RESUMEN
PURPOSE: To compare quality of life (QoL) in patients with uveal melanoma after enucleation and stereotactic radiosurgery to that in an age-matched patient collective. METHODS: QoL was assessed in a cross-sectional survey and compared among 32 uveal melanoma patients after enucleation, 48 patients after stereotactic radiosurgery (CyberKnife(®); Accuray(®) Incorporated, Sunnyvale, CA, USA), and an age-matched control group of 35 patients, using the SF-12 Health Survey. Statistical analysis was performed with Fisher's exact test, Student's t test, one-way ANOVA analysis, Wilcoxon rank-sum (Mann-Whitney test), and ordered logistic regression for multivariate analysis. RESULTS: There was no significant difference in QoL between patients treated by stereotactic radiosurgery and the age-matched control group. After enucleation, patients presented significantly lower values in Physical Functioning (PF), Role Physical (RP), and Role Emotional (RE) compared to the radiosurgery and control group. To control for the overall QoL lowering effect of visual loss, the QoL of the patients who underwent enucleation was compared with the QoL of patients suffering severe functional loss after CyberKnife radiosurgery in a subgroup analysis, which showed no statistically significant difference. The number of comorbidities had a significant impact on QoL in multivariate analysis. CONCLUSIONS: Superior performance in PF, RP, and RE suggests that CyberKnife represents a suitable first-line therapy for uveal melanoma. In cases with painful amaurosis or vast tumor recurrence, enucleation can be performed with an acceptable QoL outcome.
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Enucleación del Ojo , Melanoma/psicología , Melanoma/terapia , Calidad de Vida/psicología , Radiocirugia , Neoplasias de la Úvea/psicología , Neoplasias de la Úvea/terapia , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Masculino , Melanoma/radioterapia , Melanoma/cirugía , Persona de Mediana Edad , Estudios Retrospectivos , Perfil de Impacto de Enfermedad , Encuestas y Cuestionarios , Neoplasias de la Úvea/radioterapia , Neoplasias de la Úvea/cirugíaRESUMEN
BACKGROUND: Multikinase inhibitors (MKI) interfere effectively at different levels of the neovascularisation cascade. Early clinical and experimental data suggest that MKIs represent a promising novel approach for the treatment of neovascular age-related macular degeneration (AMD). However, so far little is known about the biocompatibility of MKIs regarding human ocular cells. This in vitro study investigates and compares the biocompatibility of three MKIs, axitinib, pazopanib, and sorafenib regarding ocular cells of the anterior and posterior segments, as well as organ-cultured donor corneas. METHODS: Primary human optic nerve head astrocytes (ONHA), trabecular meshwork cells (TMC), and retinal pigment epithelium (RPE), human corneal endothelial and lens epithelial cells (CEC and LEC) were treated with different concentrations of axitinib, pazopanib, or sorafenib (0.1 to 100 µg/mL). To simulate oxidative stress, the cells were additionally co-incubated with 400 µM hydrogen peroxide. Induction of cell death and cellular viability were examined by live-dead assay and tetrazolium dye reduction assay (MTT). In addition, the influence of the three substances on human corneal endothelium was evaluated in seropositive donor corneas in organ culture by phase contrast microscopy. RESULTS: Up to a concentration of 7.5 mg/mL of the substances tested in any cell type examined, no toxic effects were found. Even after 10 days of incubation of organ-cultured donor corneas with 7.5 µg/mL, axitinib, pazopanib, or sorafenib, no evidence for endothelial toxicity was found. CONCLUSION: All three MKIs tested, axitinib, pazopanib, and sorafenib showed a good biocompatibility on the investigated ocular cells. Even under conditions of oxidative stress, there were no toxic effects up to a concentration of 7.5 µg/mL. Only at higher concentrations, there was a dose-dependent decrease in cellular viability and pronounced induction of cell death. These effects on cellular viability and induction of cell death appeared to be stronger with pazopanib, followed by sorafenib, than with axitinib.
