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1.
Eur J Ophthalmol ; 30(1): 94-103, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30585084

RESUMO

PURPOSE: To evaluate the efficacy and safety of plasma rich in growth factors eye drops for the treatment of corneal and ocular surface disorders in patients with graft versus host disease. METHODS: This retrospective and longitudinal study included graft versus host disease patients with ocular disorders. The resolution of corneal ulcers (area and density staining) was evaluated as primary outcome. Best corrected visual acuity, intraocular pressure, tear film breakup time, Schirmer test, ocular surface disease index, and visual analog score were evaluated as secondary outcomes. All variables were analyzed before and after plasma rich in growth factors treatment. The safety of plasma rich in growth factors treatment was also assessed. RESULTS: Twelve patients (23 eyes) with ocular graft versus host disease were evaluated. Statistically significant improvement in the area (75.7%) and density (73.3%) of the corneal staining, in best corrected visual acuity (74.7%), in ocular surface disease index scale (75.4%), visual analog score frequency (81.4%) and visual analog score severity (81.9%), and an increase of 3.8 s in tear film breakup time and 6 mm in Schirmer test was observed after plasma rich in growth factors treatment (p < 0.001). Some potential modifiers of the therapeutic effect were identified. All patients achieved corneal stability without perforation risk. No adverse events associated with the plasma rich in growth factors were observed. CONCLUSION: Immunosafe plasma rich in growth factors eye drops for the treatment of patients with ocular graft versus host disease could be safe and effective, showing a high rate of corneal ulcer resolution and dry eye disease control. Plasma rich in growth factors eye drops may help to maintain corneal stability and prevent it against higher ocular complications.


Assuntos
Síndromes do Olho Seco/terapia , Doença Enxerto-Hospedeiro/complicações , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Plasma Rico em Plaquetas , Adulto , Idoso , Síndromes do Olho Seco/etiologia , Síndromes do Olho Seco/metabolismo , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas/uso terapêutico , Estudos Retrospectivos , Lágrimas/metabolismo
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.
Clin Ter ; 170(6): e478-e482, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31696913

RESUMO

In the ductal epithelium adjacent to lymphoid infiltrates and in lymphocytes of salivary glands in patients with Sjögren syndrome (SS), there is an increased expression of monokine induced by interferon (IFN)-γ(MIG) and chemokine (C-X-C motif) receptor 3 (CXCR)3, which therefore seems to participate in the SS pathogenesis. Cultured SS salivary epithelial cells treated with IFN-γ release high levels of IFN-γ-inducible protein 10 (IP-10) and MIG. MIG secreted by salivary epithelial cells (under IFN-γ influence), recruits Type-1 helper (Th1) lymphocytes that create an amplification feedback loop, and perpetuates the autoimmune process, through an enhanced IFN-γ induction, that in turn stimulates an additional MIG secretion from epithelial cells. The high levels of MIG in saliva and tears indicate an immune Th1 dependent response. An amelioration of autoimmune sialadenitis with MIG antagonists has been observed in experimental settings, suggesting a possible therapeutic approach to SS. More investigations are needed to assess whether MIG is a novel therapeutic target for SS in humans.


Assuntos
Quimiocina CXCL9/metabolismo , Síndrome de Sjogren/metabolismo , Quimiocina CXCL10 , Humanos , Receptores CXCR3 , Lágrimas/metabolismo
4.
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
5.
Invest Ophthalmol Vis Sci ; 60(14): 4889-4895, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31752018

RESUMO

Purpose: Deregulated expression of several microRNAs (miRNAs) in sera or salivary glands of patients with Sjögren syndrome (SS) has been reported. However, none have investigated miRNAs in samples that can represent lacrimal glands. We compared the miRNAs expression in the tears of SS patients and healthy controls. Moreover, we investigated the correlation between miRNAs expression and ocular staining score (OSS). Methods: Individual tear samples were collected from 18 SS patients and 8 age-matched controls. Clinical ophthalmologic assessments included Schirmer I test, tear film breakup time (tBUT), and OSS. The expression of 43 different miRNAs in tears was measured using real-time polymerase chain reaction, and compared between the SS patients and controls. And we also compared between the three groups of control, primary SS, and secondary SS patients. The correlation between the miRNA expression and OSS was evaluated. Results: The expression levels of miR-16-5p, miR-34a-5p, miR-142-3p, and miR-223-3p were significantly upregulated in patients with SS when compared with those in the control group (P < 0.05). The expression of 10 miRNAs (miR-30b-5p, miR-30c-5p, miR-30d-5p, miR-92a-3p, miR-134-5p, miR-137, miR-302d-5p, miR-365b-3p, miR-374c-5p, miR-487b-3p) was significantly downregulated in the SS patients (P < 0.05). Eight miRNAs showed statistically significant differences between the three groups of control, primary SS and secondary SS. All 14 miRNAs with significant differences in SS patients and control group were not significantly correlated with OSSs. Conclusions: The 14 differentially expressed miRNAs may be involved in the pathogenesis of SS, in particular, related to autoimmunity and neuropathy.


