RESUMO
A 66-year-old female presented for evaluation of progressively worsening edema and palpable masses in both lower eyelids. While she denied prior filler to the lower eyelid or tear trough, histopathology revealed degenerating striated muscle surrounding pools of hyaluronic acid. While cases of gradually enlarging masses associated with facial filler placement have been reported, there is no literature identifying muscle degeneration adjacent to hyaluronic acid filler.
Assuntos
Técnicas Cosméticas/efeitos adversos , Doenças Palpebrais/induzido quimicamente , Pálpebras/patologia , Ácido Hialurônico/efeitos adversos , Músculos Oculomotores/patologia , Idoso , Biópsia , Doenças Palpebrais/diagnóstico , Pálpebras/efeitos dos fármacos , Feminino , Seguimentos , Humanos , Ácido Hialurônico/administração & dosagem , Injeções Subcutâneas , Músculos Oculomotores/efeitos dos fármacos , Fatores de Tempo , Tomografia Computadorizada por Raios X , Viscossuplementos/administração & dosagem , Viscossuplementos/efeitos adversosRESUMO
A 64-year-old woman with relapsed acute myelogenous leukemia (AML) undergoing salvage chemotherapy developed rapid onset of right-sided ophthalmoplegia, proptosis, optic neuropathy, and vision loss from 20/30 to hand motions over a 3-hour period on day 4 of her treatment. CT scan of her orbits revealed a superolateral orbital mass and periocular edema. She underwent immediate canthotomy and cantholysis, and lateral orbitotomy with debulking of the mass later the same day. The histopathology was consistent with aggregates of myeloid blasts. Her vision recovered to 20/20 on postoperative day 1. Orbital granulocytic sarcoma is a rare condition often concurrent with AML, typically in the pediatric population and rarely in adults. Presentation as a fulminant orbitopathy with rapidly progressive optic neuropathy and vision loss over several hours has not been previously reported.
Assuntos
Leucemia Mieloide Aguda/complicações , Órbita/diagnóstico por imagem , Doenças Orbitárias/etiologia , Neoplasias Orbitárias/diagnóstico , Sarcoma Mieloide/diagnóstico , Doença Aguda , Biópsia , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Doenças Orbitárias/diagnóstico , Neoplasias Orbitárias/complicações , Sarcoma Mieloide/complicações , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: Idiopathic inflammatory tumor of the lacrimal gland, also called idiopathic dacryoadenitis, generally is treated with high-dose, long-term systemic corticosteroids, despite their limited success, high recurrence rate, and incidence of drug-induced side effects. This study describes the outcome of patients with idiopathic dacryoadenitis who were managed with surgical debulking. DESIGN: Retrospective case series from 2 tertiary referral centers. PARTICIPANTS: Forty-six patients (46 lacrimal glands). METHODS: Review of the clinical records, radiologic scans, and histopathologic specimens, with additional immunoglobulin G4 immunostaining. MAIN OUTCOME MEASURES: Clinical signs and symptoms at 2 months after the surgery and off medications. RESULTS: Before referral, 41% (19 of 46) of the patients had received systemic high-dose corticosteroids, after which they all showed recurrence, of whom 26% (5 of 19) became dependent on corticosteroids. At referral, all patients underwent debulking surgery of the inflammatory lacrimal gland mass for diagnostic and therapeutic reasons. Additionally, intralesional or systemic low-dose corticosteroids were given during the operation or the first postoperative days in 54% (25 of 46) of the patients. At 2 months after the debulking surgery, a full clinical recovery was seen in 80% (37 of 46) of the patients. A recurrence occurred in 8% (3 of 37) of the patients 4 months and 2.2 and 4.6 years later. Surgical failure (20%; 9 of 46) was correlated with prior corticosteroid treatment (P = 0.002, Fisher exact test), but not with sclerosing inflammation present in 28% (13 of 46). The median follow-up time was 7.2 years (range, 0.7-18 years). CONCLUSIONS: Debulking biopsy procedures for idiopathic dacryoadenitis, in addition to being diagnostic, may be therapeutic.
