Linking inflammation and angiogenesis with fibrogenesis: Expression of FXIIIA, MMP-9, and VEGF in oral submucous fibrosis / Vinculación de la inflamación y la angiogénesis con la fibrogénesis: expresión de FXIIIA, MMP-9 y VEGF en la fibrosis submucosa oral

Objectives Interplay of Factor XIIIa (FXIIIa), a transglutaminase, responsible for cross-linking of matrix proteins, Matrix Metalloproteinase-9 (MMP-9), a gelatinase, and Vascular Endothelial Growth Factor (VEGF), an angiogenic inducer, were studied in relation to fibrogenesis and disease progression in oral submucous fibrosis (OSMF). Material and methods Immunohistochemical expression of markers was studied in 60 formalin-fixed paraffin-embedded tissue blocks of OSMF and 20 normal oral mucosal tissues. FXIIIa was studied quantitatively while MMP-9 and VEGF were assessed semi-quantitatively. Expression was compared with histopathological grades of OSMF. Results FXIIIa expression significantly increased in OSMF (p-value 0.000). However, expression decreased and cells became quiescent with increasing grades (p-value 0.000). MMP-9 (p-value epithelium 0.011, p-value connective tissue 0.000) and VEGF expression (p-value epithelium 0.000, connective tissue 0.000) increased in OSMF. A negative correlation between FXIIIa and MMP-9 (−0.653) in early grade (p-value of 0.021) and a positive correlation between FXIIIa and VEGF (0.595) (p-value of 0.032) was found in the moderate grade OSMF. Regression analysis showed a significant association (p<0.01) of FXIIIa in OSMF and with increasing grades of OSMF. Conclusion FXIIIa may play a crucial role in initiation of fibrosis in OSMF. MMP-9 may have a diverse role to play in OSMF as a regulator of fibrosis. VEGF may show an angio-fibrotic switch and contribute to fibrosis in OSMF. These cytokines may show altered function and can contribute to fibrosis and chronicity of disease due to changes in the microenvironment. Tissue stiffness in OSMF itself creates an environment that enhances the chronicity of the disease. (AU)

Objetivos Se estudió la interacción del factor XIIIa (FXIIIa), una transglutaminasa responsable de los entrecruzamientos de las proteínas de la matriz, la metaloproteinasa de matriz-9 (MMP-9), una gelatinasa y el factor de crecimiento endotelial vascular (VEGF), un inductor angiogénico, en relación con la fibrogénesis y la progresión de la enfermedad en la fibrosis submucosa oral (OSMF). Material y métodos Se estudió la expresión inmunohistoquímica de marcadores en 60 bloques de tejido de OSMF fijados con formalina e incluidos en parafina y 20 tejidos de mucosa oral normales. FXIIIa se estudió cuantitativamente mientras que MMP-9 y VEGF se evaluaron semicuantitativamente. La expresión se comparó con los grados histopatológicos de OSMF. Resultados La expresión de FXIIIa aumentó significativamente en OSMF (valor de p 0,000). Sin embargo, la expresión disminuyó y las células se volvieron inactivas a medida que aumentaban los grados (valor de p 0,000). MMP-9 (valor de p epitelio 0,011, tejido conectivo valor de p 0,000) y expresión de VEGF (valor de p epitelio 0,000, tejido conectivo 0,000) aumentaron en OSMF. Se encontró una correlación negativa entre FXIIIa y MMP-9 (-0,653) en grado temprano (valor de p de 0,021) y una correlación positiva entre FXIIIa y VEGF (0,595) (valor de p de 0,032) en OSMF de grado moderado. El análisis de regresión mostró una asociación significativa (p<0,01) de FXIIIa en OSMF y con grados crecientes de OSMF. Conclusión FXIIIa puede desempeñar un papel crucial en el inicio de la fibrosis en OSMF. MMP-9 puede desempeñar un papel diverso en OSMF como regulador de la fibrosis. VEGF puede mostrar un interruptor angiofibrótico y contribuir a la fibrosis en OSMF. Estas citocinas pueden mostrar una función alterada y pueden contribuir a la fibrosis y la cronicidad de la enfermedad debido a cambios en el microambiente. La rigidez del tejido en el propio OSMF crea un entorno que mejora la cronicidad de la enfermedad. (AU)

