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1.
Invest Ophthalmol Vis Sci ; 61(12): 13, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33049061

RESUMO

Purpose: The coronavirus disease 2019 (COVID-19) pandemic severely challenges public health and necessitates the need for increasing our understanding of COVID-19 pathogenesis, especially host factors facilitating virus infection and propagation. The aim of this study was to investigate key factors for cellular susceptibility to severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection in the ocular surface cells. Methods: We combined co-expression and SARS-CoV-2 interactome network to predict key genes at COVID-19 in ocular infection based on the premise that genes underlying a disease are often functionally related and functionally related genes are often co-expressed. Results: The co-expression network was constructed by mapping the well-known angiotensin converting enzyme (ACE2), TMPRSS2, and host susceptibility genes implicated in COVID-19 genomewide association study (GWAS) onto a cornea, retinal pigment epithelium, and lung. We found a significant co-expression module of these genes in the cornea, revealing that cornea is potential extra-respiratory entry portal of SARS-CoV-2. Strikingly, both co-expression and interaction networks show a significant enrichment in mitochondrial function, which are the hub of cellular oxidative homeostasis, inflammation, and innate immune response. We identified a corneal mitochondrial susceptibility module (CMSM) of 14 mitochondrial genes by integrating ACE2 co-expression cluster and SARS-CoV-2 interactome. The gene ECSIT, as a cytosolic adaptor protein involved in inflammatory responses, exhibits the strongest correlation with ACE2 in CMSM, which has shown to be an important risk factor for SARS-CoV-2 infection and prognosis. Conclusions: Our co-expression and protein interaction network analysis uncover that the mitochondrial function related genes in cornea contribute to the dissection of COVID-19 susceptibility and potential therapeutic interventions.


Assuntos
Betacoronavirus , Córnea/metabolismo , Infecções por Coronavirus/genética , Regulação da Expressão Gênica , Genes Mitocondriais/genética , Peptidil Dipeptidase A/genética , Pneumonia Viral/genética , RNA/genética , Linhagem Celular , Córnea/patologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/metabolismo , Humanos , Pandemias , Peptidil Dipeptidase A/biossíntese , Pneumonia Viral/epidemiologia , Pneumonia Viral/metabolismo
3.
Medicine (Baltimore) ; 99(44): e22941, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33126361

RESUMO

INTRODUCTION: Ocular benign fibrous histiocytoma can involve corneoscleral limbus and adjacent cornea and usually has a good prognosis after surgical removal. Despite the low recurrence rate, we reported a rare case of ocular benign fibrous histiocytoma with twice recurrences after excision. PATIENT CONCERNS: A 12-year-old Chinese girl presented with two painless progressively enlarging masses in the right eye for 6 years. She once had the lesions excised 1 year ago. However, the primary lesions relapsed again. DIAGNOSIS: Histopathologic and immunohistochemical examinations of the excised samples supported the diagnosis of benign fibrous histiocytomas of the corneoscleral limbus. INTERVENTIONS: The patient underwent mass resection with limbal stem cell transplantation and amniotic membrane transplantation at first. As for the tumors' second recurrence, we performed extended excision combined with lamellar keratoplasty and amniotic membrane implantation. OUTCOMES: The corneal graft remained clear with no sign of tumor recurrence 3 years after the second surgery. CONCLUSION: Complete surgical resection with tumor-free margins is critical to reduce the recurrence of benign fibrous histiocytoma and appropriate ocular surface reconstruction is necessary to remedy tissue defect and maintain epithelial integrity.


Assuntos
Neoplasias Oculares/cirurgia , Histiocitoma Fibroso Benigno/cirurgia , Recidiva Local de Neoplasia/cirurgia , Criança , Neoplasias da Túnica Conjuntiva/diagnóstico por imagem , Neoplasias da Túnica Conjuntiva/patologia , Neoplasias da Túnica Conjuntiva/cirurgia , Córnea/diagnóstico por imagem , Córnea/patologia , Neoplasias Oculares/diagnóstico por imagem , Neoplasias Oculares/patologia , Feminino , Histiocitoma Fibroso Benigno/diagnóstico por imagem , Histiocitoma Fibroso Benigno/patologia , Humanos , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Tomografia de Coerência Óptica
4.
Life Sci ; 261: 118456, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32956661

