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1.
Ophthalmic Res ; 63(1): 50-58, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31117087

RESUMO

PURPOSE: Ocular graft-versus-host disease (oGvHD) following allogeneic hematopoietic stem cell transplantation develops as severe dry eye disease (DED) and is initially treated with lubricants, although no clinical trials are available using artificial tears in oGvHD. This trial was set up to test perfluorohexyloctane (NovaTears®) as nonpreserved layer-forming agent for the treatment of DED in oGvHD. METHODS: 25 patients with severe DED due to oGvHD received 1 drop perfluorohexyloctane 4 times daily during a prospective, multicenter, observational 12-week study on top of established topical therapy. Clinical parameters included Schirmer test, tear film breakup time, corneal staining, meibum secretion and ocular surface disease index. Adverse events, visual acuity and intraocular pressure were key safety parameters. RESULTS: From 25 patients recruited, 23 presented for the second visit. Perfluorohexyloctane treatment did not lead to any changes in clinical or safety parameters but led to fast relief in symptoms in 57% of the patients. One adverse reaction occurred. CONCLUSIONS: This study showed no change in clinical signs in severe DED due to oGvHD, which was not unexpected due to the underlying pathomechanisms. However, the study showed improvement of symptoms in individual patients allowing application of perfluorohexyloctane as an additional symptomatic therapy in oGvHD.


Assuntos
Síndromes do Olho Seco/tratamento farmacológico , Fluorcarbonetos/uso terapêutico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Soluções Oftálmicas/uso terapêutico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
2.
Invest Ophthalmol Vis Sci ; 60(15): 5035-5044, 2019 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-31800960

RESUMO

Purpose: To compare the changes in human tear proteome and clinical effects following topical cyclosporine A (CsA) 0.05% or diquafosol tetrasodium (DQS) 3% treatment of dry eye disease (DED), and to identify biomarkers for determining disease severity and treatment effectiveness in DED. Methods: A total of 18 patients were diagnosed with non-Sjögren DED. Nine patients in each group were treated with topical CsA 0.05% or DQS 3% for 4 weeks. Tear samples were collected after evaluation of tear breakup time, corneal and conjunctival erosion staining, and results of Schirmer's test 1 before and after treatment. Proteomes were characterized using liquid chromatography mass spectrometry, and proteins exhibiting a fold change >1.5 or <0.67 (P < 0.05) were considered differentially expressed (DEP). Results: A total of 794 proteins were identified, with no significant difference observed between pretreatment and posttreatment conditions. Proteomic analysis identified 54 and 106 DEPs between treatment groups (CsA and DQS, respectively), with gene ontology analysis indicating that both treatments enhanced innate and adaptive immune responses and cellular detoxification. Protein-network analysis showed that inflammation associated with the immune response was primarily responsible for the therapeutic process in both groups. Conclusions: These results provide insight into the broad scope of changes at the ocular surface in DED and indicated that although both drugs improved the clinical parameters, the activated tear-specific biomarkers differed significantly between treatments. Our findings suggest that the DEPs identified here and those correlated with the clinical parameters might represent candidate biomarkers for DED.


Assuntos
Ciclosporina/administração & dosagem , Síndromes do Olho Seco/tratamento farmacológico , Polifosfatos/administração & dosagem , Proteoma/metabolismo , Lágrimas/metabolismo , Nucleotídeos de Uracila/administração & dosagem , Administração Tópica , Túnica Conjuntiva/metabolismo , Túnica Conjuntiva/patologia , Córnea/metabolismo , Córnea/patologia , Relação Dose-Resposta a Droga , Síndromes do Olho Seco/metabolismo , Feminino , Seguimentos , Humanos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas/administração & dosagem , Estudos Prospectivos , Método Simples-Cego , Lágrimas/efeitos dos fármacos , Resultado do Tratamento
3.
Invest Ophthalmol Vis Sci ; 60(14): 4511-4519, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675422

RESUMO

Purpose: The present study was designed to investigate the role of ocular surface glycocalyx and mucins in graft versus host disease (GVHD)-associated dry eye. The ameliorative effect of topical rebamipide, a mucin secretagogue, on GVHD-associated dry eye was also tested. Methods: A mouse model of allogeneic transplantation was used to induce ocular GVHD with C57BL/6 as donors and B6D2F1 as recipient mice. Phenol red thread method and fluorescein staining was used to quantify tear secretion and corneal keratopathy. At 8 weeks after the allogeneic transplantation, corneas were harvested to perform glycocalyx staining and confocal microscopy. Goblet cell staining was performed using periodic acid Schiff's staining. Corneal and tear film levels of Mucin 1, 4, 16, 19, and 5AC were quantified using ELISA and real-time PCR. Rebamipide was applied topically twice daily to mice eyes. Results: Allogeneic transplantation resulted in ocular GVHD-associated dry eye characterized by a significant decrease in tear film volume and the onset of corneal keratopathy. Ocular GVHD caused a significant decrease in the area and thickness of corneal glycocalyx. A significant decrease in the goblet cells was also noted. A significant decrease in mucin 4 and 5AC levels was also observed. Topical treatment with rebamipide partially attenuated ocular GVHD-mediated decrease in tear film volume and significantly reduced the severity of corneal keratopathy. Conclusions: Ocular GVHD has detrimental impact on ocular surface glycocalyx and mucins. Rebamipide, a mucin secretagogue, partially prevents ocular GVHD-associated decrease in tear film and reduces the severity of corneal keratopathy.


