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2.
Ophthalmic Plast Reconstr Surg ; 39(6): 588-593, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37279012

RESUMO

PURPOSE: The purpose of this study was to compare the histopathologic inflammation and fibrosis of orbital adipose tissue in orbital inflammatory disease (OID) specimens. METHODS: In this retrospective cohort study, inflammation, and fibrosis in orbital adipose tissue from patients with thyroid-associated orbitopathy (TAO), granulomatosis with polyangiitis (GPA), sarcoidosis, nonspecific orbital inflammation (NSOI), and healthy controls were scored by 2 masked ocular pathologists. Both categories were scored on a scale of 0 to 3 with scoring criteria based on the percentage of specimens containing inflammation or fibrosis, respectively. Tissue specimens were collected from oculoplastic surgeons at 8 international centers representing 4 countries. Seventy-four specimens were included: 25 with TAO, 6 with orbital GPA, 7 with orbital sarcoidosis, 24 with NSOI, and 12 healthy controls. RESULTS: The mean inflammation and fibrosis scores for healthy controls were 0.0 and 1.1, respectively. Orbital inflammatory disease groups' inflammation (I) and fibrosis (F) scores, formatted [I, F] with respective p -values when compared to controls, were: TAO [0.2, 1.4] ( p = 1, 1), GPA [1.9, 2.6] ( p = 0.003, 0.009), sarcoidosis [2.4, 1.9] ( p = 0.001, 0.023), and NSOI [1.3, 1.8] ( p ≤ 0.001, 0.018). Sarcoidosis had the highest mean inflammation score. The pairwise analysis demonstrated that sarcoidosis had a significantly higher mean inflammation score than NSOI ( p = 0.036) and TAO ( p < 0.0001), but no difference when compared to GPA. GPA had the highest mean fibrosis score, with pairwise analysis demonstrating a significantly higher mean fibrosis score than TAO ( p = 0.048). CONCLUSIONS: Mean inflammation and fibrosis scores in TAO orbital adipose tissue samples did not differ from healthy controls. In contrast, the more "intense" inflammatory diseases such as GPA, sarcoidosis, and NSOI did demonstrate higher histopathologic inflammation and fibrosis. This has implications in prognosis, therapeutic selection, and response monitoring in orbital inflammatory disease.


Assuntos
Oftalmopatia de Graves , Sarcoidose , Humanos , Órbita/diagnóstico por imagem , Órbita/patologia , Estudos Retrospectivos , Inflamação/patologia , Oftalmopatia de Graves/patologia , Fibrose
3.
Orbit ; 42(1): 25-29, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36696248

RESUMO

PURPOSE: To describe the utilization of acellular cadaveric dermal matrix (ACDM) in patients undergoing orbital wall reconstruction after orbital preservation surgery for sinonasal malignancy. METHODS: Retrospective case series of seven patients with sinonasal malignancy who had orbital reconstruction with ACDM implants from January 2012 to August 2020. Orbital preservation was performed in all patients with tumor extension up to and including periorbital. The main outcome measures were implant exposure, orbital infection, diplopia in primary gaze, enophthalmos, and eyelid malposition. RESULTS: Patients ranged 37-78 years old (median: 66 years) and included 4 females and 3 males. The median follow-up time was 9 months (range 6-43 months) from the date of surgery. Squamous cell carcinoma comprised the majority of tumors with all patients needing medial wall reconstruction. Three patients received postoperative radiation therapy. No patients had any implant exposure, orbital infection, enophthalmos, or eyelid malposition. CONCLUSIONS: ACDM grafts can be used safely in orbital wall reconstruction in patients with sinonasal malignancies.


