Ocular Disease (ocular + disease)

Distribution by Scientific Domains

Selected Abstracts

Long-term remission after cessation of interferon-, treatment in patients with severe uveitis due to Behçet's disease

Christoph M. E. Deuter
Objective To retrospectively assess the development of visual acuity and the frequency and duration of relapse-free periods in patients who were treated with interferon-, (IFN,) for severe uveitis due to Behçet's disease (BD) and who completed a followup period of ,2 years. Methods IFN alfa-2a was administered at an initial dosage of 6 million IU per day, then tapered to a maintenance dosage of 3 million IU twice per week, and finally discontinued, if possible. In case of a relapse, IFN treatment was repeated. Visual acuity at the end of followup was compared with visual acuity when ocular disease was in remission. Results Of 53 patients (96 eyes), 52 (98.1%) responded to IFN. In 47 patients (88.7%), IFN could be discontinued when the disease was in remission. Twenty of these 47 (42.6%) needed a second treatment course during a median followup of 6.0 years (range 2.0,12.6 years). Visual acuity improved or remained unchanged in 91 eyes (94.8%). Ocular disease was still in remission in 50% of the patients 45.9 months after cessation of the first IFN course. The relapse rate tended to be lower in women than in men. The BD activity score decreased significantly during followup, but long-term remission of nonocular BD manifestations was not achieved. However, since local treatments were sufficient, no systemic treatment was administered. Conclusion Our findings indicate that IFN, induces long-lasting remission in patients with severe ocular BD, resulting in a notable improvement in visual prognosis. [source]

Intercellular adhesion molecule-1 gene polymorphisms in Behçet's disease

D. H. Verity
Intercellular adhesion molecule-1 (ICAM-1) gene polymorphisms have been implicated in the susceptibility to inflammatory diseases, including multiple sclerosis and inflammatory bowel disease. The expression of both soluble and tissue ICAM-1 is increased in Behçet's disease (BD) but the contribution of ICAM-1 gene polymorphisms to this disease remains unknown. Associations with BD have been reported for genes within the MHC, including HLA-B51, TNF and MICA, but the role of non-MHC genes in BD remains largely unexplored. We have investigated the frequency of the R/G 241 and K/E 469 ICAM-1 gene polymorphisms in 83 patients with BD disease and 103 healthy controls, all of Palestinian and Jordanian descent, and demonstrated an association between BD and the ICAM-1 E469 allele (Pc = 0.046, OR = 2.1). Among patients, no association was found between the presence of ocular disease and ICAM-1 polymorphisms. While the functional correlate of this polymorphism remains unclear, this finding indicates that a genetic polymorphism in the ICAM-1 gene domain, which is independent of the MHC, may contribute to disease. [source]

Disseminated aspergillosis in two dogs in Israel

MYCOSES, Issue 2 2006
Y. Bruchim
Summary Aspergillus terreus, normally a soil or plant saprophyte, causes disseminated systemic infection, involving primarily the skeletal and the cardiopulmonary system in humans and dogs.1, 2 We describe two cases of German shepherd dogs that were referred to Koret School of Veterinary Medicine Teaching Hospital with a history of anorexia and weakness. Case 1 suffered from neurological deficits, paraparesis and lumbar pain whereas case 2 suffered from unilateral uveitis and exophthalmus. Both dogs were treated symptomatically, but deteriorated progressively despite therapy and were therefore euthanised. Necropsy revealed disseminated aspergillosis, and numerous organs had multiple, miliary, white-yellow foci. Microscopically, these were identified as granulomas, containing fungal hyphae. Affected tissue included brain, heart, kidneys, spleen, lymph nodes and bones (case 2). Aspergillus terreus was isolated from different organs and from urine culture. We suggest that disseminated aspergillosis should be considered as a differential diagnosis in German shepherd dogs presenting with ocular disease, neurological deficits, spinal column pain, urinary system disorders, and radiographic evidence of skeletal and/or respiratory pathology. [source]

Measuring contrast sensitivity with inappropriate optical correction*

Russell L. Woods
Summary Spatial frequency-selective minima (notches) in the contrast sensitivity function (CSF) because of defocus can mimic those that occur with ocular disease. We examined the influence of measurement conditions on CSF shape in simulated clinical testing. CSF notches occurred with almost all levels of defocus for all subjects. Multiple notches were found under some conditions. Notches were found with defocus as small as 0.50 D. Effects of induced astigmatism depended on the orientation of the target. Notches were apparent in defocus conditions after stimulus size and room illuminance were modified and when subjects had insufficient accommodation to compensate for hypermetropic defocus. The equivalent of notches was not noted with the Pelli-Robson chart. As defocus-induced CSF notches may be mistaken for functional loss, careful refractive correction should be conducted prior to clinical or experimental CSF measurement, even at low spatial frequencies. [source]

Long-term remission after cessation of interferon-, treatment in patients with severe uveitis due to Behçet's disease