Assuntos
Alanina/análogos & derivados , Antioxidantes/uso terapêutico , Síndromes do Olho Seco/metabolismo , Doença Enxerto-Hospedeiro/metabolismo , Mucinas/metabolismo , Quinolonas/uso terapêutico , Administração Oftálmica , Alanina/uso terapêutico , Animais , Transplante de Medula Óssea , Antígeno Ca-125/metabolismo , Modelos Animais de Doenças , Síndromes do Olho Seco/tratamento farmacológico , Ensaio de Imunoadsorção Enzimática , Proteínas do Olho/metabolismo , Feminino , Células Caliciformes/metabolismo , Doença Enxerto-Hospedeiro/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Confocal , Mucina-5AC/metabolismo , Mucina-1/metabolismo , Mucina-4/metabolismo , Reação do Ácido Periódico de Schiff , Reação em Cadeia da Polimerase em Tempo Real , Lágrimas/metabolismo , Transplante Homólogo
4.
Rom J Ophthalmol ; 63(3): 297-305, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31687635

RESUMO

Introduction: It is acknowledged that leading pharmaceutical companies lately spend more on marketing than they are investing in research and technology development. Romania registers one of the largest market growths in the pharmaceutical industry from Central and Eastern Europe, and it is one of the main investors on the advertising market. The rapid changes in the pharmaceutical landscape have demanded for organizations to re-evaluate their infrastructure and the information delivery methods, as well as cut through the clutter and build competitive advantages by using effective advertising. The dry eye is a commonly disease encountered worldwide, which is treated with the help of over-the-counter (OTC) artificial tear drops. Aim: The aim of this study was twofold: to determine the profile of the Romanian consumer who uses artificial tear drops and to assess the components of experiential marketing used in a TV advertisement, which have the highest influence on the consumer's perception of effective advertising. Material and method: We selected a TV advertisement that used the magical concept of the artificial tear drops in the shape of water in a desert area, suggesting an eye irritation. The instrument for data collection was a self-administered questionnaire based on the watched advertising spot about the OTC artificial tear drops. The sample was made up of 384 participants and the sampling method was the snowball technique. Moreover, a model using Structural Equation was validated in order to assess the established relationships between the experiential marketing components and the effectiveness of the OTC artificial tear drops advertising. Findings: The findings showed that the demographic profile of the OTC artificial tear drops consumer is a female, with the mean age of 39 years, who graduated from university, with an average income of 2500 RON (Romanian currency), single, and with an office job. The mean number of hours spent in front of a computer per day was 10. The structural equation model revealed that the component think experience has the highest direct influence on the consumer's perception of an advertisement about OTC artificial tear drops as being effective. Discussion: The pharmaceutical market is different from other markets in that the decision maker is not the purchaser except for the OTC drugs that do not require a receipt from a physician. Think experience focuses on rational decision-making and problem solving but in a creative way.


Assuntos
/métodos , Síndromes do Olho Seco/tratamento farmacológico , Lubrificantes Oftálmicos/farmacologia , Marketing/métodos , Medicamentos sem Prescrição , Adulto , Feminino , Humanos , Masculino , Estudos Retrospectivos , Romênia
6.
Clin Ter ; 170(5): e357-e363, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31612193

RESUMO

AIM OF THE STUDY: Cilostazol is a phosphodiesterase III inhibitor that has anti-inflammatory and immunomodulatory effects and can act with beneficial effect in Dry Eye Syndrome (DES). This clinical trial evaluates the effects of cilostazol on the tear film. MATERIALS AND METHODS: Following the run-in period, subjects were randomly into two groups: 40 subjects treated with cilostazol and 40 no-treated subjects. The Walking Impairment Questionnaire (WIQ) has been administered to all patients. RESULT: The data obtained from comparison of the two study groups A and B were, respectively, the following: Schirmer I: 10.2±0.2 Vs 13.8±0.4 (p< 0.001); Schirmer II: 3.8±0.1 Vs 4.6±0.2 (p<0.001); Break-up time (BUT) 4.2±0.3 Vs 6.5±0.2 (p<0.001) with disappearing of symptoms. The WIQ showed a significant difference in the walking distance (p<0.05) and calf pain severity (p<0.005) of treated patients. In comparison with the placebo group, treated patients showed an improvement (p<0.03) in calf pain severity. CONCLUSION: The administration of cilostazol was effective, in reducing DES and improve walking distance questionnaire.