Assuntos
Carcinoma de Células Escamosas , Enoftalmia , Fraturas Orbitárias , Implantes Orbitários , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Resultado do Tratamento , Carcinoma de Células Escamosas/cirurgia , Cadáver , Fraturas Orbitárias/cirurgia
4.
Orbit ; 41(2): 204-210, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33386062

RESUMO

PURPOSE: To evaluate the predominant pathogens and clinical course in pediatric patients with orbital cellulitis (OC) complicated by subperiosteal abscess (SPA). METHODS: This is a single-center retrospective chart review evaluating pediatric patients with OC complicated by SPA treated at a tertiary care center in the Pacific Northwest. Data were analyzed for characteristics, rates of infection, and antibiotic resistance of the predominant pathogens in pediatric patients. RESULTS: Twenty-seven children were identified with OC complicated by SPA and bacterial cultures drawn. The average age (SD) of the patients was 9.2 years (4.8), median 9.6; 15 range 5 months to 17.2 years. Seventeen (63.0%) were male. Sinusitis was present in all patients. Streptococcus species were the most common pathogen accounting for 52% (17/33) of isolates. Streptococcus anginosus group (SAG) was the predominant species and were isolated in 10 out of 27 (37%) children in the study. Twenty-one (78%) patients required surgery for the treatment of SPA. Among surgically treated patients, females tended to be younger than males (p = .068). Pediatric patients with SAG infections required more surgery than children without this isolate, 100% and 65%, respectively (p = .030). Female patients tended to have SAG infections more often than males (p = .063). CONCLUSIONS: Orbital infections caused by SAG require surgical management more often than those caused by other pathogens. Our results suggest a difference in pathogenic organisms in male and female patients with SPA. SAG is one of the most common pathogens isolated in orbital cellulitis complicated by SPA in children.


Assuntos
Celulite Orbitária , Doenças Orbitárias , Abscesso/epidemiologia , Abscesso/etiologia , Abscesso/terapia , Antibacterianos/uso terapêutico , Celulite (Flegmão)/complicações , Celulite (Flegmão)/tratamento farmacológico , Criança , Feminino , Humanos , Masculino , Celulite Orbitária/tratamento farmacológico , Celulite Orbitária/terapia , Doenças Orbitárias/epidemiologia , Doenças Orbitárias/microbiologia , Doenças Orbitárias/terapia , Periósteo , Prevalência , Estudos Retrospectivos , Streptococcus anginosus
5.
Ocul Oncol Pathol ; 7(6): 447-448, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35087821
6.
Prog Retin Eye Res ; 81: 100885, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32717379

RESUMO

Non-specific orbital inflammation (NSOI) is a noninfectious inflammatory condition of the orbit. Although it is generally considered the most common diagnosis derived from an orbital biopsy, it is a diagnosis of exclusion, meaning that the diagnosis requires exclusion of a systemic process or another identifiable etiology of orbital inflammation. The clinical diagnosis of NSOI is ill-defined, but it is typically characterized by acute orbital signs and symptoms, including pain, proptosis, periorbital edema, chemosis, diplopia, and less commonly visual disturbance. NSOI poses a diagnostic and therapeutic challenge: The clinical presentations and histological findings are heterogeneous, and there are no specific diagnostic criteria or treatment guidelines. The etiology and pathogenesis of NSOI are poorly understood. Here we recapitulate our current clinical understanding of NSOI, with an emphasis on the most recent findings on clinical characteristics, imaging findings, and treatment outcomes. Furthermore, gene expression profiling of NSOI and its implications are presented and discussed.


Assuntos
Inflamação/diagnóstico , Doenças Orbitárias/diagnóstico , Perfilação da Expressão Gênica , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/etiologia , Humanos , Doença Relacionada a Imunoglobulina G4/diagnóstico , Doença Relacionada a Imunoglobulina G4/etiologia , Inflamação/etiologia , Inflamação/genética , Doenças Orbitárias/etiologia , Doenças Orbitárias/genética
7.
Ophthalmic Plast Reconstr Surg ; 37(3): 212-216, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32932408