Linking inflammation and angiogenesis with fibrogenesis: Expression of FXIIIA, MMP-9, and VEGF in oral submucous fibrosis / Vinculación de la inflamación y la angiogénesis con la fibrogénesis: expresión de FXIIIA, MMP-9 y VEGF en la fibrosis submucosa oral

Objectives Interplay of Factor XIIIa (FXIIIa), a transglutaminase, responsible for cross-linking of matrix proteins, Matrix Metalloproteinase-9 (MMP-9), a gelatinase, and Vascular Endothelial Growth Factor (VEGF), an angiogenic inducer, were studied in relation to fibrogenesis and disease progression in oral submucous fibrosis (OSMF). Material and methods Immunohistochemical expression of markers was studied in 60 formalin-fixed paraffin-embedded tissue blocks of OSMF and 20 normal oral mucosal tissues. FXIIIa was studied quantitatively while MMP-9 and VEGF were assessed semi-quantitatively. Expression was compared with histopathological grades of OSMF. Results FXIIIa expression significantly increased in OSMF (p-value 0.000). However, expression decreased and cells became quiescent with increasing grades (p-value 0.000). MMP-9 (p-value epithelium 0.011, p-value connective tissue 0.000) and VEGF expression (p-value epithelium 0.000, connective tissue 0.000) increased in OSMF. A negative correlation between FXIIIa and MMP-9 (−0.653) in early grade (p-value of 0.021) and a positive correlation between FXIIIa and VEGF (0.595) (p-value of 0.032) was found in the moderate grade OSMF. Regression analysis showed a significant association (p<0.01) of FXIIIa in OSMF and with increasing grades of OSMF. Conclusion FXIIIa may play a crucial role in initiation of fibrosis in OSMF. MMP-9 may have a diverse role to play in OSMF as a regulator of fibrosis. VEGF may show an angio-fibrotic switch and contribute to fibrosis in OSMF. These cytokines may show altered function and can contribute to fibrosis and chronicity of disease due to changes in the microenvironment. Tissue stiffness in OSMF itself creates an environment that enhances the chronicity of the disease. (AU)

Objetivos Se estudió la interacción del factor XIIIa (FXIIIa), una transglutaminasa responsable de los entrecruzamientos de las proteínas de la matriz, la metaloproteinasa de matriz-9 (MMP-9), una gelatinasa y el factor de crecimiento endotelial vascular (VEGF), un inductor angiogénico, en relación con la fibrogénesis y la progresión de la enfermedad en la fibrosis submucosa oral (OSMF). Material y métodos Se estudió la expresión inmunohistoquímica de marcadores en 60 bloques de tejido de OSMF fijados con formalina e incluidos en parafina y 20 tejidos de mucosa oral normales. FXIIIa se estudió cuantitativamente mientras que MMP-9 y VEGF se evaluaron semicuantitativamente. La expresión se comparó con los grados histopatológicos de OSMF. Resultados La expresión de FXIIIa aumentó significativamente en OSMF (valor de p 0,000). Sin embargo, la expresión disminuyó y las células se volvieron inactivas a medida que aumentaban los grados (valor de p 0,000). MMP-9 (valor de p epitelio 0,011, tejido conectivo valor de p 0,000) y expresión de VEGF (valor de p epitelio 0,000, tejido conectivo 0,000) aumentaron en OSMF. Se encontró una correlación negativa entre FXIIIa y MMP-9 (-0,653) en grado temprano (valor de p de 0,021) y una correlación positiva entre FXIIIa y VEGF (0,595) (valor de p de 0,032) en OSMF de grado moderado. El análisis de regresión mostró una asociación significativa (p<0,01) de FXIIIa en OSMF y con grados crecientes de OSMF. Conclusión FXIIIa puede desempeñar un papel crucial en el inicio de la fibrosis en OSMF. MMP-9 puede desempeñar un papel diverso en OSMF como regulador de la fibrosis. VEGF puede mostrar un interruptor angiofibrótico y contribuir a la fibrosis en OSMF. Estas citocinas pueden mostrar una función alterada y pueden contribuir a la fibrosis y la cronicidad de la enfermedad debido a cambios en el microambiente. La rigidez del tejido en el propio OSMF crea un entorno que mejora la cronicidad de la enfermedad. (AU)