Assuntos
Cilostazol/uso terapêutico , Síndromes do Olho Seco/tratamento farmacológico , Claudicação Intermitente/tratamento farmacológico , Doença Arterial Periférica/tratamento farmacológico , Vasodilatadores/uso terapêutico , Caminhada/fisiologia , Idoso , Síndromes do Olho Seco/etiologia , Teste de Esforço , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/complicações , Inquéritos e Questionários , Resultado do Tratamento
7.
Korean J Ophthalmol ; 33(5): 467-474, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31612658

RESUMO

PURPOSE: To evaluate the protective effect of applying an ophthalmic viscosurgical device (OVD) to the ocular surface during cataract surgery and its ability to prevent dry eye syndrome. METHODS: Twenty-four patients aged 50 to 75 years who underwent cataract surgery at Seoul National University Bundang Hospital and agreed to participate in the study were included and divided into two groups: a study group who underwent cataract surgery after application of an OVD to the ocular surface, and a control group who underwent cataract surgery without application of an OVD. DisCoVisc was used as the OVD in the study group, while other factors including surgical techniques and administration of anesthetic agents were performed in both groups in the same manner. Indicators of dry eye syndrome including ocular staining score, tear break-up time, and tear osmolality were analyzed. Ocular surface disease index and a visual analog scale were analyzed for dry eye symptoms, and the amount of balanced salt solution used during surface irrigation and operation time were also analyzed. RESULTS: Significant improvement in the tear break-up time, corneal ocular staining score, and ocular surface disease index score in the study group compared with the control group one week after operation (by the Mann-Whitney test). Use of OVD was associated with longer operating time. CONCLUSIONS: OVD applied to the ocular surface during cataract surgery had a protective effect on the ocular surface one week after surgery.


Assuntos
Extração de Catarata/instrumentação , Catarata/complicações , Síndromes do Olho Seco/complicações , Ácido Hialurônico/administração & dosagem , Idoso , Síndromes do Olho Seco/tratamento farmacológico , Feminino , Seguimentos , Humanos , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Lágrimas/metabolismo , Resultado do Tratamento , Viscossuplementos/administração & dosagem
8.
Chem Commun (Camb) ; 55(91): 13657-13660, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31595891

RESUMO

Cell penetrating peptide (CPP), LK-3, causes a ca. 10-fold increase in the cell penetration of cyclosporin A (CsA) at nanomolar concentrations. The results of an in vivo dry eye mouse model demonstrated that a 100-fold lower dose of the CsA/LK-3 complex than that of Restasis® is sufficient to cause the same therapeutic effect.


Assuntos
Peptídeos Penetradores de Células/química , Ciclosporina/química , Animais , Linhagem Celular , Ciclosporina/uso terapêutico , Modelos Animais de Doenças , Portadores de Fármacos/química , Síndromes do Olho Seco/tratamento farmacológico , Síndromes do Olho Seco/patologia , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , Camundongos , Microscopia Confocal , Solubilidade
9.
Medicine (Baltimore) ; 98(39): e17121, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574810

RESUMO

BACKGROUND: Dry eye disease is a common eye disease mainly manifests with eye fatigue, foreign body sensation, dry and astringent eyes and other symptoms. Growing evidence shows that qiming granule may have beneficial effects on the clinical treatment of dry eye disease. However, no systematic review and meta-analysis collate and assess these clinical evidences. The purpose of this study protocol is to provide a comprehensive and reliable evaluation of the clinical evidence of qiming granule in the treatment of DED. METHODS AND ANALYSIS: Three English database and 4 Chinese databases other sources will be searched. Two methodological trained researchers will read the title, abstract and full texts and independently select the qualified literature according to inclusion and exclusion criteria. After assessment of the risk of bias and data extraction, we will conduct meta-analyses for outcomes including central macular thickness, optimum corrected vision, overall effect rates and adverse effects. The heterogeneity of data will be investigated by Cochrane X and I tests. We build 3 hypotheses for subgroup analysis according to the guidance for a credible subgroup effect: Disease status at baseline, duration of intervention, type of concomitant medication. Sensitivity analysis will be conducted to evaluate the stability of the results. Then publication bias assessment will be conducted by funnel plot analysis and Egger test. Finally, we will use the Grading of Recommendations Assessment, Development and Evaluate system to evaluate the quality of evidence. RESULTS: The results of our research will be published in a peer-reviewed journal. CONCLUSION: Our study is the first meta-analysis to evaluate the clinical efficacy and safety of qiming granule in the treatment of DED. It will provide more options for clinical treatment of the disease. PROSPERO REGISTRATION NUMBER: CRD42018109183.