RESUMO

PURPOSE: To describe the demographics, clinical presentation, treatment, and outcomes of a rare cohort with simultaneous orbital and intracranial abscesses. METHODS: A historical cohort study of 17 patients with simultaneous orbital and intracranial abscesses between 2010 and 2018 was performed. The demographics, location of abscesses, treatment, and outcomes of these patients were analyzed. RESULTS: The mean age was 26.9 years (range 5-83 years). Fourteen patients (82%) were male. In this cohort, the most common orbital abscess location was the superior orbit, involved in 14 patients (82%). The most common site of intracranial abscess was the frontal lobe, involved in 16 patients (94%). Concurrent sinus disease was present in 16 patients (94%). Surgical evacuation was the standard of treatment, with 94% of patients undergoing at least one surgical procedure. Streptococcus species were the most common, isolated from 6 sinus cultures (43%), 3 orbitotomy cultures (21%), and 4 craniectomy cultures (36%). Staphylococcus species were also common. Most patients (94%) had stable or improved mental status and visual function at the conclusion of their treatment. CONCLUSIONS: Simultaneous orbital and intracranial abscesses are rare. Local invasion from the orbit into the intracranial space may occur from direct spread, thus superior orbital abscesses pose the greatest risk for intracranial spread. Additional factors such as infection with Streptococcus and Staphylococcus species as well as male sex appear to be risk factors for intracranial spread. For those who develop intracranial abscesses, young age and absence of seizures or altered mental status at presentation may be associated with favorable outcomes.


Assuntos
Abscesso , Doenças Orbitárias , Abscesso/diagnóstico , Abscesso/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Orbitárias/diagnóstico , Doenças Orbitárias/tratamento farmacológico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Adulto Jovem
8.
Sci Rep ; 10(1): 21875, 2020 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-33318556

RESUMO

Radiologic orbital imaging provides important information in the diagnosis and management of orbital inflammation. However, the diagnostic value of orbital imaging is not well elucidated. This study aimed to investigate the diagnostic accuracy of orbital imaging to diagnose orbital inflammatory diseases and its ability to detect active inflammation. We collected 75 scans of 52 patients (49 computed tomography (CT) scans; 26 magnetic resonance (MR) imaging scans). Clinical diagnoses included thyroid eye disease (TED) (41 scans, 31 patients), non-specific orbital inflammation (NSOI) (22 scans, 14 patients), sarcoidosis (4 scans, 3 patients), IgG4-related ophthalmic disease (IgG4-ROD) (5 scans, 3 patients), and granulomatosis with polyangiitis (GPA) (3 scans, 1 patient). Two experienced neuroradiologists interpreted the scans, offered a most likely diagnosis, and assessed the activity of inflammation, blinded to clinical findings. The accuracy rate of radiological diagnosis compared to each clinical diagnosis was evaluated. Sensitivity and specificity in detecting active inflammation were analyzed for TED and NSOI. The accuracy rate of radiologic diagnosis was 80.0% for IgG4-ROD, 77.3% for NSOI, and 73.2% for TED. Orbital imaging could not diagnose sarcoidosis. Orbital CT had a sensitivity of 50.0% and a specificity of 75.0% to predict active TED using clinical assessment as the gold standard. The sensitivity/specificity of orbital MR was 83.3/16.7% for the detection of active NSOI. In conclusion, orbital imaging is accurate for the diagnosis of IgG4, NSOI, and TED. Further studies with a large number of cases are needed to confirm this finding, especially with regard to uncommon diseases. Orbital CT showed moderate sensitivity and good specificity for identifying active TED.


