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2.
Nature ; 535(7611): 294-8, 2016 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-27411634

RESUMO

Vascular and haematopoietic cells organize into specialized tissues during early embryogenesis to supply essential nutrients to all organs and thus play critical roles in development and disease. At the top of the haemato-vascular specification cascade lies cloche, a gene that when mutated in zebrafish leads to the striking phenotype of loss of most endothelial and haematopoietic cells and a significant increase in cardiomyocyte numbers. Although this mutant has been analysed extensively to investigate mesoderm diversification and differentiation and continues to be broadly used as a unique avascular model, the isolation of the cloche gene has been challenging due to its telomeric location. Here we used a deletion allele of cloche to identify several new cloche candidate genes within this genomic region, and systematically genome-edited each candidate. Through this comprehensive interrogation, we succeeded in isolating the cloche gene and discovered that it encodes a PAS-domain-containing bHLH transcription factor, and that it is expressed in a highly specific spatiotemporal pattern starting during late gastrulation. Gain-of-function experiments show that it can potently induce endothelial gene expression. Epistasis experiments reveal that it functions upstream of etv2 and tal1, the earliest expressed endothelial and haematopoietic transcription factor genes identified to date. A mammalian cloche orthologue can also rescue blood vessel formation in zebrafish cloche mutants, indicating a highly conserved role in vertebrate vasculogenesis and haematopoiesis. The identification of this master regulator of endothelial and haematopoietic fate enhances our understanding of early mesoderm diversification and may lead to improved protocols for the generation of endothelial and haematopoietic cells in vivo and in vitro.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Células Sanguíneas/citologia , Células Sanguíneas/metabolismo , Diferenciação Celular/genética , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/química , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Vasos Sanguíneos/citologia , Vasos Sanguíneos/embriologia , Vasos Sanguíneos/metabolismo , Sequência Conservada , Epistasia Genética , Deleção de Genes , Sequências Hélice-Alça-Hélice , Hematopoese , Mesoderma/citologia , Mesoderma/embriologia , Mesoderma/metabolismo , Mutação , Estrutura Terciária de Proteína , Proteínas Proto-Oncogênicas/genética , Proteína 1 de Leucemia Linfocítica Aguda de Células T , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/química , Proteínas de Peixe-Zebra/genética
3.
Ophthalmology ; 125(5): 757-773, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29310963

RESUMO

TOPIC: An international, expert-led consensus initiative to develop systematic, evidence-based recommendations for the treatment of noninfectious uveitis in the era of biologics. CLINICAL RELEVANCE: The availability of biologic agents for the treatment of human eye disease has altered practice patterns for the management of noninfectious uveitis. Current guidelines are insufficient to assure optimal use of noncorticosteroid systemic immunomodulatory agents. METHODS: An international expert steering committee comprising 9 uveitis specialists (including both ophthalmologists and rheumatologists) identified clinical questions and, together with 6 bibliographic fellows trained in uveitis, conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol systematic review of the literature (English language studies from January 1996 through June 2016; Medline [OVID], the Central Cochrane library, EMBASE, CINAHL, SCOPUS, BIOSIS, and Web of Science). Publications included randomized controlled trials, prospective and retrospective studies with sufficient follow-up, case series with 15 cases or more, peer-reviewed articles, and hand-searched conference abstracts from key conferences. The proposed statements were circulated among 130 international uveitis experts for review. A total of 44 globally representative group members met in late 2016 to refine these guidelines using a modified Delphi technique and assigned Oxford levels of evidence. RESULTS: In total, 10 questions were addressed resulting in 21 evidence-based guidance statements covering the following topics: when to start noncorticosteroid immunomodulatory therapy, including both biologic and nonbiologic agents; what data to collect before treatment; when to modify or withdraw treatment; how to select agents based on individual efficacy and safety profiles; and evidence in specific uveitic conditions. Shared decision-making, communication among providers and safety monitoring also were addressed as part of the recommendations. Pharmacoeconomic considerations were not addressed. CONCLUSIONS: Consensus guidelines were developed based on published literature, expert opinion, and practical experience to bridge the gap between clinical needs and medical evidence to support the treatment of patients with noninfectious uveitis with noncorticosteroid immunomodulatory agents.


