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1.
Vestn Oftalmol ; 136(6. Vyp. 2): 155-164, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33371644

RESUMO

Examining the somatic state of glaucomatous patients that enroll for treatment, we are increasingly confronted with a serious problem of inconsistency in prescribing beta-blockers (ß-blockers) by ophthalmologists, cardiologists and therapists. PURPOSE: To assess the frequency and extent of adverse reactions at simultaneous local and systemic prescription of ß-blockers to patients with glaucoma and systemic vascular pathology. MATERIAL AND METHODS: The study included 112 patients that have been taking ß-blockers for at least 6 months. The main group consisted of 39 patients with primary open-angle glaucoma (POAG) in combination with cardiovascular disease; the first comparison group - 36 patients with POAG without systemic vascular pathology; the second comparison group - 37 patients with systemic vascular pathology without glaucoma. In the main and first comparison groups, double instillations of 0.5% timolol or 0.5% betaxolol were used as monotherapy. RESULTS: Adverse reactions to the long-term usage of ß-blockers were found in 82% of the main group patients with cardiovascular diseases. They manifested as bradycardia or bronchospasm (38% patients), combination of bradycardia and vascular hypotension or bronchospasm (18%), or combination of 3-4 types of adverse reactions (26%); in the first and second comparison groups - in 36% and 30%, respectively (p<0.05). CONCLUSION: The most severe multifactorial adverse reactions developed due to long-term use of combinations of systemic and local ß-blockers: 100 mg metoprolol or 10 mg bisoprolol with 0.5% timolol.


Assuntos
Glaucoma , Pressão Intraocular , Antagonistas Adrenérgicos beta/efeitos adversos , Doença Crônica , Glaucoma/diagnóstico , Glaucoma/tratamento farmacológico , Humanos , Timolol/efeitos adversos
2.
Drugs Today (Barc) ; 56(9): 599-608, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33025953

RESUMO

Ripasudil (K-115) is a novel Rho-associated protein kinase (ROCK) inhibitor. The Rho-ROCK pathway regulates key downstream effectors involved in many cellular functions, in particular in the actin cytoskeleton activity. The clinical effects of ripasudil expected on the eye include an intraocular pressure-lowering effect and a wound-healing activity on corneal endothelial cells, but many other functions are currently under investigation. To date, ripasudil has been approved in Japan (2014) for the treatment of glaucoma and ocular hypertension, and several clinical trials are currently investigating its role in the treatment of Fuchs' corneal dystrophy. In this review, we will discuss its pharmacokinetics, pharmacodynamics and clinical efficacy, focusing also on its safety and tolerability profile.


Assuntos
Glaucoma/tratamento farmacológico , Isoquinolinas/uso terapêutico , Hipertensão Ocular/tratamento farmacológico , Sulfonamidas/uso terapêutico , Ensaios Clínicos como Assunto , Células Endoteliais , Humanos , Japão , Quinases Associadas a rho/antagonistas & inibidores
3.
PLoS One ; 15(9): e0239233, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32925955

RESUMO

PURPOSE: This study aimed to review previous articles and evaluate the influence of topical non-steroidal anti-inflammatory drugs (NSAIDs) on intraocular pressure (IOP) in glaucoma patients who were treated with prostaglandin analogues (PGs). METHOD: The presenting study was designed as a meta-analysis of previous research. Databases include PubMed, Web of science, Cochrane library, and Embase were searched with keywords of "intraocular pressure, prostaglandin analogues, NSAIDs, latanoprost, travoprost, bimatoprost, tafluprost, unoprostone, latanoprostene bunod, ketorolac, diclofenac, nepafenac, bromfenac, flurbiprofen". Inclusion criteria were: 1. Study population were glaucoma patients; 2. Comparison between PGs monotherapy and PGs in combination with topical NSAIDs; 3. Changes of IOP as final outcomes. Studies with non-randomized design, treatments combining other anti-glaucomatous drugs, or unavailable absolute IOP were excluded from the analysis. Estimated difference in IOP were calculated using STATA 14.0. RESULT: Seven studies were retrieved for this meta-analysis. Since there is a significant heterogeneity (I2 = 94%) in these studies, random-effect model was used to calculate pooled standardized mean differences (SMD). Our results showed a significantly favorable IOP lowering effect in glaucoma patients treated with combination of topical NSAIDs and PGEs (SMD: 1.3 and -0.03, 95% CI: 0.29 to 2.38 and -0.32 to 0.26, Z = 2.50 and 0.23, p = 0.013 and 0.820, respectively). CONCLUSION: Results of our meta-analysis suggested that topical NSAIDs may enhance the IOP lowering effect of topical PGs in glaucoma patients.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Glaucoma/tratamento farmacológico , Pressão Intraocular/efeitos dos fármacos , Prostaglandinas Sintéticas/uso terapêutico , Administração Tópica , Anti-Inflamatórios não Esteroides/classificação , Glaucoma/patologia , Humanos , Prostaglandinas Sintéticas/classificação , Tonometria Ocular
4.
AAPS PharmSciTech ; 21(6): 236, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32803351