Assuntos
Oftalmopatia de Graves/diagnóstico por imagem , Doença Relacionada a Imunoglobulina G4/diagnóstico por imagem , Imageamento por Ressonância Magnética , Órbita/diagnóstico por imagem , Sarcoidose/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Idoso , Feminino , Humanos , Inflamação/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade
9.
Ophthalmic Plast Reconstr Surg ; 36(1): 70-73, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31809485

RESUMO

PURPOSE: To examine the role of adjuvant surgical resection of infantile hemangiomas after systemic ß-blocker therapy. METHODS: This is a multicentered retrospective study. Standard protocol for oral propranolol was employed by the referring physicians. Ocular indications for surgery included ptosis obstructing the visual axis, high degrees of astigmatism causing amblyopia, or disfigurement from residual tumor. Patients underwent complete excision or debulking. RESULTS: Eleven girls and 4 boys were surgically treated with mean operative age of 34.4 months. Patients were followed for a mean of 19.6 months after surgery. Four patients required surgical treatment due to an inability to tolerate medical therapy secondary to drug-related side effects (including bradycardia). The other 11 patients proceeded to surgery due to residual eyelid and orbital lesions despite medical treatment. All 15 patients underwent orbitotomy for residual hemangioma excision. Four patients also underwent simultaneous levator advancement at the time of excision. In all cases, there was resolution of ptosis with clearing of the visual axis. No complications were incurred during the surgical treatment and there were no hemangioma recurrences. CONCLUSIONS: This is the first study to report surgical management of periocular infantile hemangiomas recalcitrant to standard therapy in the ß-blocker era. In patients with infantile hemangioma who have failed medical therapy, adjuvant surgical treatment still plays an important role. For patients with persistent tumor causing ocular sequelae, surgical intervention aimed at soft tissue debulking and ptosis repair can be successful in achieving excellent functional and aesthetic outcomes with minimal side effects.For patients with periocular infantile hemangiomas with residual soft tissue deformity following propranolol therapy, surgical treatment plays an important role in improving functional and cosmetic outcomes with minimal side effects.


Assuntos
Hemangioma Capilar , Hemangioma , Antagonistas Adrenérgicos beta/uso terapêutico , Pré-Escolar , Feminino , Hemangioma/tratamento farmacológico , Hemangioma/cirurgia , Hemangioma Capilar/tratamento farmacológico , Hemangioma Capilar/cirurgia , Humanos , Lactente , Masculino , Recidiva Local de Neoplasia , Propranolol/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
10.
Ocul Oncol Pathol ; 5(6): 424-431, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31768366

RESUMO

PURPOSE: To report a case of orbital cellular epithelioid hemangioma (EH) in which FOSB and CAMTA1 immunostains were used to detect a cytogenetic rearrangement as an adjunctive tool in diagnosis. METHODS: Case report. RESULTS: A patient with a history of prior ligation of a presumed orbital varix presented with recurrent proptosis. Imaging revealed a highly vascular right orbital mass. Microscopic examination revealed a circumscribed neoplasm composed of plump epithelioid endothelial cells with copious mildly eosinophilic cytoplasm and relatively uniform vesicular nuclei. To aid in diagnosis, immunostains for FOSB and CAMTA1 were performed to detect corresponding cytogenetic rearrangements. The presence of multifocal nuclear positivity for FOSB, indicating FOSB genetic rearrangement, and negativity for CAMTA1 were considered reassuring features against a diagnosis of a malignant epithelioid hemangioendothelioma (EHE), supporting a diagnosis of benign cellular EH. CONCLUSIONS: This case report demonstrates that the use of immunohistochemical stains to detect cytogenetic rearrangements may aid in the distinction between benign EH and malignant EHE. It also reminds providers of the clinical and histopathologic features of this lesion, which occurs rarely in the orbit, and helps clarify the evolving nomenclature surrounding epithelioid hemangioma.

11.
Ophthalmic Plast Reconstr Surg ; 34(4): e123-e124, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29870438

RESUMO

Conjunctivodacryocystorhinostomy with placement of a Jones tube (JT) is the gold standard for upper lacrimal system dysfunction. However, traditional JT have been associated with various complications. In their practice, the authors have encountered challenges with postoperative dry eye in a select group of patients, with recurrence of epiphora following tube occlusion, suggesting a need for decreasing the rate of tear drainage while maintaining a patent JT. To address this issue, the senior author (J.D.N.) introduced a modified JT with a narrow lumen (reduced-flow JT) for patients who experience significant dry eye symptoms after placement of a JT. The authors describe 3 patients who experienced improvement in dry eye symptoms after the placement of reduced-flow JT.