Christoph M. E. Deuter
Objective To retrospectively assess the development of visual acuity and the frequency and duration of relapse-free periods in patients who were treated with interferon-, (IFN,) for severe uveitis due to Behçet's disease (BD) and who completed a followup period of ,2 years. Methods IFN alfa-2a was administered at an initial dosage of 6 million IU per day, then tapered to a maintenance dosage of 3 million IU twice per week, and finally discontinued, if possible. In case of a relapse, IFN treatment was repeated. Visual acuity at the end of followup was compared with visual acuity when ocular disease was in remission. Results Of 53 patients (96 eyes), 52 (98.1%) responded to IFN. In 47 patients (88.7%), IFN could be discontinued when the disease was in remission. Twenty of these 47 (42.6%) needed a second treatment course during a median followup of 6.0 years (range 2.0,12.6 years). Visual acuity improved or remained unchanged in 91 eyes (94.8%). Ocular disease was still in remission in 50% of the patients 45.9 months after cessation of the first IFN course. The relapse rate tended to be lower in women than in men. The BD activity score decreased significantly during followup, but long-term remission of nonocular BD manifestations was not achieved. However, since local treatments were sufficient, no systemic treatment was administered. Conclusion Our findings indicate that IFN, induces long-lasting remission in patients with severe ocular BD, resulting in a notable improvement in visual prognosis. [source]

Antiepiligrin (laminin 5) cicatricial pemphigoid complicated and exacerbated by herpes simplex virus type 2 infection

Tanya K Gilmour
SUMMARY A 50-year-old man with antiepiligrin (laminin 5) cicatricial pemphigoid (AeCP) involving the eyes, mouth and skin required a combination of systemic drug therapies to suppress the ocular disease. Herpes simplex virus type 2 infection of the mouth and pharynx precipitated an acute deterioration, with laryngeal involvement and an increase in oral ulceration. This is an unusual complication of long-term immunosuppression and illustrates some of the difficulties in the management of patients with AeCP. Clinical improvement was obtained with oral antiviral therapy and adjustment of his immunosuppressive regimen. [source]

Infectious bovine keratoconjunctivitis vaccine development

Infectious bovine keratoconjunctivitis is a common and highly contagious ocular disease affecting cattle worldwide. The tremendous economic losses attributable to this disease warrant continued investigation into methods of prevention. Multiple virulence factors have been linked to the primary aetiologic agent, Moraxella bovis. Efforts to develop an efficacious vaccine have primarily focused upon the use of surface pili or cytolysin to stimulate host immunity; however, M bovis possesses other virulence determinants that include proteases, fibrinolysins, phospholipases and other cell surface components such as outer membrane proteins. These potentially conserved antigens provide additional possibilities for vaccine development. Examination of appropriate antigen presentation is necessary to attain an adequate immune response. Further, the potential for antigenic diversity as well as epitope conversion requires continuous epidemiological surveillance of isolates recovered from outbreaks. Current work targeting conserved immunogens provides hope for efficacious vaccines that when used in tandem with proper management may control, if not prevent, infectious bovine keratoconjunctivitis. [source]

Increase of vascular endothelial growth factor and interleukin-6 in the aqueous humour of patients with macular oedema and central retinal vein occlusion

Hidetaka Noma
Acta Ophthalmol. 2010: 88: 646,651 Abstract. Purpose:, This study aimed to investigate whether vascular endothelial growth factor (VEGF) or interleukin-6 (IL-6) influence macular oedema in patients with central retinal vein occlusion (CRVO). Methods:, Sixteen consecutive patients with unilateral CRVO and macular oedema were studied, along with eight age- and sex-matched patients without ischaemic ocular disease. Retinal ischaemia was evaluated from capillary non-perfusion on fluorescein angiography. Macular oedema was examined by optical coherence tomography. Aqueous humour (AH) samples were obtained during combined pars plana vitrectomy and cataract surgery, and were examined by enzyme-linked immunosorbent assay. Results:, Aqueous levels of VEGF and IL-6 were significantly elevated in patients compared with controls (p = 0.0142 and p < 0.0001, respectively). Aqueous levels of both molecules were significantly higher in patients with ischaemia than in those without ischaemia (p = 0.0026 and p = 0.0487, respectively). Furthermore, AH levels of VEGF and IL-6 were correlated with the severity of macular oedema (, = 0.7265, p = 0.0049, , = 0.5324, and p = 0.0392, respectively). Conclusions:, Both VEGF and IL-6 were elevated in the AH of patients with macular oedema and ischaemic CRVO, suggesting that these molecules may be related to the increase in vascular permeability in such patients. [source]

2213: Herpetic keratitis: Herpes simplex virus versus host

Herpes simplex virus type 1 (HSV-1) is an endemic virus worldwide that causes ocular disease in a limited but significant number of infected persons. Corneal HSV-1 infection is clinically classified into herpetic epithelial keratitis (HEK) and herpetic stromal keratitis (HSK). HEK is an acute inflammation and results from viral toxicity of infected corneal epithelial cells. In contrast, HSK is characterized as a chronic immunopathogenic disease in which tissue injury and eventually blindness is due to the complex interplay between cells of the innate and adoptive immune response to viral antigens expressed in the corneal tissue. Studies performed on the experimental HSK mouse model greatly improved our understanding of the pathogenesis of HSK. This talk will recapitulate current insights on the virus-host interactions involved in the initiation and perpetuation of herpetic keratitis in mice and men. [source]