RESUMO

In recent years, with the aging of the population and the frequent use of electronic devices, many eye diseases have shown a linear upward trend, such as dry eye disease, glaucoma, cataract, age-related macular degeneration, and diabetic retinopathy. These diseases are often chronic and difficult to cure. Based on the structure and barrier of the human eye, this review describes the pathogenesis and treatments of several intractable eye diseases and summarizes the advanced ocular drug delivery systems to provide new treatment ideas for these diseases. Finally, we also look forward to the prospect of RNAi therapy in the treatment of eye diseases.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Oftalmopatias/tratamento farmacológico , Oftalmopatias/metabolismo , Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas Adrenérgicos beta/metabolismo , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/metabolismo , Catarata/diagnóstico , Catarata/tratamento farmacológico , Catarata/metabolismo , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/metabolismo , Síndromes do Olho Seco/diagnóstico , Síndromes do Olho Seco/tratamento farmacológico , Síndromes do Olho Seco/metabolismo , Oftalmopatias/diagnóstico , Glaucoma/diagnóstico , Glaucoma/tratamento farmacológico , Glaucoma/metabolismo , Humanos , Latanoprosta/administração & dosagem , Latanoprosta/metabolismo , Degeneração Macular/tratamento farmacológico , Degeneração Macular/epidemiologia , Degeneração Macular/fisiopatologia , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/metabolismo , Timolol/administração & dosagem , Timolol/metabolismo , Resultado do Tratamento , Verteporfina/administração & dosagem , Verteporfina/metabolismo
5.
Vestn Oftalmol ; 136(4): 99-104, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32779462

RESUMO

The main objectives of glaucoma treatment are normalization of IOP and slowing of the progression of glaucomatous optic neuropathy. They are achieved using conservative (medicated), surgical and laser methods. PURPOSE: To study the effectiveness of non-penetrating hypotensive laser sclerotomy (NHLS) in patients with non-stabilized primary open-angle (I-III) b glaucoma with previous laser trabeculoplasty and who are receiving drug therapy. MATERIAL AND METHODS: The study included 54 patients (102 eyes) with initial (38 eyes), developed (46 eyes) and advanced (18 eyes) glaucoma who were examined and operated on. 26 patients (46 eyes) were instilled a combined drug containing brinzolamide and timolol, 28 patients (56 eyes) received prostaglandin F2α analogues (PGA). Intraocular pressure (IOP) levels were 27±2.4 mm Hg. RESULTS: Reduction of IOP was observed in 89% of patients 2 weeks after NHLS with gradual improvement during the first 3 months of the follow-up; in 71% of patients the results preserved by the 6th month. Patients receiving combination of brinzolamide and timolol had more pronounced IOP reduction after NHLS amounting to 2.4±1.8 mm Hg in the first 3 months. By the end of the observation period IOP levels remained within normal range, drug therapy was ceased in 16 patients (21 eyes, 20.6%), 32 patients (67 eyes, 65.7%) achieved normalized intraocular pressure with antihypertensive therapy, and 9 patients (9 eyes, 8.8%) were referred to surgical treatment. CONCLUSION: Non-penetrating hypotensive laser sclerotomy (NHLS) allows measured reduction of IOP in various glaucoma stages achieving controlled and persistent hypotensive effect. In the group of patients receiving combination of brinzolamide and timolol, the effect is statistically significant and clinically superior when compared with patients receiving PGA.


Assuntos
Glaucoma/tratamento farmacológico , Terapia a Laser , Trabeculectomia , Anti-Hipertensivos/uso terapêutico , Humanos , Pressão Intraocular , Timolol , Tonometria Ocular , Resultado do Tratamento
6.
Klin Monbl Augenheilkd ; 237(10): 1241-1258, 2020 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-32777830

RESUMO

Glaucoma is the leading cause of irreversible blindness in Germany and in the world. Due to the multifactorial genesis of the disease, there are multiple therapeutic approaches for preventing its progression. The goal of the commonly used topical glaucoma medication is to reduce the intraocular pressure and therefore prevent further damage to the optic nerve. There are different medications of various pharmacological classes that are intended to reduce intraocular pressure, namely, ß-adrenergic antagonists, adrenergic agonists, parasympathomimetic agents, prostaglandin analogues, carbonic anhydrase inhibitors, hyperosmotic agents, and the 2017 U. S. FDA approved Rho kinase inhibitor, Netarsudil.After determining a patient centered target pressure, which depends upon various factors, an individual treatment regimen should be chosen with one or more agents. Although reducing the intraocular pressure remains the main therapeutic focus, there is increasing evidence indicating that oxidative stress also plays a key role in the pathogenesis of the primary open angle glaucoma. Therefore, direct and indirect neuroprotective agents like Magnesium, Coenzym Q10, Ginkgo biloba and others are getting more and more attention. While there is still a need for further clinical trials, these substances are getting more popular as an adjunct in glaucoma therapy.