RESUMO

AIMS: Corneal nerve fibers are derived from the ophthalmic division of the trigeminal ganglion (TG). Here, by sequencing of microRNAs (miRNAs) and messenger RNAs (mRNAs) from diabetic and normal TG tissues, we aimed to uncover potential miRNAs, mRNAs, and the network of their interactions involved in the pathogenesis of diabetic corneal neuropathy. MAIN METHODS: We performed RNA sequencing to systematically screen out differentially expressed miRNAs and mRNAs in TG tissues from diabetic and normal mice. Functional enrichment analyses were performed to illustrate the biological functions of differentially expressed mRNAs (DEmRNAs). Following this, miRNA-mRNA regulatory networks were built by means of bioinformatics methods to suggest regulatory role for miRNAs in the pathogenesis of diabetic corneal neuropathy. Finally, the credibility of the sequencing-based results was validated using qRT-PCR. KEY FINDINGS: Sequencing analyses disclosed that 68 miRNAs and 114 mRNAs were differentially expressed in diabetic TG tissues compared with normal TG samples. The functional analyses showed that DEmRNAs participated in diabetes-related biological processes. After applying an optimized approach to predict miRNA-mRNA pairs, a miRNA-mRNA interacting network was inferred. Subsequently, the expression and correlation of miR-350-5p and Mup20, miR-592-5p and Angptl7 as well as miR-351-5p and Elovl6 were preliminarily validated. SIGNIFICANCE: Our study provides a systematic characterization of miRNA and mRNA expression in the TG during diabetic corneal neuropathy and will contribute to the development of clinical diagnostic and therapeutic strategies for diabetic corneal neuropathy.


Assuntos
Doenças da Córnea/genética , Neuropatias Diabéticas/genética , Redes Reguladoras de Genes , MicroRNAs/genética , RNA Mensageiro/genética , Animais , Córnea/inervação , Córnea/patologia , Doenças da Córnea/patologia , Neuropatias Diabéticas/patologia , Hiperglicemia/genética , Hiperglicemia/patologia , Masculino , Camundongos Endogâmicos C57BL
5.
PLoS One ; 15(9): e0238859, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32956371

RESUMO

OBJECTIVES: The aim of this study was to utilise corneal confocal microscopy to quantify corneal nerve morphology and establish the presence of sub-clinical small fibre damage and peripheral neuropathy in children with celiac disease. METHODS: This is a cross-sectional cohort study of twenty children with celiac disease and 20 healthy controls who underwent clinical and laboratory assessments and corneal confocal microscopy. Corneal nerve fiber density (no.mm2), corneal nerve branch density (no.mm2), corneal nerve fiber length (mm.mm2), corneal nerve fiber tortuosity and inferior whorl length (mm.mm2) were quantified manually. RESULTS: Corneal nerve fiber density (34.7±8.6 vs. 32.9±8.6; P = 0.5), corneal nerve branch density (47.2±24.5 vs. 47.3±20.0; P = 0.1) and corneal nerve fiber length (20.0±5.1 vs. 19.5±4.5; P = 0.8) did not differ between children with celiac disease and healthy controls. Corneal nerve fiber tortuosity (11.4±1.9 vs 13.5±3.0; P = 0.01) was significantly lower and inferior whorl length (20.0±5.5 vs 23.0±3.8; P = 0.06) showed a non-significant reduction in children with celiac disease compared to healthy controls. Inferior whorl length correlated significantly with corneal nerve fiber density (P = 0.005), corneal nerve branch density (P = 0.04), and corneal nerve fiber length (P = 0.002). CONCLUSION: Corneal confocal microscopy demonstrates minimal evidence of neuropathy in children with celiac disease.


Assuntos
Doença Celíaca/complicações , Córnea/patologia , Oftalmopatias/diagnóstico , Fibras Nervosas/patologia , Estudos de Casos e Controles , Criança , Estudos de Coortes , Córnea/inervação , Estudos Transversais , Oftalmopatias/diagnóstico por imagem , Oftalmopatias/etiologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Microscopia Confocal , Prognóstico
6.
Medicine (Baltimore) ; 99(31): e21467, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756168

RESUMO

BACKGROUND: This study aimed to evaluate the scleral thickness and corneal parameters of patients with systemic lupus erythematosus (SLE). METHODS: Forty-seven eyes of 47 SLE patients and 44 eyes of healthy controls were included in this cross-sectional study. Anterior segment optical coherence tomography (AS-OCT) was used to measure the corneal and scleral thickness. Scleral thickness (ST) was measured based upon the segmentation at 1000 to 5000 µm from the scleral spur. Pentacam HR was used to measure corneal parameters. RESULTS: There was no statistically significant difference between SLE group and control group according to age and sex (P > .05). The ST measurements at all distances from scleral spur were found to be thicker in patients with SLE (P < .05). Central corneal thickness (CCT), cornea volume (CV), corneal densitometry (CD), and peripheral corneal thickness (PCT) measurements were similar between the groups (P > .05). CONCLUSION: ST was thicker in SLE patients compared with healthy controls. AS-OCT seems helpful in selecting optimal sites for pharmaceutical or surgical intervention in SLE patients, since it shows thickness variations in anterior sclera.