Assuntos
Imunomodulação , Imunossupressores/uso terapêutico , Uveíte/tratamento farmacológico , Medicina Baseada em Evidências , Glucocorticoides/uso terapêutico , Humanos , Medição de Risco , Inquéritos e Questionários , Fatores de Tempo , Uveíte/diagnóstico , Uveíte/fisiopatologia , Acuidade Visual/fisiologia
4.
Curr Opin Pulm Med ; 23(5): 458-467, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28622198

RESUMO

PURPOSE OF REVIEW: Ocular involvement in sarcoidosis is present in up to 80% of patients and is frequently manifested before diagnosis of the underlying systemic disease. Considering the therapeutic consequences, early diagnosis of the underlying disease is advantageous in patients presenting with ocular inflammation. There are several ocular findings suggestive of underlying sarcoidosis, such as granulomatous keratic precipitates, iris nodules, cells in the vitreous humor known as snowballs and snowbanks, and retinal periphlebitis. High suspicion is crucial for the diagnosis of sarcoidosis. This review on ocular sarcoidosis will mainly focus on new diagnostic and treatment modalities. RECENT FINDINGS: Recent studies found possible new diagnostic indicators for the diagnosis of ocular sarcoidosis which include not only serum profiles but also vitreous sample analysis. Ophthalmologic imaging techniques have improved to investigate the ocular structure in detail. Results from recent uveitis clinical trials have included sarcoidosis as an underlying cause and have reported positive results. SUMMARY: The diagnosis of ocular sarcoidosis can be challenging in some cases. High suspicion is important to diagnose ocular sarcoidosis with various laboratory and ophthalmic tools. There are many possible options for the treatment of ocular sarcoidosis including various biologic agents.


Assuntos
Oftalmopatias , Sarcoidose , Técnicas de Diagnóstico Oftalmológico , Gerenciamento Clínico , Diagnóstico Precoce , Oftalmopatias/diagnóstico , Oftalmopatias/etiologia , Oftalmopatias/terapia , Humanos , Sarcoidose/complicações , Sarcoidose/diagnóstico
5.
Ophthalmic Plast Reconstr Surg ; 33(3S Suppl 1): S116-S118, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-25902386

RESUMO

Cosmetic injection of hyaluronic acid (HA) and other fillers is increasingly common, and the late complications of these relatively new procedures are now coming to medical attention. Three patients with delayed periocular swelling that began years after injection of HA are described, with CT, MRI, and histopathologic characterization. While HA fillers are marketed as having a temporary effect of several months, the authors demonstrate that they may persist in the body for up to 9 years. Unlike most previous reports, there was no inflammatory reaction or encapsulation, simply infiltration into more superficial subcutaneous layers. All cases improved after surgical biopsy and hyaluronidase injections. Delayed periocular swelling after filler injections from several years prior can mimic serious medical conditions. With a detailed history and high index of suspicion, one may avoid a costly and invasive workup.


Assuntos
Migração de Corpo Estranho/etiologia , Ácido Hialurônico/efeitos adversos , Ritidoplastia/efeitos adversos , Adulto , Feminino , Seguimentos , Migração de Corpo Estranho/diagnóstico , Humanos , Ácido Hialurônico/administração & dosagem , Injeções Intraoculares , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Tomografia Computadorizada por Raios X , Viscossuplementos/administração & dosagem , Viscossuplementos/efeitos adversos
6.
Am J Physiol Heart Circ Physiol ; 301(5): H1841-9, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21856925