Assuntos
Glaucoma de Ângulo Aberto , Glaucoma , Antagonistas Adrenérgicos beta/uso terapêutico , Inibidores da Anidrase Carbônica/uso terapêutico , Alemanha , Glaucoma/tratamento farmacológico , Humanos , Pressão Intraocular
7.
Cochrane Database Syst Rev ; 8: CD008213, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32816311

RESUMO

BACKGROUND: Primary congenital glaucoma (PCG) is an optic neuropathy with high intraocular pressure (IOP) that manifests within the first few years of a child's life and is not associated with other systemic or ocular abnormalities. PCG results in considerable morbidity even in high-income countries. OBJECTIVES: To compare the effectiveness and safety of different surgical techniques for PCG. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2020, Issue 4); Ovid MEDLINE; Embase.com; PubMed; metaRegister of Controlled Trials (mRCT) (last searched 23 June 2014); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search. We last searched the electronic databases on 27 April 2020. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and quasi-RCTs comparing different surgical interventions in children under five years of age with PCG. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology. MAIN RESULTS: We included 16 trials (13 RCTs and three quasi-RCTs) with 587 eyes in 446 children. Eleven (69%) trials were conducted in Egypt and the Middle East, three in India, and two in the USA. All included trials involved children younger than five years of age, with follow-up ranging from six to 80 months. The interventions compared varied across trials. Three trials (on 68 children) compared combined trabeculotomy and trabeculectomy (CTT) with trabeculotomy. Meta-analysis of these trials suggests there may be little to no evidence of a difference between groups in mean IOP (mean difference (MD) 0.27 mmHg, 95% confidence interval (CI) -0.74 to 1.29; 88 eyes; 2 studies) and surgical success (risk ratio (RR) 1.01, 95% CI 0.90 to 1.14; 102 eyes; 3 studies) at one year postoperatively. We assessed the certainty of evidence as very low for these outcomes, downgrading for risk of bias (-1) and imprecision (-2). Hyphema was the most common adverse outcome in both groups (no meta-analysis due to considerable heterogeneity; I2 = 83%). Two trials (on 39 children) compared viscotrabeculotomy to conventional trabeculotomy. Meta-analysis of 42 eyes suggests there is no evidence of between groups difference in mean IOP (MD -1.64, 95% CI -5.94 to 2.66) and surgical success (RR 1.11, 95% CI 0.70 to 1.78) at six months postoperatively. We assessed the certainty of evidence as very low, downgrading for risk of bias and imprecision due to small sample size. Hyphema was the most common adverse outcome (38% in viscotrabeculotomy and 28% in conventional trabeculotomy), with no evidence of difference difference (RR 1.33, 95% CI 0.63 to 2.83). Two trials (on 95 children) compared microcatheter-assisted 360-degree circumferential trabeculotomy to conventional trabeculotomy. Meta-analysis of two trials suggests that mean IOP may be lower in the microcatheter group at six months (MD -2.44, 95% CI -3.69 to -1.19; 100 eyes) and at 12 months (MD -1.77, 95% CI -2.92 to -0.63; 99 eyes); and surgical success was more likely to be achieved in the microcatheter group compared to the conventional trabeculotomy group (RR 1.59, 95% CI 1.14 to 2.21; 60 eyes; 1 trial at 6 months; RR 1.54, 95% CI 1.20 to 1.97; 99 eyes; 2 trials at 12 months). We assessed the certainty of evidence for these outcomes as moderate due to small sample size. Hyphema was the most common adverse outcome (40% in the microcatheter group and 17% in the conventional trabeculotomy group), with greater likelihood of occurring in the microcatheter group (RR 2.25, 95% CI 1.25 to 4.04); the evidence was of moderate certainty due to small sample size (-1). Of the nine remaining trials, no two trials compared the same two surgical interventions: one trial compared CTT versus CTT with sclerectomy; three trials compared various suturing techniques and adjuvant use including mitomycin C, collagen implant in CTT; one trial compared CTT versus Ahmed valve implant in previously failed surgeries; one trial compared CTT with trabeculectomy; one trial compared trabeculotomy to goniotomy; and two trials compared different types of goniotomy. No trials reported quality of life or economic data. Many of the included trials had limitations in study design, implementation, and reporting, therefore the reliability and applicability of the evidence remains unclear. AUTHORS' CONCLUSIONS: The evidence suggests that there may be little to no evidence of difference between CTT and routine conventional trabeculotomy, or between viscotrabeculotomy and routine conventional trabeculotomy. A 360-degree circumferential trabeculotomy may show greater surgical success than conventional trabeculotomy. Considering the rarity of the disease, future research would benefit from a multicenter, possibly international trial, involving parents of children with PCG and with a follow-up of at least one year.