2243: Update on inherited ocular developmental disease

Purpose To provide an overview of progress in understanding of the genetics of developmental ocular disease. Methods A systematic review, including case presentations, to illustrate insights into genes underlying developmental ocular disorders: Results Studies suggest that, in developed countries, between a third and a half of the diagnoses underlying childhood blind or partial-sighted registration are genetic while a number of other ,non-genetic' conditions also have a substantial genetic contribution. Such a figure is likely to be an underestimate. Although most of these conditions are rare, many of the issues regarding diagnosis and counselling apply to the group as a whole and it is therefore possible to consider a common approach to many aspects of their clinical management. An important challenge, for example, is to improve genetic counselling for patients affected by, and at risk of, disorders that may be caused by a genetic change in one of many possible genes, which typifies many inherited conditions associated with blindness (developmental ocular disorders, early-onset retinal dystrophies, congenital cataract). Most diagnostic genetic testing currently being undertaken focuses on single genes; this will be illustrated for ocular conditions such as retinoblastoma, Norrie disease and microphthalmia. However future prospects will focus upon use of new higher throughput technologies (e.g Microarray technologies). Conclusion The recent identification of genes underlying, for example, anophthalmia/microphthalmia spectrum (e.g. VSX2, SOX2, BCOR), anterior segment dysgenesis (e.g. PITX2, FOXC1, FOXE3) and early,onset retinal disorders (e.g. ADVIRC, RPE65) has shed light on the pathways and processes underlying a range of the biological processes underlying ocular development. [source]

2127: Ghrelin concentration in the aqueous humour and plasma in open angle glaucoma patients

Purpose Ghrelin is a peptide hormone that exerts metabolic and smooth muscle-relaxant effects in ocular tissues. The aim of this study was to compare aqueous humor and plasma levels of ghrelin in patients with open angle glaucoma (OAG) and controls. Methods Twenty four OAG, including 7 pseudoexfoliation (PXG) and 17 primary open-angle glaucoma (POAG) patients, and 30 controls were included. All participants were patients scheduled for cataract or glaucoma surgery. Patients with other concomitant ocular disease, previous ocular surgery or diabetes were excluded. Blood samples were collected before cataract surgery. Aqueous humor was aspirated from the anterior chamber through a paracentesis with a 27 G needle under sterile conditions. Ghrelin levels in both samples were measured quantitatively with commercially available Radioimmunoassay (RIA) kits. Results Mean±SD age was 71.0±9.3 and 69.6±6.6 years in the OAG and control groups, respectively (p=0.6). Plasma levels of ghrelin were 495.6±157.7 pg/ml in the OAG and 482.2±125.4 pg/ml in the control group, respectively (Mann-Whitney test, p=0.9). Aqueous humor levels of ghrelin were 85.5±15.4 pg/ml and 123.4 ±25.5 pg/ml in the OAG and control groups, respectively (Mann-Whitney test, p<0.01). The ratio of plasma/aqueous concentration in ghrelin was higher in the OAG versus the control group (5.82± 1.94 versus 4.00±1.04, Mann-Whitney test, p<0.01). There was no difference neither in plasma nor in aqueous humor levels of ghrelin between POAG and PXG patients (p>0.5). Conclusion Aqueous humor levels of ghrelin were significantly lower in OAG patients. This difference may manifest a role of ghrelin in the disease process or a consequence of antiglaucoma treatment. [source]

Evaluation of choroidal blood flow after treatment of retinal diseases

Purpose this review aims to summarize studies which assessed the effect of treatment on choroidal blood flow. Methods this presentation will focus on studies using the laser Doppler flowmeter for the analysis of choroidal blood flow parameters (velocity, volume and flow) before and after treatment. Therapies have been assessed in different ocular disease, such as age-related macular degeneration (laser photocoagulation therapy, photodynamic therapy, transpupillary thermotherapy, sildenafil citrate, niacin, pentoxifylline), diabetes mellitus (panretinal photocoagulation, intravenous C-peptide infusion), retinal vein occlusions (isovolemic hemodilution), macular edema (diclofenac), inflammation (corticosteroid), retinal detachment (surgery) or glaucoma (nimodipine, endothelin receptor antagonist, bimatoprost, timolol, trabeculectomy). Results this paper will give insight to the effects of laser treatment (laser photocoagulation, photodynamic therapy), surgery (scleral buckling, trabeculectomy, ocular anesthesia) or systemic drugs on the choroidal blood flow. Methodological considerations will be analyzed, such as the calculation of the sensitivity of the experiments, the comparisons of different groups with or without randomization. Conclusion laser Doppler flowmetry is a useful and a non invasive technique to study the effect of treatment on choroidal blood flow. In ocular disease, investigators should be aware of the tissue scattering changes associated with a retinal or choroidal disease and the necessity of a controlled foveal fixation. [source]