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Inhibidores de la Angiogénesis/farmacología , Supervivencia Celular/efectos de los fármacos , Imidazoles/farmacología , Indazoles/farmacología , Niacinamida/análogos & derivados , Compuestos de Fenilurea/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Pirimidinas/farmacología , Sulfonamidas/farmacología , Degeneración Macular Húmeda/tratamiento farmacológico , Degeneración Macular Húmeda/patología , Inhibidores de la Angiogénesis/efectos adversos , Astrocitos/efectos de los fármacos , Astrocitos/patología , Axitinib , Córnea/efectos de los fármacos , Córnea/patología , Relación Dosis-Respuesta a Droga , Células Endoteliales/efectos de los fármacos , Células Endoteliales/patología , Endotelio Corneal/efectos de los fármacos , Endotelio Corneal/patología , Humanos , Imidazoles/efectos adversos , Indazoles/efectos adversos , Cristalino/efectos de los fármacos , Cristalino/patología , Microscopía de Contraste de Fase , Niacinamida/efectos adversos , Niacinamida/farmacología , Disco Óptico/efectos de los fármacos , Disco Óptico/patología , Técnicas de Cultivo de Órganos , Estrés Oxidativo/efectos de los fármacos , Compuestos de Fenilurea/efectos adversos , Inhibidores de Proteínas Quinasas/efectos adversos , Pirimidinas/efectos adversos , Epitelio Pigmentado de la Retina/efectos de los fármacos , Epitelio Pigmentado de la Retina/patología , Sorafenib , Sulfonamidas/efectos adversos , Malla Trabecular/efectos de los fármacos , Malla Trabecular/patologíaRESUMEN
BACKGROUND: Cumulative light exposure is significantly associated with progression of age-related macular degeneration (AMD). Inhibition of vascular endothelial growth factor A (VEGF) is the main target of current antiangiogenic treatment strategies for AMD. Previous reports indicated that sorafenib, an oral multikinase inhibitor, might have beneficial effects on exudative AMD. This study investigates the effects of sorafenib on light-induced overexpression of VEGF and its receptors VEGFR1 and 2 in human retinal pigment epithelial (RPE) cells. METHODS: The effects of sorafenib on VEGFR1 and 2 expression of primary human RPE cells was investigated by reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry and western blotting. In addition, RPE cells were exposed to white light and incubated with sorafenib. Viability, expression of VEGF and its mRNA were determined by RT-PCR, immunohistochemistry, western blotting, and enzyme-linked immunosorbent assays. RESULTS: Sorafenib reduced VEGFR1 and 2 expression of RPE cells. Light exposure decreased cell viability and increased expression and secretion of VEGF. These light-induced effects were significantly reduced when cells were treated with sorafenib at a dose of 1 µg/ml. CONCLUSION: The results show that sorafenib has promising properties as a potential antiangiogenic treatment for AMD.
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Bencenosulfonatos/farmacología , Piridinas/farmacología , Epitelio Pigmentado de la Retina/efectos de los fármacos , Epitelio Pigmentado de la Retina/metabolismo , Receptor 1 de Factores de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Adulto , Inhibidores de la Angiogénesis/farmacología , Citoprotección/efectos de los fármacos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Niacinamida/análogos & derivados , Compuestos de Fenilurea , Inhibidores de Proteínas Quinasas/farmacología , Sorafenib , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVES: Growth factors, such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and placenta growth factor (PlGF) are key players in the development of diabetic retinopathy, age-related macular degeneration, and other retinal neovascular diseases. Glial cells provide a significant source of retinal growth factor production under physiologic and pathologic conditions. Cumulative light exposure has been linked to increased retinal growth factor expression. Previous reports indicate that sorafenib, an oral multikinase inhibitor, might have a beneficial effect on retinal neovascularization. This study was designed to investigate the effects of sorafenib on light-induced overexpression of growth factors in human retinal glial cells. METHODS: Primary human optic nerve head astrocytes (ONHAs) were exposed to white light and incubated with sorafenib. Viability, expression, and secretion of VEGF-A, PDGF-BB, and PlGF and their mRNA were determined by reverse transcription-polymerase chain reaction, immunohistochemistry, and enzyme-linked immunosorbent assay. RESULTS: Light exposure decreased cell viability and increased VEGF-A, PDGF-BB, and PlGF expression and secretion. These light-induced effects were significantly reduced when cells were treated with sorafenib at a concentration of 1 microg/ml. CONCLUSION: Sorafenib significantly reduced light-induced overexpression of VEGF-A, PDGF-BB, and PlGF in primary human ONHAs. Sorafenib has promising properties as a potential supportive treatment for retinal neovascularization.