Assuntos
Glaucoma/congênito , Glaucoma/cirurgia , Pré-Escolar , Glaucoma/tratamento farmacológico , Implantes para Drenagem de Glaucoma/efeitos adversos , Humanos , Hifema/etiologia , Lactente , Recém-Nascido , Pressão Intraocular , Mitomicina/uso terapêutico , Complicações Pós-Operatórias , Ensaios Clínicos Controlados Aleatórios como Assunto , Esclera/cirurgia , Malha Trabecular/cirurgia , Trabeculectomia/efeitos adversos , Trabeculectomia/métodos , Resultado do Tratamento
8.
J Fr Ophtalmol ; 43(7): 635-641, 2020 Sep.
Artigo em Francês | MEDLINE | ID: mdl-32622636

RESUMO

INTRODUCTION: Behçet's disease is a systemic disease of unknown etiology. Its ocular manifestations are multiple and polymorphic, with uveitis at the top of the list. Classically, uveitis in Behçet's disease does not cause elevation of intraocular pressure. However, this may be found in 10 to 20% of cases, secondary to trabeculitis, trabecular obstruction by inflammatory cells, anterior or posterior synechiae, or induced by prolonged use of corticosteroids. Its occurrence is a major complication, the management of which is especially delicate when glaucoma occurs. The purpose of this study was to study the factors predictive of glaucoma in Behçet's disease. MATERIALS AND METHODS: This is a retrospective study of all the charts of patients consecutively hospitalized for Behçet's disease over a period of 8years in the ophthalmology A department of the specialty hospital of Rabat university medical center. RESULTS: Fifty patients were treated for Behçet's disease during the study period. There were 41 men (82%), and 9 women (18%). Glaucoma was diagnosed in 11 patients (22%). The mean age of this subgroup was 31years, with a gender ratio of 6 women/5 men. The glaucoma was associated with anterior synechiae in 4 cases, primary open-angle glaucoma in 5 cases, neovascular glaucoma in 1 case and seclusio pupillae in 1 case. Therapeutically, all patients were on glaucoma eye drops, and five underwent filtering surgery. Statistically, on univariate analysis, ocular hypertension was observed particularly in patients with low initial visual acuity (less than 1/10) (P=0.001), with severe posterior segment involvement, especially retinal vasculitis (29% vs. 6%, P=0.04), macular edema (40% vs. 4%, P=0.001), and optic disc edema (50% vs. 15%, P=0.02). A high number of recurrences was also associated with glaucoma (1.0 vs. 3.0, P<0.0001). On multivariate analysis, low baseline visual acuity, presence of retinal vasculitis, and high number of recurrences were independent risk factors for ocular hypertension in our patients followed for Behçet's disease. CONCLUSION: Glaucoma can complicate the management of Behçet's disease. This glaucoma will be more difficult to manage in this delicate pathological context. It requires special vigilance in patients with severe posterior segment inflammation, to institute effective management to avoid its potentially blinding complications.


Assuntos
Síndrome de Behçet/complicações , Síndrome de Behçet/epidemiologia , Glaucoma/epidemiologia , Glaucoma/etiologia , Uveíte/epidemiologia , Uveíte/etiologia , Corticosteroides/uso terapêutico , Adulto , Síndrome de Behçet/tratamento farmacológico , Feminino , Glaucoma/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Masculino , Marrocos/epidemiologia , Prevalência , Estudos Retrospectivos , Uveíte/tratamento farmacológico , Visão Ocular/efeitos dos fármacos , Adulto Jovem
9.
Medicine (Baltimore) ; 99(27): e21156, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629752