Retinal vessel oximetry using sequential and 'snapshot' hyperspectral imaging

Purpose Use of sequential, and 'snapshot' hyperspectral imagers to measure oxygen saturation in retinal vessels in normals, and examples of eye disease, eg glaucoma, and retinovascular diseases. Validation of estimated oximetry values using a model eye. Methods A sequential hyperspectral imager was constructed using a fundus camera with built-in liquid-crystal tuneable filter. Images of normals,and ocular disease are presented. A novel 'snapshot' hyperspectral imager is also described: this produces images in a single exposure. Validation of both devices using an artificial eye with capillary tubes containing human blood of known oxygen saturation, placed in front of an 'artificial retina' is described. The image analysis used to detect retinal vessels, and generate oximetric values is detailed. Results Both the sequential, and 'snapshot' retinal imagers produced accurate estimations of retinal vessel oxygen saturation, when compared with the model eye. Imaging of a small group of glaucoma eyes showed abnormally elevated venous oxygen saturation. In proliferative diabetic retinopathy, abnormally elevated venular saturation was found in areas of capillary loss on FFA. In vein occlusion, elevated venous saturation was found in eyes with ischaemic FFAs. Conclusion Both the sequential and 'snapshot' hyperspectral imagers deliver useful oximetric maps of the retina. The 'snapshot' device allows more rapid imaging. The elevated venular oxygen saturation seen in both glaucoma, and retinovascular disease, is perhaps evidence of reduced oxygen consumption in damaged inner retina in glaucoma, and/or vascular 'shunting' in retinovascular disease. [source]

Fitness to drive in glaucoma patients- Preliminary study results

Purpose To develop a useful binocular 30° visual field criterion to predict safe driving behaviour in glaucoma patients by comparing perimetric data with an actual driving test on the road. Methods The sample will consist of 200 driving glaucoma patients, recruited in 2 university based glaucoma clinics (Ghent and Leuven, Belgium). Inclusion criteria are glaucomatous optic disc damage and/or glaucomatous field defects. Exclusion criteria are concomitant ocular disease, cataract > LOCS 2, systemic disease or medication affecting the visual field. Data collection will include demographic and medical data, driving habits, and Mini Mental Status. A complete ophthalmic examination wil be done including Goldmann, SAP and Esterman visual field testing. In addition, UFOV test, stereopsis and contrast sensitivity testing will be performed. All subjects will perform an on the road driving test with a driving expert of the Belgian Institute for Traffic Safety. Subjects can pass, fail, or pass the test with limitations. An attempt will be made to develop an algorithm of visual field abnormalities that predict as accurately as possible the outcome of the practical driving test. Results Preliminary results of the first 50 included patients will be presented. [source]

Ocular rigidity in living human eyes in health and disease

Purpose It is known that the balance between aqueous humor secretion and outflow rate controls the steady - state average intraocular pressure (IOP). It has been also early identified that blood circulation results to IOP fluctuations practically synchronous to cardiac function. IOP is the primary mechanical load to several ocular structures including the optical nerve head. Methods In-vivo intraoperative measurement of these quantities as well as secretion/outflow coefficients in humans allowed us to quantify ocular rigidity, IOP and its fluctuations (and pulsatile blood flow) in a series of physiological and pathological eyes. Ocular rigidity, outflow facility and pulsatile ocular blood flow were measured intraoperatively in a cohort of 63 patients undergoing cataract surgery. Measurements were also performed in a series of age related macular degeneration (AMD) patients. Results The eye, is a living structure under a continuously varying mechanical load that is strongly related to ocular haemodynamics. Ocular rigidity ranged from 0.0122 to 0.0343 (mean 0.0208),l-1. Outflow facility coefficient (derived from pressure decay curves) was 0.33 (sd 0.15),l/min/mmHg. Pulsatile ocular blood flow exhibited a strong negative correlation to IOP in all subjects. The ocular rigidity coefficient was higher in wet AMD patients compared to patients with dry AMD and healthy controls. Conclusion There are indications that this mechanical load, associated also to ocular rigidity, can not only inter-modulate blood flow but also have a long-term effect on other structures in the eye. Understanding the role of these parameters may contribute to the understanding of ocular disease. [source]

Anterior chamber parameters measured by the Pentacam CES after uneventful phacoemulsification in normotensive eyes

Özlenen Ö. Uçakhan
Abstract. Purpose:, We set out to quantify changes in the anterior chamber volume (ACV), anterior chamber depth (ACD) and anterior chamber angle (ACA) measurements obtained by the Pentacam rotating Scheimpflug camera following uneventful phacoemulsification surgery in normotensive eyes with open iridocorneal angles. Methods:, We enrolled 44 eyes of 44 consecutive patients undergoing cataract extraction in this prospective study. Patients with a history of glaucoma, angle-closure glaucoma or any other concurrent ocular disease were excluded. A detailed eye examination including intraocular pressure (IOP) measurement was performed and ACV, ACD and inferior, superior, temporal and nasal ACA measurements were obtained in each patient eye using the Pentacam Comprehensive Eye Scanner (Pentacam CES) before and 3 months after phacoemulsification and intraocular lens (IOL) implantation with temporal clear corneal incision. Data were compared using paired t -test and one-way anova. Results:, Mean preoperative ACV, ACD, ACA and IOP measurements were 164.7 ± 49.8 mm3, 3.0 ± 0.8 mm, 35.7 ± 10.2 ° and 15.8 ± 3.7 mmHg, respectively. Three months postoperatively, mean ACV, ACD, ACA and IOP measurements were 200.9 ± 33.3 mm3, 3.9 ± 0.9 mm, 41.5 ± 6.5 ° and 13.2 ± 3.9 mmHg, respectively. Postoperative mean ACV, ACD and ACA values in all four quadrants were significantly increased (p < 0.0001, p < 0.0001, p < 0.0001, respectively), whereas IOP was significantly reduced (p < 0.0001). Conclusions:, The Pentacam CES allowed very easy, fast, automatic and non-contact quantification of the anterior chamber parameters pre- and postoperatively in all patient eyes. Measurements obtained confirm that in normotensive eyes with open iridocorneal angles, the ACV and ACD increase and the ACA widens in all quadrants 3 months after uneventful phacoemulsification and IOL implantation. These changes are accompanied by a significant fall in IOP in the short term. [source]