Assuntos
Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/uso terapêutico , Síndromes do Olho Seco/tratamento farmacológico , Protocolos Clínicos , Feminino , Humanos , Masculino
10.
Cochrane Database Syst Rev ; 9: CD010051, 2019 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-31517988

RESUMO

BACKGROUND: Topical cyclosporine A (also known as ciclosporin A) (CsA) is an anti-inflammatory that has been widely used to treat inflammatory ocular surface diseases. Two CsA eyedrops have been approved by US Food and Drug Administration for managing dry eye: Restasis (CsA 0.05%, Allergan Inc, Irvine, CA, USA), approved in 2002, and Cequa (CsA 0.09%, Sun Pharma, Cranbury, NJ, USA), approved in 2018. Numerous clinical trials have been performed to assess the effectiveness and safety of CsA for dry eye; however, there is no universal consensus with regard to its effect. OBJECTIVES: To assess the effectiveness and safety of topical CsA in the treatment of dry eye. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2018, Issue 2); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); 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 for trials. We last searched the electronic databases on 16 February 2018. SELECTION CRITERIA: We included randomized controlled trials (RCTs) of people with dry eye regardless of age, sex, severity, etiology, or classification of dry eye. We included RCTs in which different concentrations of topical CsA were compared with one another or with artificial tears, placebo, or vehicle. We also included RCTs in which CsA in combination with artificial tears was compared to artificial tears alone. DATA COLLECTION AND ANALYSIS: We followed the standard Cochrane methodology and assessed the certainty of the evidence using GRADE. MAIN RESULTS: We included 30 RCTs (4009 participants) with follow-up periods ranging from 6 weeks to 12 months. We studied dry eye of various severity and underlying causes. The interventions investigated also varied across RCTs: CsA versus artificial tears; CsA with artificial tears versus artificial tears alone; and in some studies, more than one concentration of CsA. Artificial tears were used as adjunctive to study medication in all but five trials. Almost all trials had deficiencies in the reporting of results (e.g. reporting P values or direction only), precluding the calculation of between-group estimates of effect or meta-analysis.Eighteen trials compared topical CsA 0.05% plus artificial tears versus vehicle plus artificial tears or artificial tears alone. One trial reported subjective symptoms of dry eye at 6 months and the results were in favor of CsA (mean difference (MD) -4.80, 95% confidence interval (CI) -6.41 to -3.19; low-certainty evidence). Two trials reported MD in ocular surface dye staining at 6 months, but the results were inconsistent in these two trials (MD -0.35, 95% CI -0.69 to -0.01 in one and MD 0.58, 95% CI 0.06 to 1.10 in the other; low-certainty evidence). Four trials reported MD in Schirmer test scores at 6 months and the estimates ranged from -4.05 (95% CI -6.67 to -1.73) to 3.26 (95% CI -1.52 to 5.00) (low-certainty evidence). Three trials reported risk ratio (RR) of improved Schirmer test scores at 6 months; estimates ranged from 0.98 (95% CI 0.83 to 1.17) to 3.50 (95% CI 2.09 to 5.85) (low-certainty evidence). Four trials reported MD in tear film stability measured by tear break-up time at 6 months and the estimates ranged from -1.98 (95% CI -3.59 to -0.37) to 1.90 (95% CI 1.44 to 2.36) (low-certainty evidence). Three trials reported RR of improved tear break-up time at 6 months and the estimates ranged from 0.90 (95% CI 0.77 to 1.04) to 4.00 (95% CI 2.25 to 7.12) (low-certainty evidence). Three trials reported frequency of artificial tear usage at 6 months without providing any estimates of effect; the direction of effect seem to be in favor of CsA (low-certainty evidence). Because of incomplete reporting of the results data or considerable statistical heterogeneity, we were only able to perform a meta-analysis on mean conjunctival goblet cell density. Mean conjunctival goblet cell density in the CsA treated group may be greater than that in the control group at the end of follow-up at four and 12 months (MD 22.5 cells per unit, 95% CI 16.3 to 28.8; low-certainty evidence). All but two trials reported adverse events that included burning and stinging. Participants treated with CsA may be more likely to have treatment-related adverse events than those who treated with vehicle (RR 1.33, 95% CI 1.00 to 1.78; low-certainty evidence).Other comparisons evaluated were CsA 0.05% plus artificial tears versus higher concentrations of CsA plus artificial tears (4 trials); CsA 0.05% versus placebo or vehicle (4 trials); CsA 0.1% plus artificial tears versus placebo or vehicle plus artificial tears (2 trials);CsA 0.1% cationic emulsion plus artificial tears versus vehicle plus artificial tears (2 trials); CsA 1% plus artificial tears versus placebo plus artificial tears (3 trials); and CsA 2% plus artificial tears versus placebo plus artificial tears (3 trials). Almost all of these trials reported P value or direction of effect only (mostly in favor of CsA), precluding calculation of between-group effect estimates or meta-analyses. AUTHORS' CONCLUSIONS: Despite the widespread use of topical CsA to treat dry eye, we found that evidence on the effect of CsA on ocular discomfort and ocular surface and tear film parameters such as corneal fluorescein staining, Schirmer's test, and TBUT is inconsistent and sometimes may not be different from vehicle or artificial tears for the time periods reported in the trials. There may be an increase in non-serious, treatment-related adverse effects (particularly burning) in the CsA group. Topical CsA may increase the number of conjunctival goblet cells. However, current evidence does not support that improvements in conjunctival mucus production (through increased conjunctival goblet cells) translate to improved symptoms or ocular surface and tear film parameters. All published trials were short term and did not assess whether CsA has longer-term disease-modifying effects. Well-planned, long-term, large clinical trials are needed to better assess CsA on long-term dry eye-modifying effects. A core outcome set, which ideally includes both biomarkers and patient-reported outcomes in the field of dry eye, is needed.