Assuntos
Dacriocistite/diagnóstico , Dacriocistite/cirurgia , Aparelho Lacrimal/cirurgia , Procedimentos Cirúrgicos Oftalmológicos , Adolescente , Adulto , Idoso , Criança , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto JovemRESUMO
Faithful segregation of replicated chromosomes is essential for maintenance of genetic stability and seems to be monitored by several mitotic checkpoints. Various components of these checkpoints have been identified in mammals, but their physiological relevance is largely unknown. Here we show that mutant mice with low levels of the spindle assembly checkpoint protein BubR1 develop progressive aneuploidy along with a variety of progeroid features, including short lifespan, cachectic dwarfism, lordokyphosis, cataracts, loss of subcutaneous fat and impaired wound healing. Graded reduction of BubR1 expression in mouse embryonic fibroblasts causes increased aneuploidy and senescence. Male and female mutant mice have defects in meiotic chromosome segregation and are infertile. Natural aging of wild-type mice is marked by decreased expression of BubR1 in multiple tissues, including testis and ovary. These results suggest a role for BubR1 in regulating aging and infertility.
Assuntos
Envelhecimento/genética , Infertilidade Feminina/genética , Infertilidade Masculina/genética , Proteínas Quinases/fisiologia , Aneuploidia , Animais , Proteínas de Ciclo Celular , Feminino , Masculino , Camundongos , Camundongos Mutantes , Fenótipo , Proteínas Quinases/genética , Proteínas Serina-Treonina QuinasesAssuntos
Órbita , Sarcoma Mieloide , Adulto , Diagnóstico Diferencial , Humanos , Leucemia Mieloide AgudaRESUMO
PURPOSE: To create and validate a new model of lower eyelid fibrosis in Dutch-belted rabbits. METHODS: Five Dutch-belted rabbits were injected with a transcutaneous 1-ml injection of standard 95% ethanol alcohol just inferior to the eyelid margin of one lower eyelid. A control injection of 1 ml of balanced saline solution was given to the opposite eyelid. A small tattoo was placed on the skin overlying the inferior orbital rim and used as a measuring point of reference in relation to the lower eyelid margin. Analysis was twofold: eyelid measurements were made over 8 weeks to determine the presence of eyelid shortening, and a histopathologic analysis was performed. RESULTS: Mean lower eyelid shortening was greater in the ethanol alcohol intervention eyelids than the control group (-3.4 mm +/- 1.67 mm vs. 0.5 mm +/- 0.71 mm, p = 0.01). Histopathologic analysis revealed extensive fibrosis in the ethanol alcohol invention eyelids compared with the control group. CONCLUSIONS: Ethanol alcohol induces eyelid fibrosis and lower eyelid shortening. This may be a useful model in the future testing of novel surgical or pharmacologic treatments.
Assuntos
Modelos Animais de Doenças , Pálpebras/patologia , Animais , Etanol/toxicidade , Pálpebras/efeitos dos fármacos , Fibrose/induzido quimicamente , Masculino , CoelhosRESUMO
Primary optic nerve sheath meningioma represents a proliferation of meningothelial cap cells of the arachnoid villi within the optic nerve sheath. Patients younger than 20 years of age make up less than 5% of all cases of pediatric primary optic nerve meningiomas. Histopathologically, the most common subtypes in children are transitional (54%) and meningotheliomatous (38%). This tumor has been called aggressive in the pediatric population, with surgical excision recommended. However, the tumor may spread intraorbitally, intracranially, or intraocularly after subtotal surgical resection. Recent studies examined the use of fractionated, stereotactic radiation in children with this tumor; however, follow-up is limited. Neurofibromatosis type 2 is concomitantly diagnosed in 28% of patients with pediatric primary optic nerve sheath meningioma. There have been no known deaths attributed primarily to this tumor.