Proteomic analysis of conjucntival swab by mass spectrometry

Purpose: The purpose of this study was to identify proteins present in the tears and mucosal epithelium of the ocular surface. Methods: A cotton swab was rubbed across the anaesthetized inferior conjunctiva of a dry eye patient. Protein was extracted and subjected to 1D gel electrophoresis. After excision and trypsinisation, protein profiles from swab samples were identified using mass spectrometry carried out on a 3200 Q-TRAP Hybrid ESI Quadropole linear ion trap. Protein identification was performed using MASCOT software against a human database extracted from NCBI. Curation of the protein list was achieved using the bioinformatics tool PROVALT, which also calculated false-discovery rates. Results: In total 75 validated proteins were identified including the tear proteins, lactotransferrin, lysozyme, and proline rich proteins as well as a number of proteins not previously associated with the tear proteome. Proteins identified had a wide range of physio-chemical properties and included structural and functional proteins. Conclusions: Use of a simple swab combined with a GeLC-MS proteomic protocol led to unequivocal identification of a large range of proteins associated with the ocular surface proteome. This may allow a better characterisation of the ocular surface environment and discrimination between various eye conditions. Tear collection using capillaries can be tedious and may discourage clinicians from performing such a test. Use of a swab that can be frozen for analysis may encourage the use of this methodology. Analysis of this proteome offers huge clinical potential for investigation of ocular surface biomarkers for the development of novel diagnostic tools and monitoring of ocular disease. [source]

Acute anterior uveitis in primary care

Ian F Gutteridge MScOptom FAAO
Acute anterior uveitis is an important ocular disease of considerable interest to therapeutically and non-therapeutically qualified optometrists. This review examines the role of optometrists in the primary care setting and gives guidelines for appropriate care of patients with anterior uveitis. Diagnosis and differentiation from other forms of anterior segment inflammation are the initial requirement. In parallel, possible medical conditions associated with acute anterior uveitis must be considered, with appropriate referral to medical practitioners. In uncomplicated cases of recurrent acute anterior uveitis, optometrists can initiate topical treatment and monitor resolution of inflammation, while being aware of possible complications of both the disease and its treatment. It is especially important in new attacks of anterior uveitis to liaise with the patient's general practitioner about medical investigation for underlying disease. Atypical, complicated or severe anterior uveitis should be promptly referred for specialist care. [source]

Comparison of practical methods for urinary glycosaminoglycans and serum hyaluronan with clinical activity scores in patients with Graves' ophthalmopathy

João R. M. Martins
Summary objective, Immunosuppressive treatment of Graves' opthalmopathy (GO) should be restricted to patients with active eye disease, but assessing disease activity is difficult. Several methods to evaluate GO activity have been introduced, but none of them is satisfactory. Glycosaminoglycans (GAGs) are complex polysaccharides that participate on the pathogenesis of GO and attempts to correlate its local increase to urinary GAGs (uGAGs) or serum hyaluronan (sHA) have been made, but the available techniques are labourious, time-consuming and difficult for routine use. The aim of the present study is to develop practical and simple methods for uGAGs and sHA and compare them to the activity and severity of thyroid-associated ophthalmopathy. design, patients and measurements, We developed a microelectrophoresis technique for uGAGs and a fluoroassay for sHA and assessed each in 152 patients with Graves' disease, 25 without GO and 127 with GO, classified according to the Clinical Activity Score (CAS). All patients had been euthyroid for > 2 months. results, Patients with inactive disease (CAS = 2, n = 100) had uGAGs (4·2 ± 1·3 µg/mg/creatinine) and sHA (11·1 ± 7·2 µg/l) that did not differ from normal subjects (3·1 ± 1·1 µg/mg/creatinine, n = 138 and 13·9 ± 9·6 µg/l, n = 395). In contrast, patients with active eye disease (CAS = 3, n = 27) had uGAGs (8·4 ± 2·7 µg/mg/creatinine) and sHA (32·3 ± 17·8 µg/l) 2,3 times higher than those patients with inactive eye disease. Using a cut-off of 6·1 µg/mg creatinine for uGAGs and 20·7 µg/l for sHA we found, respectively, 85% and 81% sensitivity and 93% and 91% specificity for each test. The positive and negative predictive values were 77% and 96% for uGAGs and 71% and 95% for sHA. conclusion, Employing these two new methods we have established a significant relationship between the levels of uGAGs and/or sHA and the clinical activity of GO. Therefore, together with CAS, uGAGs determination, and, to a lesser degree, sHA, would be very useful in the discrimination from active and inactive ocular disease and aid in deciding on the best therapy for GO patients. [source]

