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1.
Medicine (Baltimore) ; 99(7): e19007, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32049795

RESUMEN

Conbercept is a novel anti-vascular endothelial growth factor for the treatment of age-related macular degeneration (AMD). The most optimal injection strategy is unknown. To assess the effectiveness of intravitreal injection of conbercept using the 3 + pro re nata (PRN) and 3 + Q3 M strategies for the treatment of exudative AMD.From January 2015 to January 2018, patients confirmed with exudative AMD at Qilu Hospital of Shandong University were included in this retrospective study. Intravitreal injection of 0.5 mg of conbercept was conducted either with the 3 + PRN or 3 + Q3 M strategy. Best-corrected visual acuity (BCVA), intraocular pressure, and optical coherence tomography were conducted at 1 and 2 weeks, then every month. fundus fluorescein angiography examination was conducted every 3 months.There were 106 eyes from 106 patients. The number of follow-ups (3 + Q3 M: 12.4 ±â€Š1.3 vs 3 + PRN: 12.9 ±â€Š1.6, P = .079) and the follow-up time (3 + Q3 M: 12.7 ±â€Š0.6 vs 3 + PRN: 12.5 ±â€Š0.7 months, P = .121) were similar in the 2 groups. The number of injections was less in 3 + PRN than 3 + Q3 M (5.3 ±â€Š1.0 vs 6.0 ±â€Š0.0, P < .001) The BCVA at months 7 and 9 to 12 in the 3 + Q3 M (n = 51) group were lower than for 3 + PRN (n = 55) (all P < .05). The CRT at months 9 to 12 in the 3 + Q3 M group was lower than in the 3 + PRN group (all P < .05). There were no differences between the 2 groups regarding the exudation area during follow-up. No serious treatment-related ocular complications or serious systemic adverse events were found.The 3 + PRN and 3 + Q3 M strategies of intravitreal injection of conbercept are effective in treating exudative AMD. The 3 + Q3 M strategy needs more injection but is more effective in increasing visual acuity and reducing macular CRT than the 3 + PRN strategy.


Asunto(s)
Degeneración Macular/tratamiento farmacológico , Proteínas Recombinantes de Fusión/administración & dosificación , Anciano , Femenino , Angiografía con Fluoresceína , Humanos , Inyecciones Intravítreas , Degeneración Macular/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Proteínas Recombinantes de Fusión/uso terapéutico , Estudios Retrospectivos , Resultado del Tratamiento
2.
Adv Gerontol ; 32(4): 599-601, 2019.
Artículo en Ruso | MEDLINE | ID: mdl-31800189

RESUMEN

The article compares the course of age-related macular degeneration in elderly patients in three groups after complex therapy (intravitreal administration of angiogenesis blockers and photodynamic therapy). 339 case histories of persons with an average age of 75,6±9,7 years were analyzed (p<0,05). A slight decrease in the area of pathological autofluorescence and retinal thickness according to optical coherence tomography was revealed in all three groups of increased visual acuity. The best effect of combination therapy was observed in the first six months, no further positive dynamics was observed. Thus, timely diagnosis and complex therapy slows down and sometimes stops the progression of age-related macular degeneration and vision loss.


Asunto(s)
Inhibidores de la Angiogénesis , Degeneración Macular , Retina , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/farmacología , Angiografía con Fluoresceína , Humanos , Inyecciones Intravítreas , Degeneración Macular/tratamiento farmacológico , Fotoquimioterapia , Retina/efectos de los fármacos , Retina/patología , Estudios Retrospectivos , Resultado del Tratamiento
4.
J Biomed Nanotechnol ; 15(12): 2305-2320, 2019 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-31748013

