Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 113
Filtrar
1.
Klin Monbl Augenheilkd ; 240(4): 472-477, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37164405

RESUMO

PURPOSE: Detecting glaucoma damage progression is an essential component of follow-ups in glaucoma patients. It is still unclear which of the currently available and routinely used parameters of glaucoma damage heralds the loss of retinal ganglion cells first. We analysed local hospital data on primary open-angle glaucoma (POAG) patients and looked for correlations between the optical coherence tomography (OCT) structural, OCT angiography (OCTA), and visual field (VF) parameters. PATIENTS AND METHODS: Results of eye examinations of POAG patients at baseline, 6 months, and 12 months were analysed. Inclusion criteria were, apart from the diagnosis of POAG, availability and quality of all modalities of examination data and no surgical intervention on the eyes during the observation period. Data on VF mean defect (MD), OCT peripapillary nerve fibre layer (RNFL), OCT macular ganglion cell layer, and OCTA, peripapillary and in the macula, were parameters of interest. Correlations of structural (OCT and OCTA) on one, and functional parameters (VF MD) on the other side, at baseline and as changing over time (first 6 months vs. second 6 months) were performed. RESULTS: All together, data from 78 eyes of 78 POAG patients were included in the analysis. Correlations at baseline were all highly significant (Spearman's r-coefficients between 0.31 and 0.8, all p < 0.05). None of the correlations of parameter changes over time were significant (all p > 0.05). CONCLUSION: Whereas a robust correlation was observed at baseline between the structural (OCT and OCTA) and functional (VF MD) parameters, none of the examination modality could predict a change in the other modalities during the 1-year period. Results confirm the necessity of regularly performing both the structural and functional examinations in our glaucoma patients.


Assuntos
Glaucoma de Ângulo Aberto , Disco Óptico , Humanos , Glaucoma de Ângulo Aberto/diagnóstico , Disco Óptico/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Estudos Retrospectivos , Prognóstico , Angiofluoresceinografia/métodos , Seguimentos , Pressão Intraocular
2.
Curr Eye Res ; 45(11): 1438-1442, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32255706

RESUMO

Background: The purpose of this pilot study was to investigate the differences in neurovascular coupling between Caucasian patients with normal tension glaucoma (NTG) and healthy subjects (HS) with laser speckle flowgraphy (LSFG). Methods: Measurement of optic nerve head blood flow was performed with LSFG. The mean blur rate of the whole optic nerve head (MA), of the big retinal vessels (MV) and of the microvasculature (MT) was analysed during continuous flicker light stimulation for four minutes. Results: We included 12 eyes from 12 Caucasian patients with a diagnosis of normal tension glaucoma and 12 eyes from 12 age- and sex-matched healthy individuals. MA, MV and MT all increased significantly in both groups during the observation period with no difference between the groups. Conclusion: Neurovascular coupling is detectable in NTG patients. Flicker light stimulation leads to a comparable increase in ocular blood flow in glaucoma patients and healthy individuals.


Assuntos
Glaucoma de Baixa Tensão/fisiopatologia , Acoplamento Neurovascular/fisiologia , Disco Óptico/irrigação sanguínea , Vasos Retinianos/fisiopatologia , Idoso , Velocidade do Fluxo Sanguíneo/fisiologia , Pressão Sanguínea/fisiologia , Estudos Transversais , Feminino , Voluntários Saudáveis , Humanos , Pressão Intraocular/fisiologia , Fluxometria por Laser-Doppler , Masculino , Pessoa de Meia-Idade , Fibras Nervosas/patologia , Estimulação Luminosa , Projetos Piloto , Fluxo Sanguíneo Regional/fisiologia , Retina/efeitos da radiação , Células Ganglionares da Retina/patologia , Campos Visuais/fisiologia
3.
Ophthalmologe ; 116(1): 5-13, 2019 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-29511811

RESUMO

BACKGROUND: Structural endpoints have been discussed as surrogate endpoints for the approval of neuroprotective drugs in glaucoma. OBJECTIVE: Is the evidence strong enough to establish structural endpoints as surrogate endpoints? MATERIAL AND METHODS: Review of current understanding between structure and function in glaucoma. RESULTS: The introduction of optical coherence tomography has revolutionized imaging in glaucoma patients. Clinically either the nerve fiber layer thickness can be measured along a circle centered in the optic nerve head or the ganglion cell layer thickness can be assessed in the macular region, the latter being quantified in combination with other inner retinal layers. On a microscopic level there is a strong correlation between structural and functional loss but this relation can only partially be described with currently available clinical methods. This is particularly true for longitudinal course of the disease in glaucoma patients. Novel imaging techniques that are not yet used clinically may have the potential to increase our understanding between structure and function in glaucoma but further research in this field is required. CONCLUSION: The current evidence does not allow the establishment of structural endpoints as surrogate endpoints for phase 3 studies in glaucoma. Neuroprotective drugs have to be approved on the basis of visual field data because this is the patient-relevant endpoint. Structural endpoints can, however, play an important role in phase 2 and proof of concept studies.


