected visual acuity with ETDRS charts, blue-light fundus autofluorescence, (BL-FAF), near-infrared fundus autofluorescence (NIR-FAF), and RMI. The primary outcome was the identification of abnormal patterns on RMI. The secondary outcome was the correlation with the findings on BL-FAF and NIR-FAF.
Results:
Overall, the main feature of RMI is represented by a pseudo-3D pattern of all the lesions at the posterior pole. More specifically, any accumulation of material within the retina appears as an area of elevation of different shape and size, displaying irregular and darker borders. No precise correlations between RMI, BL-AF, and NIR-AF imaging was found.
Conclusions:
RMI and FAF appear to be useful tools for characterizing retinal dystrophies. Non-invasive diagnostic tools may yield additional information on the clinical setting and the monitoring of the patients.
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European ST80 community-associated methicillin-resistant Staphylococcus aureus orbital cellulitis in a neonate
Background:
Methicillin-resistant Staphylococcus aureus is a serious cause of morbidity and mortality in hospital environment, but also, lately, in the community. This case report is, to our knowledge, the first detailed description of a community-associated methicillin-resistant S. aureus ST80 orbital cellulitis in a previously healthy neonate. Possible predisposing factors of microbial acquisition and treatment selection are also discussed.Case presentationA 28-day-old Caucasian boy was referred to our hospital with the diagnosis of right orbital cellulitis. His symptoms included right eye proptosis, periocular edema and redness. Empirical therapy of intravenous daptomycin, rifampin and ceftriaxone was initiated. The culture of pus yielded a methicillin-resistant S. aureus isolate and the molecular analysis revealed that it was a Panton-Valentine leukocidine-positive ST80 strain. The combination antimicrobial therapy was continued for 42 days and the infection was successfully controlled.
Conclusions:
Clinicians should be aware that young infants, even without any predisposing condition, are susceptible to orbital cellulitis caused by community-associated methicillin-resistant S. aureus. Prompt initiation of the appropriate empirical therapy, according to the local epidemiology, should successfully address the infection, preventing ocular and systemic complications.
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Heightened expression of MICA enhances the cytotoxicity of NK cells or CD8+T cells to human corneal epithelium in vitro
Background:
Major-histocompatibility-complex class I-related chain A (MICA) antigens are the ligands of NKG2D which is an activating or coactivating receptor expressed on human NK cells and CD8+ T cells. We sought to determine whether MICA expression in human corneal epithelium (HCE) could affect the cytotoxicity mediated by NK cells or CD8+ T cells.
Methods:
Cell cultures of HCE were harvested from human donor eyes. Flow cytometric analysis and ELISA was performed to determine the levels of MICA expression on HCE. Then, HCE was transfected with lentivirus vector expressing MICA and GFP. Flow cytometric analysis, RT-PCR, Western blot and ELISA was performed to check the levels of MICA expression. For cytotoxicity testing, allogeneic NK cells and CD8+ T cells were isolated from peripheral blood mononuclear cells of healthy voluteers by magnetic cell sorting. The cytolytic activity of NK cells and CD8+ T cells was assessed against MICA-transfected HCE (NK cells: E:T ratio=3:1; CD8+T cells: E:T ratio=10:1) using the nonradioactive cytotoxicity detection kit lactate deshydrogenase.
Results:
Surface expression of MICA on corneal epithelium was identified at low level. A cell line of stable human MICA-transfected corneal epithelium was successfully established. Heightened expression of MICA on HCE was found to promote the cytotoxicity mediated by NK cells or CD8+T cells, which could be blocked by anti-MICA antibody.
Conclusion:
MICA molecule may contribute to cytotoxic responses mediated by activated immune effector cells in corneal epithelium immunity.
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Eye care utilization by older adults in low, middle, and high income countries
Background:
The risk of visual impairment increases dramatically with age and therefore older adults should have their eyes examined at least every 1 to 2 years. Using a world-wide, population-based dataset, we sought to determine the frequency that older people had their eyes examined . We also examined factors associated with having a recent eye exam.
Methods:
The World Health Surveys were conducted in 70 countries throughout the world in 2002-2003 using a random, multi-stage, stratified, cluster sampling design. Participants 60 years and older from 52 countries (n = 35,839) were asked "When was the last time you had your eyes examined by a medical professional?". The income status of countries was estimated using gross national income per capita data from 2003 from the World Bank website. Prevalence estimates were adjusted to account for the complex sample design.