RESUMEN

Verteporfin photodynamic therapy (PDT) has been approved for the treatment of exudative age-related macular degeneration (AMD) for over a decade. However, its extensive application has been impeded by inevitably collateral tissue damage and immediate induction of angiogenesis, in addition to the need of multiple treatments. In order to develop prospective photosensitizers for clinical use, a triphenyl phosphonium-modified cationic liposomal hypocrellin B (TPP cationic LHB) for angiogenic targeting and endothelial internalization was constructed. With optimal PDT parameters, TPP cationic LHB can lead to death of choroid-retinal vascular endothelial cells while cause negligible damage to collateral retinal pigment epithelium cells. This is likely due to the mitochondria targeting and effective intracellular singlet oxygen generation of TPP cationic LHB in vascular endothelial cells. Additionally, in vivo chick chorioallantoic membrane assay indicated the elevated neovessel-targeting ability and photo-induced anti-angiogenic activity of TPP cationic LHB. Furthermore, TPP cationic LHB PDT is able to maintain neovessel occlusion for an extended period of time compared with verteporfin PDT, without inducing significant increased expression of some angiogenic factors, such as vascular endothelial growth factor and integrin αvß3. This study describes a facile strategy that may be useful for developing new-generation photosensitizers to circumvent the limitations of PDT treatment of exudative AMD.


Asunto(s)
Degeneración Macular , Perileno/análogos & derivados , Fotoquimioterapia , Quinonas/uso terapéutico , Animales , Neovascularización Coroidal , Células Endoteliales , Liposomas , Degeneración Macular/tratamiento farmacológico , Perileno/uso terapéutico , Fármacos Fotosensibilizantes , Estudios Prospectivos , Factor A de Crecimiento Endotelial Vascular
5.
Buenos Aires; CONETEC; nov. 2019.
No convencional en Español | BRISA/RedTESA | ID: biblio-1025042

RESUMEN

INTRODUCCIÓN: La degeneración macular asociada a la edad (DMAE) es una patología que afecta la mácula (zona central de la retina) y evoluciona frecuentemente a una disminución de la agudeza visual, constituyendo la principal causa de ceguera en mayores de 50 años en países desarrollados. Existen dos formas de presentación, la seca y la húmeda o exudativa, que representan el 90% y 10% de los casos respectivamente. La húmeda se caracteriza por la formación anormal de nuevos vasos coroideos (neovascularización), exudación y edema de la retina. Esta forma es la responsable del 90% de los casos de pérdida grave de la visión y se estima que el 70% de los ojos con signos de neovascularización evolucionarán a pérdida severa de la visión a los dos años del diagnóstico. Por lo cual es fundamental el inicio temprano del tratamiento y su mantenimiento adecuado para limitar la progresión de la pérdida de la agudeza visual. OBJETIVO: El objetivo del presente informe es evaluar la eficacia, seguridad, los costos asociados al uso de bevacizumab para degeneración macular húmeda asociada a la edad, en comparación con ranibizumab. DESCRIPCIÓN DE LA TECNOLOGÍA: Bevacizumab, un anticuerpo monoclonal IgG1 humanizado recombinante, se une al FCEV e inhibe su interacción con los receptores Flt1 y KDR en la superficie de las células endoteliales. En el proceso, previene la proliferación de células endoteliales y la formación de nuevos vasos sanguíneos. BÚSQUEDA BIBLIOGRÁFICA: Se realizó una búsqueda en las principales bases de datos bibliográficas: PubMed, CRD (del inglés Centre for Reviews and Dissemination- University of York), en Tripdatabase, en los sitios web de financiadores de salud y de sociedades científicas, así como en los buscadores genéricos de internet se buscó con el nombre de la tecnología y sus sinónimos y/o la patología. Se priorizó la inclusión de revisiones sistemáticas (RS), ensayos clínicos controlados aleatorizados (ECAs), evaluaciones de tecnologías sanitarias (ETS), evaluaciones económicas, guías de práctica clínica (GPC) y políticas de cobertura de diferentes sistemas de salud. RESULTADOS: Se incluyeron cuatro RS con metaanálisis, un metaanálisis de elaboración propia, cuatro GPC y cinco informes de ETS de bevacizumab para degeneración macular asociada a la edad. Todos los estudios incluidos fueron realizados con la administración de bevacizumab de marca comercial Avastin®. La evidencia hallada no mostró diferencias entre bevacizumab y ranibizumab en lo que respecta a la agudeza visual a uno y dos años de seguimiento. Asimismo, mostró que la mejoría en la calidad de vida y los eventos adversos serían similares entre estos tratamientos. En lo que se refiere específicamente a la endoftalmitis, la incidencia también resultó similar en ambos grupos. CONCLUSIONES: La evidencia disponible no mostró diferencias entre el bevacizumab y el ranibizumab en lo que se refiere a la eficacia y seguridad. No está demostrado que exista mayor riesgo de endoftalmitis asociado al uso de bevacizumab fraccionado. Este riesgo potencial de endoftalmitis puede ser mitigado con métodos de fraccionamiento adecuado. El tratamiento con bevacizumab es notablemente menos costoso que ranibizumab o aflibercept y recomendar su utilización redundará en un mayor acceso.


