RESUMEN
BACKGROUND: To compare 12-month results of two single initial treatments--photodynamic therapy with verteporfin alone (PDT group), and this therapy combined with intravitreal bevacizumab (IVB) (COMB group)--for neovascular age-related macular degeneration (AMD), not including patients with polypoidal choroidal vasculopathy (PCV) who were presumed to have AMD. METHODS: This retrospective study evaluated 23 eyes in the PDT group and 22 eyes in the COMB group. IVB (1.25 mg) was administered within 2 weeks after PDT. Main outcome measures were best-corrected visual acuity (VA), central foveal thickness by optical coherence tomography, and number of treatments. RESULTS: At month 12, the PDT group had gained 0.7 letter mean VA and the COMB group, 8.8 letters (P = 0.04). Ten eyes (43%) in the PDT group and 19 eyes (86%) in the COMB group received only one treatment, and significant difference was found (P = 0.005). No severe ocular or systemic safety concerns were discovered. CONCLUSIONS: Our 12-month results of PDT combined with IVB for Japanese patients with AMD without PCV appeared to be more effective than those of PDT alone with fewer treatments.
Asunto(s)
Inhibidores de la Angiogénesis/administración & dosificación , Anticuerpos Monoclonales/administración & dosificación , Degeneración Macular/tratamiento farmacológico , Degeneración Macular/patología , Fotoquimioterapia/métodos , Porfirinas/administración & dosificación , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados , Pueblo Asiatico , Bevacizumab , Coroides , Ensayos Clínicos como Asunto , Femenino , Estudios de Seguimiento , Fóvea Central/patología , Humanos , Inyecciones Intraoculares , Masculino , Persona de Mediana Edad , Fármacos Fotosensibilizantes/administración & dosificación , Recuperación de la Función/efectos de los fármacos , Estudios Retrospectivos , Tomografía de Coherencia Óptica , Resultado del Tratamiento , Verteporfina , Agudeza Visual/efectos de los fármacos , Cuerpo VítreoRESUMEN
PURPOSE: To evaluate the neuroprotective effects of pitavastatin against neuronal retinal damage induced by ischemia-reperfusion injury in rats. METHODS AND RESULTS: Ischemia-reperfusion injury was induced in Sprague-Dawley rats using ocular hypertension. Pitavastatin (0.1, 0.5, or 1.0 mg/kg) was given intravenously 12 hr or 5 min before, or 12 or 24 hr after the induction of ischemia-reperfusion injury. Morphometric and retrograde labeling analyses revealed neuroprotective effects when pitavastatin (0.5 mg/kg) was administered 5 min before--even 12 and 24 hr--after induction of ischemia-reperfusion injury. These effects depended on dose; protection was noted at pitavastatin concentrations of 0.5 and 1 mg/kg but not 0.1 mg/kg. Furthermore, preadministration of pitavastatin (0.5 mg/kg) reduced expression of P-selectin and intercellular adhesion molecule-1 at 12 and 24 hr after induction of ischemia-reperfusion injury. CONCLUSIONS: As pitavastatin was efficacious in preventing retinal neuronal death, it may be a novel therapeutic modality for ischemic retinal diseases.
Asunto(s)
Inhibidores Enzimáticos/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Quinolinas/uso terapéutico , Daño por Reperfusión/complicaciones , Enfermedades de la Retina/prevención & control , Células Ganglionares de la Retina/efectos de los fármacos , Animales , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Inyecciones Intravenosas , Molécula 1 de Adhesión Intercelular/genética , Molécula 1 de Adhesión Intercelular/metabolismo , Masculino , Selectina-P/genética , Selectina-P/metabolismo , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Enfermedades de la Retina/etiología , Enfermedades de la Retina/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de TiempoRESUMEN
PURPOSE: To investigate the effects of intravitreal injection of nattokinase (subtilisin NAT), a serine protease that is produced by Bacillus subtilis (natto), for induction of posterior vitreous detachment (PVD). METHODS: Different doses of nattokinase (1, 0.1, or 0.01 fibrin-degradation units [FU]) or physiologic saline as a control were injected into the vitreous cavity of rabbit eyes. Scanning electron microscopy was used to observe the retinal surfaces of four rabbit eyes per concentration. Histologic alterations were assessed by light microscopy, using four eyes from each group. Electroretinography (ERG) was performed to observe retinal function, ranging from 1 hour to 1 week after the nattokinase (1 or 0.1 FU) or saline solution administration, using four eyes from each group at each time point. Also, findings in all rabbits were monitored by slit lamp examination and by indirect ophthalmoscopy with a 20-D lens. RESULTS: Scanning electron microscopy showed smooth retinal surfaces, indicating the occurrence of PVD at 30 minutes after intervention in all the experimental eyes injected with 0.1 or 1.0 FU nattokinase, but none of the control eyes. Light microscopy and ERG analysis showed no critical change even after the use of 0.1 FU nattokinase, an amount sufficient to induce PVD. However, toxicity in the forms of preretinal hemorrhage and ERG changes was noted with the higher dose (1 FU) of nattokinase. CONCLUSIONS: The results suggested that nattokinase is a useful enzyme for pharmacologic vitreolysis because of its efficacy in inducing PVD.