Assuntos
Córnea/diagnóstico por imagem , Lúpus Eritematoso Sistêmico/complicações , Esclera/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Adulto , Estudos de Casos e Controles , Córnea/patologia , Paquimetria Corneana/métodos , Estudos Transversais , Densitometria , Feminino , Voluntários Saudáveis , Humanos , Lúpus Eritematoso Sistêmico/patologia , Masculino , Pessoa de Meia-Idade , Esclera/patologia , Turquia/epidemiologia
7.
J Fr Ophtalmol ; 43(8): 697-703, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32792292

RESUMO

OBJECTIVE: To compare corneal densitometry and topography variables in patients with primary congenital glaucoma (PCG) and healthy subjects. MATERIAL AND METHODS: Cross sectional study, consecutive recruitment with gender- and age-matched control group. Forty eyes of 40 patients in each group were studied with Pentacam corneal topography. The variables compared between the two groups were: intraocular pressure (IOP), visual acuity (VA) and Pentacam (Oculus, Wetzlar, Germany) corneal topography measurements: mean and maximum keratometry (Km, Kmax), cylinder (Cyl), anterior elevation apex (AEA), central anterior elevation (CAE), maximum anterior elevation (MAE), posterior elevation apex (PEA), central posterior elevation (CPE), maximum posterior elevation (MPE), pachymetry and anterior, mid-stromal and posterior corneal densitometry in the 0-2mm, 2-6mm, 6-10mm zones. RESULTS: Significant differences between patients and healthy controls were detected in the topographic variables MAE (P=0.002) and MPE (P<0.001), and in all the densitometry variables (anterior, mid-stromal, posterior for the 0-2mm, 2-6mm and 6-10mm zones) (P<0.001 each). In the PCG group, negative correlation was observed between VA and total densitometry (r=-0.49; P=0.004). CONCLUSION: Patients with PCG and healthy subjects display differences in corneal densitometry and topographic measurements. PCG patients show greater corneal density with an inverse relationship between visual acuity and higher elevation (anterior and posterior values).


Assuntos
Córnea/diagnóstico por imagem , Glaucoma/congênito , Glaucoma/diagnóstico , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Córnea/patologia , Topografia da Córnea , Estudos Transversais , Densitometria , Feminino , Glaucoma/patologia , Humanos , Lactente , Recém-Nascido , Masculino , Tamanho do Órgão , Prognóstico , Adulto Jovem
8.
PLoS One ; 15(7): e0235408, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32649686

RESUMO

The tear matrix metalloproteinase-9 (MMP-9) immunoassay (Inflammadry) exhibits variable results in dry eye (DE) patients. We investigated if the tear volume in DE patients affects the results of MMP-9 immunoassay in clinical and in vitro settings. This cross-sectional study enrolled 188 eyes of 188 DE patients. The clinical symptoms and signs of DE were assessed using the Ocular Surface Disease Index and visual analog scale, strip meniscometry, tear break-up time, and tear meniscus height (TMH), area (TMA), and depth (TMD) using swept-source optical coherence tomography and corneal and conjunctival staining scores. For quantitative evaluation, the bands produced by the InflammaDry test were analyzed with ImageJ. DE subjects were grouped according to MMP-9 positivity and TMH. The InflammaDry-positive group showed greater TMH, TMA, and TMD than the MMP-9-negative group (p < 0.05). InflammaDry test band density in the high TMH group was significantly greater than that in the low and normal TMH groups (p < 0.05). InflammaDry test band density correlated positively with TMH, TMA, and TMD (all p < 0.05). InflammaDry test results were influenced by tear volume. Low tear volume in aqueous tear-deficient DE may induce false-negative results, and reflex tearing during the test may induce false-positive results.


Assuntos
Síndromes do Olho Seco/diagnóstico , Imunoensaio/métodos , Metaloproteinase 9 da Matriz/metabolismo , Síndrome de Sjogren/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Córnea/metabolismo , Córnea/patologia , Síndromes do Olho Seco/genética , Síndromes do Olho Seco/patologia , Olho/metabolismo , Olho/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome de Sjogren/genética , Síndrome de Sjogren/patologia , Lágrimas/metabolismo , Tomografia de Coerência Óptica/métodos , Adulto Jovem
9.
Am J Pathol ; 190(10): 2056-2066, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32693061

RESUMO

Glaucoma is a frequent and devastating long-term complication following ocular trauma, including corneal surgery, open globe injury, chemical burn, and infection. Postevent inflammation and neuroglial remodeling play a key role in subsequent ganglion cell apoptosis and glaucoma. To this end, this study was designed to investigate the amplifying role of monocyte infiltration into the retina. By using three different ocular injury mouse models (corneal suture, penetrating keratoplasty, and globe injury) and monocyte fate mapping techniques, we show that ocular trauma or surgery can cause robust infiltration of bone marrow-derived monocytes into the retina and subsequent neuroinflammation by up-regulation of Tnf, Il1b, and Il6 mRNA within 24 hours. This is accompanied by ganglion cell apoptosis and neurodegeneration. Prompt inhibition of tumor necrosis factor-α or IL-1ß markedly suppresses monocyte infiltration and ganglion cell loss. Thus, acute ocular injury (surgical or trauma) can lead to rapid neuroretinal inflammation and subsequent ganglion cell loss, the hallmark of glaucoma. Infiltrating monocytes play a central role in this process, likely amplifying the inflammatory cascade, aiding in the activation of retinal microglia. Prompt administration of cytokine inhibitors after ocular injury prevents this infiltration and ameliorates the damage to the retina-suggesting that it may be used prophylactically for neuroprotection against post-traumatic glaucoma.