Relationship between Changes of Serum Vascular Endothelial Growth Factor and Folate Receptor-α Levels and Clinical Efficacy of Toripalimab in Patients with Bladder Cancer

Objective: This study aims to explore the changes of serum vascular endothelial growth factor (VEGF) and folate receptor-α (FR-α) levels in patients with bladder cancer before and after treatment with toripalimab and to analyse the relationship between the changes of VEFG and FR-α and the clinical efficacy of patients. Methods: A total of 176 patients with bladder cancer admitted to our hospital from January 2020 to January 2022 were selected as the research subjects. All patients were treated with toripalimab. The clinical efficacy and changes of serum VEGF and FR-α levels before and after treatment were observed. Logistic regression was used to analyse the relationship between serum VEGF and FR-α levels and the therapeutic effect of toripalimab, and receiver operating characteristic curve was used to evaluate the predictive value of serum VEGF and FR-α on the efficacy. Results: The objective response rate and disease control rate after treatment were 31.82% and 70.45%, respectively. The serum VEGF and FR-α levels in patients after treatment were significantly lower than those before treatment (p < 0.001). The patients were divided into an effective group (n = 124) and an ineffective group (n = 52) according to clinical efficacy. The serum VEGF and FR-α levels of patients in the effective group were significantly lower than those of the ineffective group (p < 0.001). Logistic regression analysis showed that the elevated levels of serum VEGF (odds ratio = 1.226) and FR-α (odds ratio = 1.384) were the risk factors affecting the therapeutic effect of toripalimab (p < 0.05). The area under curve of the combined prediction of VEGF and FR-α was 0.920, the Youden index was 0.722, the sensitivity was 89.52%, the specificity was 82.69%, and the predictive value was higher than the single detection of VEGF or FR-α (p = 0.001, p < 0.001)(AU)

Correlación entre la sensibilidad al contraste y las características morfológicas obtenidas por OCT en pacientes con degeneración macular relacionada con la edad avanzada tratados con dosis de carga de inhibidores del factor de crecimiento endotelial vascular / Correlation between contrast sensitivity and morphological features obtained by OCT in patients with age-related macular degeneration treated with a loading dose of vascular endothelial growth factor inhibitors

Objetivo Determinar la correlación entre la sensibilidad al contraste y las características morfológicas obtenidas por tomografía de coherencia óptica en pacientes con degeneración macular relacionada con la edad avanzada tratados con dosis de carga de inhibidores del factor de crecimiento endotelial vascular (anti-VEGF). Diseño Se trata de un estudio ambispectivo (prospectivo+retrospectivo) observacional y analítico. Participantes Todos los pacientes de 55 años o más con degeneración macular relacionada con la edad que acudieron al departamento de Retina del servicio de Oftalmología y cumplieron con los criterios de inclusión entre marzo-mayo de 2022. Métodos Se recolectaron los datos por medio de la revisión de expedientes. Se analizaron los estudios de tomografía de coherencia óptica previa a la aplicación de inyecciones intravítreas de los pacientes que se encontraban en el mes posterior a la última dosis. Se incluyeron un total de 33 sujetos y un total de 30 continuaron seguimiento. Se realizaron pruebas de normalidad (Shapiro y Bartlett) entre los grupos de estudio, dando como resultado grupos no normales no homocedásticos. Los sujetos fueron sometidos a una nueva evaluación oftalmológica y nueva toma de mediciones retinianas. Resultados Se realizó un análisis de regresión lineal comparando los valores logarítmicos de la agudeza visual y la sensibilidad al contraste, obteniendo una relación significativa entre ambos valores posterior a la aplicación del tratamiento (p<0,0001). Asimismo, se demostró una correlación entre la disminución de los valores de la sensibilidad al contraste y todas las características evaluadas en el tomografía de coherencia óptica. Conclusiones Las estrategias de antiangiogénesis pueden conducir a mejores resultados en la función visual global, impactando positivamente en la sensibilidad al contraste (AU)