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Bencenosulfonatos/farmacología , Disco Óptico/efectos de los fármacos , Factor de Crecimiento Derivado de Plaquetas/antagonistas & inhibidores , Proteínas Gestacionales/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/farmacología , Piridinas/farmacología , Retina/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Adulto , Anciano , Astrocitos/efectos de los fármacos , Astrocitos/efectos de la radiación , Bencenosulfonatos/uso terapéutico , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Humanos , Luz/efectos adversos , Persona de Mediana Edad , Niacinamida/análogos & derivados , Disco Óptico/inmunología , Disco Óptico/metabolismo , Disco Óptico/efectos de la radiación , Compuestos de Fenilurea , Factor de Crecimiento Placentario , Factor de Crecimiento Derivado de Plaquetas/biosíntesis , Proteínas Gestacionales/biosíntesis , Inhibidores de Proteínas Quinasas/uso terapéutico , Piridinas/uso terapéutico , Retina/metabolismo , Retina/efectos de la radiación , Neovascularización Retiniana/tratamiento farmacológico , Sorafenib , Factor A de Crecimiento Endotelial Vascular/biosíntesisRESUMEN
METHODS: Primary human RPE cells were exposed to white light and either a SN60AT or SA60AT IOL was placed in the light beam. After 15-60 min of irradiation, viability, induction of apoptosis and cell death were determined in primary human RPE cells. Expression of vascular endothelial growth factor A (VEGF-A) and the anti-apoptotic XIAP protein and their mRNA were determined by RT-PCR, Western blot analysis and ELISA. RESULTS: Light exposure decreased cell viability depending on the duration of irradiation. Light-induced cell death and apoptosis as well as decrease of XIAP expression and cellular viability were significantly reduced by both the SN60AT and SA60AT IOL. In addition, these protective effects regarding light-induced cell damage were significantly stronger in the presence of the blue light-filtering SN60AT IOL compared to the SA60AT IOL. CONCLUSION: Both UV-filtering and blue light-absorbing IOLs reduce light-induced RPE damage. The blue light-absorbing IOL further reduced damage compared to the conventional IOL, which supports the hypothesis of possibly also preventing retinal damage in clinical use.
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Filtración/instrumentación , Lentes Intraoculares , Luz/efectos adversos , Epitelio Pigmentado Ocular/efectos de la radiación , Diseño de Prótesis , Protección Radiológica/instrumentación , Rayos Ultravioleta/efectos adversos , Apoptosis/efectos de la radiación , Supervivencia Celular/efectos de la radiación , Ensayo de Inmunoadsorción Enzimática , Regulación de la Expresión Génica/efectos de la radiación , Humanos , Técnicas In Vitro , Degeneración Macular/etiología , Degeneración Macular/prevención & control , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor A de Crecimiento Endotelial Vascular/genética , Proteína Inhibidora de la Apoptosis Ligada a X/genéticaRESUMEN
BACKGROUND: Moxifloxacin (Vigamox), a 4th-generation fluoroquinolone, covers most isolates causing endophthalmitis. It is safe and effective for systemic and topical use; however, only very limited data are available on prophylactic intracameral administration to prevent endophthalmitis. This study investigated the safety of Vigamox for intracameral application in a cell-culture model. METHODS: The endothelial toxicity of moxifloxacin (Vigamox) was evaluated in cultured human corneas. Primary human retinal pigment epithelium cells (RPEs), trabecular meshwork cells (TMCs), lens epithelium cells (LECs), and corneal endothelial cells (CECs) were treated with concentrations of Vigamox. Toxic effects were evaluated after 24 h (MTT assay and live-dead assay). By treating TMC, CEC, and RPE cells either with oxidative stress or tumor necrosis factor-alpha (TNF-a), lipopolysaccharide (LPS), and interleukin-6 (IL-6), the effects of moxifloxacin on cellular viability under conditions of inflammation were investigated. RESULTS: No corneal endothelial toxicity could be detected after 30 days of treatment with moxifloxacin 500 microg/ml. Primary RPEs, TMCs, LECs, and CECs showed adverse effects on proliferation and viability only at concentrations higher than 150 microg/ml moxifloxacin. After preincubation with TNF-a, LPS, and IL-6 for 24 h and subsequent treatment with moxifloxacin at concentrations of 10-150 microg/ml for 24 h, no significant decrease in proliferation or viability was observed. H2O2 exposure did not increase cellular toxicity CONCLUSION: Vigamox did not show significant toxicity on primary RPEs, TMCs, LECs, CECs, or human corneal endothelium at concentrations up to 150 microg/ml. The MIC90 of moxifloxacin for pathogens commonly encountered in endophthalmitis is known to be in the range of 0.25-2.5 microg/ml. Therefore, intracameral use of Vigamox at concentrations up to 150 microg/ml may be safe and effective for preventing endophthalmitis after intraocular surgery.