Asunto(s)
Humanos , Bevacizumab/uso terapéutico , Ranibizumab/uso terapéutico , Degeneración Macular/tratamiento farmacológico , Evaluación de la Tecnología Biomédica , Análisis Costo-Eficiencia
7.
Int J Mol Sci ; 20(20)2019 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-31614647

RESUMEN

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of blindness and can be classified into two types called atrophic AMD (dry AMD) and neovascular AMD (wet AMD). Dry AMD is characterized by cellular degeneration of the retinal pigment epithelium, choriocapillaris, and photoreceptors. Wet AMD is characterized by the invasion of abnormal vessels from the choroid. Although anti-vascular endothelial growth factor (VEGF) therapy has a potent therapeutic effect against the disease, there is a possibility of chorio-retinal atrophy and adverse systemic events due to long-term robust VEGF antagonism. We focused on hypoxia-inducible factor (HIF) regulation of VEGF transcription, and report the suppressive effects of HIF inhibition against ocular phenotypes in animal models. Many of the known HIF inhibitors are categorized as anti-cancer drugs, and their systemic side effects are cause for concern in clinical use. In this study, we explored food ingredients that have HIF inhibitory effects and verified their effects in an animal model of AMD. METHODS: Food ingredients were screened using a luciferase assay. C57BL6/J mice were administered the Garcinia cambogia extract (Garcinia extract) and hydroxycitric acid (HCA). Choroidal neovascularization (CNV) was induced by laser irradiation. RESULTS: Garcinia extract and HCA showed inhibitory effects on HIF in the luciferase assay. The laser CNV model mice showed significant reduction of CNV volume by administering Garcinia extract and HCA. Conclusions: Garcinia extract and HCA showed therapeutic effects in a murine AMD model.


Asunto(s)
Citratos/administración & dosificación , Garcinia cambogia/química , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Degeneración Macular/tratamiento farmacológico , Extractos Vegetales/administración & dosificación , Animales , Citratos/química , Citratos/farmacología , Modelos Animales de Enfermedad , Regulación hacia Abajo , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Terapia por Luz de Baja Intensidad/efectos adversos , Degeneración Macular/etiología , Degeneración Macular/genética , Masculino , Ratones , Extractos Vegetales/química , Extractos Vegetales/farmacología , Resultado del Tratamiento
8.
Klin Monbl Augenheilkd ; 236(9): 1081-1090, 2019 Sep.
Artículo en Alemán | MEDLINE | ID: mdl-31509858

RESUMEN

Currently, for non-exudative age-related macular degeneration (AMD), therapy is not possible-in contrast to the exudative form. Many patients hope for a preventive effect and a slower progression of the disease from the dietary supplements on the market. The substances contained in them are supposed to reduce the oxidative environment in the outer retina and, thereby, slow down the cell damage and the progression of AMD. The Age-Related Eye Disease Studies (AREDS) examined certain supplements for their effectiveness in reducing the risk of AMD progression. They are the only interventional large-scale, prospective, randomized and controlled clinical trials and are repeatedly used as the basis for dietary supplementation in AMD. This article discusses the rationale for the use of certain ingredients of AREDS supplements and critically examines the results of AREDS. Furthermore, the modern term "lifestyle" will be discussed in the context of AMD as a possibility to influence the progression of this disease.


Asunto(s)
Suplementos Dietéticos , Degeneración Macular , Vitaminas , Antioxidantes , Progresión de la Enfermedad , Humanos , Estilo de Vida , Degeneración Macular/tratamiento farmacológico , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto
9.
BMJ Case Rep ; 12(9)2019 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-31511273

RESUMEN

Peripheral exudative haemorrhagic chorioretinopathy (PEHCR) is considered a variant of polypoidal choroidal vasculopathy. It may have varried presentations and systemic associations. We present a case of PEHCR which dramatically responded to intravitreal steroid and ziv-aflibercept injection. This case not only highlights the promising role of combination therapy with intravitreal steroids and ziv-aflibercept but also the need to look for any associated systemic comorbidity.