Assuntos
Neoplasias Meníngeas/patologia , Meningioma/patologia , Neoplasias do Nervo Óptico/patologia , Adolescente , Criança , Pré-Escolar , Humanos , Lactente , Neoplasias Meníngeas/terapia , Meningioma/terapia , Neoplasias do Nervo Óptico/terapiaRESUMO
PURPOSE: To analyze 3 unusual mesenchymal transformations within the eye: adipose or osseous metaplasia of the lens and adipose tissue in the vitreous cavity. DESIGN: Observational case series. METHODS: Reevaluation of clinicopathologic diagnoses and histopathologic findings in sections stained with hematoxylin-eosin, periodic acid-Schiff (PAS) reaction, and Masson trichrome method. RESULTS: The 3 cases of mesenchymal transformation occurred in microphthalmic eyes with persistent hyperplastic primary vitreous (more recently termed persistent fetal vasculature). In 1 case there was total lens replacement with lamellar bone; in another, total replacement of the crystalline lens by adipose tissue; and in a third, an anomalous pocket of adipose tissue in the central vitreous. Multifocal remnants of the lens capsule were seen in the osseous case but were absent from the adipocytic cases. The vitreous adipose tissue was surrounded by an elaborate capillary plexus with an empty, collapsed PAS-positive lens capsule in the pupillary region. Anterior pigmented neuroectodermal disorganization, dysgenesis of angle structures, and a hypoplastic or disorganized iris were also observed in the 3 cases. CONCLUSIONS: After review of the literature, it appears that lenticular osseous replacement occurs more often than adipocytic. In addition to vascularization of the lens through a capsular dehiscence, other causes are explored, including direct epithelial-mesenchymal transformations of the lens epithelium or, less likely, of the disorganized adjacent neuroectoderm. The focus of vitreous adipose tissue may represent a transformed luxated lens extruded from its capsule, which was left behind in the pupillary zone.
Assuntos
Cápsula do Cristalino/cirurgia , Cristalino/patologia , Vítreo Primário Hiperplásico Persistente/diagnóstico , Capsulotomia Posterior/métodos , Acuidade Visual , Vitrectomia/métodos , Corpo Vítreo/diagnóstico por imagem , Pré-Escolar , Humanos , Cápsula do Cristalino/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Vítreo Primário Hiperplásico Persistente/cirurgia , Tomografia de Coerência Óptica , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Corpo Vítreo/cirurgia , Adulto JovemRESUMO
Critical to the clinical management of a patient with malignant melanoma is an understanding of its natural history. As with most malignant disorders, prognosis is highly dependent on the clinical stage (extent of tumor burden) at the time of diagnosis. The patient's clinical stage at diagnosis dictates selection of therapy. We review the state of the art in melanoma staging, prognosis, and therapy. Substantial progress has been made in this regard during the past 2 decades. This progress is primarily reflected in the development of sentinel lymph node biopsies as a means of reducing the morbidity associated with regional lymph node dissection, increased understanding of the role of neoangiogenesis in the natural history of melanoma and its potential as a treatment target, and emergence of innovative multimodal therapeutic strategies, resulting in significant objective response rates in a disease commonly believed to be drug resistant. Although much work remains to be done to improve the survival of patients with melanoma, clinically meaningful results seem within reach.
Assuntos
Melanoma/patologia , Melanoma/terapia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Humanos , Linfonodos/patologia , Metástase Neoplásica , Estadiamento de Neoplasias , PrognósticoRESUMO
Malignant melanoma is an aggressive, therapy-resistant malignancy of melanocytes. The incidence of melanoma has been steadily increasing worldwide, resulting in an increasing public health problem. Exposure to solar UV radiation, fair skin, dysplastic nevi syndrome, and a family history of melanoma are major risk factors for melanoma development. The interactions between genetic and environmental risk factors that promote melanomagenesis are currently the subject of ongoing research. Avoidance of UV radiation and surveillance of high-risk patients have the potential to reduce the population burden of melanoma. Biopsies of the primary tumor and sampling of draining lymph nodes are required for optimal diagnosis and staging. Several clinically relevant pathologic subtypes have been identified and need to be recognized. Therapy for early disease is predominantly surgical, with a minor benefit noted with the use of adjuvant therapy. Management of systemic melanoma is a challenge because of a paucity of active treatment modalities. In the first part of this 2-part review, we discuss epidemiology, risk factors, screening, prevention, and diagnosis of malignant melanoma. Part 2 (which will appear in the April 2007 issue) will review melanoma staging, prognosis, and treatment.