RESUMO

Survivin (SVV) is a multifunctional protein that has been implicated in the development of neointimal hyperplasia. Nuclear SVV is essential for mitosis, whereas in mitochondria SVV has a cytoprotective function. Here, we investigated the effects of RNA interference (RNAi)-mediated SVV knockdown on cell cycle kinetics, apoptosis, migration, and gene expression in primary cultured vascular smooth muscle cells (VSMCs) from the human saphenous vein. Primary Human VSMCs were obtained from saphenous veins and cultured under standard conditions. SVV knockdown was achieved by either small interfering RNA or lentiviral transduction of short hairpin RNA, reducing SVV gene expression by quantitative PCR (>75%, P < 0.01) without a loss of cell viability. Subcellular fractionation revealed that RNAi treatment effectively targeted the nuclear SVV pool, whereas the larger mitochondrial pool was much less sensitive to transient knockdown. Both p53 and p27 protein levels were notably increased. SVV RNAi treatment significantly blocked VSMC proliferation in response to serum and PDGF-AB, arresting VSMC growth. Cell cycle analysis revealed an increased G(2)/M fraction consistent with a mitotic defect; 4',6-diamidino-2-phenylindole staining confirmed an increased frequency of polyploid and abnormal nuclei. In a transwell assay, SVV knockdown reduced migration to PDGF-AB, and actin-phalloidin staining revealed disorganized actin filaments and polygonal cell shape. However, apoptosis (DNA content and annexin V flow cytometry) was not directly induced by SVV RNAi, and sensitivity to apoptotic agonists (e.g., staurosporine and cytokines) was unchanged. In conclusion, RNAi-mediated SVV knockdown in VSMCs leads to profound cell cycle arrest at G(2)/M and impaired chemotaxis without cytotoxicity. The regulation of mitosis and apoptosis in VSMC involves differentially regulated subcellular pools of SVV. Thus, treatment of VSMC with RNAi targeting SVV might limit the response to vascular injury without destabilizing the vessel wall.


Assuntos
Pontos de Checagem do Ciclo Celular , Proliferação de Células , Quimiotaxia , Técnicas de Silenciamento de Genes , Proteínas Inibidoras de Apoptose/metabolismo , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Interferência de RNA , Citoesqueleto de Actina/metabolismo , Apoptose , Células Cultivadas , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Regulação da Expressão Gênica , Humanos , Hiperplasia , Proteínas Inibidoras de Apoptose/genética , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/patologia , Fator de Crescimento Derivado de Plaquetas/metabolismo , Veia Safena/metabolismo , Veia Safena/patologia , Survivina , Fatores de Tempo , Proteína Supressora de Tumor p53/metabolismo
7.
J Ophthalmic Inflamm Infect ; 10(1): 14, 2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32462470

RESUMO

A 64-year-old man with a past medical history of liver transplantation on chronic immunosuppressive therapy presented with gradual worsening of vision over 2 months in his right eye. His recent history of Aspergillus and Nocardia pneumonia with positive bronchoalveolar lavage, in concert with vitritis and subretinal abscess, were concerning for endogenous endophthalmitis. A sputum culture and transbronchial lung biopsy stains grew Nocardia farcinica although aqueous humor sampling was negative. He was treated with four serial amikacin intravitreal injections over the course of 4 weeks. Pars plana vitrectomy for worsening macular traction and subsequent cataract surgery resulted in significant clinical and anatomic improvement of vision to 20/60 and consolidation of the subretinal abscess.

8.
Clin Ophthalmol ; 14: 1979-1986, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764863

RESUMO

OBJECTIVE: To report and analyze the causes and outcomes of malpractice litigation in ophthalmic trauma. METHODS: The Westlaw® database was reviewed for ophthalmology litigation in the United States between 1930 and 2014. All ophthalmic trauma cases were included and compared to non-traumatic ophthalmology malpractice cases. RESULTS: Forty-four ophthalmic trauma cases were included. Of these cases, 90.9% of ophthalmic trauma plaintiffs were male compared to 54.8% of plaintiffs in ophthalmology as a whole (P=<0.001); 34.1% of cases involved minor plaintiffs compared to 6.4% in ophthalmology as a whole (P=<0.001). Cases involving minors were more likely to be resolved in favor of the plaintiff than cases involving adult plaintiffs (53.3% vs 37.9%); however, this was not found to statistically significant (P=0.35). Overall, 54.5% of cases were resolved in favor of defendants; 40.9% of cases were resolved via jury trial with 50.0% resulting in payments to plaintiffs compared to the 29.6% rate of plaintiff verdicts in ophthalmology as a whole. Open globe injuries represented 61.4% of cases; 55.6% of these cases had intraocular foreign bodies and 37.0% developed endophthalmitis. Most cases (63.6%) alleged insufficient intervention. Of these cases, 31.8% of cases involved surgical or procedural claims, and 4.5% involved medical claims only. CONCLUSION: Males and minors were overrepresented among plaintiffs in ocular trauma litigation. Most cases involved open globe injuries, often complicated by retained intraocular foreign bodies and endophthalmitis. Analysis of malpractice litigation in ophthalmic trauma calls attention to commonly litigated scenarios to improve clinical practice and to inform risk management.