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Antiinflamatorios/uso terapéutico , Degeneración Macular/tratamiento farmacológico , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Proteínas Recombinantes de Fusión/uso terapéutico , Hemorragia Retiniana/tratamiento farmacológico , Triamcinolona Acetonida/uso terapéutico , Anciano , Inhibidores de la Angiogénesis/administración & dosificación , Antiinflamatorios/administración & dosificación , Quimioterapia Combinada , Femenino , Humanos , Inyecciones Intravenosas , Inyecciones Intravítreas , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Triamcinolona Acetonida/administración & dosificación
10.
Expert Opin Investig Drugs ; 28(10): 861-869, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31513439

RESUMEN

Introduction: The Tie-2/Angiopoietin pathway is a therapeutic target for the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). Activation of Tie-2 receptor via Ang-1 maintains vascular stability to limit exudation. Ang-2, a competitive antagonist to Ang-1, and VE-PTP, an endothelial-specific phosphatase, interfere with the Tie-2-Ang-1 axis, resulting in vascular leakage. Areas covered: Faricimab, a bispecific antibody that inhibits VEGF-A and Ang-2, is in phase 3 trials for nAMD and DME. Nesvacumab is an Ang-2 inhibitor; when coformulated with aflibercept, it failed to show benefit over aflibercept monotherapy in achieving visual gains in phase 2 studies of nAMD and DME. ARP-1536 is an intravitreally administered VE-PTP inhibitor undergoing preclinical studies. AKB-9778 is a subcutaneously administered VE-PTP inhibitor that, when combined with monthly ranibizumab, reduced DME more effectively than ranibizumab monotherapy in a phase 2 study. AKB-9778 monotherapy did not reduce diabetic retinopathy severity score compared to placebo. AXT107, currently in the preclinical phase, promotes conversion of Ang-2 into a Tie-2 agonist and blocks signaling through VEGFR2 and other receptor tyrosine-kinases. Expert opinion: Tie-2/Angiopoietin pathway modulators show promise to reduce treatment burden and improve visual outcomes in nAMD and DME, with potential to treat cases refractory to current treatment modalities.


Asunto(s)
Inhibidores de la Angiogénesis/administración & dosificación , Retinopatía Diabética/tratamiento farmacológico , Degeneración Macular/tratamiento farmacológico , Inhibidores de la Angiogénesis/farmacología , Angiopoyetina 1/antagonistas & inhibidores , Angiopoyetina 2/antagonistas & inhibidores , Animales , Retinopatía Diabética/fisiopatología , Humanos , Degeneración Macular/fisiopatología , Edema Macular/tratamiento farmacológico , Edema Macular/fisiopatología , Receptor TIE-2/efectos de los fármacos , Receptor TIE-2/metabolismo , Transducción de Señal/efectos de los fármacos
11.
Expert Opin Ther Pat ; 29(10): 761-767, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31540558

RESUMEN

Introduction: Macular degeneration (MD) and macular edema (ME) are ophthalmologic diseases affecting an increasing number of the aging population. Until recently, there were few therapeutic options for both conditions but the last two decades saw important advances. Areas covered: This review summarizes the agents used for the treatment of age-related MD (AMD), which include verteporfin, for photodynamic therapy, and anti-VEGF agents, the aptamer pegaptanib, the monoclonal antibodies (MAbs) ranibizumab (Lucentis®) and bevacizumab (Avastin®) and the fusion protein aflibercept (Eylea®). All these drugs are effective only for the wet form of AMD, whereas for the dry form there is no treatment available. ME is, on the other hand, treated with nonsteroidal anti-inflammatory drugs and carbonic anhydrase (CA) inhibitors. Recently, MAbs such as ranibizumab and bevacizumab were also shown to be effective for the management of the cystoid and diabetic ME. Expert opinion: There are important advances made in the field in the last years but longer-acting anti-VEGF agents or drugs with less ocular side effects are needed. Many such agents are in clinical development.