Assuntos
Melanoma , Neoplasias Cutâneas , Diagnóstico Diferencial , Humanos , Melanoma/diagnóstico , Melanoma/epidemiologia , Melanoma/patologia , Melanoma/prevenção & controle , Fatores de Risco , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/prevenção & controleRESUMO
PURPOSE: To report a case of amebic keratitis that showed unusually rapid clinical progression after corneal trauma in a patient 1 year after successful laser in situ keratomileusis (LASIK) surgery. METHODS: A 42-year-old pilot with a previous history of 20/20 uncorrected vision 1 year after LASIK surgery developed a clinical picture suggestive of acute microbial keratitis 7 days after the eye was traumatized by an ice chip. The correct diagnosis of amebic keratitis was confirmed by tissue biopsy 17 days after initial trauma when rapid progression of the keratitis necessitated excision of the LASIK flap. RESULTS: Pathology from the excised LASIK flap showed a mean of 30 amebic cysts per high power field. Thirty-three days after beginning 0.02% polyhexamethylene biguanide every hour, the patient developed culture negative hypopyon and an endothelial inflammatory plaque. Six months after starting antiamebic treatment, he developed sterile iris nodules and focal hemorrhages in the anterior chamber. Penetrating keratoplasty revealed persistence of amebic cysts in the anterior corneal stroma. Fifteen months after his initial injury, his vision remains hand motion. CONCLUSIONS: Amebic keratitis presented atypically and progressed rapidly to a stage of severe ring infiltrate within 10 days of trauma in a patient whose only risk factor was a history of uncomplicated LASIK more than 1 year before the trauma. Amebic keratitis should be included in the differential diagnosis of rapidly progressive corneal ulcer after trauma in patients with a history of LASIK.
Assuntos
Ceratite por Acanthamoeba/etiologia , Lesões da Córnea , Traumatismos Oculares/complicações , Ferimentos não Penetrantes/complicações , Ceratite por Acanthamoeba/parasitologia , Ceratite por Acanthamoeba/patologia , Adulto , Amoeba/isolamento & purificação , Animais , Biópsia , Córnea/parasitologia , Córnea/patologia , Diagnóstico Diferencial , Progressão da Doença , Seguimentos , Humanos , Gelo , Masculino , Fatores de TempoRESUMO
PURPOSE: To review the clinical, radiological, and histopathologic features in 8 patients with natural killer/T-cell lymphoma (NKTL) involving the orbit and/or ocular adnexa, and to describe the responses of these patients to various treatment regimens. DESIGN: Retrospective observational case series. PARTICIPANTS: Eight patients (5 male, 3 female) with NKTL involving the orbit and/or ocular adnexa were identified from 1999 through 2005. The mean age at presentation was 45 years (range, 26-65). METHODS: We retrospectively identified patients with NKTL of the ocular adnexa treated in the authors' medical centers from 1999 through 2004 using computerized diagnostic index retrieval. The clinical records and radiologic studies were analyzed to define modes of presentation and progression, response to therapy, and areas of anatomic involvement. Histopathologic findings, including the presence of CD3, CD56, and Epstein-Barr virus-encoded mRNA in each patient, were reviewed. MAIN OUTCOME MEASUREMENTS: Time of survival from presentation to last known follow-up and tumor-related death. RESULTS: Four of the 8 patients (50%) with NKTL involving the orbit or ocular adnexa had systemic involvement at presentation. Five of the 8 patients (62.5%) had concurrent sinonasal involvement, whereas 3 (37.5%) had orbital involvement alone. All lesions demonstrated CD3, CD56, and/or Epstein-Barr virus positivity on immunopathology studies. Therapy consisted of various chemotherapeutic regimens typically employed in the treatment of non-Hodgkins lymphoma, steroids, surgical intervention, and radiation. Seven (87.5%) patients died 5 weeks to 13 months after presentation, and 1 (12.5%) is alive without disease (5-year follow-up). CONCLUSIONS: Natural killer/T-cell orbital lymphoma is a rare Epstein-Barr virus-associated neoplasm that may occur with or without associated sinonasal involvement. Our series, the largest cohort reported to date, demonstrates the high lethality of this condition despite aggressive conventional therapy, suggesting that new treatment options should be considered early in the course of treatment of patients with this disorder.