Objective To determine the correlation between contrast sensitivity and morphological characteristics obtained by optical coherence tomography in patients with age-related macular degeneration treated with a loading dose of vascular endothelial growth factor inhibitors (anti-VEGF). Design This is an ambispective (prospective+retrospective) observational, cross-sectional, and analytical study. Participants All patients over 55 years of age with age-related macular degeneration who attended the Retina service of the Ophthalmology department and met the inclusion criteria between March-May 2022. Methods Data collection was carried out by reviewing the records of patients.Optical coherence tomography studies prior to the application of intravitreal injections of patients who were currently in the first month after the last dose of anti-VEGF were analyzed. A total of 33 subjects were included, of which 30 continued follow-ups. Normality tests (Shapiro and Bartlett) were performed where a nonparametric data distribution was demonstrated. The subjects underwent a new ophthalmological evaluation and new retinal measurements of the affected eye. Results A linear regression analysis was performed comparing the logarithmic values of both visual acuity and contrast sensitivity, obtaining a significant relationship between both values after the application of treatment (P<.0001). Likewise, correlation was demonstrated between the decrease in contrast sensitivity values and all the characteristics evaluated in the patients’ optical coherence tomography. Conclusions Antiangiogenesis strategies can lead to better results in global visual function, positively impacting contrast sensitivity (AU)

Resultados funcionales de tratamiento con bevacizumab intravítreo en pacientes con retinopatía del prematuro / Functional results in children with retinopathy of prematurity treated with intravitreal bevacizumab

Objetivo El propósito del presente estudio es determinar la eficacia y describir los resultados funcionales en términos de agudeza visual y defecto refractivo a largo plazo del tratamiento con una dosis de bevacizumab intravítreo en pacientes con retinopatía del prematuro (ROP) tipo1 de alto riesgo. Métodos Se trata de un estudio clínico retrospectivo en el que se seleccionaron todos los pacientes con ROP preumbral tipo1 de alto riesgo tratados según práctica clínica habitual con bevacizumab intravítreo entre diciembre de 2013 y enero de 2018. Los pacientes con un seguimiento inferior a tres años fueron excluidos. Se registraron los datos de agudeza visual y refracción bajo cicloplejia de la última exploración oftalmológica realizada. Se definió la variable éxito como ausencia de retratamiento con anti-VEGF intravítreo o láser durante el tiempo de seguimiento. Resultados Se incluyeron en el análisis 76 ojos de 38 pacientes. Un total de 20 pacientes (40 ojos) tenían valoración de mejor agudeza visual corregida tomada utilizando la prueba de Snellen. La edad media de estos pacientes era de 6años (intervalo 4-9). La agudeza visual mediana fue de 0,80 (RIQ: 0,50; 1,00). Treinta y cuatro ojos (85%) tenían buena agudeza visual (mayor o igual a 0,5). Se obtuvo la refracción bajo cicloplejia de 74 ojos de 37 pacientes. La mediana del equivalente esférico en la última revisión fue de +0,94 (RIQ: −0,25; 1,88). La tasa de éxito fue del 96,05%. Conclusión El bevacizumab intravítreo es una terapia efectiva con buenos resultados funcionales para ROP tipo1 de alto riesgo. En nuestro estudio se observó buena respuesta al tratamiento, con una tasa de éxito superior al 95% (AU)

Background/aim The aim of the study is to describe the efficacy and to determine the functional outcome in terms of visual acuity and refractive defect of a single dose of intravitreal bevacizumab in patients with high-risk ROP type1. Methods In this retrospective clinical study patients diagnosed between December 2013 and January 2018 with high-risk pre-threshold ROP type1 and treated with intravitreal bevacizumab were selected. All patients were treated following the established protocol at our centre. Those patients with less than three-year follow-up were excluded. Visual acuity and cycloplegic refraction in the last visit were registered. Treatment efficacy was defined as the absence of retreatment with intravitreal anti-VEGF or laser during follow-up. Results A total of 38 infants (76eyes) were included in the analysis. Twenty infants (40eyes) completed visual acuity testing. Mean age was 6years (IQR: 4-9). Median visual acuity was 0.8 (IQR: 0.5-1). Thirty-four eyes (85%) had good visual acuity (greater than or equal to 0.5). Thirty-seven patients (74eyes) had cycloplegic refraction measured. Median spherical equivalent at the last visit was +0.94 (IQR: −0.25; 1.88). Treatment success rate was 96.05%. Conclusion Intravitreal bevacizumab treatment showed good functional outcome in patients with high-risk ROP type1. In our study, good response to treatment was observed with a success rate over 95% (AU)

The Relationship between VEGF and AGT Gene Single Nucleotide Polymorphisms and Susceptibility to Renal and Bladder Cancers