Assuntos
Glaucoma , Disco Óptico , Estudos Transversais , Humanos , Pressão Intraocular , Células Ganglionares da Retina , Tomografia de Coerência Óptica , Testes de Campo Visual
4.
Eye (Lond) ; 30(11): 1509-1516, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27472215

RESUMO

PurposeTo define optical coherence tomography (OCT) characteristics of type-1, type-2, and mixed big bubbles (BB) seen in deep anterior lamellar keratoplasty.MethodsHuman sclero-corneal discs were obtained from UK (30) and Canada (16) eye banks. Air was injected into corneal stroma until a BB formed. UK samples were fixed in formalin before scanning with Fourier-domain (FD-OCT). One pair of each type of BB was scanned fresh. All BB obtained from Canada were scanned fresh with time-domain (TD-OCT). For each OCT machine used, type-1 BB from which Descemets membrane (DM) was partially peeled, were also scanned. The morphological characteristics of the scans were studied.ResultsFD-OCT of the posterior wall of type-1 (Dua's layer (DL) with DM) and type-2 BB (DM alone) both revealed a double-contour hyper-reflective curvilinear image with a hypo-reflective zone in between. The anterior line of type-2 BB was thinner than that seen with type-1 BB. In mixed BB, FD-OCT showed two separate curvilinear images. The anterior image was a single hyper-reflective line (DL), whereas the posterior image, representing the posterior wall of type-2 BB (DM) was made of two hyper-reflective lines with a dark space in between. TD-OCT images were similar with less defined component lines, but the entire extent of the BB could be visualised.ConclusionOn OCT examination the DM and DL present distinct features, which can help identify type-1, type-2, and mixed BB. These characteristics will help corneal surgeons interpret intraoperative OCT during lamellar corneal surgery.


Assuntos
Córnea , Substância Própria/diagnóstico por imagem , Transplante de Córnea , Lâmina Limitante Posterior/diagnóstico por imagem , Tomografia de Coerência Óptica , Vacúolos , Idoso , Idoso de 80 Anos ou mais , Ar , Substância Própria/cirurgia , Bancos de Olhos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doadores de Tecidos , Obtenção de Tecidos e Órgãos
5.
Klin Monbl Augenheilkd ; 232(9): 1061-8, 2015 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-26372783

RESUMO

New developments in retinal imaging have revolutionised ophthalmology in recent years. In particular, optical coherence tomography (OCT) provides highly resolved and well reproducible images and has rung in a new era in ophthalmological imaging. The technology was introduced in the early 1990 s, and has rapidly developed. There have been improvements in resolution, sensitivity and processing speed. There have also been developments in functional processing. OCT angiography is the first application in routine clinical work.


Assuntos
Angiofluoresceinografia/métodos , Doenças Retinianas/diagnóstico , Retinoscopia/métodos , Tomografia de Coerência Óptica/métodos , Humanos , Aumento da Imagem/métodos
6.
Klin Monbl Augenheilkd ; 232(2): 141-6, 2015 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-25700252

RESUMO

Ocular perfusion pressure is defined as the difference between arterial and venous pressure in ocular vessels. In practice, mean arterial pressure is used to substitute for arterial pressure in ocular vessels while intraocular pressure gives an estimate for ocular venous pressure. This results in a value that is easy to calculate and which is of importance since several studies have shown that it is correlated to the prevalence, incidence and progression of primary open angle glaucoma. Today, ocular perfusion pressure is used to estimate individual risks. Since no target value for ocular perfusion pressure can be defined, direct therapeutic intervention is difficult. Still, it has to be kept in mind that lowering intraocular pressure automatically leads to an increase in ocular perfusion pressure. The present article also points out problems and limitations in the concept of ocular perfusion pressure and suggests possible solutions for these problems in the future.