Assuntos
Neoplasias Palpebrais/patologia , Células Matadoras Naturais/patologia , Doenças do Aparelho Lacrimal/patologia , Linfoma de Células T/patologia , Neoplasias Orbitárias/patologia , Neoplasias dos Seios Paranasais/patologia , Adulto , Idoso , Complexo CD3/metabolismo , Antígeno CD56/metabolismo , Terapia Combinada , Infecções por Vírus Epstein-Barr/diagnóstico por imagem , Infecções por Vírus Epstein-Barr/metabolismo , Infecções por Vírus Epstein-Barr/mortalidade , Infecções por Vírus Epstein-Barr/patologia , Neoplasias Palpebrais/diagnóstico por imagem , Neoplasias Palpebrais/mortalidade , Neoplasias Palpebrais/virologia , Feminino , Herpesvirus Humano 4/isolamento & purificação , Humanos , Doenças do Aparelho Lacrimal/diagnóstico por imagem , Doenças do Aparelho Lacrimal/mortalidade , Doenças do Aparelho Lacrimal/virologia , Linfoma de Células T/diagnóstico por imagem , Linfoma de Células T/mortalidade , Linfoma de Células T/virologia , Masculino , Pessoa de Meia-Idade , Neoplasias Orbitárias/diagnóstico por imagem , Neoplasias Orbitárias/mortalidade , Neoplasias Orbitárias/virologia , Neoplasias dos Seios Paranasais/diagnóstico por imagem , Neoplasias dos Seios Paranasais/mortalidade , Neoplasias dos Seios Paranasais/virologia , Estudos Retrospectivos , Taxa de Sobrevida , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: To evaluate the retinal toxicity of intravitreal bevacizumab in an animal model. DESIGN: Animal study. METHODS: Bevacizumab was injected into the vitreous of one eye of each of eight Dutch-belted rabbits; the other eye served as a control. Four rabbits received a dose of 1.25 mg/0.05 ml of bevacizumab intravitreally into one eye, and the other four rabbits were injected with 2.5 mg/0.1 ml of bevacizumab intravitreally into one eye. At one month, the rabbits were killed and both eyes enucleated. The eyes were fixed with paraformaldehyde 2% and examined by light microscopy. RESULTS: In all injected and control eyes, there was mild vacuolization in the ganglion cell layer, and disruption of photoreceptor outer segments in both treated and control eyes, to the same degree, consistent with autolysis. The optic nerve, retina, and retinal pigment epithelium were otherwise normal by light microscopy with no evidence of toxicity. CONCLUSIONS: Intravitreal bevacizumab at doses of 1.25 mg and 2.5 mg showed no signs of retinal or optic nerve toxicity by light microscopy in this rabbit model.
Assuntos
Inibidores da Angiogênese/toxicidade , Anticorpos Monoclonais/toxicidade , Modelos Animais , Retina/efeitos dos fármacos , Animais , Anticorpos Monoclonais Humanizados , Bevacizumab , Injeções , Masculino , Nível de Efeito Adverso não Observado , Coelhos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Corpo VítreoRESUMO
PURPOSE: To describe, test, and evaluate the pharmacokinetics of a novel posterior drug delivery system (PDS) by means of microcannulation of the suprachoroidal space in both the primate and pig animal model. DESIGN: Animal study. METHODS: A rhesus macaque (Macaca mulatta) (n = 1) and pig model (n = 93) were used to evaluate the PDS, a microcannula that combines a drug delivery channel with a fiber-optic illumination and optimal transition properties. The surgical technique, safety profile, histopathology, retinal and choroidal blood flow, injection of tracer dyes, and triamcinolone pharmacokinetics were studied. Pre- and postsurgical high-speed video confocal scanning laser ophthalmoscopy (cSLO) that used fluorescein and indocyanine green (ICG) imaging and wide-field fundus imaging studies were performed. Globes were enucleated for either histopathology or pharmacokinetics. RESULTS: Cannulation was performed in 93 of 94 animals. Complications included: endophthalmitis (1/94), choroidal tear (1/94), choroidal blood flow irregularities (4/94), postoperative inflammation (6/94), scleral ectasia (4/94), wound abscess (1/94), and others. Histopathology demonstrated normal anatomy in uncomplicated cases. Triamcinolone remains in the local ocular tissue for at least 120 days, and measurable at very low levels in the systemic circulation. CONCLUSIONS: Accessing the suprachoroidal space by the microcannulation system can be performed in a safe and reproducible manner by using careful surgical technique. Forceful PDS tip impact into connective tissues in the macular and optic nerve regions should be avoided. Triamcinolone pharmacokinetics are unique and suggest long-term local tissue levels with low systemic levels. PDS access to the suprachoroidal space represents a novel drug delivery method, applicable to a wide variety of pharmacotherapies to the macula, optic nerve, and posterior pole.