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Antiinfecciosos/administración & dosificación , Antiinfecciosos/toxicidad , Compuestos Aza/administración & dosificación , Compuestos Aza/toxicidad , Endoftalmitis/prevención & control , Células Endoteliales/efectos de los fármacos , Epitelio Corneal/efectos de los fármacos , Cristalino/efectos de los fármacos , Epitelio Pigmentado Ocular/efectos de los fármacos , Quinolinas/administración & dosificación , Quinolinas/toxicidad , Malla Trabecular/efectos de los fármacos , Cámara Anterior , Recuento de Células , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Endoftalmitis/inmunología , Células Endoteliales/inmunología , Epitelio Corneal/inmunología , Fluoroquinolonas , Humanos , Técnicas In Vitro , Mediadores de Inflamación/metabolismo , Cristalino/inmunología , Lipopolisacáridos/inmunología , Moxifloxacino , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/inmunología , Epitelio Pigmentado Ocular/inmunología , Malla Trabecular/inmunologíaAsunto(s)
Amaurosis Fugax/etiología , Coriorretinitis , Sífilis/complicaciones , Adulto , Coriorretinitis/complicaciones , Coriorretinitis/diagnóstico , Coriorretinitis/etiología , Diagnóstico Diferencial , Angiografía con Fluoresceína , Estudios de Seguimiento , Humanos , Masculino , Penicilinas/administración & dosificación , Penicilinas/uso terapéutico , Sífilis/tratamiento farmacológico , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Proliferative vitreoretinopathy (PVR) is a major complication after retinal detachment surgery, but there is no established pharmacotherapy available to control the cell biology of the disease. The aim of this study was to investigate the role of alkylphosphocholines [APCs; erucylphosphocholine (ErPC) was used in this study], novel pharmacologic substances with antiproliferative properties, on intraretinal proliferation initiated by experimental retinal detachment in a well-established in vivo model. METHODS: Retinal detachments were created in adult pigmented rabbits. ErPC was injected intravitreally on either day 1 or day 2 after detachment. Bromodeoxyuridine (5-bromo-2-deoxyuridine, BrdU) was injected on day 3. Following fixation, retinas were triple-labelled with anti-BrdU (proliferation marker), Isolectin B4 (retinal microglia marker), and anti-vimentin (retinal Mueller glia cell marker). The number of anti-BrdU-labelled cells per millimeter of retina was determined from sections imaged by laser scanning confocal microscopy. Toxicity was assessed by light and electron microscopy. RESULTS: A single intravitreal injection of ErPC had a significant effect on reducing the number of proliferating non-neural retinal cells on day 3 after experimental retinal detachment in the rabbit. Injection of ErPC on day 1 was more effective than when given on day 2. No evidence of toxicity was observed in the retina on day 3 for any of the conditions. CONCLUSIONS: APCs are novel pharmacologic substances that significantly inhibited intraretinal proliferation after experimental retinal detachment in this in vivo model. They could be considered as an adjunct therapy at the time of retinal reattachment surgery to potentially prevent proliferative vitreoretinal diseases such as PVR. However, long-term toxicity studies must be performed before APCs can be considered for clinical application.