Assuntos
Citocinas/antagonistas & inibidores , Glaucoma/metabolismo , Monócitos/patologia , Neuroglia/patologia , Retina/cirurgia , Animais , Queimaduras Químicas/metabolismo , Queimaduras Químicas/patologia , Córnea/metabolismo , Córnea/patologia , Modelos Animais de Doenças , Glaucoma/patologia , Camundongos Transgênicos , Monócitos/metabolismo , Retina/metabolismo
10.
PLoS One ; 15(7): e0236183, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32697805

RESUMO

BACKGROUND: Herpetic keratitis (HK) models using whole human corneas are essential for studying virus-host relationships, because of high species specificity and the role of interactions between corneal cell populations that cell culture cannot reproduce. Nevertheless, the two current corneal storage methods (hypothermia and organ culture (OC)) do not preserve corneas in good physiological condition, as they are characterized by epithelial abrasion, stromal oedema, and excessive endothelial mortality. METHODS: To rehabilitate human corneas intended for scientific use, we used an active storage machine (ASM) that restores two physiological parameters that are essential for corneal homeostasis: intraocular pressure and storage medium renewal (21mmHg and 2.6 µL/min, respectively). ASM storage regenerates a normal multilayer epithelium in 2 weeks. We infected six pairs of corneas unsuitable for graft by inoculating the epithelium with herpes simplex virus type 1 (HSV-1), and compared each ASM-stored cornea with the other cornea stored in the same medium using the conventional OC method. RESULTS: Only corneas in the ASM developed a dendritic (n = 3) or geographic (n = 2) epithelial ulcer reproducing typical HSV-1-induced clinical lesions. Corneas in OC showed only extensive desquamations. None of the uninfected controls showed epithelial damage. Histology, immunohistochemistry, transmission electron microscopy and polymerase chain reaction on corneal tissue confirmed infection in all cases (excluding negative controls). CONCLUSIONS: The ASM provides an innovative ex vivo model of HK in whole human cornea that reproduces typical epithelial lesions.


Assuntos
Córnea/patologia , Herpesvirus Humano 1/patogenicidade , Ceratite Herpética/patologia , Técnicas de Cultura de Órgãos/instrumentação , Preservação de Órgãos/instrumentação , Idoso , Idoso de 80 Anos ou mais , Córnea/diagnóstico por imagem , Córnea/ultraestrutura , Córnea/virologia , Interações entre Hospedeiro e Microrganismos , Humanos , Ceratite Herpética/diagnóstico , Ceratite Herpética/tratamento farmacológico , Ceratite Herpética/virologia , Microscopia Eletrônica de Transmissão , Pessoa de Meia-Idade , Técnicas de Cultura de Órgãos/métodos , Preservação de Órgãos/métodos , Microscopia com Lâmpada de Fenda
11.
J Fr Ophtalmol ; 43(8): 794-798, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32616318

RESUMO

Diabetes mellitus may affect the cornea at various levels. Ocular surface changes and dry eye had been studied. Researchers are concerned that medical treatment of diabetes or retinal complications may result in endothelial damage and cell loss. This report summarizes the possibility of endothelial cell loss in diabetic patients. A decrease in endothelial cell density (ECD) in diabetic patients has been reported. In addition, corneal thickness may increase in diabetic patients. Significant endothelial cell loss has been demonstrated in long-term disease and in cases of poor metabolic control. No association between the use of oral hypoglycemics and ECD has been reported. There is also no evidence of an association between the use of insulin and corneal endothelial damage. No difference in ECD among the various degrees of retinopathy or with a history of photocoagulation has been shown. Regarding the studies comparing diabetic and non-diabetic patients undergoing cataract surgery, in all cases, the decrease in ECD is higher in diabetic patients than that seen in non-diabetic patients. However, there is no evidence of increased endothelial damage in diabetics compared to non-diabetics during vitreo-retinal surgery in phakic eyes. No significant changes in corneal endothelium after intravitreal anti-VEGF injections have been referenced.