RESUMO

BACKGROUND: Glaucoma is a common ophthalmic neurodegenerative disease and the main cause of blindness, which seriously affects the life and work of patients, without more effective treatment for optic nerve damage. Bushen Huoxue (BSHX) method is a traditional Chinese medicine (TCM) therapy that has been widely used as an alternative therapy to treat optic nerve damage in glaucoma patients with growing beneficial effect evidence, however, there is no current systematic review has addressed its effect for glaucoma. This study will conduct a systematic review and meta-analysis of the currently published randomized controlled trials (RCTs) of BSHX method for the treatment of glaucoma, aim to assess the efficacy and safety of BSHX method for patients with glaucoma. METHODS: We will thoroughly search literatures of RCTs related to BSHX method for glaucoma in PubMed, Medline, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP and Wanfang database and other databases from the establishment of the database to November 2019, with no language restriction. After reviewing the title, abstract and full text, 2 reviewers will independently select the study, extract the data, after assess the risk of bias, we will conduct a meta-analysis of the data extracted from the included RCTs, including total effective rate, intraocular pressure (IOP), visual acuity, visual field, TCM syndrome score, and adverse events. The meta-analysis will be performed using Review Manager 5.3 software and the results will be based on either random effects or fixed effects models, depending on the heterogeneity. Trial sequential analysis (TSA) and Grading of Recommendations, Development and Evaluate system (GRADE) will be conduct to evaluate the reliability and quality of evidence. RESULTS: The results of the study will be published in a peer-reviewed journal, and provide a reasonable and high-quality evidence for the efficacy and safety of BSHX method for glaucoma. CONCLUSION: This study will be the first meta-analysis to evaluate the efficacy of BSHX method in the treatment of glaucoma comprehensively, and will to provide helpful evidence for the clinical treatment of this disease. REGISTRATION: PROSPERO CRD42020159897.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Glaucoma/tratamento farmacológico , Medicina Tradicional Chinesa/métodos , China/epidemiologia , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Glaucoma/diagnóstico , Humanos , Pressão Intraocular/efeitos dos fármacos , Masculino , Doenças Neurodegenerativas/complicações , Doenças Neurodegenerativas/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Reprodutibilidade dos Testes , Segurança , Resultado do Tratamento , Acuidade Visual/efeitos dos fármacos , Campos Visuais/efeitos dos fármacos
11.
Doc Ophthalmol ; 141(3): 253-257, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32507902

RESUMO

PURPOSE: The photopic negative response (PhNR) correlates with ganglion cell function and has previously been examined as an indicator of glaucomatous optic nerve damage. However, it is a prolonged response that is measured against baseline, and its clinical utility has been limited by extensive variability, poor repeatability, and baseline instability. We have observed a distinct brief negative wave ("N-wave") commonly present within the slow PhNR trough, which may provide practical and analytic advantages as a clinical measure. METHODS: We reviewed data from an interventional trial of 59 glaucoma patients who had 4 exams over an 8-month period. The PhNR was recorded with standard ISCEV stimuli (1 Hz and in some cases 4 Hz stimulation), and N-waves were measured manually, relative to return to baseline. RESULTS: N-waves, when present, could be measured easily despite shifting baselines and a degree of background noise. The PhNR median amplitude centered around 18 µV, while the N-wave median centered around 7 µV, with a distribution of responses skewed toward low or zero amplitudes. CONCLUSIONS: The N-wave appears to be a component of the longer PhNR, though its exact origin and significance remain unclear. As a rapid waveform that is independent of baseline, the N-wave is in many ways easier to measure accurately than the slower PhNR, which is highly dependent on baseline stability. The N-wave may prove useful clinically if further studies can optimize its stimulation, show its behavior in normal individuals and find correlation with markers of optic nerve disease.


Assuntos
Visão de Cores/fisiologia , Glaucoma/fisiopatologia , Doenças do Nervo Óptico/fisiopatologia , Retina/fisiopatologia , Células Ganglionares da Retina/fisiologia , Administração Oftálmica , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Eletrorretinografia , Feminino , Glaucoma/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Fator de Crescimento Neural/uso terapêutico , Soluções Oftálmicas , Doenças do Nervo Óptico/tratamento farmacológico , Estimulação Luminosa , Estudos Prospectivos , Proteínas Recombinantes , Adulto Jovem
12.
J Med Chem ; 63(13): 7422-7444, 2020 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-32519851

RESUMO

The "tail approach" has become a milestone in human carbonic anhydrase inhibitor (hCAI) design for various therapeutics, including antiglaucoma agents. Besides the classical hydrophobic/hydrophilic division of hCAs active site, several subpockets have been identified at the middle/outer active sites rim, which could be targeted to increase the CAI isoform selectivity. This postulate is explored here by three-tailed benzenesulfonamide CAIs (TTI) to fully exploit such amino acid differences among hCAs. In this proof-of-concept study, an extensive structure-activity relationship (SAR) study was carried out with 32 such benzenesulfonamides differing in tails combination that were assayed for hCAs I, II, IV, and XII inhibition. A structural study was undertaken by X-ray crystallography and in silico tools to assess the ligand/target interaction mode. The most active and selective inhibitors against isoforms implicated in glaucoma were assessed in a rabbit model of the disease achieving an intraocular pressure-lowering action comparable to the clinically used dorzolamide.