Asunto(s)
Desarrollo de Medicamentos , Degeneración Macular/tratamiento farmacológico , Edema Macular/tratamiento farmacológico , Anciano , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/farmacología , Animales , Humanos , Degeneración Macular/fisiopatología , Degeneración Macular/prevención & control , Edema Macular/fisiopatología , Edema Macular/prevención & control , Patentes como Asunto , Fotoquimioterapia/métodos
12.
Mar Drugs ; 17(9)2019 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-31527536

RESUMEN

Fucoidan extracts may have beneficial effects in age-related macular degeneration(AMD). Over-the-counter fucoidan preparations are generally undefined, crude extracts. In thisstudy, we investigated the effect of a crude fucoidan extract from Fucus distichus subspeciesevanescens (Fe) on the retinal pigment epithelium (RPE). Fe extract was investigated for chemicalcomposition and molar mass. It was tested in primary RPE and RPE cell line ARPE19. Oxidativestress was induced with tert-butyl hydroperoxide, cell viability evaluated with MTT assay, VEGFsecretion assessed in ELISA. Phagocytosis was evaluated in a fluorescence microscopic assay.Wound healing ability was tested in a scratch assay. Additionally, the inhibition of elastase andcomplement system by Fe extract was studied. The Fe extract contained about 61.9% fucose andhigh amounts of uronic acids (26.2%). The sulfate content was not as high as expected (6.9%). It wasnot toxic and not protective against oxidative stress. However, Fe extract was able to reduce VEGFsecretion in ARPE19. Phagocytosis was also reduced. Concerning wound healing, a delay could beobserved in higher concentrations. While some beneficial effects could be found, it seems tointerfere with RPE function, which may reduce its beneficial effects in AMD treatment.


Asunto(s)
Fucus/química , Degeneración Macular/tratamiento farmacológico , Extractos Vegetales/farmacología , Polisacáridos/farmacología , Epitelio Pigmentado de la Retina/efectos de los fármacos , Animales , Línea Celular , Supervivencia Celular , Evaluación Preclínica de Medicamentos , Humanos , Degeneración Macular/patología , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/uso terapéutico , Polisacáridos/aislamiento & purificación , Polisacáridos/uso terapéutico , Cultivo Primario de Células , Epitelio Pigmentado de la Retina/metabolismo , Porcinos , Pruebas de Toxicidad , Factor A de Crecimiento Endotelial Vascular/metabolismo , Cicatrización de Heridas/efectos de los fármacos
14.
Arch. Soc. Esp. Oftalmol ; 94(9): 430-435, sept. 2019. tab, graf
Artículo en Español | IBECS | ID: ibc-186221

RESUMEN

Objetivo: Evaluar los resultados visuales y anatómicos de aflibercept en pacientes naïve con degeneración macular asociada a la edad neovascular (DMAEnv) no seleccionados tras un año de tratamiento en régimen bimestral fijo en un entorno de práctica clínica real. Métodos: Estudio retrospectivo, serie de casos consecutivos no aleatorizados que incluye 35 pacientes naïve, 38 ojos con DMAEnv, tratados con aflibercept intravítreo (Eylea(R)). Los pacientes recibieron una dosis de carga de 3 inyecciones mensuales (2 mg/0,05 ml) seguida de inyecciones cada 2 meses. Resultados: Tras la dosis de carga y a los 12 meses de tratamiento, el cambio en la mejor agudeza visual corregida (MAVC) mejoró significativamente respecto a la MAVC basal (ETDRS 50,5 ± 14,5 y 53,1 ± 14,5 vs. 39,6 ± 14,7, respectivamente, p < 0,05). Al mes 3 y al mes 12, la proporción de pacientes que mejoró la agudeza visual en ≥ 15 letras fue de 37,1% y de 45,7%, respectivamente. La disminución media del espesor central de la retina fue también significativa tras la dosis de carga (239,6 ± 52,0 μm) y al mes 12 (227 ± 53,2μm) comparada con los valores pretratamiento (370,3 ± 117,6; p < 0,001). También se observó la resolución del desprendimiento del epitelio pigmentario en 14 de los 20 ojos (70%) con ese desprendimiento previo al tratamiento. Conclusión: Mejorías funcionales y anatómicas significativas fueron observadas tras el tratamiento con aflibercept intravítreo en pacientes naïve con DMAEnv en práctica clínica real