Assuntos
Diabetes Mellitus/patologia , Retinopatia Diabética/patologia , Retinopatia Diabética/terapia , Células Endoteliais/patologia , Epitélio Posterior/patologia , Procedimentos Cirúrgicos Oftalmológicos , Contagem de Células , Córnea/citologia , Córnea/patologia , Córnea/cirurgia , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/cirurgia , Células Endoteliais/citologia , Epitélio Posterior/citologia , Epitélio Posterior/cirurgia , Humanos , Hipoglicemiantes/uso terapêutico , Procedimentos Cirúrgicos Oftalmológicos/efeitos adversos
12.
J Fr Ophtalmol ; 43(8): 753-760, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32620412

RESUMO

PURPOSE: The objective of this study is to evaluate the preoperative and short- and long-term postoperative results in terms of visual acuity, refractive error, and corneal wavefront aberrations in patients with myopia and myopic astigmatism undergoing small incision lenticule extraction (SMILE). METHODS: Seventy-nine eyes of 52 myopes with or without astigmatism (41 right and 38 left) were enrolled in this retrospective study. The measurements included uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), spherical equivalent (SE) and wavefront aberrations. All the measurements before and after SMILE surgery were systematically recorded. RESULTS: Mean preoperative UDVA was 1.19±0.24 logMAR and improved to 0.06±0.17 logMAR at the 3-year postoperative follow-up. At the conclusion of the 3-year follow-up, UDVA was better than or equal to 20/20 and 20/25 in 73% and 84% of eyes, respectively. At 1 month postoperatively, CDVA was 0.05±0.23 logMAR and significantly lower than the preoperative CDVA, 0.02±0.04 log MAR (P>0.05). However, at 1 year and 3 years after surgery, CDVA showed a significant increase compared to preoperative CDVA. At the conclusion of the 3-year follow-up, SE was -0.47 D, and 69.6% and 83.5% of the eyes were within±0.50 D and±1.00 D, respectively, of the intended correction. HOA's, coma, and spherical aberration increased significantly. No significant change in trefoil was detected. CONCLUSION: This study showed that SMILE produces a stable, safe outcome for surgical treatment of myopia and myopic astigmatism.


Assuntos
Astigmatismo/cirurgia , Cirurgia da Córnea a Laser/efeitos adversos , Microcirurgia/efeitos adversos , Miopia/cirurgia , Adulto , Astigmatismo/complicações , Astigmatismo/epidemiologia , Astigmatismo/patologia , Córnea/patologia , Córnea/cirurgia , Cirurgia da Córnea a Laser/métodos , Topografia da Córnea , Aberrações de Frente de Onda da Córnea/epidemiologia , Aberrações de Frente de Onda da Córnea/etiologia , Feminino , Humanos , Lasers de Excimer/efeitos adversos , Masculino , Microcirurgia/métodos , Microcirurgia/estatística & dados numéricos , Pessoa de Meia-Idade , Miopia/complicações , Miopia/epidemiologia , Miopia/patologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Período Pós-Operatório , Refração Ocular/fisiologia , Erros de Refração/epidemiologia , Erros de Refração/etiologia , Estudos Retrospectivos , Ferida Cirúrgica/patologia , Centros de Atenção Terciária/estatística & dados numéricos , Fatores de Tempo , Resultado do Tratamento , Acuidade Visual/fisiologia , Adulto Jovem
13.
J Fr Ophtalmol ; 43(8): 731-741, 2020 Oct.
Artigo em Francês | MEDLINE | ID: mdl-32622634

RESUMO

The clinical evaluation of infectious keratitis takes place largely through biomicroscopic examination, which presents limitations in the evaluation of the depth of the infiltrate and the exact thickness of the cornea, whether edematous or thinned. In this study, we aim to quantify the human corneal inflammatory response in treated infectious keratitis by anterior segment optical coherence tomography (AS-OCT). Patients with infectious keratitis were recruited prospectively in the ophthalmology department of the military hospital of Rabat between November 2017 and May 2019. Over the study period, 32 patients were included. A standardized scanning protocol was used. The thickness of the infiltrate, when present, and corneal thickness in any area of thinning and any surrounding edematous areas were measured. The various thicknesses gradually decreased over the course of follow-up, providing objective evidence of therapeutic efficacy in the early stages. Improvement in corneal edema and thinning was faster in the early stage. AS-OCT scanning can be used along with slit lamp examination to quantify and objectively follow infectious keratitis.


Assuntos
Segmento Anterior do Olho/diagnóstico por imagem , Infecções Oculares/diagnóstico , Ceratite/diagnóstico , Tomografia de Coerência Óptica/métodos , Adolescente , Adulto , Idoso , Segmento Anterior do Olho/microbiologia , Segmento Anterior do Olho/patologia , Segmento Anterior do Olho/virologia , Córnea/diagnóstico por imagem , Córnea/microbiologia , Córnea/patologia , Córnea/virologia , Efeitos Psicossociais da Doença , Progressão da Doença , Infecções Oculares/epidemiologia , Infecções Oculares/etiologia , Infecções Oculares/patologia , Feminino , Humanos , Ceratite/epidemiologia , Ceratite/etiologia , Ceratite/patologia , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Estudos Prospectivos , Fatores de Risco , Microscopia com Lâmpada de Fenda , Adulto Jovem
14.
Ann Afr Med ; 19(2): 119-123, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32499468