Assuntos
Inibidores da Anidrase Carbônica/química , Inibidores da Anidrase Carbônica/farmacologia , Sulfonamidas/química , Animais , Anidrases Carbônicas/química , Anidrases Carbônicas/metabolismo , Simulação por Computador , Cristalografia por Raios X , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos/métodos , Glaucoma/tratamento farmacológico , Humanos , Pressão Intraocular/efeitos dos fármacos , Ligantes , Masculino , Estudo de Prova de Conceito , Coelhos , Relação Estrutura-Atividade , Sulfonamidas/farmacologia
13.
PLoS One ; 15(6): e0234690, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32555666

RESUMO

The alternative mechanical theory of glaucoma, in which an increased pressure difference across the lamina cribrosa (difference between intraocular and intracranial pressure; IOP and ICP), rather than solely an elevated IOP, leads to structural and functional vision loss, is still controversial. If the theory is true, a drug that simultaneously lowers both the IOP and ICP may be ineffective. The aim of this study was to determine how acetazolamide (AAZ; a drug prescribed in glaucoma that aims to lower the IOP) affects both IOP and ICP in glaucoma patients and to compare the magnitude and time course of the induced pressure changes with those of healthy subjects not taking AAZ. IOP and noninvasive ICP (measured through emissions from the ear) were measured in 20 glaucoma patients taking 125 mg of AAZ twice daily. Measurements were taken for 30 minutes before taking the drug and for 2 hours post-ingestion. Comparisons were made with 13 age-similar controls. After 12 hours with no anti-glaucoma medication, AAZ did not further reduce IOP in glaucoma patients compared to controls (P = 0.58) but did reduce ICP compared to controls (P = 0.035), by approximately 4 mmHg. Our findings suggest that there are periods during the day when the pressure difference across the lamina cribrosa is larger in case of AAZ use. Future studies should focus on improving the noninvasive ICP testing, different doses and dosing schedules of AAZ, and the time course of IOP in glaucoma patients not taking AAZ.


Assuntos
Acetazolamida/farmacologia , Inibidores da Anidrase Carbônica/farmacologia , Glaucoma/tratamento farmacológico , Pressão Intracraniana/efeitos dos fármacos , Pressão Intraocular/efeitos dos fármacos , Acetazolamida/uso terapêutico , Idoso , Inibidores da Anidrase Carbônica/uso terapêutico , Feminino , Glaucoma/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade
15.
Sci Rep ; 10(1): 8535, 2020 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-32444682

RESUMO

Glaucoma is a group of optic neuropathies associated with aging and sensitivity to intraocular pressure (IOP). Early progression involves retinal ganglion cell (RGC) axon dysfunction that precedes frank degeneration. Previously we demonstrated that p38 MAPK inhibition abates axonal dysfunction and slows degeneration in the inducible microbead occlusion model of glaucoma in rat. Here, we assessed the neuroprotective effect of topical eye delivery of the p38 MAPK inhibitor BIRB 796 in three models of glaucoma (microbead occlusion in rat and squirrel monkey and the genetic DBA/2 J mouse model) with distinct durations of IOP elevation. While BIRB 796 did not influence IOP, treatment over four weeks in rats prevented degradation of anterograde axonal transport to the superior colliculus and degeneration in the optic nerve. Treatment over months in the chronic DBA/2 J model and in the squirrel monkey model reduced expression and activation of p38 downstream targets in the retina and brain but did not rescue RGC axon transport or degeneration, suggesting the efficacy of BIRB 796 in preventing associated degeneration of the RGC projection depends on the duration of the experimental model. These results emphasize the importance of evaluating potential therapeutic compounds for neuroprotection in multiple models using elongated treatment paradigms for an accurate assessment of efficacy.


Assuntos
Glaucoma/tratamento farmacológico , Naftalenos/farmacologia , Fármacos Neuroprotetores/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Pirazóis/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Animais , Transporte Axonal/efeitos dos fármacos , Modelos Animais de Doenças , Pressão Intraocular/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos DBA , Nervo Óptico/efeitos dos fármacos , Nervo Óptico/metabolismo , Ratos , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/metabolismo , Saimiri
16.
Invest Ophthalmol Vis Sci ; 61(5): 51, 2020 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-32460313