Asunto(s)
Subtilisinas/farmacología , Cuerpo Vítreo/efectos de los fármacos , Desprendimiento del Vítreo/inducido químicamente , Animales , Electrorretinografía , Inyecciones , Microscopía Electrónica de Rastreo , Conejos , Retina/fisiología , Retina/ultraestructura , Subtilisinas/toxicidad , Desprendimiento del Vítreo/patologíaRESUMEN
PURPOSE: N-acetyl-cysteine (NAC) is a potent antioxidant known to be a precursor of glutathione. The purpose of this study was to investigate the role of NAC in the development of choroidal neovascularization (CNV). METHODS: CNV was induced in C57BL/6 mice by laser photocoagulation of the ocular fundus. Mice were injected intraperitoneally with NAC or vehicle alone. The levels of 4-hydoroxy-2-nonenal (4-HNE)-modified protein and nucleus factor (NF)-κB were determined by wester blotting. The recruitment of macrophages and neutrophils after laser injury was analyzed immunohistochemically and in myeloperoxidase (MPO) assays. Enzyme-linked immunosorbent assays (ELISA) were used to measure monocyte chemotactic protein (MCP)-1, CXCL1, vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR)-1, and VEGFR-2. The extent of CNV was evaluated 7 d after laser injury by lectin staining. RESULTS: In NAC-treated mice with laser-induced injuries, the induction of 4-HNE-modified protein after 3 hr and the activation of NF-κB in nuclear extracts after 6 hr were markedly suppressed compared to vehicle-treated mice. Macrophage and neutrophil recruitment were inhibited and the levels of MCP-1, CXCL1, VEGF, and VEGFR-1 were also lower in NAC-treated mice compared to vehicle-treated mice. Furthermore, the extent of CNV induced was significantly lower in NAC-treated compared to vehicle-treated mice (p = 0.027). CONCLUSIONS: Our results clearly showed that NAC inhibited indicators of oxidative stress and the activation of NF-κB induced by laser injury, and, consequently, suppressed macrophage and neutrophil infiltration and the development of CNV. This suggests novel preventative and interventional therapeutic strategies for age-related macular degeneration.
Asunto(s)
Acetilcisteína/farmacología , Antioxidantes/farmacología , Neovascularización Coroidal/prevención & control , Modelos Animales de Enfermedad , Depuradores de Radicales Libres/farmacología , Aldehídos/metabolismo , Animales , Western Blotting , Quimiocina CCL2/metabolismo , Quimiocina CXCL1/metabolismo , Neovascularización Coroidal/metabolismo , Ensayo de Inmunoadsorción Enzimática , Inyecciones Intraperitoneales , Macrófagos/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Neutrófilos/fisiología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Receptor 1 de Factores de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
PURPOSE: To demonstrate the feasibility of autologous plasmin for treatment of proliferative diabetic retinopathy. METHODS: The study examined prospectively six patients with bilateral proliferative diabetic retinopathy. Comparisons of the surgical time and the incidence of retinal tears were made between the eyes treated with autologous plasmin and their respective opposite eyes, which were treated without plasmin. RESULTS: All eyes treated with autologous plasmin required significantly less surgical time (68 versus 89 minutes, P = 0.04, paired t-test). In the plasmin group, no additional surgical procedures for removing the proliferative membrane were needed, including membrane delamination or segmentation. Moreover, with plasmin pretreatment, there were no retinal tears, which was in contrast to the control group, where three eyes with retinal tears were observed. There was no significant difference found between the two groups for final visual outcomes. CONCLUSION: Autologous plasmin may be beneficial in the surgical management of proliferative diabetic retinopathy.
Asunto(s)
Retinopatía Diabética/terapia , Fibrinolisina/uso terapéutico , Fibrinolíticos/uso terapéutico , Neovascularización Retiniana/terapia , Vitrectomía/métodos , Adulto , Terapia Combinada , Retinopatía Diabética/tratamiento farmacológico , Retinopatía Diabética/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Pronóstico , Estudios Prospectivos , Neovascularización Retiniana/tratamiento farmacológico , Neovascularización Retiniana/cirugía , Agudeza VisualRESUMEN
The association between the use of statins and age-related macular degeneration (AMD), a leading cause of blindness, has been evaluated in many clinical studies; however, the results have been contradictory. We evaluated the effect of pitavastatin administration on laser-induced experimental choroidal neovascularization (CNV) in rats. Brown Norway rats received pitavastatin (1.0mg/kg per day) for 1day prior to laser-induced CNV and continued to receive the drug for 14days. Fluorescein angiograms were graded by masked observers. CNV area and thickness were assessed by fluorescein isothiocyanate-labeled dextran angiography and histology, respectively. Vascular endothelial growth factor (VEGF), monocyte chemoattractant protein-1 (Ccl-2; also known as MCP-1), and intercellular adhesion molecule-1 (ICAM-1) mRNA levels were measured using reverse-transcription polymerase chain reaction (RT-PCR) and real-time quantitative RT-PCR. Pitavastatin-treated rats had significantly less fluorescence leakage compared with the vehicle-treated rats estimated by CNV score using fluorescein angiography. Both the area and the thickness of CNV in pitavastatin-treated rats were significantly reduced compared with the vehicle-treated rats. Gene expression of VEGF, Ccl-2, and ICAM-1 were significantly decreased by pitavastatin administration in experimental CNV. Thus, we demonstrated that the therapeutic dose of pitavastatin for human hypocholesterolemia effectively suppressed experimental CNV in rats. The use of pitavastatin may be helpful in preventing CNV development in AMD patients.