RESUMO

Purpose: The cornea is the most significant refractive medium in the eye. Pathologies affecting the cornea usually have a great impact on vision. The etiology of corneal disorder varies from one geographical location to another. The objective of this study was to determine the pattern of corneal disorders at Ekiti State University Teaching Hospital, Ado-Ekiti. Materials and Methods: A retrospective study of case records of patients with cornea disorders over a 5-year period was carried out. Demographic characteristics, presenting visual acuity, and risk factor for cornea disorders were retrieved. Data were entered into the Statistical Package for the Social Sciences version 20, and statistical significance was inferred at P < 0.05. Results: Corneal disorders accounted for 3.3% of the eye disorders seen during the period of study. The median age was 37 years. Males outnumbered females giving a ratio of 1.9:1 and the age range from 0.25 to 92 years. There were more females than males in the 11-20 years' age group. Students (84, 25.4%) and artisans (62, 18.8%) were the two leading occupational groups. Infectious cases constituted 27.2% of the cases. Visual acuity at presentation was <3/60 in 131 (39.7%) cases. Foreign body entry was the leading etiologic agent in 101 (30.6%) cases. Conclusion: Half of the patients were blind at presentation, and many of them presented after more than 1 week of the onset of symptoms. Corneal foreign body, trauma, and vernal keratoconjunctivitis were the leading known predisposing factors. There will be need to emphasize more on the role of protective eye devices among our people, especially those who engage in outdoor activities.


Assuntos
Córnea/patologia , Doenças da Córnea/epidemiologia , Acuidade Visual/fisiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Distribuição por Sexo , Adulto Jovem
15.
J Vis Exp ; (159)2020 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-32478743

RESUMO

When developing novel antimicrobials, the success of animal trials is dependent on accurate extrapolation of antimicrobial efficacy from in vitro tests to animal infections in vivo. The existing in vitro tests typically overestimate antimicrobial efficacy as the presence of host tissue as a diffusion barrier is not accounted for. To overcome this bottleneck, we have developed an ex vivo porcine corneal model of bacterial keratitis using Pseudomonas aeruginosa as a prototypic organism. This article describes the preparation of the porcine cornea and protocol for establishment of the infection. Bespoke glass molds enable straightforward setup of the cornea for infection studies. The model mimics in vivo infection as bacterial proliferation is dependent on the ability of the bacterium to damage corneal tissue. Establishment of infection is verified as an increase in the number of colony forming units assessed via viable plate counts. The results demonstrate that infection can be established in a highly reproducible fashion in the ex vivo corneas using the method described here. The model can be extended in the future to mimic keratitis caused by microorganisms other than P. aeruginosa. The ultimate aim of the model is to investigate the effect of antimicrobial chemotherapy on the progress of bacterial infection in a scenario more representative of in vivo infections. In so doing, the model described here will reduce the use of animals for testing, improve success rates in clinical trials and ultimately enable rapid translation of novel antimicrobials to the clinic.


Assuntos
Córnea/microbiologia , Córnea/patologia , Infecções Oculares Bacterianas/tratamento farmacológico , Ceratite/tratamento farmacológico , Ceratite/microbiologia , Infecções por Pseudomonas/tratamento farmacológico , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Córnea/efeitos dos fármacos , Modelos Animais de Doenças , Infecções Oculares Bacterianas/microbiologia , Infecções Oculares Bacterianas/terapia , Ceratite/terapia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Esterilização , Suínos
16.
Nucleic Acids Res ; 48(12): 6740-6758, 2020 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-32463444

RESUMO

How genetic defects trigger the molecular changes that cause late-onset disease is important for understanding disease progression and therapeutic development. Fuchs' endothelial corneal dystrophy (FECD) is an RNA-mediated disease caused by a trinucleotide CTG expansion in an intron within the TCF4 gene. The mutant intronic CUG RNA is present at one-two copies per cell, posing a challenge to understand how a rare RNA can cause disease. Late-onset FECD is a uniquely advantageous model for studying how RNA triggers disease because: (i) Affected tissue is routinely removed during surgery; (ii) The expanded CTG mutation is one of the most prevalent disease-causing mutations, making it possible to obtain pre-symptomatic tissue from eye bank donors to probe how gene expression changes precede disease; and (iii) The affected tissue is a homogeneous single cell monolayer, facilitating accurate transcriptome analysis. Here, we use RNA sequencing (RNAseq) to compare tissue from individuals who are pre-symptomatic (Pre_S) to tissue from patients with late stage FECD (FECD_REP). The abundance of mutant repeat intronic RNA in Pre_S and FECD_REP tissue is elevated due to increased half-life in a corneal cells. In Pre_S tissue, changes in splicing and extracellular matrix gene expression foreshadow the changes observed in advanced disease and predict the activation of the fibrosis pathway and immune system seen in late-stage patients. The absolute magnitude of splicing changes is similar in pre-symptomatic and late stage tissue. Our data identify gene candidates for early drivers of disease and biomarkers that may represent diagnostic and therapeutic targets for FECD. We conclude that changes in alternative splicing and gene expression are observable decades prior to the diagnosis of late-onset trinucleotide repeat disease.