Assuntos
Pressão Sanguínea , Glaucoma/fisiopatologia , Hipertensão Ocular/fisiopatologia , Artéria Retiniana/fisiopatologia , Veia Retiniana/fisiopatologia , Animais , Humanos , Pressão Intraocular , Modelos Cardiovasculares
7.
Ophthalmologe ; 110(10): 960-5, 2013 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-23779250

RESUMO

Human visual acuity is used as an indicator in everyday clinical work and ophthalmological studies to decide on therapy indications and success. This extensively used parameter needs a very structured workflow in order to preserve validity and prevent bias. Therefore, it should be kept in mind that especially in clinical studies investigators should strictly adhere to the study protocol. The intention of this article is to impart interesting facts about the early treatment diabetic retinopathy study (ETDRS) on visual acuity assessment, adhering to the original protocol of the ETDRS dating back to 1979-1989. Furthermore, the history of visual acuity assessment protocols prior to ETDRS, namely those of Snellen and Bailey-Lovie and finally the logMAR system will be discussed.


Assuntos
Ensaios Clínicos como Assunto , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/terapia , Transtornos da Visão/diagnóstico , Transtornos da Visão/prevenção & controle , Acuidade Visual , Retinopatia Diabética/complicações , Medicina Baseada em Evidências , Humanos , Resultado do Tratamento , Transtornos da Visão/etiologia
8.
Cell Tissue Res ; 353(2): 261-8, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23512142

RESUMO

Imaging has gained a key role in modern glaucoma management. Traditionally, interest was directed toward the appearance of the optic nerve head and the retinal nerve fiber layer. With the improvement of the resolution of optical coherence tomography, the ganglion cell complex has also become routinely accessible in the clinic. Further advances have been made in understanding the structure-function relationship in glaucoma. Nevertheless, direct imaging of the retinal ganglion cells in glaucoma would be advantageous. With the currently used techniques, this goal cannot be achieved, because the transversal resolution is limited by aberrations of the eye. The use of adaptive optics has significantly improved transversal resolution, and the imaging of several cell types including cones and astrocytes has become possible. Imaging of retinal ganglion cells, however, still remains a problem, because of the transparency of these cells. However, the visualization of retinal ganglion cells and their dendrites has been achieved in animal models. Furthermore, attempts have been made to visualize the apoptosis of retinal ganglion cells in vivo. Implementation of these techniques in clinical practice will probably improve glaucoma care and facilitate the development of neuroprotective strategies.


Assuntos
Diagnóstico por Imagem/métodos , Glaucoma/diagnóstico , Glaucoma/patologia , Células Ganglionares da Retina/patologia , Animais , Humanos , Tomografia de Coerência Óptica
9.
Curr Opin Pharmacol ; 13(1): 36-42, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23009741

RESUMO

Glaucoma is a progressive optic neuropathy of unknown origin. It has been hypothesized that a vascular component is involved in glaucoma pathophysiology. This hypothesis has gained support from studies showing that reduced ocular perfusion pressure is a risk factor for the disease. The exact nature of the involvement is, however, still a matter of debate. Based on recent evidence we propose a model including primary and secondary insults in glaucoma. The primary insult appears to happen at the optic nerve head. Increased intraocular pressure and ischemia at the post-laminar optic nerve head affects retinal ganglion cell axons. Modulating factors are the biomechanical properties of the tissues and cerebrospinal fluid pressure. After this primary insult retinal ganglion cells function at a reduced energy level and are sensitive to secondary insults. These secondary insults may happen if ocular perfusion pressure falls below the lower limit of autoregulation or if neurovascular coupling fails. Evidence for both faulty autoregulation and reduced hyperemic response to neuronal stimulation has been provided in glaucoma patients. The mechanisms appear to involve vascular endothelial dysfunction and impaired astrocyte-vessel signaling. A more detailed understanding of these pathways is required to direct neuroprotective strategies via the neurovascular pathway.


Assuntos
Olho/irrigação sanguínea , Glaucoma/fisiopatologia , Pressão Intraocular/fisiologia , Homeostase , Humanos , Fluxo Sanguíneo Regional
10.
Exp Eye Res ; 92(6): 545-51, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21443871

RESUMO

Impaired ocular blood flow is involved in the pathogenesis of numerous ocular diseases like glaucoma or AMD. The purpose of the present study was to introduce and validate a novel, microscope based, non-invasive Laser Doppler Flowmeter (NI-LDF) for measurement of blood flow in the choroid. The custom made NI-LDF was compared with a commercial fiber optic based laser Doppler flowmeter (Perimed PF4000). Linearity and stability of the NI-LDF were assessed in a silastic tubing model (i.d. 0.3 mm) at different flow rates (range 0.4-3 ml/h). In a rabbit model continuous choroidal blood flow measurements were performed with both instruments simultaneously. During blood flow measurements ocular perfusion pressure was changed by manipulations of intraocular pressure via intravitreal saline infusions. The NI-LDF measurement correlated linearly to intraluminal flow rates in the perfused tubing model (r = 0.99, p < 0.05) and remained stable during a 1 h measurement at a constant flow rate. Rabbit choroidal blood flow measured by the PF4000 and the NI-LDF linearly correlated with each other over the entire measurement range (r = 0.99, y = x∗1.01-12.35 P.U., p < 0.001). In conclusion, the NI-LDF provides valid, semi quantitative measurements of capillary blood flow in comparison to an established LDF instrument and is suitable for measurements at the posterior pole of the eye.