Assuntos
Túnica Conjuntiva/cirurgia , Dacriocistorinostomia/efeitos adversos , Síndromes do Olho Seco/cirurgia , Intubação/instrumentação , Ducto Nasolacrimal/cirurgia , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Desenho de Prótese
12.
Ophthalmic Plast Reconstr Surg ; 34(3): 258-261, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28582371

RESUMO

PURPOSE: To evaluate the clinical and anatomical location of orbital plasmacytomas and assess local control following therapy. METHODS: The American Society of Ophthalmic Plastic and Reconstructive Surgery Oncology Database was queried to identify patients diagnosed with orbital plasmacytoma. These patients' records were reviewed for demographic characteristics, clinical and radiologic findings, treatments, and outcomes. RESULTS: Thirty patients from 4 institutions (24 from MD Anderson Cancer Center, 3 from SUNY Downstate Medical Center, 2 from University of California, Los Angeles, and 1 from Oregon Health and Science University) were identified. Eighteen patients (60%) were diagnosed with multiple myeloma (MM) before and 11 (37%) were diagnosed with MM immediately after orbital plasmacytoma. Based on imaging, 4 distinct anatomical patterns were identified: 1) bony plasmacytoma affecting the superotemporal orbit, epidural space, and temporal fossa (15 patients; 50%); 2) discrete orbital plasmacytoma (7 patients; 23%); 3) infiltrative plasmacytoma either originating from a sinus (4 patients; 13%); or 4) originating from the orbital floor and infiltrating facial soft tissue (4 patients; 13%). Of the 29 patients with available treatment data, 2 had radiation only, 3 had chemotherapy only, 6 had chemoradiation, and 18 had stem cell transplant following chemoradiation (n = 17) or only chemotherapy (n = 1). Following treatment, 10 patients achieved complete and 11 achieved partial responses. CONCLUSION: Orbital plasmacytomas were found exclusively in patients with MM diagnosed before or immediately after orbital plasmacytoma. Plasmacytomas can have 4 distinct anatomical patterns of origin. Following treatment, all patients had good to excellent local control of their orbital lesions.


Assuntos
Mieloma Múltiplo/complicações , Neoplasias Orbitárias/patologia , Plasmocitoma/patologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
13.
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
14.
Int J Ophthalmol ; 9(12): 1751-1755, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28003974

RESUMO

AIM: To investigate the etiology, diagnosis, management and outcome of epiphora referrals to an oculoplastic practice. METHODS: Retrospective chart review of patients referred for epiphora to an oculoplastic clinic between 2005 and 2009. Patient demographics, past history, ophthalmic examination, treatment and outcome were analyzed. RESULTS: There were 237 subjects with a primary complaint of epiphora. They included 130 (55%) females and 107 (45%) males with an average age of 55.9±25.9y. The most common cause of epiphora was lacrimal obstruction (46%); followed by multifactorial epiphora (22%), reflex tearing (22%) and eyelid malposition (11%). Differences in prevalence of etiology were noted in terms of age and gender distribution. Of the 182 (77%) patients who returned for follow up, 41 (23%) reported a complete resolution and 102 (56%) reported a significant improvement in their symptoms. CONCLUSION: Epiphora is a common condition with many causes. A thorough history and examination are required to provide the appropriate treatment tailored to the underlying cause.