Assuntos
Distrofia Endotelial de Fuchs/genética , Fator de Transcrição 4/genética , Expansão das Repetições de Trinucleotídeos/genética , Repetições de Trinucleotídeos/genética , Adulto , Idoso , Biomarcadores/metabolismo , Córnea/metabolismo , Córnea/patologia , Feminino , Distrofia Endotelial de Fuchs/patologia , Distrofia Endotelial de Fuchs/terapia , Regulação da Expressão Gênica/genética , Predisposição Genética para Doença , Humanos , Íntrons/genética , Masculino , Pessoa de Meia-Idade , Mutação/genética , Especificidade de Órgãos/genética , Análise de Sequência de RNA
17.
J Fr Ophtalmol ; 43(6): 477-483, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32444133

RESUMO

BACKGROUND AND PURPOSE: The purpose of this study is to compare two alternative methods of collecting and transporting media for the diagnosis of corneal ulcers, as not all clinical settings have conventional culture materials and transport media available. METHODS: In this open-label, prospective, comparative, and randomized study, patients with clinical suspicion of infectious keratitis with high risk of loss of vision had corneal specimens collected using two methods and transport media: Eswab scraping with Amies transport medium and 23-gauge needle scraping in BACTEC Peds broth. The order of each collection method was randomized. The samples were processed by standard methods, comparing the positivity frequencies for both by parametric and nonparametric tests, according to normality criteria. RESULTS: Corneal infiltrates from 40 eyes of 40 patients were analyzed. Culture positivity rate was 50% for Eswab and 35% for 23-gauge needle (P=0.258). The overall growth rate of the two methods combined was not higher than with the swab alone. The results obtained with a swab were not influenced by the collection sequence (P=0.112); however, the positivity rate was significantly higher when the sample taken with the needle was performed first (P=0.046). CONCLUSIONS: The single sample Eswab method of collection and transportation for the diagnosis of high risk corneal ulcers is a valid alternative and can be used in cases in which, for various reasons, there is no access to the full set of traditional culture materials.


Assuntos
Córnea , Úlcera da Córnea/patologia , Infecções Oculares Bacterianas/patologia , Ceratite/patologia , Manejo de Espécimes/métodos , Coleta de Tecidos e Órgãos/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Córnea/patologia , Úlcera da Córnea/diagnóstico , Úlcera da Córnea/microbiologia , Meios de Cultura/química , Meios de Cultura/farmacologia , Infecções Oculares Bacterianas/diagnóstico , Infecções Oculares Bacterianas/microbiologia , Feminino , Humanos , Ceratite/diagnóstico , Ceratite/microbiologia , Masculino , Pessoa de Meia-Idade , Técnicas de Cultura de Tecidos/métodos , Transportes , Adulto Jovem
18.
Am J Ophthalmol ; 217: 212-223, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32353368

RESUMO

PURPOSE: To report the outcomes of initial high-dose and extended taper of antiviral and steroid prophylaxis for the treatment of eyes with high-risk vascularized herpetic corneal scars that underwent 2-piece mushroom keratoplasty (MK). DESIGN: Prospective interventional case series. METHODS: In this single-center study, 52 consecutive eyes with vascularized (≥2 quadrants) herpetic corneal scars underwent 2-piece microkeratome-assisted MK. Initial high-dose and extended taper of combined oral and topical antiviral and steroid prophylaxis was administered. Outcome measures were best spectacle-corrected visual acuity (BSCVA), refractive astigmatism (RA), endothelial cell density, immunologic rejection, herpetic recurrence, and graft failure rates. RESULTS: Excluding patients with vision-impairing comorbidities, baseline BSCVA (1.73 ± 0.67 logMAR) significantly improved annually during the first 2 years (P < .001, P = .016), reaching 0.17 ± 0.18 logMAR at year 2, and remaining stable up to 10 years (P = .662). At 2 years, 86% of eyes saw ≥20/40, 55% saw ≥20/25, and 18% saw ≥20/20 Snellen BSCVA. RA exceeded 4.5 diopters in 7% of cases after wound revision for high-degree astigmatism in 7 cases. Endothelial cell loss was 40.9% at 1 year with an annual decline of 3.1% over 10 years. The 10-year cumulative risk for immunologic rejection, herpetic recurrence, and graft failure was 9.7%, 7.8%, and 7.6%, respectively. CONCLUSIONS: Initial high dose and extended taper of antiviral and steroid prophylaxis for MK in high-risk, vascularized herpetic corneal scars achieves clinical outcomes that remain stable for up to 10 years after surgery with minimal risk of immunologic rejection, herpetic recurrence and graft failure.