Assuntos
Regulação da Expressão Gênica/fisiologia , MicroRNAs/genética , Síndrome de Sjogren/metabolismo , Lágrimas/metabolismo , Adulto , DNA Complementar/genética , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real
6.
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
7.
Int J Mol Sci ; 20(20)2019 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-31614909

RESUMO

The use of eyewash solutions in Japan, especially in patients with allergic conjunctivitis and contact lens wearers, has been increasing. Our aim was to investigate how the use of preservative-free eyewash solution in healthy eyes for one month affects corneal safety and ocular surface mucin. We analyzed 42 eyes of 21 individuals (17 males, four females; mean age: 36.1 ± 7.4 years) without ocular allergies, dry eyes, or other ocular diseases through a prospective study. Eyes were randomized to a wash group (group one) and a nonwash follow up group (group two). We evaluated the dry eye-related quality-of-life score (DEQS), tear film breakup time (TBUT), fluorescein staining score, mRNA expression of MUC5AC and MUC16, MUC16 immunohistochemistry, and MUC5AC periodic acid Schiff (PAS) staining. There was a significant decrease in DEQS scores after one month of eyewash use (p < 0.05). There were no significant differences in other evaluation items that were analyzed (all p > 0.05). Furthermore, no significant differences were observed between group one and group two in all endpoints (all p > 0.05). The results suggest that one month use of a nonpreserved eyewash solution has no detrimental effects on the tear film and the ocular surface mucins.


Assuntos
Antígeno Ca-125/metabolismo , Túnica Conjuntiva/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Mucina-5AC/metabolismo , Soluções Oftálmicas/efeitos adversos , Adulto , Túnica Conjuntiva/metabolismo , Córnea/metabolismo , Síndromes do Olho Seco/metabolismo , Feminino , Fluoresceína/metabolismo , Ácido Glicirrízico/farmacologia , Células Caliciformes/citologia , Células Caliciformes/metabolismo , Humanos , Japão , Masculino , Estudos Prospectivos , Lágrimas/metabolismo
8.
Invest Ophthalmol Vis Sci ; 60(13): 4234-4240, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31618427

RESUMO

Purpose: To use a human-based model to study the effects of repeated tear film instability on corneal detection thresholds to cold, mechanical, and chemical stimuli. Methods: Twenty-five subjects participated in three study visits. A computer-controlled Belmonte esthesiometer was used to estimate corneal detection thresholds to cold, mechanical, and chemical stimuli before, after, and 30 minutes following 10 consecutive sustained tear exposure (STARE) trials. Subjects turned a pain knob (0-10) to indicate discomfort during STARE trials. The area of tear breakup and thinning in each trial was analyzed. Symptoms were evaluated by the Current Symptom Questionnaire (CSQ). Results: There was a significant time effect on CSQ symptoms during both visits (Friedman test, P < 0.001), with immediately after repeated STARE and 30 minutes later significantly differing from before STARE (Wilcoxon, P < 0.017). Tear breakup occurred in every trial, ranging from 25% to 88% of the exposed corneal area and all subjects indicated discomfort during trials. There was a significant time effect on mechanical thresholds between before STARE mechanical thresholds and 30 minutes later (repeated measures analysis of variance [ANOVA] P < 0.001), but not cold (P = 0.057) or chemical (P = 0. 565) thresholds. Conclusions: In this study, tear breakup during STARE trials was associated with discomfort, which when repeated, resulted in increased symptoms of ocular discomfort and alterations of mechanical sensory thresholds after 30 minutes. These results suggest that tear film instability, which is thought to occur repeatedly during normal blinking among dry eye patients over the day, can produce neurosensory alterations.