9.
Saudi J Ophthalmol ; 33(3): 260-267, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31686968

RESUMO

With fewer than 100 peer-reviewed cases reported in the world to date, the underlying etiology of torpedo maculopathy has remained elusive. In this literature review, we provide new evidence to better support, reject and unify claims regarding cause, diagnosis, and proper clinical management of this disease. We reviewed 44 case reports and case series, which included 77 patients (after exclusions). We additionally introduced 3 new cases from our clinical practice for a total of 80 cases. Ages at presentation ranged from 6 months old to 73 years old (mean: 24.2 years old). The nasal aspects of torpedo maculopathy lesions pointed toward the optic disc and localized to a kite-shaped region of the temporal macula, correlating with the anatomic junction of the superior arcuate, inferior arcuate, and papillomacular bundles of retinal nerve fiber layer distribution. No patterns were observed among the temporal aspects of the lesions. These findings support a congenital etiology of torpedo maculopathy and a possible influence of the retinal nerve fiber layer in the development of mature retinal pigment epithelium.

10.
JAMA Ophthalmol ; 136(2): 109-115, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29327057

RESUMO

Importance: Idiopathic disease is the most frequent diagnosis in a uveitis clinic. The need to distinguish sarcoidosis from idiopathic uveitis is controversial. However, cardiac involvement in sarcoidosis can be life-threatening. Objective: To report a series of patients with uveitis and cardiac sarcoidosis to illustrate the importance of categorizing the causes of uveitis. Design, Setting, and Participants: This retrospective observational case series reviewed the medical records of 249 patients with uveitis who were referred to the Casey Eye Institute between July 1, 2008, and February 28, 2017. Main Outcomes and Measures: We describe patients who initially received a diagnosis of idiopathic uveitis but subsequently received a diagnosis of sarcoidosis. Clinical data, including ophthalmologic findings, were collected. We summarized the number of patients who initially presented with idiopathic uveitis, the number of patients who recived a classification of idiopathic uveitis after evaluation, the number of patients who underwent chest computed tomography or an electrocardiogram, and the number of patients with ocular sarcoidosis. Results: Of 33 patients with sarcoidosis, 21 (63.6%) were women and the mean (SD) age was 53.5 (13.8) years. Of 249 patients, the referring diagnosis was idiopathic uveitis for 179 (72%). After history, examination, and laboratory testing, 127 (51%) were still considered to have idiopathic disease. Fifty-three of the 179 patients (30%) with idiopathic disease underwent chest computed tomography scanning. A diagnosis of presumed sarcoidosis, usually on the basis of a chest computed tomography scan, was made in 19 patients (36.2%). As 14 patients (5.6%) were previously known to have sarcoidosis, 33 patients (13.3%) were evaluated with definite or presumed ocular sarcoidosis. We obtained electrocardiograms as a screen for cardiac sarcoidosis on 14 (42.4%) of these patients. Nine patients with abnormal electrocardiogram results were referred to cardiologists. Four of the 19 patients (21.1%) who were referred for idiopathic uveitis but subsequently received a diagnosis of presumed sarcoidosis were found to have episodes of ventricular tachycardia that required implantable cardiac defibrillators. Distinguishing ocular sarcoidosis from idiopathic uveitis had potentially life-saving implications for these patients. Conclusions and Relevance: The present case series shows the potential utility of distinguishing sarcoidosis-associated uveitis from idiopathic uveitis. We suggest that patients older than 40 years with a history of idiopathic uveitis be evaluated with chest computed tomography and an electrocardiogram if sarcoidosis is suggested on ophthalmic examination.