Assuntos
Ciclosporina/administração & dosagem , Síndromes do Olho Seco/tratamento farmacológico , Lubrificantes Oftálmicos/administração & dosagem , Ciclosporina/uso terapêutico , Humanos , Lubrificantes Oftálmicos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
Invest Ophthalmol Vis Sci ; 60(12): 3776-3785, 2019 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-31503282

RESUMO

Purpose: To investigate the therapeutic effects of targeting signal transducer and activator of transcription-3 (STAT3) activation on the ocular surface damage of dry eye in mice. Methods: Adult Balb/C and C57BL/6 mice with benzalkonium chloride (BAC) treatment, lacrimal gland excision, and meibomian gland dysfunction were used as dry eye models. The levels of phosphorylated STAT3 (p-STAT3) were detected with immunofluorescence staining and Western blotting. STAT3 inhibition was performed by topical application of STAT3 inhibitor S3I-201. Corneal epithelial barrier function, tear production, and conjunctival goblet cell density were quantified with fluorescein sodium staining, phenol red cotton test, and histochemical staining. The expressions of matrix metalloproteinase (MMP)-3/9, TUNEL, and inflammation cytokines were assessed with immunofluorescence staining, qPCR, and ELISA assays. The therapeutic effect of S3I-201 was further compared with the Janus kinase inhibitor tofacitinib and ruxolitinib. Results: Elevated levels of nuclear p-STAT3 were detected in the corneal and conjunctival epithelium of three dry eye models. Topical application of S3I-201 improved corneal epithelial barrier function, increased tear production and conjunctival goblet cell density in BAC-induced dry eye mice. Moreover, S3I-201 decreased the expression of MMP-3/9, suppressed the apoptosis of corneal and conjunctival epithelial cells, and reduced the levels of IL-1ß, IL-6, IL-17A, and IFN-γ. Compared with tofacitinib and ruxolitinib, the STAT3 inhibitor S3I-201 showed superior improvement of tear production and inflammatory cytokine expression in lacrimal gland. Conclusions: Elevated STAT3 activation is involved in the pathogenesis of dry eye, while targeting STAT3 effectively alleviates BAC-induced ocular surface damage.


Assuntos
Modelos Animais de Doenças , Síndromes do Olho Seco/tratamento farmacológico , Proteínas Inibidoras de STAT Ativados/uso terapêutico , Fator de Transcrição STAT3/antagonistas & inibidores , Administração Oftálmica , Animais , Western Blotting , Túnica Conjuntiva/metabolismo , Citocinas/metabolismo , Síndromes do Olho Seco/metabolismo , Síndromes do Olho Seco/patologia , Ensaio de Imunoadsorção Enzimática , Epitélio/metabolismo , Epitélio Anterior/metabolismo , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Células Caliciformes/patologia , Marcação In Situ das Extremidades Cortadas , Metaloproteinase 3 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Soluções Oftálmicas , Fosforilação , Reação em Cadeia da Polimerase em Tempo Real , Fator de Transcrição STAT3/metabolismo , Lágrimas/fisiologia
12.
Cornea ; 38 Suppl 1: S25-S33, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31498249