Assuntos
Córnea/fisiologia , Síndromes do Olho Seco/fisiopatologia , Lágrimas/metabolismo , Adulto , Análise de Variância , Dióxido de Carbono/farmacologia , Temperatura Baixa , Córnea/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Limiar Sensorial/fisiologia , Estresse Mecânico
9.
Exp Eye Res ; 189: 107837, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31626800

RESUMO

Pseudoexfoliation syndrome (PEX) may lead to the development of pseudoexfoliative glaucoma (PEG), a potential cause of irreversible blindness, if left untreated. This type of glaucoma often presents with much higher intraocular pressure (IOP) values than observed in primary open angle glaucoma, and patients are often unaware of their condition. Therefore, early diagnosis is of utmost importance in PEX and PEG. Unfortunately, no valid objective biomarkers are available that can be used for this purpose. The excessive synthesis and deposition of elastic microfibrillar pseudoexfoliation material is observed in the pathophysiology of PEX, therefore, growth factors may play roles in this pathology. Thus, in this study, we sought to determine the roles of phenotypes and genotypes of connective tissue growth factor (CTGF) as objective biomarkers for early diagnosis of PEX and PEG. Thus, we investigated possible associations involving tear and aqueous humor CTGF concentrations and four single nucleotide polymorphisms (SNPs) of the CTGF gene in PEX and PEG. The study was designed as a 2-year case-control study in the Turkish population. Study population was composed of 214 patients with PEG, 214 patients with PEX, and 214 age-matched controls for CTGF SNP analysis. Tear fluid study group consisted of 78 patients with PEG, 77 patients with PEX, and 78 controls. Aqueous humor analysis included 8 patients with PEG, 17 patients with PEX, and 23 controls. Tear fluid was collected using Schirmer strips, and aqueous humor samples were taken during cataract surgery. CTGF concentration was determined by ELISA, and total protein concentration was determined by Bradford assay in tear and aqueous humor samples. PCR followed by restriction fragment length polymorphism analysis was used for genotyping of rs6918698 G/C and rs9399005 C/T, while real-time PCR was used for rs9402373 C/G and rs12526196 T/C. Intraocular pressure, visual field score, mean deviation, and pattern standard deviation parameters were also evaluated. CTGF concentration in tear fluid was significantly higher in PEG patients compared with controls (P = 0.001), while it was lower in PEX patients. Similarly, total protein concentration in tear fluid was significantly increased in PEG patients relative to PEX patients (P = 0.026) and controls (P = 0.004). CTGF concentration in aqueous humor did not differ markedly between the groups, whereas total protein was significantly higher in the PEG group compared with the PEX group (P = 0.012) and controls (P = 0.003). Receiver operating characteristic analysis revealed that total protein in aqueous humor was a robust classifier for evaluating the presence of PEG against controls (Area under the curve = 0.897, P = 0.001). The genotypes of the studied SNPs were not significantly correlated with CTGF concentration in aqueous humor or tear fluid, and did not exhibit significant association with PEG or PEX. In conclusion, this was the first study to investigate tear fluid CTGF concentration in PEX and PEG, which came out not to be a good classifier for PEG or PEX. Total protein level in tear fluid and CTGF SNPs also did not predict PEG or PEX status successfully.


Assuntos
Humor Aquoso/metabolismo , Fator de Crescimento do Tecido Conjuntivo/genética , Síndrome de Exfoliação/genética , Glaucoma de Ângulo Aberto/genética , Pressão Intraocular/fisiologia , Polimorfismo de Nucleotídeo Único , Lágrimas/metabolismo , Idoso , Biomarcadores/metabolismo , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Diagnóstico Precoce , Síndrome de Exfoliação/diagnóstico , Síndrome de Exfoliação/metabolismo , Feminino , Seguimentos , Genótipo , Glaucoma de Ângulo Aberto/diagnóstico , Glaucoma de Ângulo Aberto/metabolismo , Humanos , Masculino , RNA/genética , Estudos Retrospectivos
10.
Cornea ; 38 Suppl 1: S11-S24, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31490785