Assuntos
Segmento Anterior do Olho/diagnóstico por imagem , Cardiomiopatias/diagnóstico , Sarcoidose/diagnóstico , Uveíte/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Cardiomiopatias/etiologia , Criança , Diagnóstico Diferencial , Eletrocardiografia , Eletroculografia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sarcoidose/complicações , Tomografia Computadorizada por Raios X , Uveíte/etiologia , Adulto Jovem
11.
Am J Ophthalmol ; 185: 68-74, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29101009

RESUMO

PURPOSE: To describe the phenotype of the uveitis that accompanies juvenile psoriatic arthritis or psoriasis. DESIGN: Observational case series. METHODS: Setting: Two university-based referral clinics: 1 in England, 1 in the United States. STUDY POPULATION: Five children with uveitis and psoriatic arthritis and 1 with uveitis and psoriasis Observational Procedure: Retrospective chart review. MAIN OUTCOME MEASURES: Demographics of subjects such as age and sex; description of ocular and joint disease; surgical and other complications; medical treatment. RESULTS: Five of the 6 children in this series had the onset of disease at or before age 6 (P = .0008 compared to expected age of onset for psoriatic arthritis in childhood). All children in this series had an inadequate response to topical corticosteroids. Most of the children were treated with systemic corticosteroids for many months, yet all of them went on to require methotrexate. Therapy with systemic methotrexate did not suffice, as all the patients also required some form of biologic therapy. Five of 6 had surgeries such as vitrectomy, cataract extraction, or a procedure for glaucoma control. CONCLUSIONS: The observations suggest that the uveitis that accompanies juvenile psoriatic arthritis might be a distinct disease that is particularly severe when its onset affects children aged 6 years or younger.


Assuntos
Artrite Juvenil/complicações , Psoríase/complicações , Uveíte/etiologia , Idade de Início , Artrite Juvenil/diagnóstico , Criança , Pré-Escolar , Inglaterra/epidemiologia , Feminino , Humanos , Incidência , Masculino , Fenótipo , Psoríase/diagnóstico , Fatores de Risco , Estados Unidos/epidemiologia , Uveíte/diagnóstico , Uveíte/epidemiologia
12.
Am J Ophthalmol ; 179: 179-189, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28501392

RESUMO

PURPOSE: To identify determinants of adverse outcomes in acute retinal necrosis (ARN), presenting characteristics and incidence rates of vision loss and ocular complications in a cohort of polymerase chain reaction (PCR)-positive eyes were analyzed. DESIGN: Retrospective observational cohort study. METHODS: Forty-one eyes of 36 patients with clinically diagnosed ARN, PCR-positive for herpes simplex virus or varicella zoster virus and evaluated between January 2002 and June 2013, were included. Main outcome measures included incidence rates of vision loss and retinal detachment (RD). RESULTS: Presenting visual acuity was generally poor (20/50 to >20/200 in 27%; 20/200 or worse in 56%). The incidence rate of ≤20/200 was 0.66/eye-year (EY), (95% confidence interval [CI], 0.32/EY to 1.22/EY); the rate of light perception or no light perception vision was 0.07/EY (95% CI, 0.02/EY to 0.16/EY). During follow-up, 59% of eyes developed at least 1 RD (rate = 0.40/EY, 95% CI, 0.19/EY to 0.58/EY). Eyes with retinitis involving ≥25% of the retina at presentation detached at nearly 12 times the rate, as compared to those with <25% retinal involvement (0.70/EY vs 0.06/EY; P = .001). Development of an RD was the greatest determinant of adverse visual outcomes, with 4% of eyes, that had experienced at least 1 RD, achieving a best-corrected visual acuity of ≥20/40 compared to 53% of eyes that never detached (P = .0003). CONCLUSIONS: Poor outcomes in ARN were common in this cohort. RD confers the greatest risk of incident vision loss, and once 25% or more of the retina is involved the risk of RD and visual loss increases significantly.