Assuntos
Corioide/irrigação sanguínea , Fluxometria por Laser-Doppler/instrumentação , Microscopia/instrumentação , Fluxo Sanguíneo Regional/fisiologia , Animais , Velocidade do Fluxo Sanguíneo/fisiologia , Feminino , Pressão Intraocular/fisiologia , Masculino , Coelhos
11.
Microvasc Res ; 81(1): 117-22, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20934440

RESUMO

There is evidence that vascular beds distal to the ophthalmic artery (OA) show vasoconstriction in response to a step decrease in systemic blood pressure (BP). The mediators of this response are mostly unidentified. The aim of the current study was to test the hypothesis that α2-adrenoreceptors may contribute to the regulatory process in response to a decrease in BP. In this randomized, double-masked, placebo-controlled study 14 healthy male volunteers received either 22mg yohimbine hydrochloride or placebo. Beat-to-beat BP was measured by analysis of arterial pressure waveform; blood flow velocities in the middle cerebral artery (MCA) and the OA were measured with Doppler ultrasound. Measurements were done before, during and after a step decrease in BP. The step decrease in BP was induced by bilateral thigh cuffs at a suprasystolic pressure followed by a rapid cuff deflation. After cuff deflation, BP returned to baseline after 7-8 pulse cycles (PC). Blood velocities in the MCA returned to baseline earlier (4 PC) than BP indicating peripheral vasodilatation. Blood velocities in the OA returned to baseline later (15-20 PC) indicating peripheral vasoconstriction. Yohimbine did not affect the blood velocity response in the MCA, but significantly shortened the time of OA blood velocities to return to baseline values (6-7 PC, p<0.05). In conclusion, our results indicate that yohimbine did not alter the regulatory response in the MCA, but modified the response of vascular beds distal to the OA. This suggests that α2-adrenoceptors play a role in the vasoconstrictor response of the vasculatures distal to the OA.


Assuntos
Artéria Cerebral Média/fisiologia , Artéria Oftálmica/fisiologia , Receptores Adrenérgicos alfa 2/fisiologia , Vasoconstrição/fisiologia , Ioimbina/farmacologia , Antagonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Antagonistas de Receptores Adrenérgicos alfa 2/farmacologia , Adulto , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Velocidade do Fluxo Sanguíneo/fisiologia , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Método Duplo-Cego , Humanos , Masculino , Artéria Cerebral Média/efeitos dos fármacos , Artéria Oftálmica/efeitos dos fármacos , Resistência Vascular/efeitos dos fármacos , Resistência Vascular/fisiologia , Vasoconstrição/efeitos dos fármacos , Ioimbina/administração & dosagem , Adulto Jovem
12.
Clin Pharmacol Ther ; 87(1): 87-92, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19890250

RESUMO

Nitric oxide (NO) plays a key role in the regulation of ocular blood flow and may be an interesting therapeutic target in ocular ischemic disease. In the present study, we hypothesized that NO-releasing drugs may increase blood flow to the head of the optic nerve and also in the choroid. The study employed a randomized, placebo-controlled, double blind, four-way crossover design. On separate study days, 12 healthy subjects received infusions of nitroglycerin, isosorbide dinitrate, sodium nitroprusside, or placebo. All three study drugs reduced the mean arterial pressure (MAP) and ocular perfusion pressure (OPP) (P < 0.001). None of the administered drugs increased the ocular hemodynamic variables. By contrast, vascular resistance decreased dose dependently during administration of the study drugs (P < 0.001). These results indicate that systemic administration of NO-donor drugs is associated with a decrease in vascular resistance in the ocular vasculature. However, because these drugs also reduce blood pressure, they do not improve perfusion to the posterior eye pole.