RESUMO

Patients with corneal and conjunctival disorders report an array of ocular surface symptoms including stinging, foreign body sensation, and itching. The intensity and perceptual quality of these sensations and their duration, from brief intervals to long-term symptoms, also vary. We hypothesize that symptomatic differences across disorders reflect differences in the balance between ocular inflammation and nerve injury, with different conditions resulting from predominant effects of one of these, or a combined effect. This article provides an overview of corneal and conjunctival nerve cells, such as nociceptors and thermoreceptors, with descriptions of their morphological and molecular characteristics and their nerve-firing patterns and evoked sensations, as determined by earlier studies in animals and humans. Detailed descriptions of the changes in neuronal responses (such as abnormal responsiveness and spontaneous firing) due to local inflammation and nerve injury are provided, and assorted ocular surface disorders are discussed. Eye conditions in which inflammation is predominant include allergic conjunctivitis and photokeratitis, whereas nerve injury is the primary factor underlying complaints of dry eye after photorefractive keratectomy and in elderly patients. Both factors contribute substantially to dry eye disease and varicella-zoster infections. This model of the combined effects of inflammation and nerve injury serves to explain the different sensations reported in various eye surface disorders, including short-term versus chronic pain and dysesthesias, and may help to improve diagnoses and treatment methods.


Assuntos
Córnea/inervação , Síndromes do Olho Seco/diagnóstico , Dor Ocular/diagnóstico , Ceratite/diagnóstico , Nociceptores/fisiologia , Sensação/fisiologia , Termorreceptores/fisiopatologia , Síndromes do Olho Seco/fisiopatologia , Dor Ocular/etiologia , Humanos , Ceratite/fisiopatologia , Lágrimas/metabolismo
11.
Curr Opin Ophthalmol ; 30(5): 386-394, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31393326

RESUMO

PURPOSE OF REVIEW: Dry eye disease (DED) is a chronic multifactorial disease that affects millions of people worldwide. Despite ongoing research, treatment for DED remains a challenge. Neurostimulation for tear production is a rapidly evolving field that culminated in the development of the intranasal tear neurostimulator (ITN). In this article, we review the neuroanatomy and pathophysiology of tear production and the evolution of neurostimulation for the treatment of DED. RECENT FINDINGS: The ITN was approved for commercial use in April 2017. This innovation stemmed from the success of lacrimal nerve and anterior ethmoid nerve stimulation animal studies. Since then, numerous pilot studies and multicenter randomized controlled trials demonstrate increased aqueous tear production, improved DED-related symptoms, and device safety. Recent studies also report the positive effects of intranasal stimulation on mucin and lipid secretion. SUMMARY: Neurostimulation for enhanced tear production is a promising new treatment option for DED. Stimulation of the lacrimal nerve and anterior ethmoid nerve both effectively increase tear volume. The ITN is a noninvasive device that effectively increases aqueous tear volume and may improve tear composition, including mucin and lipid concentrations. Further studies are needed to determine proper patient selection and the long-term efficacy of neurostimulation for DED.


Assuntos
Síndromes do Olho Seco/terapia , Terapia por Estimulação Elétrica/métodos , Aparelho Lacrimal/inervação , Nervos Periféricos/fisiopatologia , Lágrimas/metabolismo , Animais , Síndromes do Olho Seco/metabolismo , Síndromes do Olho Seco/fisiopatologia , Humanos , Aparelho Lacrimal/metabolismo
12.
Biomed Pharmacother ; 117: 109177, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31387168

RESUMO

Exposure to ambient fine particulate matter (fine PM) pollution has been previously associated with ocular surface diseases. But, to the best of our knowledge, the in vivo long-term effects of fine PM on the ocular surface have not been investigated. We aimed to evaluate the effects of fine PM on cultured human corneal epithelial (HCE) cells and on the ocular surfaces of mice, with standard reference material of fine PM(SRM 2786). We applied fine PM suspension to the eyes of C57BL/6 mice for up to 6 months. In vivo examinations, including tear secretion, tear film break-up time (TBUT) and corneal fluorescein staining, were performed in the 3rd and 6th month. At the end of the in vivo study, the corneal histological changes and conjunctival goblet cells were examined by staining, and cytokines in tissue were also detected. In addition, HCE cells were treated with fine PM for 12 h and 24 h. Then, cell apoptosis and reactive oxygen species (ROS) formation was detected. We found that fine PM damages the mouse eye in a dose- and time-dependent manner. In mice, the tear secretion and tear film break-up time were significantly reduced, along with the development of corneal epithelial damage, apoptosis of conjunctival epithelial cells and hypoplasia of conjunctival goblet cells. In addition, IL-18, IL-22, IL-23 and MCP-1 were increased in both conjunctiva and cornea of the fine PM-treated animals. Furthermore, increased apoptosis and ROS production were observed in time- and dose-dependent manner in HCE cells after fine PM exposure for 12 h and 24 h. Our results indicate that fine PM is cytotoxic to both HCE cells and the ocular surface. Long-term topical application of fine PM suspension in mice results in ocular surface changes that are similar to those observed with dry eye.