15.
Ophthalmic Plast Reconstr Surg ; 32(3): e62-4, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-25105519

RESUMO

Two infants were referred for progressive orbital proptosis. MRI in both cases demonstrated a homogenous mass in the orbit adherent to and isointense with a rectus muscle. Histopathology in both cases demonstrated a bland proliferation of spindle cells with entrapped skeletal muscle. Immunochemistry demonstrated that the abnormal tissue was of skeletal muscle origin, consistent with rhabdomyomatous mesenchymal hamartoma (RMH). Observation was elected due to the reported benign nature of RMH. In contrast to RMH of the cutaneous tissues that typically follows a benign course, RMH of the orbit may present with rapid growth.


Assuntos
Exoftalmia/etiologia , Hamartoma/complicações , Músculo Esquelético/patologia , Órbita/diagnóstico por imagem , Exoftalmia/diagnóstico , Hamartoma/diagnóstico , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino
16.
PLoS One ; 10(9): e0137654, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26371757

RESUMO

BACKGROUND: Although thyroid eye disease is a common complication of Graves' disease, the pathogenesis of the orbital disease is poorly understood. Most authorities implicate the immune response as an important causal factor. We sought to clarify pathogenesis by using gene expression microarray. METHODS: An international consortium of ocular pathologists and orbital surgeons contributed formalin fixed orbital biopsies. RNA was extracted from orbital tissue from 20 healthy controls, 25 patients with thyroid eye disease (TED), 25 patients with nonspecific orbital inflammation (NSOI), 7 patients with sarcoidosis and 6 patients with granulomatosis with polyangiitis (GPA). Tissue was divided into a discovery set and a validation set. Gene expression was quantified using Affymetrix U133 Plus 2.0 microarrays which include 54,000 probe sets. RESULTS: Principal component analysis showed that gene expression from tissue from patients with TED more closely resembled gene expression from healthy control tissue in comparison to gene expression characteristic of sarcoidosis, NSOI, or granulomatosis with polyangiitis. Unsupervised cluster dendrograms further indicated the similarity between TED and healthy controls. Heat maps based on gene expression for cytokines, chemokines, or their receptors showed that these inflammatory markers were associated with NSOI, sarcoidosis, or GPA much more frequently than with TED. CONCLUSION: This is the first study to compare gene expression in TED to gene expression associated with other causes of exophthalmos. The juxtaposition shows that inflammatory markers are far less characteristic of TED relative to other orbital inflammatory diseases.


Assuntos
Oftalmopatias/complicações , Oftalmopatias/imunologia , Doenças da Glândula Tireoide/complicações , Adulto , Estudos de Casos e Controles , Oftalmopatias/genética , Oftalmopatias/patologia , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Órbita/patologia
17.
Exp Mol Pathol ; 99(2): 271-8, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26163757

RESUMO

Biopsies and ANCA testing for limited forms of granulomatosis with polyangiitis (GPA) are frequently non-diagnostic. We characterized gene expression in GPA and other causes of orbital inflammation. We tested the hypothesis that a sub-set of patients with non-specific orbital inflammation (NSOI, also known as pseudotumor) mimics a limited form of GPA. Formalin-fixed, paraffin-embedded orbital biopsies were obtained from controls (n=20) and patients with GPA (n=6), NSOI (n=25), sarcoidosis (n=7), or thyroid eye disease (TED) (n=20) and were divided into discovery and validation sets. Transcripts in the tissues were quantified using Affymetrix U133 Plus 2.0 microarrays. Distinct gene expression profiles for controls and subjects with GPA, TED, or sarcoidosis were evident by principal coordinate analyses. Compared with healthy controls, 285 probe sets had elevated signals in subjects with GPA and 1472 were decreased (>1.5-fold difference, false discovery rate adjusted p<0.05). The immunoglobulin family of genes had the most dramatic increase in expression. Although gene expression in GPA could be readily distinguished from gene expression in TED, sarcoidosis, or controls, a comparison of gene expression in GPA versus NSOI found no statistically significant differences. Thus, forms of orbital inflammation can be distinguished based on gene expression. NSOI/pseudotumor is heterogeneous but often may be an unrecognized, localized form of GPA.