Assuntos
Hemodinâmica/efeitos dos fármacos , Doadores de Óxido Nítrico/farmacologia , Nervo Óptico/irrigação sanguínea , Nervo Óptico/efeitos dos fármacos , Vasodilatadores/farmacologia , Adulto , Estudos Cross-Over , Método Duplo-Cego , Seguimentos , Hemodinâmica/fisiologia , Humanos , Pressão Intraocular/efeitos dos fármacos , Pressão Intraocular/fisiologia , Masculino , Nervo Óptico/fisiologia , Fluxo Sanguíneo Regional/efeitos dos fármacos , Fluxo Sanguíneo Regional/fisiologia , Resistência Vascular/efeitos dos fármacos , Resistência Vascular/fisiologia , Adulto Jovem
13.
Br J Ophthalmol ; 93(4): 486-91, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19029154

RESUMO

BACKGROUND/AIMS: To investigate the fluctuations of ocular blood flow parameters over 13 h in patients with primary open-angle glaucoma (POAG) and in healthy eyes, and to relate these fluctuations with variations in intraocular pressure (IOP) and mean ocular perfusion pressure (OPP). METHODS: 15 patients with POAG and 15 control subjects were included. Measurements of systemic blood pressure (SBP), fundus pulsation amplitude (FPA), choroidal blood flow (CHBF), optic nerve head blood flow (ONHBF) and IOP were performed at 08:00, 12:00, 17:00 and 21:00. OPP was calculated from IOP and SBP. The coefficient of variation (CV) was calculated for all individual parameters to assess their variability. RESULTS: The time response of the ocular haemodynamic variables was not different between the groups. Most of the outcome variables showed significantly larger fluctuations in patients with POAG compared with healthy controls (CV: FPA: 0.085 (SD 0.033) vs 0.054 (0.029), p = 0.012; CHBF: 0.082 (0.030) vs 0.052 (0.023), p = 0.005; ONHBF: 0.086 (0.044) vs 0.059 (0.032), p = 0.063). These changes were not associated with OPP or IOP. Changes over time correlated among the different ocular haemodynamic outcome measures in patients with POAG (r = 0.678, r = 0.557, r = 0.545; p<0.04) but not in the control subjects (r = 0.336, r = -0.227, r = -0.130; p>0.22). CONCLUSION: Patients with POAG show a larger diurnal fluctuation of ocular blood flow parameters. These fluctuations appear not to be related to a higher statistical error of the applied measurement techniques in POAG patients. These data support the hypothesis that POAG is associated with vascular dysregulation.


Assuntos
Ritmo Circadiano/fisiologia , Olho/irrigação sanguínea , Glaucoma de Ângulo Aberto/fisiopatologia , Adulto , Idoso , Pressão Sanguínea/fisiologia , Corioide/irrigação sanguínea , Feminino , Humanos , Pressão Intraocular/fisiologia , Fluxometria por Laser-Doppler/métodos , Masculino , Pessoa de Meia-Idade , Disco Óptico/irrigação sanguínea , Fluxo Pulsátil/fisiologia
14.
Graefes Arch Clin Exp Ophthalmol ; 246(10): 1423-7, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18575879

RESUMO

BACKGROUND: In this study, patients with optic neuritis were treated with high-dose prednisolone. Little information is available about the effects of this treatment on ocular blood flow. We set out to investigate the effects of high-dose prednisolone on optic nerve head (ONH) blood flow in patients with acute optic neuritis. METHODS: Thirteen patients with acute optic neuritis were included in the study. 1000 mg of prednisolone was infused intravenously over 30 minutes on 3 consecutive days. On each study day, ONH blood flow was measured using laser Doppler flowmetry. The ocular hemodynamic measurements were performed on the unaffected eye of the patients with unilateral acute optic neuritis before and immediately after cessation of the infusion. Intraocular pressure (IOP) and systemic blood pressure was measured before and after the infusion on each study day. Data was analyzed using a repeated measures ANOVA model. RESULTS: Prednisolone increased ONH blood flow in the patients under study (p = 0.04), although the effects were in generally small. No significant change in mean arterial pressure (p = 0.70) or IOP (p = 0.20) could be detected in the patients treated with high-dose prednisolone. CONCLUSIONS: A small but significant increase in ONH blood flow resulted from infusion of high-dose prednisolone. Further studies are required to investigate whether this effect contributes to the therapeutic efficacy of cortisone in patients with optic neuritis.