Assuntos
Córnea/efeitos dos fármacos , Material Particulado/efeitos adversos , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , Túnica Conjuntiva/efeitos dos fármacos , Túnica Conjuntiva/metabolismo , Modelos Animais de Doenças , Síndromes do Olho Seco/induzido quimicamente , Síndromes do Olho Seco/metabolismo , Feminino , Células Caliciformes/efeitos dos fármacos , Células Caliciformes/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Espécies Reativas de Oxigênio/metabolismo , Lágrimas/efeitos dos fármacos , Lágrimas/metabolismo
13.
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
14.
Int J Mol Sci ; 20(15)2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31374809

RESUMO

Dry eye disease (DED) is a multifactorial syndrome that can be caused by alteration in the quality or quantity of the precorneal tear film. It is considered one of the most common ocular conditions leading patients to seek eye care. The current method for diagnostic evaluations and follow-up examinations of DED is a combination of clinical signs and symptoms determined by clinical tests and questionnaires, respectively. The application of powerful omics technologies has opened new avenues toward analysis of subjects in health and disease. Metabolomics is a new emerging and complementary research discipline to all modern omics in the comprehensive analysis of biological systems. The identification of distinct metabolites and integrated metabolic profiles in patients can potentially inform clinicians at an early stage or during monitoring of disease progression, enhancing diagnosis, prognosis, and the choice of therapy. In ophthalmology, metabolomics has gained considerable attention over the past decade but very limited such studies have been reported on DED. This paper aims to review the application of tear metabolomics in DED.


Assuntos
Síndromes do Olho Seco/metabolismo , Metaboloma , Metabolômica/métodos , Lágrimas/metabolismo , Animais , Síndromes do Olho Seco/diagnóstico , Humanos , Prognóstico
15.
Indian J Ophthalmol ; 67(9): 1405-1409, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31436182

RESUMO

Purpose: The purpose of this study was to assess the effect of long-lasting botulinum A toxin injections on ocular surface parameters and to further investigate the relationship between these parameters and the duration of the treatment. Methods: In this retrospective study, patients with unilateral hemifacial spasm who were receiving botulinum A toxin injections for at least 1 year were analyzed. Healthy contralateral eyes acted as controls. The ocular surface examination included Ocular Surface Disease Index questionnaire, Schirmer test type I, tear film break-up time (TFBUT), tear osmolarity, corneal sensitivity, and corneal fluorescein staining. Results: Twenty-six patients (6 males and 20 females; mean age 76.4 ± 8.9 years) were included in the study. The mean duration of the treatment was 7.2 ± 5.4 years, and the mean frequency of injections was of one every 3.3 ± 0.4 months. TFBUT, Schirmer test, and corneal sensitivity were significantly lower in the eye homolateral to hemifacial spasm compared with the contralateral one (5.9 ± 3.2 vs 7.5 ± 4.2 s, P = 0.001; 6.2 ± 3.4 vs 9.2 ± 6.6 mm, P = 0.031; 50.8 ± 3.7 mm vs 52.3 ± 2.9 mm, P = 0.048, respectively). One month after the last injection, TFBUT further decreased from 5.9 ± 3.2 to 2.3 ± 1.2 s (P = 0.028). A significant positive correlation was found between the duration of treatment and tear osmolarity (ρ = 0.542, P = 0.025). Conclusion: Patients with hemifacial spasm under long-lasting treatment with serial botulinum A toxin injections showed a reduction in tear film production and stability, as well as corneal sensitivity in the treated eye compared with the contralateral one. Tear film stability further decreased 1 month after the last injection.