Assuntos
Biomarcadores/metabolismo , Perfilação da Expressão Gênica , Granulomatose com Poliangiite/genética , Oftalmopatia de Graves/genética , Inflamação/genética , Pseudotumor Orbitário/genética , Sarcoidose/genética , Adulto , Estudos de Casos e Controles , Feminino , Granulomatose com Poliangiite/patologia , Oftalmopatia de Graves/patologia , Humanos , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Pseudotumor Orbitário/patologia , Sarcoidose/patologia
18.
Br J Ophthalmol ; 99(10): 1424-9, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26038391

RESUMO

BACKGROUND/AIMS: To clarify the pathogenesis of fibrosis in inflammatory orbital diseases, we analysed the gene expression in orbital biopsies and compared our results with those reported for idiopathic pulmonary fibrosis. METHODS: We collected 140 biopsies from 138 patients (58 lacrimal glands; 82 orbital fat). Diagnoses included healthy controls (n=27), non-specific orbital inflammation (NSOI) (n=61), thyroid eye disease (TED) (n=29), sarcoidosis (n=14) and granulomatosis with polyangiitis (GPA) (n=7). Fibrosis was scored on a 0-3 scale by two experts, ophthalmic pathologists. Gene expression was quantified using Affymetrix U133 plus 2.0 microarray. RESULTS: Within orbital fat, fibrosis was greatest among subjects with GPA (2.75±0.46) and significantly increased in tissue from subjects with GPA, NSOI or sarcoidosis (p<0.01), but not for TED, compared with healthy controls (1.13±0.69). For lacrimal gland, the average score among controls (1.36±0.48) did not differ statistically from any of the four disease groups. Seventy-three probe sets identified transcripts correlating with fibrosis in orbital fat (false discovery rate <0.05) after accounting for batch effects, disease type, age and sex. Transcripts with increased expression included fibronectin, lumican, thrombospondin and collagen types I and VIII, each of which has been reported upregulated in pulmonary fibrosis. CONCLUSIONS: A pathologist's recognition of fibrosis in orbital tissue correlates well with increased expression of transcripts that are considered essential in fibrosis. Many transcripts implicated in orbital fibrosis have been previously implicated in pulmonary fibrosis. TED differs from other causes of orbital fat inflammation because fibrosis is not a major component. Marked fibrosis is less common in the lacrimal gland compared with orbital adipose tissue.


Assuntos
Perfilação da Expressão Gênica/métodos , Expressão Gênica , Órbita/patologia , RNA/genética , Adulto , Biópsia , Feminino , Fibrose/genética , Fibrose/patologia , Humanos , Aparelho Lacrimal/patologia , Masculino , Análise em Microsséries/métodos , Pessoa de Meia-Idade , Pseudotumor Orbitário/diagnóstico , Pseudotumor Orbitário/genética
19.
JAMA Ophthalmol ; 133(7): 770-7, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25880323