Assuntos
Glucocorticoides/administração & dosagem , Disco Óptico/irrigação sanguínea , Neurite Óptica/fisiopatologia , Prednisolona/administração & dosagem , Doença Aguda , Adulto , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Feminino , Humanos , Infusões Intravenosas , Pressão Intraocular/efeitos dos fármacos , Fluxometria por Laser-Doppler , Masculino , Pessoa de Meia-Idade , Neurite Óptica/tratamento farmacológico , Fluxo Sanguíneo Regional/efeitos dos fármacos
15.
Horm Metab Res ; 40(8): 549-55, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18500678

RESUMO

PPARgamma agonists have been proposed to exert more than metabolic benefits, particularly by anti-inflammatory mechanisms. We hypothesized that pioglitazone might modulate inflammatory and vascular responses to lipopolysaccharide (LPS). In a placebo-controlled parallel-group study in 18 healthy male subjects, the E. coli endotoxin model of inflammation (20 IU/kg i. v.) was employed to test the effect of 60 mg pioglitazone over nine days on inflammatory cytokines. Macrovascular function and microvascular blood flow were assessed by brachial artery ultrasound and retinal blood flow parameters, respectively. Pioglitazone increased brachial artery diameter by 5.6% but had no effect on other outcome parameters under resting conditions. LPS increased cytokine levels to peak concentrations of 91.3+/-22.5 ng/ml (IL-6), 261.4+/-60.0 ng/ml (TNFalpha), and 524.5+/-15.3 ng/ml (VCAM-1). The endotoxin caused microvascular vasodilation and increased retinal white blood cell flux, while baseline brachial artery diameter remained unchanged. Pioglitazone had no effect on inflammatory cytokine or adhesion molecule release but mitigated LPS-induced hypotension (p<0.05). Neither brachial artery function nor microvascular blood flow was altered by pioglitazone. In conclusion, acute immune reactions to LPS are not affected by pioglitazone, which exerts subtle vascular effects alone and during endotoxemia. The anti-inflammatory properties of short-term pioglitazone to endotoxins in healthy subjects are therefore limited.


Assuntos
Endotoxemia/tratamento farmacológico , Endotoxemia/patologia , Hipoglicemiantes/uso terapêutico , Inflamação/patologia , Tiazolidinedionas/uso terapêutico , Vasculite/patologia , Adulto , Artéria Braquial/anatomia & histologia , Artéria Braquial/fisiologia , Endotélio Vascular/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Eritrócitos/fisiologia , Humanos , Imunidade Inata/efeitos dos fármacos , Interleucina-6/sangue , Fluxometria por Laser-Doppler , Lipopolissacarídeos , Masculino , Pioglitazona , Vasos Retinianos/efeitos dos fármacos , Trinitrotolueno/farmacologia , Fator de Necrose Tumoral alfa/sangue , Molécula 1 de Adesão de Célula Vascular/sangue , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia
16.
Cochrane Database Syst Rev ; (4): CD003167, 2007 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-17943780

RESUMO

BACKGROUND: Primary open angle glaucoma (POAG) is a progressive optic neuropathy with an elevated intraocular pressure (IOP), where the optic nerve head becomes pathologically excavated and the visual field (VF) is characteristically altered. Ocular hypertension (OHT) is a condition with elevated IOP but without discernible pathology of the optic nerve head or the VF. It is a major risk factor for development of POAG. OBJECTIVES: To assess and compare the effectiveness of topical pharmacological treatment for POAG or OHT to prevent progression or onset of glaucomatous optic neuropathy. SEARCH STRATEGY: We searched CENTRAL, MEDLINE and EMBASE in May 2007. We searched the bibliographies of identified articles and contacted experts, investigators and pharmaceutical companies for additional published and unpublished studies. SELECTION CRITERIA: Randomised controlled trials comparing topical pharmacological treatment to placebo, no treatment or other treatment for specified endpoints which included people with POAG or OHT, and with duration of treatment of at least one year. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed trial quality. Where appropriate, we summarised data using Peto odds ratio and mean difference after testing for heterogeneity between studies. MAIN RESULTS: We included 26 trials, which randomised 4979 participants, in this review. Meta-analysis of 10 trials clearly demonstrated reduction of onset of VF defects in treated OHT (OR 0.62, 95% CI 0.47 to 0.81). No single drug showed a significant VF protection compared to placebo or untreated controls. We did identify some border line evidence for a positive influence of treatment on VF prognosis (OR 0.67, 95% CI 0.45 to 1.00) for the beta-blockers . AUTHORS' CONCLUSIONS: The results of this review support the current practice of IOP lowering treatment of OHT. A visual field protective effect has been clearly demonstrated for medical IOP lowering treatment. Positive but weak evidence for a beneficial effect of the class of beta-blockers has been shown. Direct comparisons of prostaglandins or brimonidine to placebo are not available and the comparison of dorzolamide to placebo failed to demonstrate a protective effect. However, absence of data or failure to prove effectiveness should not be interpreted as proof of absence of any effect. The decision to treat a patient or not, as well as the decision regarding the drug with which to start treatment, should remain individualised, taking in to account the amount of damage, the level of IOP, age and other patient characteristics.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Glaucoma de Ângulo Aberto/tratamento farmacológico , Hipertensão Ocular/tratamento farmacológico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
17.
Clin Exp Immunol ; 146(3): 533-9, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17100775