Assuntos
DNA Viral/análise , Infecções Oculares Virais/complicações , Herpes Simples/genética , Herpes Zoster Oftálmico/complicações , Herpesvirus Humano 3/genética , Síndrome de Necrose Retiniana Aguda/diagnóstico , Acuidade Visual , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Infecções Oculares Virais/diagnóstico , Infecções Oculares Virais/virologia , Feminino , Seguimentos , Herpes Zoster Oftálmico/diagnóstico , Herpes Zoster Oftálmico/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos , Síndrome de Necrose Retiniana Aguda/etiologia , Estudos Retrospectivos , Adulto Jovem
13.
Am J Ophthalmol Case Rep ; 8: 11-13, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29260107

RESUMO

PURPOSE: To report novel optical coherence tomography findings in a case of anti-α-enolase cancer associated retinopathy. OBSERVATIONS: An elderly female presented with bilateral decreased vision and a recent diagnosis of ovarian carcinoma. Optical coherence tomography demonstrated bilateral loss of outer retinal structures and macular edema. Serum testing found antibodies against α-enolase and 82-84 kDa proteins. Outer retinal structures showed recovery, macular edema resolved and repeat anti-retinal antibody testing became negative following cancer therapy and topical difluprednate treatment. CONCLUSIONS AND IMPORTANCE: Cancer associated retinopathy is a paraneoplastic disease that results in damage to retinal structures through an autoimmune response. The damage is generally considered to be irreversible; however, in rare cases, such as observed here, retinal structures may demonstrate recovery after treatment.

14.
JAMA Ophthalmol ; 135(11): 1156-1162, 2017 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-28975236

RESUMO

Importance: Although a variety of well-characterized diseases, such as sarcoidosis and granulomatosis with polyangiitis, affect the lacrimal gland, many patients with dacryoadenitis are diagnosed as having nonspecific orbital inflammation (NSOI) on the basis of histology and systemic disease evaluation. The ability to further classify the disease in these patients should facilitate selection of effective therapies. Objective: To test the a priori hypothesis that gene expression profiles would complement clinical and histopathologic evaluations in identifying well-characterized diseases and in subdividing NSOI into clinically relevant groups. Design, Setting, and Participants: In this cohort study, gene expression levels in biopsy specimens of inflamed and control lacrimal glands were measured with microarrays. Stained sections of the same biopsy specimens were used for evaluation of histopathology. Tissue samples of patients were obtained from oculoplastic surgeons at 7 international centers representing 4 countries (United States, Saudi Arabia, Canada, and Taiwan). Gene expression analysis was done at Oregon Health & Science University. Participants were 48 patients, including 3 with granulomatosis with polyangiitis, 28 with NSOI, 7 with sarcoidosis, 4 with thyroid eye disease, and 6 healthy controls. The study dates were March 2012 to April 2017. Main Outcomes and Measures: The primary outcome was subdivision of biopsy specimens based on gene expression of a published list of approximately 40 differentially expressed transcripts in blood, lacrimal gland, and orbital adipose tissue from patients with sarcoidosis. Stained sections were evaluated for inflammation (none, mild, moderate, or marked), granulomas, nodules, or fibrosis by 2 independent ocular pathologists masked to the clinical diagnosis. Results: Among 48 patients (mean [SD] age, 41.6 [19.0] years; 32 [67%] female), the mclust algorithm segregated the biopsy specimens into 4 subsets, with the differences illustrated by a heat map and multidimensional scaling plots. Most of the sarcoidosis biopsy specimens were in subset 1, which had the highest granuloma score. Three NSOI biopsy specimens in subset 1 had no apparent granulomas. Thirty-two percent (9 of 28) of the NSOI biopsy specimens could not be distinguished from biopsy specimens of healthy controls in subset 4, while other examples of NSOI tended to group with gene expression resembling granulomatosis with polyangiitis or thyroid eye disease. The 4 subsets could also be partially differentiated by their fibrosis, granulomas, and inflammation pathology scores but not their lymphoid nodule scores. Conclusions and Relevance: Gene expression profiling discloses clear heterogeneity among patients with lacrimal inflammatory disease. Comparison of the expression profiles suggests that a subset of patients with nonspecific dacryoadenitis might have a limited form of sarcoidosis, while other patients with NSOI cannot be distinguished from healthy controls.