RESUMO

Surgical intervention is the most effective treatment for decreased vision resulting from cataracts. Although the current procedures for cataract surgery are safe and effective, it is well known that several complications can develop after surgery. Postoperative cystoid macular edema (CME) is a well-known complication, and prophylactic medications such as steroids and/or nonsteroidal antiinflammatory drugs are routinely used for its prevention. Ocular surface abnormalities, such as dry eye, have also been reported to develop after cataract surgery. However, the causative mechanisms for postoperative dry eye have not been definitively determined. At present, there are no prophylactic medications that are commonly used to prevent the development of postoperative dry eye. Although nonsteroidal antiinflammatory drugs are very effective in reducing the incidence and degree of postoperative CME, it is known that they can cause adverse side effects, including ocular surface abnormalities. Thus, perioperative medications must be carefully selected to improve surgical outcomes and patient satisfaction. Here, we summarize the results of recent studies on postoperative dry eye and CME that can develop after cataract surgery. We suggest appropriate combinations of medications that can be used to minimize these postsurgical complications.


Assuntos
Anti-Inflamatórios/administração & dosagem , Extração de Catarata/efeitos adversos , Gerenciamento Clínico , Síndromes do Olho Seco/tratamento farmacológico , Edema Macular/tratamento farmacológico , Cuidados Pós-Operatórios/métodos , Complicações Pós-Operatórias , Administração Tópica , Síndromes do Olho Seco/epidemiologia , Síndromes do Olho Seco/etiologia , Saúde Global , Humanos , Incidência , Edema Macular/epidemiologia , Edema Macular/etiologia
13.
Artigo em Inglês | MEDLINE | ID: mdl-31487776

RESUMO

Dry eye disease (DED) is a multifactorial inflammatory disease that severely impairs patients' quality of life. Particulate matter comprises a harmful mixture of particles less than 10 µm in size, which on contact with the eye, causes inflammation in the cornea/conjunctival epithelium, threatening eye health and triggering the onset of DED. Achyranthis radix is an ingredient of traditional medicine generally used for treating osteoporosis, trauma, and thrombosis in Asian countries. However, the effect of Achyranthis radix on eye health has not been elucidated. In this study, we evaluate the protective effect of Achyranthis radix hot water extract (ARE) in a rat model of urban particulate matter (UPM)-induced DED. UPM with or without ARE were topically administered on both eyes thrice daily for 10 days. ARE induced tear secretion and improved corneal irregularity. Additionally, ARE treatment protected the corneal epithelial cells from UPM-induced apoptosis. It also restored rMuc4 expression in the cornea and increased goblet cell density in the conjunctiva. These results are suggestive of the potential of ARE as a topical therapeutic agent for treating DED.


Assuntos
Achyranthes/química , Síndromes do Olho Seco/tratamento farmacológico , Extratos Vegetais/farmacologia , Administração Oftálmica , Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/efeitos adversos , Animais , Modelos Animais de Doenças , Feminino , Material Particulado/efeitos adversos , Raízes de Plantas/química , Ratos , Ratos Sprague-Dawley
14.
Korean J Ophthalmol ; 33(4): 343-352, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31389210

RESUMO

PURPOSE: To evaluate the efficacy and safety of cyclosporine nanoemulsion 0.05% compared to cyclosporine emulsion 0.05% and diquafosol sodium 3%. METHODS: This was a multicenter, randomized, evaluator-masked, active control, parallel, phase IV study. A total of 227 patients were randomly allocated to instill cyclosporine nanoemulsion 0.05% (CN) twice daily, cyclosporine emulsion 0.05% (CE) twice daily, or diquafosol sodium 3% (DQ) six times daily. Non-inferiority of CN was analyzed by primary endpoint (cornea and conjunctival staining scores at week 12). The secondary endpoints were scores of corneal staining, conjunctival staining, tear break-up time, Schirmer test, and Ocular Surface Disease Index at weeks 4 and 12. RESULTS: Primary endpoints showed statistically significant improvements in all groups. Primary endpoints were -6.60 for the CN group, -5.28 for the CE group, and -6.63 for the DQ group (National Eye Institute scale from 0 to 33), verifying the non-inferiority of CN compared to CE (95% confidence interval, -0.15 to 2.80, Δ>-2.88). In intergroup comparison between CN and CE groups, the CN group had significantly more decreased conjunctival staining score at week 12. Intergroup comparison between CN and DQ groups showed consistent statistically significant improvements in TBUT and Schirmer test in the CN group. In the DQ group, TBUT showed late statistically significant improvement at week 12 and Schirmer test showed relatively short-term statistically significant improvement at week 4. CONCLUSIONS: Cyclosporine nanoemulsion 0.05% was equivalently efficient compared to cyclosporine emulsion 0.05% and diquafosol sodium 3%. In addition, CN showed significant improvements in several parameters for treatment of dry eyes.


