Resultados de aflibercept en degeneración macular asociada a la edad refractaria a ranibizumab / Aflibercept in exudative age related macular degeneration refractory to ranibizumab

OOBJETIVO: El objetivo de este estudio es analizar la efectividad, seguridad y costes de aflibercept en el tratamiento de la degeneración macular relacionada con la edad (DMAE) refractaria al ranibizumab. MÉTODOS: Estudio observacional retrospectivo en el que se incluyó a pacientes diagnosticados de DMAE húmeda tratados previamente con ranibizumab. Las variables de eficacia evaluadas fueron cambios en la agudeza visual corregida (AV) y mejoras anatómicas en el ojo más afectado. Se estudiaron factores asociados a la mejora de la AV con aflibercept. Se recogieron los eventos adversos relacionados con el tratamiento. El análisis de costes se realizó desde la perspectiva del hospital, teniendo en cuenta solo los costos médicos directos. El análisis coste-efectividad respecto a la terapia previa con ranibizumab se calculó mediante el coste del tratamiento y la efectividad del tratamiento calculada como AV ganada. RESULTADOS: Se incluyeron un total de 50 ojos correspondientes a 46 pacientes, con una mediana de seguimiento de 4,6 meses (rango: 1,0-6,0). El porcentaje de ojos tratados que mostraron una mejora en la AV después de las 2 primeras dosis y al final del período de seguimiento fue de 32,0 y 28,0%. Ninguna de las variables estudiadas se asoció con una mejoría en la AV corregida después del tratamiento. No se encontraron diferencias significativas en el coste medio mensual entre tratamientos. CONCLUSIONES: Aflibercept es un tratamiento efectivo en un número significativo de pacientes resistentes al tratamiento con ranibizumab, con un coste similar al generado durante las etapas finales de tratamiento con ranibizumab

PURPOSE: The aim of this study is to determine the effectiveness, safety and cost of aflibercept in the treatment of wet age-related macular degeneration (ARMD) refractory to ranibizumab. METHODS: Retrospective observational study was conducted on patients diagnosed with wet ARMD, and previously treated with ranibizumab. Efficacy variables assessed were changes in visual acuity (BCVA) and anatomical improvements in the most affected eye. Factors associated with improvement of BCVA with aflibercept were also studied. Adverse events related to the aflibercept administration were recorded. Cost analysis data were collected from the hospital perspective, and only taking the direct medical costs into account. Cost-effectiveness analysis was calculated using the aflibercept treatment cost, and effectiveness calculated as BCVA gained. RESULTS: A total of 50 eyes corresponding to 46 patients were included. The median follow-up period was 4.6 months (range: 1.0-6.0). Improvement in visual acuity after the first 2 doses and at the end of the follow-up period was observed in 32.0 and 28.0% of treated eyes, respectively. None of the variables studied was associated with an improvement in the BCVA after treatment. No significant differences were found in the average monthly cost between treatments. CONCLUSIONS: Aflibercept is shown to be an effective treatment in a significant number of patients resistant to treatment with ranibizumab, presenting a cost similar to that generated during the final stages of treatment with ranibizumab

Changes in motor nerve terminals during bupivacaine-induced postsynaptic deprivation.

The local anaesthetic agent bupivacaine induces a rapid degeneration of muscle cells when injected in the sternocleidomastoid muscle of the adult rat with no damage to intramuscular nerves. Nevertheless, silver impregnation and electron microscopy reveal a sequence of retraction and sprouting of the motor nerve endings during the period of the bupivacaine-induced muscle cell deprivation by necrosis. These morphological changes seem to be qualitatively similar to the retraction and growth phenomena described as forming part of the remodelling process affecting normal untreated neuromuscular junctions of the adult amphibia and mammals. The results are discussed in the context of the regulatory mechanisms governing the maintenance of motor nerve terminals.

Morphometric study of the neuromuscular synapses in the adult rat with special reference to the remodelling concept.

There is increasing morphologic evidence that neuromuscular synapses are not rigid structures in the mature muscles of adult animals. On the contrary, they may be submitted to a continuous process of remodelling. In silver-impregnated sternocleidomastoid muscles of the young adult rat, we measured synaptic parameters such as nerve terminal length, the number of branching points of terminal arborization, and muscle fiber diameter, and used a morphometric approach to explore specific questions concerning neuromuscular remodelling. Quantitative data indicate that: (a) The complexity and maturation of the nerve endings in this muscle are very variable and the increase in branching points is not paralleled by an increase in terminal length; (b) Muscle fiber diameter is related only marginally to presynaptic parameters; (c) Accessory ending formation occurs when the original ending does not reach the mean size of endings in singly innervated areas; (d) The complexity of individual endings at dually innervated junctions is smaller than the mean development of singly innervated synapses, indicating the existence of some mutual inhibitory influence between closely spaced endings. Morphometric results suggest a continuous process of synaptic formation in this adult muscle.