Assuntos
Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica , Doenças do Aparelho Lacrimal/genética , Aparelho Lacrimal/metabolismo , Pseudotumor Orbitário/genética , RNA/genética , Adulto , Biópsia , Feminino , Marcadores Genéticos/genética , Humanos , Aparelho Lacrimal/patologia , Doenças do Aparelho Lacrimal/etiologia , Doenças do Aparelho Lacrimal/patologia , Masculino , Pseudotumor Orbitário/complicações , Pseudotumor Orbitário/patologia , Estudos Retrospectivos , Análise Serial de Tecidos/métodos
15.
Artigo em Inglês | MEDLINE | ID: mdl-25626974

RESUMO

Purpose: To assess the impact of glaucoma-related vision loss on measures of out-loud reading, including time to say individual words, interval time between consecutive words, lexical errors, skipped words, and repetitions. Methods: Glaucoma subjects (n=63) with bilateral visual field loss and glaucoma suspect controls (n=57) were recorded while reading a standardized passage out loud. A masked evaluator determined the start and end of each recorded word and identified reading errors. Results: Glaucoma subjects demonstrated longer durations to recite individual words (265 vs 243 milliseconds (ms), p<0.001), longer intervals between words (154 vs 124 ms, p<0.001), and longer word/post-word interval complexes (the time spanned by the word and the interval following the word) (419 vs. 367 ms, p<0.001) than controls. In multivariable analyses, each 0.1 decrement in log contrast sensitivity (logCS) was associated with a 15.0 ms longer word/post-interval complex (95% CI=9.6-20.4; p<0.001). Contrast sensitivity was found to significantly interact with word length, word frequency, and word location at the end of a line with regards to word/post-word interval complex duration (p<0.05 for all). Glaucoma severity was also associated with more lexical errors (Odds ratio=1.20 for every 0.1 logCS decrement; 95% CI=1.02-1.39, p<0.05), but not with more skipped or repeated words. Conclusions: Glaucoma patients with greater vision loss make more lexical errors, are slower in reciting longer and less frequently used words, and more slowly transition to new lines of text. These problem areas may require special attention when designing methods to rehabilitate reading in patients with glaucoma.

16.
Invest Ophthalmol Vis Sci ; 56(3): 1537-45, 2015 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-25737150

RESUMO

PURPOSE: To assess the impact of glaucoma-related vision loss on measures of out-loud reading, including time to say individual words, interval time between consecutive words, lexical errors, skipped words, and repetitions. METHODS: Glaucoma subjects (n = 63) with bilateral visual field loss and glaucoma suspect controls (n = 57) were recorded while reading a standardized passage out loud. A masked evaluator determined the start and end of each recorded word and identified reading errors. RESULTS: Glaucoma subjects demonstrated longer durations to recite individual words (265 vs. 243 ms, P < 0.001), longer intervals between words (154 vs. 124 ms, P < 0.001), and longer word/post-word interval complexes (the time spanned by the word and the interval following the word; 419 vs. 367 ms, P < 0.001) than controls. In multivariable analyses, each 0.1 decrement in log contrast sensitivity (logCS) was associated with a 15.0 ms longer word/post-interval complex (95% confidence interval [CI] = 9.6-20.4; P < 0.001). Contrast sensitivity was found to significantly interact with word length, word frequency, and word location at the end of a line with regards to word/post-word interval complex duration (P < 0.05 for all). Glaucoma severity was also associated with more lexical errors (Odds ratio = 1.20 for every 0.1 logCS decrement; 95% CI = 1.02-1.39, P < 0.05), but not with more skipped or repeated words. CONCLUSIONS: Glaucoma patients with greater vision loss make more lexical errors, are slower in reciting longer and less frequently used words, and more slowly transition to new lines of text. These problem areas may require special attention when designing methods to rehabilitate reading in patients with glaucoma.