RESUMO

Purpose: The purpose of this study was to determine if treatment with telmisartan, an angiotensin II type 1 receptor blocker (ARB), protects against retinal ganglion cell (RGC) degeneration in a mouse glaucoma model with induced elevation of intraocular pressure (IOP). Methods: IOP elevation was induced by injection of polystyrene microbeads into the anterior chamber of the right eye of 3-month-old C57BL/6J mice, with the left eye serving as contralateral control. Starting the day of microbead injection, mice were maintained on solid food pellets with or without incorporated telmisartan. IOP was measured by Tono Lab tonometry prior to and weekly after microbead injection. Twelve weeks postinjection, mice were euthanized to obtain optic nerves for analysis of RGC axons. The total numbers of optic nerve axons were determined manually and automatedly using AxonJ. Degenerating axons were counted manually. Results: IOP elevation induced by microbead injection was similar in magnitude and duration in vehicle and telmisartan-fed mice, although IOP was reduced 5.8% in uninjected mice treated with telmisartan (P = 0.0027). Axon loss determined by manual and automated methods was greater in vehicle compared to telmisartan-treated mice (manual: 9.5% vs. 1.8%, P = 0.044; automated: 14.2% vs. 2.9%, P = 0.0375). An increase in the percent of axons undergoing degeneration was observed in nerves from microbead-injected eyes that was greater in vehicle-treated compared to telmisartan-treated mice (49.0% vs. -0.58%, P = 0.0019). Conclusions: Elevation of IOP by microbead injection led to loss of RGC axons in vehicle-treated mice that was largely prevented by telmisartan treatment, suggesting a neuroprotective effect of telmisartan.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Axônios/efeitos dos fármacos , Axônios/patologia , Glaucoma/tratamento farmacológico , Glaucoma/patologia , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/patologia , Telmisartan/farmacologia , Telmisartan/uso terapêutico , Animais , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL
17.
Zhonghua Yan Ke Za Zhi ; 56(5): 376-382, 2020 May 11.
Artigo em Chinês | MEDLINE | ID: mdl-32450671

RESUMO

Objective: To explore the potential neuroprotection effects and associated mechanism of baicalin in a rodent acute hypertensive glaucoma model and oxygen-glucose deprivation/reperfusion (OGD/R) induced retinal ganglion cell (RGC) injury. Methods: Experiment research. A rapid and substantial elevation of intraocular pressure was performed to establish an acute hypertensive glaucoma model, and retinal thickness was assessed at 1, 3, 5, and 7 days. The mice were then randomly divided into three groups: normal control group, hypertension group, and baicalin (50 mg/kg) for hypertension group. The effects of baicalin on the RGCs were evaluated by retrograde transporting of Fluoro-Gold. The mRNA levels of tumor necrosis factor-α, interleukine-1ß (IL-1ß), and inducible nitric oxide synthase were detected by real-time PCR, and the protein levels were measured by Western blot in the retina tissue of acute hypertensive glaucoma model. Purified primary RGC survival under OGD/R stress was measured by flow cytometry, which was also performed to measure the survival rate of RGCs pretreated by different doses of baicalin (2.5 µmol/L, 5.0 µmol/L, and 10.0 µmol/L). The effects of baicalin on primary RGCs co-cultured with mouse microglia cell line BV2 were evaluated by flow cytometry. The cytokine IL-1ß in the culture supernatant was measured by immunochemical analyses. Statistical analysis was performed using analysis of variance. Results: Retinal tissue injuries and RGC loss were observed both in vivo and in vitro. Retinal thickness was decreased to 87.32%±0.94% at 3 days (t=6.73, P<0.01), 74.86%±2.43% at 5 days (t=13.40, P<0.01), and 63.53%±2.15% at 7 days (t=19.46, P<0.01). Treatment of 50 mg/kg baicalin significantly promoted the RGC survival from 61.32%±5.94% to 89.93%±10.08% (t=4.84, P<0.01). Baicalin alleviated the retinal damages by suppressing the expression of inflammatory cytokines as revealed by Western blot and real-time PCR. In vitro the RGC survival under OGD/R stress was increased from 51.53%±1.36% to 69.37%±7.09% and 66.23%±4.25% with 5.0, 10.0 µmol/L baicalin administration (t=5.50, 4.53; both P<0.01). BV2 under OGD/R stress did extra damage to RGCs, and baicalin could reverse the damages and increase the survival from 69.37%±7.09% to 73.00%±5.20% (t=2.82, P=0.048) by reducing the release of IL-1ß [(39.97±8.76) pg/ml vs. (61.33±5.78) pg/ml, t=4.19, P=0.010]. Conclusion: Baicalin could alleviate retina tissue injury directly and promote the survival of RGCs by downregulating the expression of inflammatory cytokines and protecting RGCs from ischemia reperfusion injury. (Chin J Ophthalmol, 2020, 56: 376-382).