Assuntos
Ciclosporina/administração & dosagem , Síndromes do Olho Seco/tratamento farmacológico , Polifosfatos/administração & dosagem , Nucleotídeos de Uracila/administração & dosagem , Administração Tópica , Adulto , Relação Dose-Resposta a Droga , Síndromes do Olho Seco/diagnóstico , Emulsões/administração & dosagem , Feminino , Seguimentos , Humanos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Nanotecnologia , Estudos Prospectivos , Método Simples-Cego , Lágrimas/metabolismo , Resultado do Tratamento
16.
Nat Med ; 25(8): 1310-1318, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31384041

RESUMO

Here we present a miniaturized analog of a blinking human eye to reverse engineer the complexity of the interface between the ocular system and the external environment. Our model comprises human cells and provides unique capabilities to replicate multiscale structural organization, biological phenotypes and dynamically regulated environmental homeostasis of the human ocular surface. Using this biomimetic system, we discovered new biological effects of blink-induced mechanical forces. Furthermore, we developed a specialized in vitro model of evaporative dry-eye disease for high-content drug screening. This work advances our ability to emulate how human physiological systems interface with the external world, and may contribute to the future development of novel screening platforms for biopharmaceutical and environmental applications.


Assuntos
Piscadela/fisiologia , Síndromes do Olho Seco/etiologia , Engenharia Tecidual/métodos , Fenômenos Biomecânicos , Células Cultivadas , Síndromes do Olho Seco/tratamento farmacológico , Síndromes do Olho Seco/fisiopatologia , Glicoproteínas/uso terapêutico , Humanos , Fenótipo
17.
Medicine (Baltimore) ; 98(31): e16710, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374063

RESUMO

BACKGROUND: Dry eye disease (DED) is a chronic ocular surface disease that affects hundreds of millions of people worldwide. Although 0.05% cyclosporine ophthalmic emulsion (CsA OE) has long been prescribed in the U.S. for the treatment of DED, it is not commercially available in China. Our study aims to compare the efficacy and safety profile of 0.05% CsA OE versus vehicle in Chinese patients with moderate to severe DED. METHODS: This was a multicenter, randomized, double-masked, 2-parallel-arm, 3-month phase III study. Patients with moderate to severe DED were randomized to receive twice-daily 0.05% CsA OE or its vehicle, along with unpreserved hypromellose eye drops 3 times per day. Patients were followed up at day 7, 28, 56, and 84, as well as 2 weeks after the medications were discontinued for safety assessment. RESULTS: A total of 240 patients were randomized. The overall effective rate (OER) and efficacy index were significantly better in the CsA OE than vehicle group at all follow up times (all P < .05), and the OER of CsA OE and vehicle group at month 3 was 70.6% and 27.8%, respectively (P < .001) (primary endpoint). The patients in CsA OE group displayed a significant improvement in dry eye symptoms from day 28 and ocular surface test results from day 7 (all P < .05). The ocular surface disease index scores of 0.05% CsA OE treated patients were significantly better than those treated with vehicle control at day 56 and 84 (P = .0061 and <.001, respectively). Drug related adverse events (AEs) were recorded in 6(5%) and 3(2.5%) patients in the CsA OE and vehicle groups respectively (P = .4061) with ocular pain as the most frequently reported AEs, and it was mostly mild to moderate. There were no detrimental effects on visual acuity, intraocular pressure, or vital signs. CONCLUSIONS: Twice-daily instillation of 0.05% CsA OE was effective and well tolerated for the treatment of moderate to severe DED in Chinese population during the 3 months of the study.


Assuntos
Ciclosporina/administração & dosagem , Síndromes do Olho Seco/tratamento farmacológico , Soluções Oftálmicas/administração & dosagem , Adulto , China , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do Tratamento
18.
Drug Des Devel Ther ; 13: 2381-2391, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31409972

RESUMO

Purpose: To present a new ocular nebulization therapy for the treatment of dry eye disease (DED) and investigate the efficacy of vitamin B12 (VB12) and oxytocin (OXT) nebulization with clinical parameters and in vivo confocal microscopy (IVCM). Patients and methods: Thirty-eight patients with DED were enrolled, with 19 receiving VB12 nebulization and 19 receiving OXT nebulization twice weekly for 3 months. Clinical signs and symptoms including Ocular Surface Disease Index, self-assessment of light sensitivity and dryness, tear meniscus height, tear break-up time (BUT), and corneal staining, along with IVCM data of basal epithelial cell density, sub-basal dendritic cell (DC) density, nerve density, and nerve tortuosity were acquired at baseline, 1 month, and 3 months after starting treatment. Results: Patients treated with VB12 improved significantly in all signs and symptoms except for nerve tortuosity during the three-month treatment, while OXT demonstrated similar effects apart from BUT and nerve tortuosity. VB12 group revealed a higher BUT at 1 month and 3 months with a higher basal epithelial cell density at 3 months compared with OXT group, and a lower DC density was observed in OXT group at 1 month. Change of basal epithelial cell density was more significant at 3 months in VB12 group, with OXT group showing a significantly higher DC reduction at 1 month. Conclusion: The nebulization therapy delivering VB12 and OXT appears to be effective in improving the symptoms and signs of dry eye, with a relatively stronger effect of BUT elevation and epithelial repair in VB12 and anti-inflammation in OXT nebulization.