Background: We aimed to examine the relationships between the angiotensinogen (AGT) and vascular endothelial growth factor (VEGF) gene single nucleotide polymorphisms and susceptibility to bladder and kidney cancers. Methods: A 1:1 paired case-control study was conducted, which included 143 newly diagnosed kidney cancer cases, 182 newly diagnosed bladder cancer cases, and healthy subjects in the same period collected from two hospitals. Medical records and a questionnaire were used to obtain relevant information. Genotypes were determined by improved multiple ligase detection reaction (iMLDR) and VEGF serum expression levels were detected by enzyme-linked immunosorbent assays (ELISAs). Results: The VEGF gene/genotype frequencies of rs833061 and rs1570360 were statistically different among various pathological grades of kidney cancer, while the AGT rs699 gene/genotype frequencies were statistically different among various pathological types of bladder cancer. In kidney cancer, rs699 was associated with smoking, drinking, and hair coloring, while in bladder cancer, rs699, rs1570360, rs3025039, and rs833061 were associated with smoking, drinking, hair coloring, exercise, and urine holding. Conclusions: This work will help identify biomarkers that can predict the early metastasis and recurrence of kidney or bladder cancer, as well as help improve patient survival rates by predicting their susceptibility. Significance: This work will provide reference for the prevention and treatment of kidney and bladder cancers (AU)

Role of papillary thyroid carcinoma patients with Hashimoto thyroiditis: evaluation of oxidative stress and inflammatory markers

Purpose Papillary thyroid carcinoma (PTC) is the most frequent subtype of thyroid cancer; Hashimoto's thyroiditis (HT), autoimmune disease, commonly affects the thyroid gland; there is possibly a correlation between both, but the exact mechanisms that involve this relationship are still under debate. Since oxidative stress (OS) and the inflammatory environment participate in the development of several types of cancer, the objective of the present study was to establish the microenvironment and systemic participation of OS and inflammatory markers in patients with PTC and HT. Methods Blood and tissue samples were collected from 115 patients: BENIGN (n = 63); PTC (n = 27); HT (n = 15) and PTC + HT (n = 10), and sixty-three were samples from healthy individuals (control group). Results Superoxide dismutase, Catalase, reduced Glutathione, markers of lipid peroxidation and inflammation were evaluated in blood. Immunohistochemistry was performed on 3-nitrotyrosine, 4-hydroxynonenal, Ki-67 and VEGF. The results indicate that antioxidant enzymes were more active in groups with thyroid disorders compared to control, while the concentration of Reduced glutathione was reduced in BENIGN and PTC groups. When PTC and PTC + HT groups were analyzed, no significant differences were found in relation to the antioxidant defense and inflammatory markers. The ability to contain the induced lipid peroxidation was lower and a high level of malondialdehyde was observed in the PTC group. All immunohistochemical markers had higher scores in the PTC group compared to PTC + HT. Conclusion There was a more pronounced presence of OS and a greater activity of cell proliferation and angiogenesis markers in PTC than in PTC + HT group (AU)

CircRNAs: promising factors for regulating angiogenesis in colorectal cancer

Colorectal cancer (CRC) is one of the most common cancers in the world. The incidence rate of cancer is high. The overall response to traditional treatment methods such as surgery, radiotherapy, and chemotherapy is not very satisfactory. Therefore, finding new therapeutic targets is very important for improving CRC treatment. In recent reports, the role of circRNAs in regulating colorectal angiogenesis has been gradually revealed. CircRNAs can indirectly act on angiogenesis pathways and regulate the expression of growth factors such as vascular endothelial growth factor (VEGF). CircRNAs are endogenous noncoding RNAs formed by pre-mRNAs through exon circular splicing. The covalent closed-loop structure makes these RNAs highly conserved and stable. CircRNAs have been found in human plasma, serum, urine, and other body fluids. Their highly conserved characteristics play important roles in many biological activities. CircRNAs can participate in the progression of many diseases by sponging miRNAs, interacting with proteins, and regulating transcription. Angiogenesis can provide nutrients and oxygen for tumour proliferation and metastasis. Angiogenesis is an important sign of the formation of the tumour microenvironment. Here, we will summarize the role of the latest circRNAs in the mechanism of angiogenesis in CRC and provide potential therapeutic targets for clinical treatment. (AU)