Results:
Overall, only 18% (95% CI 17, 19) of older adults had an eye exam in the last year. The rate of an eye exam in the last year in low, lower middle, upper middle, and high income countries was 10%, 24%, 22%, and 37% respectively. Factors associated with having an eye exam in the last year included older age, female gender, more education, urban residence, greater wealth, worse self-reported health, having diabetes, and wearing glasses or contact lenses (p < 0.05).
Conclusions:
Given that older adults often suffer from age-related but treatable conditions, they should be seen on a regular basis to prevent visual impairment and its disabling consequences.
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Intrinsically photosensitive retinal ganglion cell function in relation to age
A pupillometric study in humans with special reference to the age-related optic properties of the lens
Background:
The activity of melanopsin containing intrinsically photosensitive ganglion retinal cells (ipRGC) can be assessed by a means of pupil responses to bright blue (appr.480 nm) light. Due to age related factors in the eye, particularly, structural changes of the lens, less light reaches retina. The aim of this study was to examine how age and in vivo measured lens transmission of blue light might affect pupil light responses, in particular, mediated by the ipRGC.
Methods:
Consensual pupil responses were explored in 44 healthy subjects aged between 26 and 68 years. A pupil response was recorded to a continuous 20 s light stimulus of 660 nm (red) or 470 nm (blue) both at 300 cd/m2 intensity (14.9 and 14.8 log photons/cm2/s, respectively). Additional recordings were performed using four 470 nm stimulus intensities of 3, 30, 100 and 300 cd/m2.The baseline pupil size was measured in darkness and results were adjusted for the baseline pupil and gender. The main outcome parameters were maximal and sustained pupil contraction amplitudes and the postillumination response assessed as area under the curve (AUC) over two time-windows: early (0-10 s after light termination) and late (10-30 s after light termination). Lens transmission was measured with an ocular fluorometer.
Results:
The sustained pupil contraction and the early poststimulus AUC correlated positively with age (p=0.02, p=0.0014, respectively) for the blue light stimulus condition only.The maximal pupil contraction amplitude did not correlate to age either for bright blue or red light stimulus conditions.Lens transmission decreased linearly with age (p<0.0001). The pupil response was stable or increased with decreasing transmission, though only significantly for the early poststimulus AUC to 300 cd/m2 light (p=0.02).
Conclusions:
Age did not reduce, but rather enhance pupil responses mediated by ipRGC. The age related decrease of blue light transmission led to similar results, however, the effect of age was greater on these pupil responses than that of the lens transmission. Thus there must be other age related factors such as lens scatter and/or adaptive processes influencing the ipRGC mediated pupil response enhancement observed with advancing age.
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Fibrin membrane pupillary-block glaucoma after uneventful cataract surgery treated with intracameral tissue plasminogen activator: a case report
Background:
Fibrin pupillary-block glaucoma is a rare complication after cataract surgery. The treatment for this condition is still controversial, since Nd:YAG laser fibrin membranotomy tends to reocclude and laser peripheral iridotomy entails the risk of damaging the corneal endothelium in the presence of corneal edema associated with elevated intraocular pressure.Case presentationA 62-year-old man with diabetes mellitus developed acute elevation of intraocular pressure with a shallow anterior chamber five days after uneventful cataract surgery. Initially, slit lamp examination provided only limited information due to severe corneal edema. After resolution of corneal edema with systemic glaucoma therapy, a complete fibrin membrane was observed across the pupil by slit lamp examination. Anterior segment optic coherence tomography clearly revealed a thin fibrin membrane covering the entire pupillary space, a shallow anterior chamber, and a deep posterior chamber. The intraocular lens was not observed by anterior segment optic coherence tomography. In contrast, ultrasound biomicroscopy, which has superior penetration depth, was able to visualize the intraocular lens deep in the posterior chamber. Injection of tissue plasminogen activator into the anterior chamber resulted in complete fibrinolysis and released the pupillary block.
Conclusion:
This case suggests that ocular anterior segment imaging modalities, especially ultrasound biomicroscopy, serve as powerful diagnostic tools to identify mechanisms of acute angle closure glaucoma, which is often accompanied by poor intraocular visibility. This is the first reported case of fibrin pupillary-block glaucoma after cataract surgery successfully treated with intracameral tissue plasminogen activator.