Assuntos
Cateterismo/métodos , Corioide/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Espaço Extracelular/efeitos dos fármacos , Glucocorticoides/administração & dosagem , Triancinolona Acetonida/administração & dosagem , Animais , Corioide/irrigação sanguínea , Corioide/metabolismo , Corantes , Espaço Extracelular/metabolismo , Angiofluoresceinografia , Glucocorticoides/farmacocinética , Humanos , Verde de Indocianina , Macaca mulatta , Oftalmoscopia , Vasos Retinianos/fisiologia , Suínos , Triancinolona Acetonida/farmacocinética , Gravação em VídeoRESUMO
A number of eyelid lesions in early childhood, most commonly dacryoceles and hemangiomas, have been documented to cause astigmatic changes of the cornea. Juvenile xanthogranuloma (JXG) is typically reported to include both cutaneous skin and anterior ocular segment lesions. We report a case of a 10-month-old infant in which a subcutaneous JXG lesion of the lower eyelid resulted in visually significant astigmatic amblyopia.
Assuntos
Ambliopia/etiologia , Astigmatismo/etiologia , Doenças Palpebrais/complicações , Xantogranuloma Juvenil/complicações , Ambliopia/fisiopatologia , Ambliopia/terapia , Astigmatismo/fisiopatologia , Astigmatismo/terapia , Bandagens , Movimentos Oculares , Doenças Palpebrais/patologia , Doenças Palpebrais/cirurgia , Feminino , Seguimentos , Humanos , Lactente , Procedimentos Cirúrgicos Oftalmológicos , Refração Ocular , Privação Sensorial , Xantogranuloma Juvenil/patologia , Xantogranuloma Juvenil/cirurgiaRESUMO
PURPOSE: To evaluate the functionality of a corneal endothelium reconstituted by injection of corneal endothelial cells (CEC) in the anterior chamber of a feline model. METHODS: We operated the right eyes of 16 animals. Eight underwent central endothelial scraping and injection with 2 × 10(5) (n = 4) or 1 × 10(6) (n = 4) feline CEC supplemented with Y-27632 and labeled with 3,3'-Dioctadecyl-5,5'-Di(4-Sulfophenyl)Oxacarbocyanine (SP-DiOC18[3] or DiOC). After total endothelial scraping, two eyes were injected with 1 × 10(6) labeled CEC and Y-27632. The central (n = 3) or entire (n = 3) endothelium was scraped in six eyes followed by Y-27632 injection without CEC. Subjects were positioned eyes down for 3 hours. Outcomes included graft transparency, pachymetry, CEC morphometry, histology, electron microscopy, and function and wound healing-related protein immunostaining. RESULTS: Postoperatively, corneas grafted with 2 × 10(5) CEC and centrally scraped controls displayed the best transparency and pachymetry. Corneas grafted with 1 × 10(6) CEC yielded intermediate results. Entirely scraped controls remained hazy and thick. Histopathology revealed a confluent endothelial monolayer expressing sodium-potassium adenosine triphosphatase (Na(+)/K(+)-ATPase) and zonula occludens-1 (ZO-1) in corneas grafted with 2 × 10(5) CEC and centrally scraped controls, a nonuniform endothelial multilayer without expression of functional proteins in centrally scraped corneas grafted with 1 × 10(6) CEC, and a nonfunctional fibrotic endothelium in entirely scraped grafts and controls. Expression of DiOC in grafts was scarce. CONCLUSIONS: Injected CEC contributed little to the incompletely functional endothelium of grafted corneas. Y-27632 injection without CEC following scraping reconstituted the healthiest endothelium. Further studies investigating the therapeutic effect of Y-27632 alone are needed to validate these conclusions.
Assuntos
Terapia Baseada em Transplante de Células e Tecidos , Modelos Animais de Doenças , Endotélio Corneano/fisiologia , Endotélio Corneano/transplante , Amidas/farmacologia , Animais , Gatos , Contagem de Células , Células Cultivadas , Paquimetria Corneana , Inibidores Enzimáticos/farmacologia , Sobrevivência de Enxerto/fisiologia , Injeções Intraoculares , Microscopia Eletrônica , Piridinas/farmacologia , ATPase Trocadora de Sódio-Potássio/metabolismo , Transplante Homólogo , Cicatrização/fisiologia , Proteína da Zônula de Oclusão-1/metabolismoRESUMO
PURPOSE: To measure the concentration of toxic heavy metals in the fluids and tissues of human eyes. DESIGN: Laboratory investigation. METHODS: Thirty autopsy eyes of 16 subjects were dissected to obtain the aqueous, vitreous, lens, ciliary body, retina, and retinal pigment epithelium/choroid. Concentrations of lead, cadmium, mercury, and thallium in ocular tissues, ocular fluids, and blood were determined using an inductively coupled plasma-mass spectrometer and expressed as ng/g. Heavy metal concentrations in ocular tissues were compared using a paired t test. RESULTS: Lead and cadmium were found in all of the pigmented ocular tissues studied, concentrating to the greatest extent in the retinal pigment epithelium/choroid (mean, 432 +/- 485 ng/g and 2,358 +/- 1,522 ng/g). Cadmium was found in the retina in all eyes (mean, 1,072 +/- 489 ng/g) whereas lead was found in the retina in 9 (30%) of 30 eyes (mean, 53 +/- 54 ng/g). Trace concentrations of lead and cadmium were detected in the vitreous (mean, 0.5 +/- 1.0 ng/dl and 19 +/- 29 ng/dl), lens (mean, 13 +/- 18 ng/g and 20 +/- 18 ng/g), and blood (mean, 0.5 +/- 1.2 mug/dl and 3.1 +/- 4.1 mug/l) but were not detected in the aqueous. Mercury and thallium were not detected in any ocular tissues or fluids or in the blood. CONCLUSIONS: Lead and cadmium accumulate in human ocular tissues, particularly in the retinal pigment epithelium and choroid. The potential ocular toxicity of these heavy metals and their possible role in eye disease requires further study.
Assuntos
Cádmio/análise , Olho/química , Chumbo/análise , Mercúrio/análise , Tálio/análise , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Espectrometria de Massas/métodos , Pessoa de Meia-Idade , Estudos Prospectivos , Valores de ReferênciaRESUMO
The Association of Directors of Anatomic and Surgical Pathology developed recommendations for the surgical pathology report for common malignant tumors. The recommendations for tumors of the eye and its adnexa are reported.