RESUMO

C-reactive protein (CRP) protects against bacterial pathogens and is a predictor of cardiovascular events. CRP is produced by vascular and organ-specific cells but the generation of CRP from peripheral blood mononuclear cells (PBMC) is poorly established. In a randomized, double-blind, placebo-controlled, two-way cross-over trial six healthy volunteers received a bolus infusion of 20 IU/kg Escherichia coli endotoxin [lipopolysaccharide (LPS)] or placebo. Intracellular CRP protein and CRP secretion of peripheral blood mononuclear cells (PBMC) was measured at baseline and 6 h after LPS by flow cytometry and enzyme-linked immubosorbent assay (ELISA), respectively. CRP mRNA expression was determined by real-time polymerase chain reaction (PCR). Regulation of the expression pathway was assessed using specific inhibitors in vitro. Small amounts of CRP protein and mRNA were detectable in PBMC, which were up-regulated between two- and eightfold by endotoxaemia in vivo. Augmented expression and release of CRP by LPS was consistent in PBMC cell culture experiments. LPS, interleukin (IL)-1, IL-6 and tumour necrosis factor (TNF)-alpha increased and IL-10 reduced CRP expression in PBMC. Toll-like receptor (TLR)-4, nuclear factor (NF)-kappaB and protein kinase C (PKC) activation were identified as intracellular signal transduction pathways of LPS-induced CRP expression. Constitutive CRP expression and release in PBMC is enhanced by inflammatory stimuli in vivo and in vitro. LPS might induce CRP generation via activation of TLR-4, NF-kappaB and PKC.


Assuntos
Proteína C-Reativa/metabolismo , Leucócitos Mononucleares/metabolismo , Lipopolissacarídeos/imunologia , Adulto , Proteína C-Reativa/genética , Células Cultivadas , Estudos Cross-Over , Método Duplo-Cego , Endotoxemia/imunologia , Regulação da Expressão Gênica/imunologia , Humanos , Masculino , NF-kappa B/metabolismo , Proteína Quinase C/metabolismo , RNA Mensageiro/genética , Transdução de Sinais/imunologia , Receptor 4 Toll-Like/metabolismo
18.
Br J Ophthalmol ; 89(10): 1293-7, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16170119

RESUMO

BACKGROUND: There is evidence that perfusion abnormalities of the optic nerve head are involved in the pathogenesis of glaucoma. There is therefore considerable interest in the effects of topical antiglaucoma drugs on ocular blood flow. A study was undertaken to compare the ocular haemodynamic effects of dorzolamide and timolol in patients with primary open angle glaucoma (POAG) or ocular hypertension (OHT). METHODS: One hundred and forty patients with POAG or OHT were included in a controlled, randomised, double blind study in two parallel groups; 70 were randomised to receive timolol and 70 to receive dorzolamide for a period of 6 months. Subjects whose intraocular pressure (IOP) did not respond to either of the two drugs were switched to the alternative treatment after 2 weeks. Scanning laser Doppler flowmetry was used to measure blood flow in the temporal neuroretinal rim and the cup of the optic nerve head. Pulsatile choroidal blood flow was assessed using laser interferometric measurement of fundus pulsation amplitude. RESULTS: Five patients did not respond to timolol and were changed to the dorzolamide group, and 18 patients changed from dorzolamide treatment to timolol. The effects of both drugs on IOP and ocular perfusion pressure were comparable. Dorzolamide, but not timolol, increased blood flow in the temporal neuroretinal rim (8.5 (1.6)%, p<0.001 versus timolol) and the cup of the optic nerve head (13.5 (2.5)%, p<0.001 versus timolol), and fundus pulsation amplitude (8.9 (1.3)%, p<0.001 versus timolol). CONCLUSIONS: This study indicates augmented blood flow in the optic nerve head and choroid after 6 months of treatment with dorzolamide, but not with timolol. It remains to be established whether this effect can help to reduce visual field loss in patients with glaucoma.