,-synuclein has a dynamic intracellular localization

CYTOSKELETON, Issue 8 2006
Irina Surgucheva
Abstract ,-Synuclein is a member of the synuclein family consisting of three proteins. Within the last several years increasing attention has focused on these proteins because of their role in human diseases. ,-Synuclein relevance to Parkinson's disease is based on mutations found in familial cases of the disease and its presence in filaments and inclusion bodies in sporadic cases. ,-Synuclein is implicated in some forms of cancer and ocular diseases, while ,-synuclein may antagonize their pathological functions. In this paper we present data on the localization and properties of ,-synuclein in several neuronal and nonneuronal cell cultures. We show that contrary to the current opinion, ,-synuclein is not an exclusively cytoplasmic protein, but has a dynamic localization and can associate with subcellular structures. It is present in the perinuclear area and may be associated to centrosomes. On late steps of mitosis ,-synuclein is not found in the centrosomes, and redistributes to the midbody in telophase. Under stress conditions a translocation of ,-synuclein from the perinuclear area to the nucleus occurs exhibiting nucleocytoplasmic shuttling. ,-Synuclein overexpression reduces neurite outgrowth in a greater extent then ,-synuclein overexpression. These data support the view that ,-synuclein may change its intracellular localization and associate with subcellular structures in response to intracellular signaling or stress. Cell Motil. Cytoskeleton 2006. © 2006 Wiley-Liss, Inc. [source]

Sustained ophthalmic in situ gel of ketorolac tromethamine: rheology and in vivo studies

A.S. Manjappa
Abstract Most ocular diseases are treated with topical eye drops. The poor bioavailability and therapeutic response exhibited by these conventional eye drops due to rapid precorneal elimination of the drug may be overcome by the use of in situ gelling systems that are instilled as drops into the eye and undergo a sol-to-gel transition in the cul-de-sac. The present work describes the formulation and evaluation of an ophthalmic delivery system of the nonsteroidal anti-inflammatory drug (NSAID), ketorolac tromethamine, based on the concept of pH-triggered in situ gelation. Polyacrylic acid (Carbopol® 934) was used as the gelling agent in combination with hydroxypropylmethylcellulose (Methocel E15LV), which acted as a viscosity enhancer. The prepared formulations were characterized for clarity, pH, drug content, rheology, and in vivo drug release. Clarity, pH, and drug content of the developed formulations were found to be satisfactory. The developed formulation showed pseudo-plastic rheology. The formulation with benzalkonium chloride and edetate disodium improved the rate of corneal absorption but not the extent. The developed formulation is a viable alternative to conventional eye drops by virtue of its ability to enhance bioavailability through its longer precorneal residence time and ability to sustain drug release. Also importantly is the ease of instillation afforded and decreased frequency of instillation resulting in better patient acceptance. Drug Dev Res, 2009. © 2009 Wiley-Liss, Inc. [source]

Determination of amino acids in rat vitreous perfusates by capillary electrophoresis

Kongthong Thongkhao-On
Abstract In vivo determinations of amino acids are important for improving our understanding of physiological states of biological tissue function and dysfunction. However, the chemically complex matrix of different biological fluids complicates the assay of this important class of molecules. We introduce a method for characterizing the amino acid composition of submicroliter volumes of vitreous humor perfusates. Low-flow push-pull perfusion sampling is compatible with collecting small volume samples in a complicated matrix that are potentially difficult to separate. An efficient, sensitive, and rapid analysis of amino acids from in vivo perfusates of the vitreous is presented with 3-(4-carboxybenzoyl)-2-quinoline-carboxaldehyde (CBQCA) derivatitation and capillary electrophoresis (CE) separation with laser-induced fluorescence detection (LIF). Derivatization with CBQCA for up to 2 h provided high sensitivity and low detection limits at the nM level. Seventeen amino acids including D -serine (D -Ser) and D -aspartate (D -Asp) were resolved in less than 10 min. Importantly, D -Ser is separated from its enantiomeric pair. Characterization of vitreal amino acids with this assay technique will be useful for understanding ocular diseases and physiological mechanisms in vision. [source]

3251: From elementary concept in animal models to new frontiers in humans: neurovascular coupling in the ocular circulation

Purpose The retina and optic nerve, both optically accessible components of the central nervous system, are ideally suited for the investigation of the intrinsic physiological process by which blood ,ow, metabolism and neural activity are tightly coupled (Roy and Sherrington. 1890). Methods Using various techniques in the cat and human eye, the changes in blood flow in the retina and optic nerve in response to increased neural activity by flicker stimulation have been determined. The effect of varying the stimulus parameters, such as flicker modulation depth, frequency, luminance and red-green color ratio, on the blood flow response was investigated. Putative mediators of the activity-induced flow changes and the relationship between activity, blood flow and metabolic changes were assessed. Results Visual stimulation with flicker increases rapidly and markedly both retinal and optic nerve blood ,ows (functional hyperemia). Moreover, the data reveal unequivocally the presence, under specific conditions of flicker, of a neurovascular/neurometabolic coupling in these tissues, partly mediated by local potassium ions and nitric oxide production. Furthermore, the activity-induced hyperemia is altered during a number of physiological and pharmacological interventions and in some pathologic conditions. Conclusion Flicker stimulation of the retina offers a new and powerful means to modulate blood flow and investigate the neurovascular coupling in the neural eye tissues. Exploration of this activity-induced hyperemia and the mechanism(s) underlying the neurovascular coupling will lead to an increased understanding of the pathophysiology of various ocular diseases. [source]