Assuntos
Glaucoma/diagnóstico , Presbiacusia/diagnóstico , Leitura , Semântica , Baixa Visão/diagnóstico , Idoso , Sensibilidades de Contraste , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Acuidade Visual , Campos Visuais
17.
Am J Ophthalmol ; 159(2): 334-43.e1, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25447116

RESUMO

PURPOSE: To describe the clinical outcomes of ocular syphilis. DESIGN: Retrospective chart review. METHODS: The charts of patients with ocular syphilis (regardless of human immunodeficiency virus [HIV] status) seen in a uveitis referral center between 1984 and 2014 were reviewed. RESULTS: The study included 35 patients (61 eyes). Panuveitis was the most common type of ocular inflammation (28 eyes), independent of HIV status. Thirty-three of 35 patients received systemic antibiotics with 24 patients treated with intravenous (IV) penicillin only. When compared to the HIV-positive patients, HIV-negative patients with ocular syphilis were older (P < .001), were more likely to be female (P = .004), and had poorer visual acuity at presentation (P = .01). During follow-up, the incidence rates of visual impairment were 0.29 per eye-year (EY; 95% confidence interval [CI]: 0.06/EY-0.86/EY) and 0.12/EY (95% CI: 0.01/EY-0.42/EY) among the HIV-negative and the HIV-positive patients, respectively. The incidence of blindness was 0.07/EY (95% CI: 0.009/EY-0.27/EY) and 0.06/EY (95% CI: 0.002/EY-0.35/EY) among the HIV-negative and the HIV-positive patients, respectively. Longer duration of uveitis prior to diagnosis and chorioretinitis in the macula at presentation were associated with ≥ 2 Snellen lines of visual loss (P < .01) and visual acuity loss to 20/50 or worse (P = .03) in HIV-negative patients, respectively. CONCLUSIONS: Syphilis is an uncommon cause of ocular inflammation in both HIV-negative and HIV-positive patients. Visual loss and ocular complications were common among HIV-negative patients even with systemic antibiotic treatment. Delay of diagnosis and chorioretinitis in the macula were associated with visual loss in these patients.


Assuntos
Infecções Oculares Bacterianas/diagnóstico , Pan-Uveíte/diagnóstico , Sífilis/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Infecções Oculares Bacterianas/tratamento farmacológico , Infecções Oculares Bacterianas/epidemiologia , Feminino , Soropositividade para HIV , Humanos , Incidência , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Pan-Uveíte/tratamento farmacológico , Pan-Uveíte/epidemiologia , Penicilina G Benzatina/uso terapêutico , Estudos Retrospectivos , Sífilis/tratamento farmacológico , Sífilis/epidemiologia , Transtornos da Visão/epidemiologia , Acuidade Visual , Adulto Jovem
18.
Ocul Immunol Inflamm ; 21(4): 257-63, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23617776

RESUMO

PURPOSE: To describe the effectiveness of periocular corticosteroid injections for the control of intraocular inflammation associated with noninfectious uveitis. METHODS: A total of 81 patients (109 eyes) who received a periocular injection were evaluated for active inflammation, visual acuity, intraocular pressure, degree of intraocular inflammation, and the presence of ocular complications, including macular edema. RESULTS: Of all eyes, 36% (95%CI: 25%, 45%) demonstrated clinical resolution of inflammation at the 1-month visit after first injection, and 48% (95%CI: 37%, 59%) at 3 months. For multiple injections, 50% (95%CI: 28%, 72%) demonstrated resolution of inflammation at 1 month after the last injection, and 41% (95%CI: 20%, 63%) resolution of inflammation at 3 months after the last injection. Of the 49 eyes that initially responded, the estimated median time to recurrence was 7.6 months. CONCLUSIONS: Approximately half of the treated eyes had resolution of intraocular inflammation at 3 months after corticosteroid injection.


Assuntos
Triancinolona Acetonida/administração & dosagem , Uveíte/tratamento farmacológico , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Seguimentos , Glucocorticoides/administração & dosagem , Humanos , Injeções Intraoculares , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Uveíte/fisiopatologia , Acuidade Visual , Adulto Jovem
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