Objective: To investigate the visual and anatomical outcomes of aflibercept as therapy in patients with treatment-naïve neovascular age-related macular degeneration during one year in routine clinical practice. Methods: The study was a retrospective, case series, including 35 patients, 38 eyes, with neovascular age-related macular degeneration that received aflibercept injections (Eylea(R)). Patients received a loading dose of 3 monthly injections (2 mg / 0.05 ml) followed by intravitreal injections every 2 months. Results: At 3 and 12 months, the mean best-corrected visual acuity improved significantly as compared with baseline (ETDRS 50.5 ± 14.5 and 53.1 ± 14.5 vs. 39.6 ± 14.7, respectively, P < .05). At 3 and 12 months, the proportion of patients who improved visual acuity by ≥ 15 letters was 37.1% and 45.7%, respectively. The mean decrease in central macular thickness was also significant after loading dose (239.6 ± 52.0μm) and at 12 month (227 ± 53.2 μm) compared with pre-treatment values (370.3 ± 117, 6) (P < .001). Resolution of pigment epithelial detachment (PED) was also observed in 14 out of 20 (70%) eyes with PED at baseline. Conclusion: Aflibercept administered by fixed dosing over one year improved visual acuity and macular morphology in treatment-naïve eyes in routine daily practice


Asunto(s)
Humanos , Masculino , Femenino , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/uso terapéutico , Degeneración Macular/tratamiento farmacológico , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Proteínas Recombinantes de Fusión/uso terapéutico , Evaluación de Medicamentos , Estudios de Seguimiento , Mácula Lútea/patología , Degeneración Macular/patología , Desprendimiento de Retina/tratamiento farmacológico , Desprendimiento de Retina/etiología , Hemorragia Retiniana/etiología , Epitelio Pigmentado de la Retina/patología , Estudios Retrospectivos , Resultado del Tratamiento , Agudeza Visual
15.
Drug Des Devel Ther ; 13: 2413-2425, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31409975

RESUMEN

Age-related macular degeneration (AMD) is directly attributable to vision loss, posing significant pressure on public health. AMD is recognized to be a multi-factorial disease and among them, complement system is under heated discussion in recent years. In this review, we start with an overview of complement pathways involved in AMD and their therapies correspondingly. Finally, we discuss the development of the therapeutics existed now. Also, we enclose a list of drugs undergoing clinical trials.


Asunto(s)
Proteínas del Sistema Complemento/inmunología , Degeneración Macular/tratamiento farmacológico , Degeneración Macular/inmunología , Animales , Ensayos Clínicos como Asunto , Activación de Complemento , Humanos
16.
Health Qual Life Outcomes ; 17(1): 140, 2019 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-31412873

RESUMEN

BACKGROUND: Although visual acuity and optical coherence tomography (OCT) are most widely used as outcomes in treatment of neovascular age-related Macular Degeneration (nAMD), patient reported outcome measures are increasingly recognized. National Eye Institute Visual Function Questionnaire (NEI-VFQ 25) was developed to capture the perceived visual function. Yet, evidence of psychometric performance in the target population is required. The aim of this study was to examine the psychometric properties of NEI-VFQ 25 in a Norwegian cohort of newly diagnosed nAMD patients followed with a Treat and Extend (T/E) protocol. METHODS: Patients receiving intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection treatment according to a T/E protocol completed a Norwegian translation of NEI-VFQ 25, EuroQoL Health Questionnaire (EQ-5D), and Patient acceptable symptom state (PASS 5) at baseline, 3, 6 and 12 months. In addition, a control population completed the same questionnaires. Visual acuity was assessed with LogMar for best/treated eye. Validity testing comprised face validity by a 0-10 numeric rating scale about relevance of NEI-VFQ 25 as well as regression analyses and correlations between NEI-VFQ 25 and other relevant variables. Reliability was examined with Intraclass Correlation Coefficient (ICC) and Cronbach's alpha for internal consistency were performed. Responsiveness, discriminatory power and predictive value were also explored. RESULTS: Number of respondents at baseline, after 3, 6 and 12 months was 197, 186, 176 and 168, respectively. The control population comprised 26 individuals. Face validity of NEI-VFQ 25 had a mean (SD) of 7.8 (1.7) (n = 84). NEI-VFQ was significantly correlated to visual acuity and PASS 5 as well as EQ-5D at baseline. Reliability (ICC) of the overall and sub scores for the patients/controls ranged from 0.49-0.97/0.59-0.97. Cronbach's alpha was 0.61-0.85. Discriminatory power was confirmed by significant differences of the overall score between controls and patients (P < 0.001). NEI-VFQ 25 indicates responsiveness showing overall score improved significantly (P ≤ 0.001) from baseline to 3 months. NEI-VFQ 25, general health and visual acuity at baseline were the strongest predictors for how patients reported vision after 6 months follow-up. CONCLUSION: NEI-VFQ 25 showed acceptable psychometric performance, which supports that the Norwegian version can be used to monitor patients treated for nAMD.