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Results at seven years after the use of Intracamerular cefazolin as an endophthalmitis prophylaxis in cataract surgery
Background:
To evaluate results after seven years using prophylactic intracameral cefazolin for the prevention of endophthalmitis in cataract surgery.
Methods:
A prospective, observational study of all patients submitted to cataract surgery over the period January 1996 to December 2009. All cases of postoperative endophthalmitis over that period were reviewed. The patients were classified in two groups: Group 1 (11,696 patients) operated on between January 1996 and December 2002, Group 2 (13,305 patients) between January 2003 and December 2009 (in whom a 1 mg/0.1 bolus of intracameral cefazolin was instilled).
Results:
During the study period, 76 cases of endophthalmitis were observed in Group 1, and seven in Group 2. The rate of postoperative endophthalmitis reduced from 0.63% to 0.05% with a cefazolin injection. The relative risk (RR) for endophthalmitis in Group 1 against group 2 was 11.45 [95% CI 5.72-22.84, p < 0.001].
Conclusions:
An intracameral bolus injection of cefazolin (1 mg in 0.1 ml solution) at the conclusion of the cataract surgery significantly reduced the rate of postoperative endophthalmitis.
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The improving outcomes in intermittent exotropia study: outcomes at 2 years after diagnosis in an observational cohort.
Background:
The purpose of this study was to investigate current patterns of management and outcomes of intermittent distance exotropia [X(T)] in the UK.
Methods:
This was an observational cohort study which recruited 460 children aged < 12 years with previously untreated X(T). Eligible subjects were enrolled from 26 UK hospital ophthalmology clinics between May 2005 and December 2006. Over a 2-year period of follow-up, clinical data were prospectively recorded at standard intervals from enrolment. Data collected included angle, near stereoacuity, visual acuity, control of X(T) measured with the Newcastle Control Score (NCS), and treatment. The main outcome measures were change in clinical outcomes (angle, stereoacuity, visual acuity and NCS) in treated and untreated X(T), 2 years from enrolment (or, where applicable, 6 months after surgery). Change over time was tested using the chi-square test for categorical, Wilcoxon test for non-parametric and paired-samples t-test for parametric data.
Results:
At follow-up, data were available for 371 children (81% of the original cohort). Of these: 53% (195) had no treatment; 17% (63) had treatment for reduced visual acuity only (pure refractive error and amblyopia); 13% (50) had non surgical treatment for control (spectacle lenses, occlusion, prisms, exercises) and 17% (63) had surgery. Only 0.5% (2/371) children developed constant exotropia. The surgically treated group was the only group with clinically significant improvements in angle or NCS. However, 8% (5) of those treated surgically required second procedures for overcorrection within 6 months of the initial procedure and at 6-month follow-up 21% (13) were overcorrected.
Conclusions:
Many children in the UK with X(T) receive active monitoring only. Deterioration to constant exotropia, with or without treatment, is rare. Surgery appears effective in improving angle of X(T) and NCS, but rates of overcorrection are high.
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Optical effects of exposing intact human lenses to ultraviolet radiation and visible light
Background:
The human lens is continuously exposed to high levels of light. Ultraviolet radiation is believed to play a causative role in the development of cataract. In vivo, however, the lens is mainly exposed to visible light and the ageing lens absorbs a great part of the short wavelength region of incoming visible light. The aim of the present study was to examine the optical effects on human lenses of short wavelength visible light and ultraviolet radiation.
Methods:
Naturally aged human donor lenses were irradiated with UVA (355 nm), violet (400 and 405 nm) and green (532 nm) lasers. The effect of irradiation was evaluated qualitatively by photography and quantitatively by measuring the direct transmission before and after irradiation. Furthermore, the effect of pulsed and continuous laser systems was compared as was the effect of short, intermediate and prolonged exposures.
Results:
Irradiation with high intensity lasers caused scattering lesions in the human lenses. These effects were more likely to be seen when using pulsed lasers because of the high pulse intensity. Prolonged irradiation with UVA led to photodarkening whereas no detrimental effects were observed after irradiation with visible light.
Conclusions:
Irradiation with visible light does not seem to be harmful to the human lens except if the lens is exposed to laser irradiances that are high enough to warrant thermal protein denaturation that is more readily seen using pulsed laser systems.
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