Ocular findings among young men: a 12-year prevalence study of military service in Poland

Michal S. Nowak
Abstract. Purpose:, To determine the prevalence of ocular diseases among young men and to assess the main ocular causes reflecting discharge from military service in Poland. Methods:, A retrospective review of the medical records of 105 017 men undergoing a preliminary examination for military service during the period 1993,2004. Sample size for the study was calculated with 99% confidence within an error margin of 5%. All of the study participants were White men of European origin, most of whom live or lived in Poland. Data regarding the vision status were assessed in 1938 eyes of 969 participants. Two groups were distinguished based on the age of the participants: group I aged 18,24 years, and group II aged 25,34 years. Results:, Presented visual impairment [visual acuity (VA) < 20/40)] followed by colour vision defects were the most common ocular disorders, accounting for 13.2%. There were statistically significant differences in uncorrected VA as well as in the rates of particular refractive errors in between the age groups (p < 0.05). The prevalence of glaucoma and ocular hypertension was significantly higher in older participants. Six hundred and sixty-seven (68.8%) participants examined medically in the study period were accepted for military service. However, 302 (31.2%) failed their examination and were temporarily or permanently discharged from duty. Fifty-two of them (17.2%) were discharged because of various ocular disorders. The most common causes were high refractive errors, which accounted for 38.5% of all the ocular discharges, followed by chronic and recurrent diseases of the posterior segment of the eye, which accounted for 19.2%. Conclusion:, The prevalence of ocular disorders among young men in an unselected military population was closer to the results obtained in other population-based studies comprising both men and women in the same age group. High refractive errors followed by chronic and recurrent diseases of the posterior segment of the eye are important causes of medical discharges from military service in Poland. [source]

Role of NO in retinal vascular disease

Purpose Nitric oxide (NO) is a key regulator of vascular tone in all vascular beds including the eye. Hence, inhibition of NO synthase with L-arginine analogues leads to a reduction of blood flow to all ocular tissues. This enables the investigation of the role of NO in the physiology of blood flow regulation, but also abnormalities of the vascular L-arginine/NO system in ocular vascular disease. Methods A variety of studies investigating the role of NO in healthy humans but also in patients with vascular disease is summarized. Results Inhibition of NO synthase reduces retinal, choroidal and optic nerve head blood. A variety of studies also indicate that NO plays a role in the ocular vasodilator effects of numerous agonists including acetylcholine, bradykinin, carbon dioxide, histamine and insulin. In addition, NO appears to modulate the autoregulatory behavior of ocular vascular beds and is involved in retinal neurovascular coupling. In several ocular diseases such as diabetic retinopathy or open angle glaucoma abnormalities in the NO system can be observed. Conclusion NO is a major regulator of ocular blood flow in humans. The existence of different NO synthase isoforms makes it, however, difficult to therapeutically intervent via the L-arginine/NO pathway. Further studies are required to characterize the role of the NO synthase isoforms in the control of ocular blood flow in more detail and to allow for therapeutic interventions in ischemic ocular eye disease via this attractive pathway. [source]

Ocular blood flow autoregulation and the clinical implications of its alteration

Autoregulation is commonly defined as the ability of a vascular bed to adapt blood flow to changes in ocular perfusion pressure (pressure autoregulation) or to adapt to changes in metabolic need (metabolic autoregulation). Considering the high metabolic turnover of the eye, its intact function is strongly dependent on a stable blood supply, assured by an intact vascular autoregulation. However, it has been shown that in the recent years that several ocular diseases such as glaucoma, diabetic retinopathy or age related macula degeneration are associated with an impaired autoregulation. This vascular dysregulation may lead to an under- or overperfusion of the tissue and in turn to ischemia and/or oxidative stress. This talk seeks to summarize our current knowledge of autoregulation in the ocular vascular beds. Furthermore, the possible reasons of impaired autoregulation and how this may relate to ocular pathologies will be discussed. [source]