Assuntos
Toxinas Botulínicas Tipo A/administração & dosagem , Córnea/patologia , Síndromes do Olho Seco/etiologia , Previsões , Espasmo Hemifacial/tratamento farmacológico , Lágrimas/metabolismo , Idoso , Preparações de Ação Retardada , Síndromes do Olho Seco/diagnóstico , Síndromes do Olho Seco/metabolismo , Feminino , Seguimentos , Espasmo Hemifacial/complicações , Humanos , Injeções Intramusculares , Masculino , Fármacos Neuromusculares/administração & dosagem , Concentração Osmolar , Estudos Retrospectivos , Resultado do Tratamento
16.
Int J Mol Sci ; 20(16)2019 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-31426571

RESUMO

Primary open-angle glaucoma (POAG) represents the leading cause of irreversible blindness worldwide and is a multifactorial, chronic neurodegenerative disease characterized by retinal ganglion cell and visual field loss. There are many factors that are associated with the risk of developing POAG, with increased intraocular pressure being one of the most prevalent. Due to the asymptomatic nature of the disease, the diagnosis of POAG often occurs too late, which necessitates development of new effective screening strategies for early diagnosis of the disease. However, this task still remains unfulfilled. In order to provide further insights into the pathophysiology of POAG, we applied a targeted metabolomics strategy based on a high-throughput screening method for the determination of tear amino acids, free carnitine, acylcarnitines, succinylacetone, nucleosides, and lysophospholipids in naïve to therapy glaucomatous patients and normal controls. Also, we conducted proteomic analyses of the whole lacrimal fluid and purified extracellular vesicles obtained from POAG patients and healthy subjects. This multi-omics approach allowed us to conclude that POAG patients had lower levels of certain tear amino acids and lysophospholipids compared with controls. These targeted analyses also highlighted the low amount of acetylcarnitine (C2) in POAG patient which correlated well with proteomics data. Moreover, POAG tear proteins seemed to derive from extracellular vesicles, which carried a specific pro-inflammatory protein cargo.


Assuntos
Glaucoma de Ângulo Aberto/metabolismo , Metaboloma , Proteoma/metabolismo , Lágrimas/metabolismo , Idoso , Biomarcadores/metabolismo , Carnitina/metabolismo , Feminino , Glaucoma de Ângulo Aberto/patologia , Heptanoatos/metabolismo , Humanos , Lisofosfolipídeos/metabolismo , Masculino , Pessoa de Meia-Idade
17.
Sensors (Basel) ; 19(15)2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31382386

RESUMO

Tear fluid is a heterogeneous solution containing mainly proteins, lipids, mucins and electrolytes, which regulates the physiology of the human eye. The complex composition of tears can be altered in the presence of eye inflammations. The use of contact lenses is one of the most frequent causes of inflammatory responses of the eye, with the related discomfort often causing the wearer to give up using them. In this paper, we exploit the potentiality of Raman Spectroscopy to analyse the biochemical changes in tear fluid in a contact lens wearer. In particular, we analysed the tear fluid collected from a volunteer as a function of the wearing time for two types of monthly contact lenses (Hydrogel and Si-Hydrogel). Our experimental results show an alteration of the relative concentrations of proteins and lipids in both of the analysed cases. More importantly, our results highlight the diagnostic sensitivity of Raman analysis to select the proper contact lens type for each wearer and optimise the lens wearing conditions.


Assuntos
Análise Espectral Raman , Lágrimas/química , Lentes de Contato , Humanos , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Lipídeos/análise , Análise de Componente Principal , Proteínas/análise , Lágrimas/metabolismo
18.
Invest Ophthalmol Vis Sci ; 60(8): 2935-2941, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31284310

RESUMO

Purpose: To investigate the effects of tear film instability (TFI) induced by sustained tear exposure (STARE) on sensory responses to corneal cold, mechanical, and chemical stimuli. Methods: Fifteen normal subjects were enrolled. TFI was induced during 10 repeated trials of STARE. Pneumatic cold, mechanical, and chemical stimuli were delivered using a computer-controlled Belmonte esthesiometer on three separate visits. The magnitude of the sensory responses to threshold and suprathreshold (1.25 and 1.50 times threshold levels) stimuli were assessed for intensity, coolness or warmness, irritation and pain, using a 0 (none) to 100 (very strong) scale, before and after STARE trials. Symptoms of ocular discomfort were evaluated using the Current Symptom Questionnaire (CSQ). Repeated measures ANOVA was used for data analysis. Results: Following STARE trials, the intensity and coolness ratings to cooling stimuli decreased (P = 0.043 and 0.044 for intensity and coolness, respectively), while rated irritation to mechanical stimuli was increased (P = 0.024). The CSQ scores also increased regardless of visits (all P < 0.001). Intensity ratings, coolness to room temperature stimuli and irritation to mechanical and chemical stimuli increased for all suprathreshold stimuli with increasing stimulus levels (P ≤ 0.005). Conclusions: Repeated TFI induced by STARE affects neurosensory function of the ocular surface. The decrease in reports of cooling and increase in irritation after repeated TFI suggest a complex interaction of neural mechanisms (particularly nonnociceptive cold and nociceptive mechanical) giving rise to ocular surface sensation in humans.