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Fosforilcolina/análogos & derivados , Desprendimiento de Retina/tratamiento farmacológico , Desprendimiento de Retina/cirugía , Vitrectomía/efectos adversos , Vitreorretinopatía Proliferativa/etiología , Vitreorretinopatía Proliferativa/patología , Vitreorretinopatía Proliferativa/prevención & control , Animales , Estudios de Factibilidad , Fosforilcolina/administración & dosificación , Conejos , Desprendimiento de Retina/complicaciones , Desprendimiento de Retina/patología , Resultado del TratamientoAsunto(s)
Cuerpos Extraños en el Ojo/diagnóstico , Reacción a Cuerpo Extraño/diagnóstico , Cabello , Queratitis/diagnóstico , Arañas , Uveítis/diagnóstico , Adulto , Animales , Diagnóstico Diferencial , Cuerpos Extraños en el Ojo/complicaciones , Femenino , Reacción a Cuerpo Extraño/complicaciones , Humanos , Queratitis/etiología , Uveítis/etiologíaRESUMEN
BACKGROUND: The assessment of patient's quality of life is not only of vital importance for clinical trials of new therapies but also becomes more and more implemented into daily clinical therapeutical decisions. METHODS: Different methods for evaluating quality of life are available. A well-known questionnaire for measuring global quality of life is the Short Form 36 (SF 36). However, in ophthalmology more specific instruments for measuring visual quality of life are needed. We review the usefulness of specific questionnaires such as the Visual Function 14 (VF-14) or the National Eye Institute Visual Function Questionnaire (NEI-VFQ) in their application to common ophthalmologic diseases such as cataract, age-related macular degeneration and glaucoma. Studies applying these methods were identified by a search in the Medline database. RESULTS: Several instruments to measure visual life quality in ophthalmologic patients are available. Internal consistency and validity are shown. CONCLUSIONS: Evaluating visual quality of life is an important parameter for assessing ophthalmologic diseases and the value of different therapies. It is an important outcome variable in clinical studies. Furthermore, individual visual quality of life should be considered in individual therapeutic decisions and helps to assess the economic effect of current and new therapies.
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Oftalmopatías , Oftalmología , Calidad de Vida , Encuestas y Cuestionarios , Visión Ocular , Anciano , Extracción de Catarata , Trasplante de Córnea , Glaucoma , Humanos , Degeneración Macular , Enfermedades de la Retina , Agudeza VisualRESUMEN
BACKGROUND: The combined hamartoma of the retina and the retinal pigment epithelium (CHR-RPE) is an important differential diagnosis of retinal and choroidal diseases with variable degrees of pigmentation. PATIENTS: The clinical picture and typical fluorescence angiography findings of two adult patients who were first diagnosed to have a combined hamartoma of the retina and retinal pigment epithelium are presented. The referral diagnosis macular pucker and malignant melanoma of the choroid, respectively, are discussed regarding severe therapeutic interventions such as pars plana vitrectomy with membrane peeling (macular pucker), and radiotherapy, or enucleation (malignant melanoma of the choroid) as well as other important differentials. RESULTS: The combined hamartoma of the retina and the retinal pigment epithelium is a benign congenital, mostly unilateral retinal lesion. The presenting symptom is a painless, unilateral, often silent loss of vision. Histologically, three cell populations can be identified: glial, vascular, and pigmented cells. Variations in composition of these three cell types are responsible for the heterogeneous clinical picture and thus diagnostic challenges. The greyish retinal tumor located peripapillary in most cases with varying degrees of pigmentation and surrounding vascular tortuosity can result in secondary changes at the vitreoretinal interface with deterioration of vision. Combined fluorescein-/indocyaningreen angiography and ultrasound are crucial for diagnostic evaluation. Documentation and regular clinical follow-up examinations are essential for successful management of this disorder. CONCLUSION: Recognition of this rare clinical entity is crucial for administering the appropriate therapy.