Assuntos
Anti-Inflamatórios não Esteroides , Flavonoides , Glaucoma , Hipertensão Ocular , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Modelos Animais de Doenças , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Glaucoma/tratamento farmacológico , Camundongos , Hipertensão Ocular/tratamento farmacológico , Células Ganglionares da Retina
18.
J Glaucoma ; 29(7): 529-535, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32332333

RESUMO

PRéCIS:: To assess the after-visit summary (AVS) as a tool for glaucoma medication recall. Medication recall was associated with level of education and complexity of medication regimen. Receiving an AVS was not associated with better medication recall. PURPOSE: The purpose of this study was to determine whether patients given the AVS have better or worse glaucoma medication recall. MATERIALS AND METHODS: Observational clinical study. Adults on ≥1 glaucoma medications examined between June 30, 2017 and August 2, 2017. DATA COLLECTION: in-person questionnaire and retrospective chart review. Self-reported glaucoma medications compared with prescribed glaucoma medication regimen verified by electronic medical record. Medication recall assessed using 3-point scoring: 1 point each for; (1) name or color of bottle or cap; (2) treatment eye(s); and (3) dosing regimen. DATA ANALYSIS: 2-sample Welch t test, 2-proportion z-test, analysis of variance, univariate, and multivariate regression. RESULTS: A total of 118 patients enrolled: age 69.7±12.9 years (mean±SD), 55.9% of patients had received an AVS at the previous visit. Of these, 33.3% reported receiving an AVS, 51.2% reported not receiving one (15.1% did not recall or respond). Patients who had received AVSs had lower medication recall scores than those who did not (2.4±1.0 vs. 2.7±0.6, P=0.04). Receipt of an AVS was associated with having Nisha Chadha as their provider (P=0.01), fewer days since prior visit (P=0.0001), and medication regimen change at prior visit (P<0.0001). Multivariate analysis revealed completion of associate's degree or higher and fewer prescribed medications to be independent predictors of higher recall score (P=0.0002 and 0.002). CONCLUSIONS: AVSs were conceived to enhance patient care. This study indicates this goal is not achieved consistently. Less education and more complex medication regimens were identified as barriers to medication recall. Additional investigations should explore if modifying this document and enhanced explanation of its use will impact medication recall and health outcomes.


Assuntos
Anti-Hipertensivos/administração & dosagem , Glaucoma/tratamento farmacológico , Adesão à Medicação/estatística & dados numéricos , Rememoração Mental/fisiologia , Visita a Consultório Médico , Idoso , Idoso de 80 Anos ou mais , Prescrições de Medicamentos , Registros Eletrônicos de Saúde , Feminino , Glaucoma/fisiopatologia , Humanos , Pressão Intraocular/efeitos dos fármacos , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Estudos Retrospectivos , Autorrelato , Inquéritos e Questionários
19.
20.
J Glaucoma ; 29(6): 441-447, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32217995

RESUMO

PRECIS: Central corneal thickness (CCT) may increase over time in children affected by primary congenital glaucoma and treated with latanoprost for at least 30 months. PURPOSE: The purpose of this study was to investigate CCT modification over time in a population of primary pediatric glaucoma (PPG) patients prescribed a monotherapy of latanoprost. MATERIALS AND METHODS: The present paper reports the results of a post hoc analysis on patients enrolled in the Glaucoma Italian Pediatric Study (GIPSy). Children affected by PPG, with a postsurgical intraocular pressure between 22 and 26 mm Hg and treated with latanoprost monotherapy for at least 30 months were eligible for the analysis. CCT variation from baseline was investigated over the follow-up using univariable and multivariable longitudinal linear mixed models. The impact of age, sex, and intraocular pressure on CCT variation were evaluated taking into account the interaction of each variable with time. RESULTS: Twenty-seven eyes (20 patients) were included in the analysis. Mean duration of latanoprost treatment was 36.6 months (SD 2.5) and mean CCT at baseline was 551 µm (SD 37.7). A significant increase of CCT over time was revealed by multivariable analysis, taking into account the impact of age at baseline and its interaction with time (P=0.03). The interaction between age and time was significant (P=0.04), indicating that older age at baseline was associated with lower increase of CCT over time. No variation of CCT was found in univariable analysis (P=0.28). CONCLUSION: In this population of PPG patients treated with latanoprost for at least 30 months, CCT significantly increased over time, when the impact of age and its interaction with time were considered.


Assuntos
Córnea/efeitos dos fármacos , Paquimetria Corneana , Glaucoma/tratamento farmacológico , Latanoprosta/administração & dosagem , Latanoprosta/efeitos adversos , Administração Tópica , Adolescente , Idade de Início , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Criança , Pré-Escolar , Córnea/patologia , Feminino , Glaucoma/congênito , Glaucoma/epidemiologia , Humanos , Lactente , Pressão Intraocular/efeitos dos fármacos , Itália/epidemiologia , Assistência de Longa Duração , Masculino , Tamanho do Órgão/efeitos dos fármacos , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Tiofenos/administração & dosagem , Tiofenos/efeitos adversos , Fatores de Tempo , Tonometria Ocular
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