Assuntos
Anti-Hipertensivos/farmacologia , Olho/irrigação sanguínea , Hipertensão Ocular/tratamento farmacológico , Sulfonamidas/farmacologia , Tiofenos/farmacologia , Timolol/farmacologia , Idoso , Corioide/irrigação sanguínea , Método Duplo-Cego , Feminino , Glaucoma de Ângulo Aberto/tratamento farmacológico , Glaucoma de Ângulo Aberto/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Humanos , Pressão Intraocular/efeitos dos fármacos , Fluxometria por Laser-Doppler , Masculino , Pessoa de Meia-Idade , Hipertensão Ocular/fisiopatologia , Disco Óptico/irrigação sanguínea , Fluxo Sanguíneo Regional/efeitos dos fármacos , Análise de Regressão , Vasos Retinianos/efeitos dos fármacos
19.
Br J Ophthalmol ; 89(6): 704-8, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15923506

RESUMO

BACKGROUND: The ocular pressure/volume relation, which is described by the Friedenwald equation, forms the basis of intraocular pressure (IOP) measurement with Schiotz tonometry and measurement of pulsatile ocular blood flow (POBF) with pneumotonometry. Changes in intraocular volume during the cardiac cycle are caused by arterial inflow and venous outflow and are accompanied by changes in IOP. The relation between volume and pressure changes is dependent on the elastic properties of the eye coats as described by the ocular rigidity coefficient. Previous studies indicate that there is a vascular contribution to ocular rigidity and that the volume/pressure relationship may depend on the mean arterial pressure. METHODS: The effect of a nifedipine induced reduction in systemic blood pressure on pulse amplitude (PA) as assessed with pneumotonometry and fundus pulsation amplitude (FPA), as measured with laser interferometry was investigated in 16 untreated patients with moderate to severe systemic hypertension (mean arterial pressure 123 (SD 12) mm Hg). RESULTS: The ratio between PA and FPA was taken as a measure of the ocular rigidity coefficient. Nifedipine reduced mean arterial pressure by 17.3% and increased pulse rate by 11.0% (p<0.001 each). Whereas PA was significantly reduced after administration of nifedipine (-15.6%; p<0.001), FPA remained unchanged. Accordingly, the ratio of PA/FPA was reduced from 0.86 mm Hg/mum to 0.73 mm Hg/mum after administration of nifedipine. CONCLUSION: These data are in keeping with previous animal experiments indicating a blood pressure dependent vascular component to the rigidity of the eye coats in vivo. This needs to be taken into account for measurement of IOP with Schiotz tonometry and POBF with pneumotonometry.


Assuntos
Olho/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Nifedipino/farmacologia , Vasos Retinianos/efeitos dos fármacos , Vasodilatadores/farmacologia , Idoso , Pressão Sanguínea/efeitos dos fármacos , Elasticidade/efeitos dos fármacos , Olho/irrigação sanguínea , Olho/fisiopatologia , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipertensão/fisiopatologia , Pressão Intraocular/efeitos dos fármacos , Lasers , Masculino , Pessoa de Meia-Idade , Fluxo Pulsátil/efeitos dos fármacos , Vasos Retinianos/fisiopatologia , Tonometria Ocular
20.
Br J Ophthalmol ; 89(2): 185-8, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15665350

RESUMO

BACKGROUND/AIM: Current evidence suggests that vascular insufficiencies in the optic nerve head play an important part in the pathogenesis of glaucomatous optic neuropathy. Trabeculectomy is the most common operative procedure for the treatment of medically uncontrolled glaucoma. This study was conducted to investigate whether trabeculectomy may improve ocular haemodynamics. METHODS: 30 patients with primary open angle glaucoma about to undergo trabeculectomy were included in the study. Patients were evaluated before surgery and at 2 and 10 weeks after trabeculectomy. Optic nerve head blood flow (OnhBF) was assessed with scanning laser Doppler flowmetry. Fundus pulsation amplitude (FPA) measurements were obtained with laser interferometry. RESULTS: Because of the decrease in intraocular pressure there was a significant increase in ocular perfusion pressure (OPP) following trabeculectomy (18.5% (SD 12.0%) and 19.0% (17.1%) at 2 and 10 weeks postoperatively; p <0.001). A significant increase in OnhBF was observed after trabeculectomy (11.6% (16.4%) and 16.2% (20.2%) for each postoperative visit, respectively; p <0.001). FPA was also significantly higher compared with baseline values (17.2% (17.3%) and 17.4% (16.3%), respectively; p <0.001). A significant association between the increase in OPP and the increase in OnhBF and FPA was observed 10 weeks after surgery (r = 0.47; p = 0.009, and r = 0.50; p = 0.005, respectively). CONCLUSION: The results of this study suggest that trabeculectomy improves ocular blood flow in patients with chronic open angle glaucoma.


Assuntos
Glaucoma de Ângulo Aberto/cirurgia , Disco Óptico/irrigação sanguínea , Trabeculectomia/métodos , Idoso , Análise de Variância , Pressão Sanguínea/fisiologia , Feminino , Fundo de Olho , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Interferometria/métodos , Pressão Intraocular/fisiologia , Fluxometria por Laser-Doppler/métodos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA