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1.
Invest Ophthalmol Vis Sci ; 48(7): 2967-74, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17591861

RESUMO

PURPOSE: To model the behavior of uveal melanoma in the liver. METHODS: A 15-muL suspension of metastatic MUM2B or either primary OCM1 or M619 uveal melanoma cells was injected into the liver parenchyma of 105 CB17 SCID mice through a 1-cm abdominal incision. Animals were killed at 2, 4, 6, or 8 weeks after injection. Before euthanatization, 3% FITC-BSA buffer was injected into the retro-orbital plexus of one eye of three mice. Liver tissues were examined by light and fluorescence microscopy, and were stained with human anti-laminin. Vasculogenic mimicry patterns were reconstructed from serial laser scanning confocal microscopic stacks. RESULTS: OCM1a cells formed microscopic nodules in the mouse liver within 2 weeks after injection and metastasized to the lung 6 weeks later. By contrast, M619 and MUM2B cells formed expansile nodules in the liver within 2 weeks and gave rise to pulmonary metastases within 4 weeks after injection. Vasculogenic mimicry patterns, composed of human laminin and identical with those in human primary and metastatic uveal melanomas, were detected in the animal model. The detection of human rather than mouse laminin in the vasculogenic mimicry patterns in this model demonstrates that these patterns were of tumor cell origin and were not co-opted from the mouse liver microenvironment. CONCLUSIONS: There are currently no effective treatments for metastatic uveal melanoma. This direct-injection model focuses on critical interactions between the tumor cell and the liver. It provides for translationally relevant approaches to the development of new modalities to detect small tumor burdens in patients, to study the biology of clinical dormancy of metastatic disease in uveal melanoma, to design and test novel treatments to prevent the emergence of clinically manifest liver metastases after dormancy, and to treat established uveal melanoma metastases.


Assuntos
Modelos Animais de Doenças , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/secundário , Melanoma/secundário , Neoplasias Uveais/patologia , Animais , Endotélio Vascular/patologia , Humanos , Laminina/metabolismo , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/metabolismo , Neoplasias Pulmonares/irrigação sanguínea , Neoplasias Pulmonares/metabolismo , Masculino , Melanoma/irrigação sanguínea , Melanoma/metabolismo , Camundongos , Camundongos SCID , Microscopia Confocal , Microscopia de Fluorescência , Transplante de Neoplasias , Neovascularização Patológica , Células Tumorais Cultivadas , Neoplasias Uveais/irrigação sanguínea , Neoplasias Uveais/metabolismo
2.
Invest Ophthalmol Vis Sci ; 48(10): 4399-402, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17898257

RESUMO

PURPOSE: To develop a method to screen for serum biomarkers of early hepatic metastasis from uveal melanoma. METHODS: Cytokeratin 18 (TPS) was identified from gene expression profiles as protein generated by highly invasive uveal melanoma cells. Sera were collected from two groups of 15 SCID mice 2 weeks after injection of either tissue culture medium or MUM2B human metastatic uveal melanoma cells into the mouse liver. Serum TPS levels were assayed in 53 healthy human controls, 64 uveal melanoma patients who were disease free for at least 10 years, and 37 patients with metastatic uveal melanoma. RESULTS: After 2 weeks, small hepatic nodules (0.1-2.8 mm; mean, 0.80 mm) developed in 11 of 15 mice injected with MUM2B cells. Serum TPS levels in media-injected mice (84.7 U/L) were substantially lower than levels in MUM2B-injected mice (601 mug/L). TPS levels were significantly higher (P < 0.0001) in patients with metastatic uveal melanoma (139.63 +/- 22.20) than in healthy controls (54.23 +/- 0.01) or in patients free of disease (69.29 +/- 9.76). Significant differences were found between TPS levels before and after the development of hepatic metastases (P < 0.01), and serum TPS levels became elevated in four patients at least 6 months before the detection of hepatic metastases by abdominal ultrasonography. CONCLUSIONS: The direct-injection model of uveal melanoma in the mouse liver may be used to screen for potential serum biomarkers of metastatic uveal melanoma.


Assuntos
Biomarcadores Tumorais/sangue , Modelos Animais de Doenças , Neoplasias Hepáticas/sangue , Melanoma/sangue , Peptídeos/sangue , Neoplasias Uveais/sangue , Animais , Antígenos de Neoplasias/sangue , Ensaio de Imunoadsorção Enzimática , Perfilação da Expressão Gênica , Humanos , Queratina-18/sangue , Neoplasias Hepáticas/secundário , Melanoma/secundário , Camundongos , Camundongos SCID , Células Tumorais Cultivadas , Neoplasias Uveais/patologia
3.
Br J Ophthalmol ; 91(6): 743-5, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17215269

RESUMO

AIM: To determine the value of a topical carbonic anhydrase inhibitor for extended treatment of cystoid macular oedema (CME) in patients with retinitis pigmentosa (RP). METHOD: Eight patients with RP and foveal cystic-appearing lesions observed on fundus examination and by optical coherence tomography (OCT) testing were treated with a topical form of carbonic anhydrase inhibitor. RESULTS: Foveal cystic-like spaces were documented by OCT testing in all eight patients before treatment. All patients had a significant reduction in their foveal thickness (FT) and foveal zone thickness (FZT) in at least one eye after using 2% dorzolamide three times a day for 1 or 2 months. Six patients had an improvement in both eyes. After an additional 6-13 months of the same treatment regimen, out of six patients who had a sustained reduction in FT and FZT in at least one eye, four had this reduction in both eyes. While they were still taking Trusopt, a recurrence (rebound) of CME in both eyes was observed in two patients, whereas one patient had a sustained improvement in one eye and rebound of CME in the other eye. Out of 8 patients, 3 showed an improvement in their visual acuity by > or =7 letters, in at least one eye, on Snellen acuity charts, which was determined as clinically significant. CONCLUSION: Results from this study suggest that patients with RP could potentially sustain a beneficial effect from continued treatment with a topical form of carbonic anhydrase inhibitor.


Assuntos
Inibidores da Anidrase Carbônica/uso terapêutico , Edema Macular/tratamento farmacológico , Retinose Pigmentar/complicações , Sulfonamidas/uso terapêutico , Tiofenos/uso terapêutico , Esquema de Medicação , Seguimentos , Fóvea Central/patologia , Humanos , Edema Macular/etiologia , Edema Macular/patologia , Edema Macular/fisiopatologia , Estudos Prospectivos , Tomografia de Coerência Óptica , Resultado do Tratamento , Acuidade Visual
4.
Arch Ophthalmol ; 124(6): 887-9, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16769844

RESUMO

OBJECTIVE: To report a novel de novo vitelliform macular dystrophy (VMD2) mutation in a patient with Best macular dystrophy. METHODS: Best-corrected visual acuity, dilated fundus examination, and electro-oculography were performed in a patient with Best macular dystrophy and his parents. Both the patient and his parents also had blood samples drawn, and their DNA was analyzed by direct genomic sequencing. RESULTS: A heterozygous VMD2 gene missense mutation in exon 2 (Thr6Ala [ACA>GCA]) was identified in the proband. This mutation was not present in his clinically unaffected parents. CONCLUSIONS: A novel de novo mutation in the VMD2 gene was found in a patient whose phenotype and electro-oculographic findings were characteristic of Best macular dystrophy, whereas both parents were phenotypically and genetically unaffected. The findings in this family document that a de novo mutation needs to be considered when an isolated family member is found to have a Best disease phenotype.


Assuntos
Proteínas do Olho/genética , Degeneração Macular/genética , Mutação de Sentido Incorreto , Bestrofinas , Criança , Canais de Cloreto , Análise Mutacional de DNA , Eletroculografia , Éxons/genética , Humanos , Degeneração Macular/fisiopatologia , Masculino , Reação em Cadeia da Polimerase , Retina/fisiopatologia , Acuidade Visual
5.
Am J Ophthalmol ; 141(5): 850-8, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16546110

RESUMO

PURPOSE: To determine if topical dorzolamide, as observed with the use of systemic acetazolamide and methazolamide, would be effective in treating cystoid macular edema (CME) in patients with retinitis pigmentosa (RP). DESIGN: Prospective, nonrandomized clinical trial. METHODS: setting: Institutional. patients: Fifteen patients with CME and RP. intervention: A baseline visual acuity and optical coherence tomography (OCT) measurements were obtained in all patients. Each one of them was then treated with topical dorzolamide, three times a day, for at least four weeks in both eyes. main outcome measures: Significant decrease in "foveal thickness" (more than 16%) and "foveal zone thickness" (more than 11%), as measured by OCT. RESULTS: Thirteen (87%) of 15 patients showed a significant decrease in retinal thickness in at least one eye after use of topical dorzolamide for at least four weeks. Five patients (33%) demonstrated improvement in both eyes. All patients, except one, who responded showed the effect within four weeks, but were monitored for a period of two to nine months (average 4.5 months). Four patients (31%) who showed an initial improvement in macular edema showed worsening with continued treatment. CONCLUSIONS: The present study documents the potential efficacy of topical dorzolamide for treating CME in patients with RP. We observed that some patients may show a "rebound phenomenon" with continued use of the medication; hence, there is a need for careful follow-up in patients being treated.


Assuntos
Inibidores da Anidrase Carbônica/uso terapêutico , Edema Macular/tratamento farmacológico , Retinose Pigmentar/complicações , Sulfonamidas/uso terapêutico , Tiofenos/uso terapêutico , Administração Tópica , Adolescente , Adulto , Técnicas de Diagnóstico Oftalmológico , Feminino , Humanos , Edema Macular/complicações , Edema Macular/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tomografia de Coerência Óptica , Acuidade Visual
6.
Ophthalmology ; 112(3): 495-501, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15745780

RESUMO

PURPOSE: To evaluate and correlate findings obtained by optical coherence tomography (OCT) imaging with visual acuity (VA) and macular lesions in patients with X-linked retinoschisis (XLRS). DESIGN: Prospective comparative case series. PARTICIPANTS: Thirty-one patients with confirmed XLRS. METHODS: Best-corrected VA was determined using Early Treatment Diabetic Retinopathy Study charts, and a dilated funduscopic examination was performed on all patients. For all patients, the macula in each eye was OCT imaged. A correlation between VA, macular presentation, and OCT images was determined. MAIN OUTCOME MEASURES: Analysis of findings on OCT images, including foveal thickness and the area of macular cystic-appearing lesions, and their correlation with VA. RESULTS: Twenty-five patients with funduscopically evident cystic-appearing macular lesions demonstrated cysticlike spaces on OCT images. No statistically significant correlation was observed between the macular area of the cysticlike spaces, foveal thickness, and VA. Three patients with no funduscopic or OCT evidence of foveal cysts demonstrated thinning of the fovea on OCT images and more extensive reduction of their VA. Retinal papillomacular bundle nerve fiber layer thickness on OCT images showed no significant difference between control and patient groups. CONCLUSIONS: In XLRS patients with cystic-appearing macular lesions, there was a lack of correlation between VA, foveal thickness, and cystic area. The anatomical appearance of smaller perifoveal cysts on OCT imaging was most consistent with their location being primarily within the inner nuclear layer of the retina. In older patients, macular cysts were no longer apparent clinically or by OCT imaging, and foveal thickness was reduced. The findings on OCT images are consistent with the hypothesis of a primary Muller cell defect in patients with XLRS.


Assuntos
Técnicas de Diagnóstico Oftalmológico , Macula Lutea/patologia , Retinosquise/diagnóstico , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Adolescente , Adulto , Criança , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
7.
Neuroimaging Clin N Am ; 15(1): 49-67, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15927860

RESUMO

Although the diagnosis of retinoblastoma (Rb) is made primarily by means of clinical examination, CT and MR imaging are helpful to confirm the diagnosis, determine the extent of the intraocular tumor, and exclude extraocular or intracranial involvement. They are also valuable in differentiating Rb from lesions that simulate Rb.


Assuntos
Imageamento por Ressonância Magnética , Neoplasias da Retina/diagnóstico por imagem , Neoplasias da Retina/patologia , Retinoblastoma/diagnóstico por imagem , Retinoblastoma/patologia , Tomografia Computadorizada por Raios X , Diagnóstico Diferencial , Humanos , Distúrbios Pupilares/etiologia , Neoplasias da Retina/complicações , Retinoblastoma/complicações
8.
Ophthalmology ; 111(10): 1899-904, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15465554

RESUMO

PURPOSE: To determine the value of optical coherence tomography (OCT) imaging in the diagnosis and monitoring of cystoid macular edema (CME) in patients with retinitis pigmentosa (RP). DESIGN: Prospective, noncomparative, small case series. PARTICIPANTS: Three patients with RP and cystic-appearing spaces in the macula on OCT images. INTERVENTION: All 3 patients were treated with a carbonic anhydrase inhibitor, and 1 also received topical and systemic steroids. MAIN OUTCOME MEASURES: Changes in OCT images, fluorescein angiography, and best-corrected visual acuity (VA). RESULTS: Although foveal cysticlike spaces were evident on OCT images in all 3 patients, only 1 patient showed CME on fluorescein angiography at baseline. Two of the 3 patients showed funduscopic evidence of macular cystic lesions, whereas a third showed no clinically evident fundus changes in the macula. Optical coherence tomography images documented improvement in the cystic-appearing spaces after treatment with the carbonic anhydrase inhibitor. Changes on fluorescein angiography were either not apparent or considerably less apparent. An improvement of > or =1 line on a Snellen acuity chart was recorded in 2 patients, whereas a third showed no change of VA in either eye. CONCLUSIONS: Optical coherence tomography is a potential method for the diagnosis and monitoring of CME in patients with RP. It was more sensitive in this regard than either fluorescein angiography or funduscopic examination.


Assuntos
Edema Macular/diagnóstico , Retinose Pigmentar/diagnóstico , Tomografia de Coerência Óptica/métodos , Adolescente , Adulto , Inibidores da Anidrase Carbônica/uso terapêutico , Terapia Combinada , Feminino , Angiofluoresceinografia , Glucocorticoides/uso terapêutico , Humanos , Edema Macular/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Retinose Pigmentar/tratamento farmacológico , Acuidade Visual
9.
Retina ; 27(3): 349-57, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17460591

RESUMO

PURPOSE: : To determine the association between retinal thickness and visual function in patients with retinitis pigmentosa (RP). METHODS: : Retinal thickness was estimated from optical coherence tomography (OCT) images obtained for six patients with RP. The thickness measurements were compared with dark-adapted rod and minimally light-adapted cone thresholds obtained by psychophysical testing using a Tübinger perimeter and with standard light-adapted Humphrey visual field (HVF) perimetric thresholds. RESULTS: : Four patterns of association between retinal thickness and visual function were observed: normal retinal thickness and normal visual thresholds; normal retinal thickness and normal cone thresholds but elevated rod thresholds; reduced retinal thickness and elevated rod and cone thresholds; and normal retinal thickness and normal Humphrey thresholds but elevated rod and cone thresholds by Tübinger perimetry. CONCLUSION: : Retinal thinning was observed only when both rod and cone thresholds were elevated. However, normal retinal thickness was not necessarily accompanied by normal visual sensitivity. The determination of retinal thickness by OCT and its association with psychophysical measurements of visual function could be useful for identifying those RP patients who might respond most optimally to therapeutic interventions.


Assuntos
Retina/patologia , Retinose Pigmentar/fisiopatologia , Limiar Sensorial/fisiologia , Acuidade Visual/fisiologia , Adulto , Eletrorretinografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Células Fotorreceptoras de Vertebrados/fisiologia , Estudos Prospectivos , Psicometria , Tomografia de Coerência Óptica , Testes de Campo Visual , Campos Visuais/fisiologia
10.
Retina ; 27(8): 1112-8, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18040255

RESUMO

PURPOSE: To demonstrate the presence of a rebound effect with the use of acetazolamide for the treatment of cystoid macular edema (CME) in patients with retinitis pigmentosa (RP). METHODS: Six patients with RP and cystic-appearing lesions in the macula demonstrated by fluorescein angiography and/or optical coherence tomography (OCT) were treated with an oral form of carbonic anhydrase inhibitor (acetazolamide [500 mg]) as a single daily dose. RESULTS: All patients, treated with acetazolamide for a period of 3 weeks to 5 weeks, had initial improvement of macular edema demonstrated by OCT. However, extended use of acetazolamide, for at least 8 weeks to 12 weeks, resulted in recurrence (rebound) of CME in 3 of the 6 patients. CONCLUSIONS: Results from our study suggest that rebound of CME with the continued use of acetazolamide observed by OCT may occur more frequently than previously appreciated.


Assuntos
Acetazolamida/efeitos adversos , Inibidores da Anidrase Carbônica/efeitos adversos , Edema Macular/induzido quimicamente , Retinose Pigmentar/complicações , Administração Oral , Adulto , Feminino , Angiofluoresceinografia , Humanos , Edema Macular/tratamento farmacológico , Edema Macular/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Tomografia de Coerência Óptica , Acuidade Visual
11.
Retina ; 26(7): 741-5, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16963845

RESUMO

PURPOSE: To determine the value of a topical carbonic anhydrase inhibitor for the treatment of foveal lesions in patients with X-linked retinoschisis (XLRS). METHODS: Eight patients with XLRS and foveal cystic-appearing spaces by fundus examination and by optical coherence tomography (OCT) were treated with a topical form of carbonic anhydrase inhibitor. Changes in "foveal thickness" and "foveal zone thickness" were measured by OCT, and changes of best-corrected visual acuity were measured by Early Treatment Diabetic Retinopathy Study (ETDRS) charts. RESULTS: Seven of eight patients treated with 2% dorzolamide had a noticeable reduction in foveal thickness as well as cystic-appearing spaces by OCT. This reduction was found in both eyes in four of these patients and in one eye in one patient after 1 month of treatment. After an additional 1 month to 2 months of the same treatment regimen, two additional patients also had a noticeable reduction in foveal thickness as well as cystic-appearing spaces. Of these seven patients who had an improvement shown by OCT with treatment, five also had improvement of their visual acuity by >or=7 letters in at least one eye on ETDRS charts. CONCLUSION: The present study shows the efficacy of topical dorzolamide for treating foveal cystic-appearing lesions in patients with XLRS.


Assuntos
Inibidores da Anidrase Carbônica/uso terapêutico , Retinosquise/tratamento farmacológico , Sulfonamidas/uso terapêutico , Tiofenos/uso terapêutico , Administração Tópica , Adulto , Cistos/diagnóstico , Cistos/tratamento farmacológico , Fóvea Central/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Soluções Oftálmicas/uso terapêutico , Estudos Prospectivos , Retinosquise/diagnóstico , Tomografia de Coerência Óptica , Acuidade Visual
12.
Retina ; 25(5): 612-8, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16077359

RESUMO

PURPOSE: To determine the presence of fundus findings and natural course of visual acuity change in patients with juvenile X-linked retinoschisis (XLRS). METHODS: A retrospective longitudinal study of 38 patients with juvenile XLRS (age range, 9-65 years) was conducted. Best-corrected visual acuity, Goldmann visual fields, and results of slit-lamp biomicroscopy of the anterior segment and dilated fundus examination were obtained for all patients. Visual acuity findings at the most recent and initial visits were compared. Follow-up ranged from 1 year to 28 years (mean, 10.2 years). Twenty-five patients were observed for > 5 years, and 11, for > or = 15 years. RESULTS: Foveal lesions varied from predominantly radial striations (3%), microcystic lesions (34%), honeycomblike cysts (8%), or their combinations (31%) to non-cystic-appearing foveal changes, such as pigment mottling (8%), loss of the foveal reflex (8%), or an atrophic-appearing lesion (8%). Twelve patients (32%) had situs inversus of their retinal vessels. We observed a superior nasal restriction in the peripheral visual field even in the absence of clinically apparent peripheral retinoschisis. Of the 38 patients who were seen more than once, using logarithm of the minimum angle of resolution (logMAR) comparison, 4 had a decrease in visual acuity of > 0.1 logMAR, equivalent to > 1 line on an ETDRS chart, in their better seeing eye, and 3 had a reduction in visual acuity of > 0.2 logMAR in their better eye. CONCLUSIONS: A limited change in visual acuity was observed in our cohort of 38 patients with XLRS even over an extended period. However, those patients with non-cystic-appearing changes within the fovea, including pigment mottling or an atrophic-appearing lesion, tended to have a more appreciable degree of visual acuity impairment compared with those patients with a cystic-appearing foveal change.


Assuntos
Fundo de Olho , Retinosquise/fisiopatologia , Transtornos da Visão/fisiopatologia , Acuidade Visual , Adolescente , Adulto , Idoso , Criança , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
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