Assuntos
Dióxido de Carbono/farmacologia , Resposta ao Choque Frio/fisiologia , Córnea/efeitos dos fármacos , Estresse Mecânico , Lágrimas/metabolismo , Adulto , Temperatura Baixa , Córnea/metabolismo , Feminino , Voluntários Saudáveis , Humanos , Masculino , Limiar Sensorial , Estimulação Química , Inquéritos e Questionários
19.
Exp Eye Res ; 186: 107724, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31325452

RESUMO

Dry eye disease is a common and multifactorial disease with a high prevalence worldwide. Water loss, reduced expression of glycocalyx mucins, and loss of goblet cells secreting gel-forming mucins are hallmarks of dry eye disease. Mucins are large and complex heavily glycosylated proteins. Their organization in the tear film remains unclear, but they play a key role to protect and maintain integrity of the ocular surface. Mice have been extremely valuable mammalian models with which to study ocular physiology and disease, and to evaluate eye therapies. Genetically modified mice and spontaneously occurring mutants with eye defects have proven to be powerful tools for the pharmaceutical industry, clinicians, and basic researchers investigating dry eye disease. However, ocular mucins remain relatively under-studied and inadequately characterized. This review aims to summarize current knowledge about mucin production at the ocular surface in healthy individuals and in dry eye disease, and to compile an overview of mouse models available for the study of mucins in dry eye disease.


Assuntos
Síndromes do Olho Seco/metabolismo , Mucinas/metabolismo , Animais , Túnica Conjuntiva/metabolismo , Células Epiteliais/metabolismo , Células Caliciformes/metabolismo , Humanos , Camundongos , Lágrimas/metabolismo
20.
Cornea ; 38(10): 1245-1252, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31335532

RESUMO

PURPOSE: To present a new method to directly visualize meibum secretion on the tear film from meibomian gland orifices and show that meibum is continuously secreted between blinking. METHODS: Eighteen patients with dry eye syndrome and 17 healthy subjects were included in the study. We used the Lipiscanner to evaluate the tear film lipid layer. The lipid layer was classified into thick, normal, and thin lipid layer. The lipid layer on the lower tear meniscus of the right eye was observed after a drop of saline solution was applied to the eye. We recorded continuous meibum secretion onto the tear meniscus surface. We calculated the rate of continuous meibum secretion by analyzing videos. Noncontact meibography was performed for meibomian glands in the lower eyelid. The quality of meibum from the 5 orifices at the same area was then scored. RESULTS: The mean continuous meibum secretion rate was 2.7 pL/s in the healthy group and 8.0 pL/s in the dry eye group. The rates were 1.3, 6.7, and 9.4 pL/s in the thin, normal, and thick tear film lipid layer group, respectively. They were 3.4, 3.4, 10.7, and 18.1 pL/s in grade 0, 1, 2, and 3 meibomian gland dropout groups, respectively. The rates were 0.00, 4.7, 10.1, 2.0, and 0.7 pL/s in the normal meibum, yellow without increased viscosity, yellow with increased viscosity, toothpaste, and no meibum groups, respectively. CONCLUSIONS: We showed how to visualize meibum being secreted into the tear film from the meibomian gland orifices, and we were able to observe the continuous secretion of meibum between blinks.


Assuntos
Piscadela/fisiologia , Síndromes do Olho Seco/diagnóstico , Glândulas Tarsais/metabolismo , Microscopia Acústica/métodos , Lágrimas/metabolismo , Síndromes do Olho Seco/metabolismo , Feminino , Humanos , Masculino , Glândulas Tarsais/diagnóstico por imagem , Pessoa de Meia-Idade , Viscosidade
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