Asunto(s)
Degeneración Macular/psicología , Medición de Resultados Informados por el Paciente , Calidad de Vida , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Estudios Transversales , Femenino , Humanos , Degeneración Macular/tratamiento farmacológico , Masculino , Noruega , Reproducibilidad de los Resultados , Traducciones , Factor A de Crecimiento Endotelial Vascular/uso terapéutico , Agudeza Visual
17.
Cell Physiol Biochem ; 53(2): 400-412, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31403270

RESUMEN

BACKGROUND/AIMS: Mutations in ABCA4 cause Stargardt macular degeneration, which invariably ends in legal blindness. We studied two common mutants, A1038V (in NBD1) and G1961E (in NBD2), with the purpose of exploring how they interact with the cell's quality control mechanism. The study was designed to determine how these mutants can be rescued. METHODS: We expressed wt and mutant ABCA4 in HEK293 cells and studied the effect of the mutations on trafficking and processing and the ability of correctors to rescue them. We used a combination of western blotting, confocal microscopy and surface biotinylation coupled with pulldown of plasma membrane proteins. RESULTS: G1961E is sensitive to inhibitors of the aggresome, tubacin and the lysosome, bafilomycin A. Both mutants cause a reduction in heat shock protein, Hsp27. Incubation of HEK293 cells expressing the mutants with VX-809, an FDA approved drug for the treatment of cystic fibrosis, increased the levels of A1038V and G1961E by 2- to 3-fold. Importantly, VX-809 increased the levels of both mutants at the plasma membrane suggesting that trafficking had been restored. Transfecting additional Hsp27 to the cells also increased the steady state levels of both mutants. However, in combination with VX-809 the addition of Hsp27 caused a dramatic increase in the protein expression particularly in the G1961 mutant which increased approximately 5-fold. CONCLUSION: Our results provide a new mechanism for the rescue of ABCA4 trafficking mutants based on the restoration of Hsp27. Our results provide a pathway for the treatment of Stargardt disease.


Asunto(s)
Transportadoras de Casetes de Unión a ATP/metabolismo , Aminopiridinas/farmacología , Benzodioxoles/farmacología , Transportadoras de Casetes de Unión a ATP/genética , Aminopiridinas/uso terapéutico , Anilidas/farmacología , Benzodioxoles/uso terapéutico , Membrana Celular/metabolismo , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Células HEK293 , Proteínas de Choque Térmico HSP27/metabolismo , Humanos , Ácidos Hidroxámicos/farmacología , Leupeptinas/farmacología , Lisosomas/metabolismo , Degeneración Macular/congénito , Degeneración Macular/tratamiento farmacológico , Degeneración Macular/metabolismo , Degeneración Macular/patología , Mutación , Transporte de Proteínas/efectos de los fármacos
18.
Expert Opin Ther Pat ; 29(10): 749-752, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31456444

RESUMEN

Introduction: Age-related macular degeneration (AMD) is the leading cause of central vision loss in developed countries. Effective therapy for AMD is currently limited to the treatment of the patient with intravitreal injections of anti-VEGF drugs. Areas covered: A method for the management of age-related macular degeneration (AMD) is claimed. It consists of the administration of pure botulinum-toxin or a serogroup of recombinant botulinum-toxins or their peptide fragments or neurotoxin associated with accessory proteins in extra-ocular regions of the eye. The toxin modifies the retinal pigment epithelium, maintaining its structure and function, and delaying the various stages of the macular degeneration. Expert opinion: The botulinum-toxin (BT) is administrated as extra-ocular infusions avoiding the risk of direct intraocular injection and the complications associated with the patients. The possibility to administer BT with accessory proteins (hemagglutinin, monoclonal antibody (anti-VEGF)), makes the novel system interesting for developing combined approaches for AMD treatment. The use of BT (alone or conjugated to other agents) as a method for treating or preventing AMD requires necessarily a patient case report study, as well as the in vitro or in vivo data, for supporting all the claims of the present patent.