Assuntos
Neoplasias Oculares/cirurgia , Prontuários Médicos/normas , Procedimentos Cirúrgicos Oftalmológicos/normas , Patologia Cirúrgica/normas , Neoplasias Oculares/patologia , Humanos , Patologia Cirúrgica/métodos , Garantia da Qualidade dos Cuidados de Saúde , Sociedades Médicas , Estados UnidosRESUMO
PURPOSE: Gene therapy for chronic retinal diseases will require long-term expression of therapeutic transgenes. Lentiviral and adenoviral (Ad) vectors are gene delivery systems with markedly different properties. Lentiviral vectors require integration into the host genome, which facilitates long-term expression, while Ad vectors remain episomal. We compared time course, location, and extent of transgene expression from replication-deficient feline immunodeficiency virus (FIV) vectors and Ad vectors in neonatal rat retina. METHODS: A dose-response study was conducted to determine the optimal subretinal dose for comparison of FIV and Ad vectors with an internal cassette expressing beta-galactosidase under transcriptional control of the CMV immediate-early gene promoter/enhancer. Forty-two five-day old Sprague-Dawley rats received subretinal injections of 2 microl containing 2x10(3) transducing units (TU, n=14), 2x10(4) TU (n=14) or 2x10(5) TU (n=14) of FIV vector (right eye) and Ad vector (left eye). Expression was evaluated 48 h after transduction. In the subsequent long-term expression study, 60 five-day old rats received a subretinal injection of 2x10(5) TU FIV vector (right eye) and Ad vector (left eye). Ten pairs of eyes were analyzed at 1 week, 1 month, 3 months, 6 months, 12 months, and the remainder at 16 months. Eye cups were evaluated in a masked manner for extent of beta-galactosidase expression (graded 0-5) by whole mount microscopy and by cross sectional histology. RESULTS: In the dose-response study, 2x10(5) TU resulted in consistent, widespread retinal transduction with both vectors and was selected as the dose for the subsequent study. In the long-term expression study, FIV vector resulted in a higher grade of expression than Ad at multiple single time points and produced higher overall expression when data from all eyes across the entire 16 month study were analyzed (p=0.01). Retinal expression was present at 16 months with both vectors. beta-galactosidase expression was limited to the retinal pigment epithelium (RPE) until the first month, but later was also found to a lesser extent in neurosensory retina with each vector. In contrast to FIV, most Ad injected eyes showed signs of focal accumulation of macrophage-like cells with disrupted retinal architecture. CONCLUSIONS: Both FIV and Ad vectors result in long-term transgene expression in RPE after subretinal injection. FIV vectors show more promise than Ad as delivery systems for retinal diseases since they transduce greater areas of RPE, result in less cellular infiltrate, and cause less disruption of retinal architecture. The persistent expression at 16 months of follow-up suggests that these lentiviral vectors are useful for gene therapy of chronic retinal diseases.
Assuntos
Adenoviridae/genética , Regulação Enzimológica da Expressão Gênica/fisiologia , Vetores Genéticos , Vírus da Imunodeficiência Felina/genética , Retina/enzimologia , beta-Galactosidase/genética , Animais , Vírus Defeituosos , Seguimentos , Técnicas de Transferência de Genes , Ratos , Ratos Sprague-Dawley , Retina/virologia , Transgenes , beta-Galactosidase/metabolismoRESUMO
PURPOSE: To determine the probability of converting from pigment dispersion syndrome to pigmentary glaucoma. DESIGN: Retrospective community-based study of all newly diagnosed cases of pigment dispersion syndrome or pigmentary glaucoma. METHOD: Subjects were patients newly diagnosed with pigment dispersion syndrome or pigmentary glaucoma from 1976 to 1999 in Olmsted County, Minnesota. Criteria for pigment dispersion syndrome were two of three signs: midperipheral, radial iris transillumination defects; Krukenberg spindle; heavy trabecular meshwork pigmentation. Criteria for pigmentary glaucoma were pigment dispersion syndrome and two of three findings: intraocular pressure (IOP) greater than 21 mm, optic nerve damage, or visual field loss. Kaplan-Meier survival curves were used to determine the probability of conversion to pigmentary glaucoma. RESULTS: A total of 113 patients were newly diagnosed with pigment dispersion syndrome over the 24-year period. Of these, 9 persons developed pigmentary glaucoma or elevated IOP requiring therapy. The probability of converting to pigmentary glaucoma was 10% at 5 years and 15% at 15 years. An additional 23 patients were found to have pigmentary glaucoma at their initial examination. The mean age at diagnosis of pigmentary glaucoma was 42 +/- 12 years; 78% of patients were male, whereas 58% of patients with pigmentary dispersion syndrome glaucoma were male. The most significant risk factor for conversion to pigmentary glaucoma was an IOP greater than 21 mm Hg at initial examination, whereas age, refractive error, and family history of glaucoma were not correlated with conversion. CONCLUSIONS: The risk of developing pigmentary glaucoma from pigment dispersion syndrome was 10% at 5 years and 15% at 15 years. Young, myopic men were most likely to have pigmentary glaucoma. An IOP greater than 21 mm Hg at initial examination was associated with an increased risk of conversion.