RESUMO

IMPORTANCE: Sarcoidosis is a major cause of ocular or periocular inflammation. The pathogenesis of sarcoidosis is incompletely understood and diagnosis often requires a biopsy. OBJECTIVE: To determine how gene expression in either orbital adipose tissue or the lacrimal gland affected by sarcoidosis compares with gene expression in other causes of orbital disease and how gene expression in tissue affected by sarcoidosis compares with gene expression in peripheral blood samples obtained from patients with sarcoidosis. DESIGN, SETTING, AND PARTICIPANTS: In a multicenter, international, observational study, gene expression profiling of formalin-fixed biopsy specimens, using GeneChipp U133 Plus 2 microarrays (Affymetrix), was conducted between October 2012 and January 2014 on tissues biopsied from January 2000 through June 2013. Participants included 12 patients with orbital sarcoidosis (7 in adipose tissue; 5 affecting the lacrimal gland) as well as comparable tissue from 6 healthy individuals serving as controls or patients with thyroid eye disease, nonspecific orbital inflammation, or granulomatosis with polyangiitis. In addition, results were compared with gene expression in peripheral blood samples obtained from 12 historical individuals with sarcoidosis. MAIN OUTCOMES AND MEASURES: Significantly differentially expressed transcripts defined as a minimum of a 1.5-fold increase or a comparable decrease and a false discovery rate of P < .05. RESULTS: Signals from 2449 probe sets (transcripts from approximately 1522 genes) were significantly increased in the orbital adipose tissue from patients with sarcoidosis. Signals from 4050 probe sets (approximately 2619 genes) were significantly decreased. Signals from 3069 probe sets (approximately 2001 genes) were significantly higher and 3320 (approximately 2283 genes) were significantly lower in the lacrimal gland for patients with sarcoidosis. Ninety-two probe sets (approximately 69 genes) had significantly elevated signals and 67 probe sets (approximately 56 genes) had significantly lower signals in both orbital tissues and in peripheral blood from patients with sarcoidosis. The transcription factors, interferon-response factor 1, interferon-response factor 2, and nuclear factor κB, were strongly implicated in the expression of messenger RNA upregulated in common in the 3 tissues. CONCLUSIONS AND RELEVANCE: Gene expression in sarcoidosis involving the orbit or lacrimal gland can be distinguished from gene expression patterns in control tissue and overlaps with many transcripts upregulated or downregulated in the peripheral blood of patients with sarcoidosis. These observations suggest that common pathogenic mechanisms contribute to sarcoidosis in different sites. The observations support the hypothesis that a pattern of gene expression profiles could provide diagnostic information in patients with sarcoidosis.


Assuntos
Oftalmopatias/diagnóstico , Oftalmopatias/genética , Perfilação da Expressão Gênica/métodos , Sarcoidose/diagnóstico , Sarcoidose/genética , Tecido Adiposo/patologia , Adulto , Idoso , Biópsia por Agulha , Estudos de Casos e Controles , Oftalmopatias/sangue , Feminino , Regulação da Expressão Gênica , Humanos , Internacionalidade , Aparelho Lacrimal/patologia , Masculino , Pessoa de Meia-Idade , Órbita , RNA Mensageiro/genética , Valores de Referência , Sarcoidose/sangue , Sarcoidose/patologia , Sensibilidade e Especificidade , Regulação para Cima
20.
Ophthalmic Plast Reconstr Surg ; 31(4): 303-5, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25230119

RESUMO

PURPOSE: To evaluate changes in intraocular pressure (IOP) during orbital floor fracture repair. METHODS: Retrospective chart review of patients undergoing isolated orbital floor fracture repair with implant placement at a level 1 trauma center and tertiary care center. Patients with combined zygomaticomaxillary or medial wall fracture repair, or other significant ocular injuries were excluded. IOP measurements using a handheld applanation tonometer were recorded immediately after induction of anesthesia, immediately after orbital floor implant placement, and on postoperative day 1. RESULTS: Nine patients who underwent isolated orbital floor fracture repair were examined. There was a statistically significant mean decrease of 4.66 mmHg (p < 0.05) in IOP from prior to surgical to immediately after implant placement. There was also a significant mean increase in IOP of 7.44 mmHg (p < 0.05) at postoperative day 1 compared with immediately after implant placement. There was no statistically significant difference in IOP between prior to surgical incision and postoperative day 1. CONCLUSIONS: All patients who underwent orbital floor fracture repair in this study had a significant decrease in IOP during orbital floor fracture repair that returned to immediately preoperative levels by postoperative day 1. This initial decrease in IOP may be because of intraoperative manipulation of the globe.


Assuntos
Pressão Intraocular/fisiologia , Fraturas Orbitárias/cirurgia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fraturas Orbitárias/fisiopatologia , Implantes Orbitários , Estudos Retrospectivos , Tonometria Ocular , Adulto Jovem
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