Assuntos
Córnea/efeitos dos fármacos , Síndromes do Olho Seco/tratamento farmacológico , Ocitocina/uso terapêutico , Vitamina B 12/uso terapêutico , Idoso , Estudos de Coortes , Córnea/patologia , Síndromes do Olho Seco/diagnóstico , Feminino , Humanos , Masculino , Microscopia Confocal , Pessoa de Meia-Idade , Ocitocina/administração & dosagem , Estudos Prospectivos , Vitamina B 12/administração & dosagem
19.
Int J Mol Sci ; 20(16)2019 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-31426602

RESUMO

Rebamipide ophthalmic solution is a mucin secretagogue which is an important therapeutic agent in the treatment of dry eye. It has been noted that dry eye in office workers is associated with a decrease in secretory mucin. This study aimed to evaluate the effects of 2% rebamipide ophthalmic solution in mice subjected to environmental dry eye stress (EDES), which mimics the conditions of office workers. Thirty eyes from thirty BALB/c mice (eight-week-old males) were divided into three treatment groups: artificial tear (vehicle), 2% rebamipide ophthalmic solution, and 0.1% hyaluronic acid (HA) ophthalmic solution. After four days of pretreatment, mice were exposed to EDES for three days. The corneal subbasal nerve and inflammatory cells were then examined using in vivo confocal microscopy. Following EDES exposure, the lissamine green staining score was significantly lower and corneal sensitivity was more preserved in the 2% rebamipide group than in the HA group. In addition, the subbasal nerve fiber density was significantly higher and the DC density was significantly lower in the 2% rebamipide group than in the HA group. Overall, the topical rebamipide ophthalmic solution showed more favorable therapeutic effects when compared to the HA ophthalmic solution in a mouse model of EDES, likely owing to its anti-inflammatory and neuroprotective effects.


Assuntos
Alanina/análogos & derivados , Anti-Inflamatórios/uso terapêutico , Córnea/efeitos dos fármacos , Síndromes do Olho Seco/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Nervos Periféricos/efeitos dos fármacos , Quinolonas/farmacologia , Alanina/farmacologia , Alanina/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Córnea/inervação , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fármacos Neuroprotetores/uso terapêutico , Quinolonas/uso terapêutico
20.
Med Sci Monit ; 25: 4583-4589, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31257361

RESUMO

BACKGROUND The apoptosis of corneal epithelial cells participates in the pathological processes of dry eye, which is expected to be a treatment target for dry eye. The aim of this study was to investigate the effects of vitamin A (VA) on apoptosis of corneal epithelial cells in a mouse model with dry eye induced by benzalkonium chloride (BAC). MATERIAL AND METHODS We randomly divided 60 male BALB/c mice aged 8-10 weeks into 3 groups: the blank control group, the dry eye + vehicle group, and the dry eye + drug group. On the 7th day after the dry eye model successfully induced, the mouse eyeballs removed, and the mouse corneal tissues were isolated. The expression levels of Bax and Bcl-2 in corneal tissues were detected via reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. The apoptotic corneal epithelial cells were quantified using terminal deoxynucleotidyl transferase (TdT) deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL) staining technique. RESULTS VA suppressed the upregulation of the Bax gene at the mRNA and protein levels, and upregulated the expression of the Bcl-2 gene (P<0.05). TUNEL results revealed that the number of apoptotic epithelial cells in the dry eye group was 40 times larger as that in the blank control group. After the intervention of VA at an appropriate concentration, the number of apoptotic corneal epithelial cells was remarkably reduced to about 10 times that in the blank control group (P<0.05). CONCLUSIONS VA can inhibit upregulation of the expressions of Bax and Bcl-2 in the epithelial cells of mice with dry eye induced by BAC, so as to suppress the apoptosis of epithelial cells in mice with dry eye.


Assuntos
Proteínas Proto-Oncogênicas c-bcl-2/genética , Vitamina A/farmacologia , Proteína X Associada a bcl-2/genética , Animais , Apoptose/efeitos dos fármacos , Compostos de Benzalcônio/farmacologia , Córnea/efeitos dos fármacos , Córnea/metabolismo , Córnea/patologia , Modelos Animais de Doenças , Síndromes do Olho Seco/tratamento farmacológico , Síndromes do Olho Seco/metabolismo , Células Epiteliais/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Proteína X Associada a bcl-2/biossíntese
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