Most readily usable methods to measure ocular blood flow

Purpose SIS Lecture. Methods Literature search. Results Ocular Blood Flow Research Association (OBFRA, recently merged with another organization - ISOCO, into one single Association for Ocular CDirculation - AOC) made a significant contribution to standardization of the blood flow measuring techniques in the field of ophthalmology. A consens was reached on the number of OBF measurements techniques that occured in the past decades. Particular emphasis was placed on the basic technology, specific parameters and interpretation, accuracy and reproducibility, field of clinical applications. Open questions were extensively discussed, limits of each technique clearly postulated. and a consensus statement put together for each of the technique involved. It encompassed techniques like color Doppler imaging, laser Doppler flowmetry (continuous as well as scanning LDF), laser Doppler velocimetry, Retinal Vessel Analyzer, combination of the vessel diameter measurement and the LDV, laser interferometry of the fundus pulsations amplitude, retinal oxymetry, measurements of the pulsatile component of the blood flow, blue field entoptic method and the newest - Doppler OCT. Conclusion There is no overwhelming measuring technique able to cover all the aspects of the research and the daily clinical routine. Various parameters and various vascular beds are involved, which makes the interpretation of the obtained results strenuous. Of particular importance is the capability of OBF measuring techniques to capture one dynamic feature of ocular circulation - its ability to regulate and to response to various challenges. It is widely believed that not the constantly reduced blood flow, but rather the lack of regulation thereof, leads to prevalent ocular diseases. [source]

Effects of moxaverine on ocular blood flow in patients with age-related macular degeneration, patients with primary open angle glaucoma and in healthy controls

Purpose Several common eye diseases including age-related macular degeneration (AMD) and primary open angle glaucoma (POAG) are associated with ocular perfusion abnormalities. Moxaverine has been shown to increase ocular blood flow in young, healthy volunteers after intravenous administration. The present study investigated whether moxaverine alters ocular blood flow in elderly patients with AMD or POAG and in healthy control subjects. Methods 20 patients with AMD, 20 patients with POAG and 20 age-matched healthy subjects were included in this trial. 150 mg moxaverine (Ursapharm, Saarbrücken, Germany) was administered intravenously over 30 minutes. Systemic haemodynamics, retinal vessel diameters, choroidal, optic nerve head and retrobulbar blood flow were measured before and up to 90 minutes after drug administration. Results Administration of moxaverine increased choroidal blood flow by 8.7 ± 21.8% (p=0.012) and optic nerve head blood flow by 12.9 ± 33.3% (p=0.021). Additionally, an increase in the mean flow velocities of posterior ciliary arteries (24.8 ± 34.7%, p<0.001) and in the ophthalmic artery (23.3 ± 33.5%, p<0.001) was found after administration of moxaverine. However, no differences were found between the 3 study groups. No significant change of retinal vessel diameters was observed. Conclusion The present study indicates an increase of ocular blood flow after systemic administration of a single dose of moxaverine in patients with POAG, patients with AMD and in age-matched healthy controls. Further studies are needed to investigate possible beneficial effects after long-term treatment in patients with ocular diseases associated with hypoperfusion. [source]

In vitro transcorneal and transscleral diffusion of radiolabeled compounds in human and rabbit cornea and in human, monkey, dog, and rabbit sclera

Purpose To determine the in vitro diffusion of selected compounds across the cornea or sclera of humans, monkeys, dogs, and rabbits. Methods Human and NZW rabbit corneas were obtained and the epithelium was removed from one cornea of each pair. Corneas were mounted in chambers with 3H-water or 3H-dexamethasone on the epithelial side and BSS solution on the endothelial side. Serial aliquots were taken from each chamber and assayed by LSC. Scleral sections from human, NZW rabbit, dog, or monkey eyes were mounted in perfusion chambers. Adjacent sclera was used for H&E histology. 3H-water, 3H-dexamethasone, or 70kD-14C-dextran were added to the episcleral surface while perfusing BSS across the choroidal side. Serial aliquots were collected up to 5 hrs and assayed by LSC. Scleral permeability (ktrans) was calculated. H&E slides were used to determine scleral thickness. Results 3H-water diffused through cornea faster than 3H-dexamethasone, especially with denuded epithelium. Scleral thickness and molecular weight were determinant of diffusion in sclera. Monkey sclera was thinnest, followed by dog, rabbit, and human. ktrans for 70kD-14C-Dextran and 3H-dexamethasone were greatest in monkey, followed by dog, rabbit, and human. ktrans values for 3H-water were similar in all species, and greater than values for 14C-dextran and 3H-dexamethasone. Conclusion These studies demonstrate permeability of cornea and sclera in human and animal models with compounds of varied molecular weights representative of drugs being developed for treatment of ocular diseases. The results of this study indicate that these techniques are valuable as screening tools in the development of ocular drugs. [source]

Endothelial dysfunction in glaucoma

Hemma Resch
Abstract. Glaucoma is a group of ocular diseases characterized by optic neuropathy associated with loss of the retinal nerve fibre layer and re-modelling of the optic nerve head, and a subsequent particular pattern of visual field loss. Increased intraocular pressure is the most important risk factor for the disease, but the pathogenesis of glaucoma is not monofactorial. Among other factors, ischaemia and vascular dysregulation have been implicated in the mechanisms underlying glaucoma. The vascular endothelium plays an important role in the regulation of ocular blood flow and pathological alterations of vascular endothelial cells may induce ischaemia and dysregulation. The present review summarizes our current evidence of endothelial dysfunction in glaucoma. This is of interest because endothelial dysfunction is a good prognostic factor for progression in several diseases. Although such data are lacking for glaucoma, endothelial dysfunction may provide an attractive target for therapeutic intervention in open-angle glaucoma and other vascular disorders of the eye. [source]