Assuntos
Cicatriz/prevenção & controle , Córnea/patologia , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/métodos , Infecções Oculares Virais/cirurgia , Glucocorticoides/administração & dosagem , Ceratite Herpética/complicações , Complicações Pós-Operatórias/prevenção & controle , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Cicatriz/diagnóstico , Cicatriz/etiologia , Córnea/cirurgia , Relação Dose-Resposta a Droga , Infecções Oculares Virais/complicações , Infecções Oculares Virais/diagnóstico , Feminino , Sobrevivência de Enxerto , Humanos , Ceratite Herpética/diagnóstico , Ceratite Herpética/cirurgia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Refração Ocular , Microscopia com Lâmpada de Fenda , Acuidade Visual , Adulto Jovem
19.
Am J Ophthalmol ; 217: 278-286, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32387431

RESUMO

PURPOSE: To evaluate the renewal of corneal nerve structure and function in patients with neurotrophic keratopathy (NK) treated with recombinant human nerve growth factor (rhNGF) eye drops. DESIGN: Prospective, interventional, before-and-after case series. METHODS: This study included 18 patients with NK with a persistent epithelial defect or corneal ulcer, treated with topical rhNGF, and age-matched healthy controls. Patients underwent clinical examination with corneal fluorescein staining, Schirmer 1 tear test, assessment of corneal sensitivity with the Cochet-Bonnet esthesiometer, and morphologic examination of the nerves by in vivo confocal microscopy (IVCM) at baseline and at 4 and 8 weeks of treatment. IVCM analysis was used to assess corneal sub-basal nerve density, number of nerve branches, and the diameter of nerve fibers. RESULTS: A complete resolution of the epithelial defect was observed in all patients within 8 weeks. Schirmer 1 test showed a significant improvement of tear film secretion. Change from baseline in corneal sensation was significant (P < .001) but did not approach that of healthy controls. After 8 weeks of treatment, there was a significant increase in the mean nerve density in affected eyes as compared to baseline (P = .007) as well as in the number of nerve branches (P = .008) and nerve fiber diameter (P = .007). CONCLUSIONS: Topical treatment with rhNGF was effective in promoting complete corneal healing of persistent epithelial defects and corneal ulcers in patients with NK. This was associated with an improvement of corneal sensitivity and an increase of sub-basal nerve density, diameter, and number of nerve branches, indicating improvement in structure and function of corneal nerves.


Assuntos
Córnea/inervação , Úlcera da Córnea/diagnóstico , Epitélio Anterior/patologia , Fibras Nervosas/patologia , Fator de Crescimento Neural/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Córnea/patologia , Córnea/fisiopatologia , Úlcera da Córnea/tratamento farmacológico , Úlcera da Córnea/fisiopatologia , Feminino , Humanos , Masculino , Microscopia Confocal , Pessoa de Meia-Idade , Estudos Prospectivos , Proteínas Recombinantes , Sensação/fisiologia
20.
Am J Ophthalmol ; 217: 297-304, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32437668

RESUMO

PURPOSE: To compare outcomes of management in the early stage of severe chemical injury (grade 4 and worse; Dua classification) with amniotic membrane grafting (AMG) alone vs allogenic simple limbal epithelial transplantation (alloSLET). DESIGN: Retrospective comparative interventional case series. METHODS: Retrospective comparative interventional series. Records of patients with severe ocular chemical injury who underwent AMG alone (between 2009 and 2013) vs alloSLET (between 2013 and 2017) were analyzed for grade of injury, time of and interventions for epithelial healing, ocular surface status post healing (grade of symblepharon, and limbal stem cell deficiency [LSCD]), and type of and need for interventions in the chronic stage. RESULTS: Among patients presenting in early stage of severe chemical injury, 38 eyes (median age 11 years) managed with AMG alone were compared with 39 eyes (median age 8 years) managed with alloSLET. The mean time of presentation post injury was 33.85 ± 27.5 and 40.6 ± 23.5 days in the AMG and alloSLET group, respectively. The rate of epithelial healing was faster in the alloSLET group and the difference was noted to be statistically significant (odds ratio [OR] 0.966, P = .001). Similarly, the lower occurrence of LSCD (OR 0.137, P = .004) and need for keratoplasty (OR 0.093, P = .003) favored alloSLET over AMG. Final best-corrected visual acuity of >20/200 was achieved in 39.4% and 53.8% in the AMG and alloSLET groups, respectively. CONCLUSION: AlloSLET helps in faster epithelialization of the surface, thus reducing the need for subsequent surgeries in the chronic stage and aiding faster visual rehabilitation. The outcomes of alloSLET appear superior to amniotic membrane grafting alone and should be considered in eyes with grade 4 and above (Dua classification) chemical injuries in the early stage.


Assuntos
Âmnio/transplante , Queimaduras Químicas/cirurgia , Córnea/patologia , Transplante de Córnea/métodos , Epitélio Anterior/transplante , Queimaduras Oculares/cirurgia , Limbo da Córnea/citologia , Adolescente , Adulto , Idoso , Queimaduras Químicas/diagnóstico , Criança , Pré-Escolar , Córnea/cirurgia , Queimaduras Oculares/diagnóstico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Transplante Homólogo , Índices de Gravidade do Trauma , Resultado do Tratamento , Adulto Jovem
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