Asunto(s)
Toxinas Botulínicas/administración & dosificación , Degeneración Macular/tratamiento farmacológico , Epitelio Pigmentado de la Retina/efectos de los fármacos , Humanos , Degeneración Macular/fisiopatología , Patentes como Asunto , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores
19.
Expert Opin Pharmacother ; 20(15): 1879-1891, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31298960

RESUMEN

Introduction: Investigational anti-VEGF treatments for neovascular age-related macular degeneration (nAMD) aim to improve visual outcomes and reduce treatment burden; these include long-acting agents, combination strategies, topical agents, sustained-release, and genetic therapies. Areas covered: The authors provide a comprehensive review of investigational therapies for nAMD, focusing on therapies currently in clinical trial. Expert opinion: Long-acting anti-VEGF agents have demonstrated promising results in phase 3 studies, and include Brolucizumab, a single-chain antibody fragment, and Abicipar, a designed ankyrin repeat protein (DARPin). Other unique anti-VEGF agents in current trials include Conbercept - a fusion protein of the VEGF receptor domains, KSI-301 - an anti-VEGF antibody biopolymer conjugate, and OPT-302 - an inhibitor of VEGF-C/D. Strategies to activate the Tie-2 receptor, some in combination with VEGF inhibition, are of interest, with recent trials of Faricimab, ARP-1536, and nesvacumab. Topical anti-VEGF ± anti-PDGF agents, such as pazopanib, squalamine lactate, regorafenib, and LHA510 have shown limited efficacy and/or have not been advanced, although PAN-90806 continues to advance with promising initial results. Sustained-release anti-VEGF treatments, to address treatment burden, include the ranibizumab Port Delivery System, GB-102, NT-503, hydrogel depot, Durasert, and ENV1305. Similarly, genetic therapies, including RGX-314 and ADVM-022, aim to provide sustained anti-VEGF expression from the retina.


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Degeneración Macular/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/farmacología , Humanos , Degeneración Macular/patología
20.
Free Radic Res ; 53(8): 865-874, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31257945

RESUMEN

Oxidative stress has a key role in the pathogenesis of age-related macular degeneration (AMD). Cigarette smoking is known to the one of the main risk factors of AMD through oxidative stress-mediated endoplasmic reticulum (ER) stress and lipid accumulation in human retinal pigment epithelium (RPE) cells. A number of studies have investigated the benefits of antioxidants in the AMD. However, previous studies have not shown that efficacy of antioxidant in the treatment of AMD. Recent studies demonstrated that morin hydrate (MH) has antioxidant properties, anti-inflammatory, and antiapoptosis effects, however, the protective effects of MH against cigarette smoke extract (CSE)-induced AMD have not been studied in detail. We tested the potential effect of MH against the CSE-induced lipid accumulation in RPE cells and mice RPE layer. Herein, we observed that expose of RPE cells to CSE reduced cell viability, increased the lipid accumulation, ER stress, and oxidative stress. Concomitantly, CSE treatment to mice induced AMD associated histopathological changes, lipid accumulation, ER stress and oxidative stress in RPE layer. MH significantly attenuated cytotoxicity, lipid accumulation, ER stress, and oxidative stress via activated AMPK-Nrf2 signaling pathway in RPE cells and mice RPE layer. In addition, AMPK inhibition reversed MH-induced RPE cell protection against CSE. Thus, we conclude that MH protects RPE cells from CSE through reduced oxidative stress, ER stress, and lipid accumulation via activated AMPK-Nrf2-HO-1 signaling pathway. These findings suggest that MH treatment may be exploited in effective strategy against CSE-induced AMD.


Asunto(s)
Estrés del Retículo Endoplásmico , Flavonoides/farmacología , Estrés Oxidativo , Epitelio Pigmentado de la Retina/efectos de los fármacos , Transducción de Señal , Humo/efectos adversos , Animales , Antioxidantes/farmacología , Línea Celular , Humanos , Peroxidación de Lípido , Degeneración Macular/tratamiento farmacológico , Degeneración Macular/metabolismo , Degeneración Macular/fisiopatología , Masculino , Ratones , Ratones Endogámicos C57BL , Factor 2 Relacionado con NF-E2/metabolismo , Epitelio Pigmentado de la Retina/metabolismo , Epitelio Pigmentado de la Retina/fisiopatología , Tabaco/química
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