Resultados del tratamiento de los pacientes con DMAE exudativa durante la pandemia por COVID-19 / Results of the treatment of patients with exudative AMD during the COVID-19 pandemic

Antecedentes y objetivo La pandemia SARS-CoV-2 ha supuesto un caos organizativo para todos los sistemas sanitarios del planeta. No solo ha sido complicado hacer frente a la COVID 19, sino también ajustar la actividad asistencial en otras especialidades. En oftalmología las recomendaciones de las sociedades científicas eran dar asistencia urgente y dentro de esta se contemplaba el tratamiento intravítreo de los pacientes con degeneración macular asociada a la edad neovascular (DMAEn) activa, puesto que el retraso en el tratamiento supone una pérdida potencialmente irrecuperable de agudeza visual (AV). El objetivo primario del presente estudio es medir el impacto en la actividad y los resultados visuales del confinamiento por coronavirus en los pacientes con DMAEn en el área 3 de la Comunidad de Madrid. Material y método Se plantea un estudio observacional retrospectivo de todos los pacientes con DMAEn que habían acudido a consulta y/o recibido tratamiento intravítreo los 3 meses previos al inicio del confinamiento. Resultados Los 3 meses previos al confinamiento se atendieron a 144 pacientes con DMAEn de los cuales solo 51 acudieron durante el confinamiento y a los 6 meses tras el confinamiento solo 117 pacientes han retomado su seguimiento. La AV media antes del confinamiento era de 58±23,7 letras y se redujo de forma estadísticamente significativa a 53±27,1 letras a los 6 meses tras el confinamiento. También observamos una disminución significativa del número de visitas durante el confinamiento a pesar de las medidas de seguridad implementadas. Conclusiones Nuestro estudio demuestra que los pacientes con DMAEn presentan una disminución estadísticamente significativa de la AV durante el confinamiento. De una AV de casi 58 letras, se redujo a 53 a los 6 meses del confinamiento. El porcentaje de pacientes que perdió 15 o más letras se duplicó (AU)

Background and objective The SARS-CoV-2 pandemic has caused chaos in all health systems on the planet. It has been difficult to cope with COVID 19, but also to maintain the activity in other specialties. In ophthalmology, the scientific societies recommended providing urgent care, including the intravitreal treatment of patients with active neovascular age-related macular degeneration (AMD), since a delay in treatment implies a potential loss of visual acuity (VA). The main objective of this study was to measure the impact of the coronavirus lockdown on the activity and visual results in patients with neovascular AMD in Area 3 of Madrid. Material and method A retrospective observational study was conducted of all patients with neovascular AMD who attended a consultation and/or received intravitreal treatment in the 3 months before the lockdown. Results In the 3 months before the lockdown, 144 patients with neovascular AMD were treated, of whom only 51 attended a consultation during the lockdown and, at 6 months after it, only 117 patients had resumed their follow-up. Mean VA before the lockdown was 58.0±23.7 letters and was statistically significantly reduced to 53.0±27.1 letters at 6 months after the lockdown. We also observed a significant decrease in the number of visits during the lockdown, despite the security measures implemented. onclusions Our study shows that patients with neovascular AMD have had a statistically significant decrease in VA due to the lockdown. A VA of almost 58 letters was reduced to 53 at 6 months after the lockdown. The percentage of patients who lost 15 or more letters doubled. We observed a 63.3% loss of temporary follow-up during the lockdown and a 14.58% loss of permanent follow-up at 6 months after the lockdown (AU)

Resultados de vida real en el tratamiento de la degeneración macular asociada a la edad neovascular con terapia anti-VEGF. Análisis de 122 pacientes de un solo centro / Real-life results in treating neovascular age-related macular degeneration with anti-VEGF therapy. Analysis of 122 patients from a single centre

Antecedentes El pronóstico de la degeneración macular asociada a la edad (DMAE) ha mejorado significativamente desde la aparición de los tratamientos antiangiogénicos. Sin embargo, diversos estudios realizados en «vida real» han demostrado un número de inyecciones inferior y un pronóstico visual notablemente peor de los ensayos clínicos pivotales. Objetivo Valorar la efectividad y seguridad del tratamiento de la DMAE neovascular y analizar factores clínicos relacionados con el pronóstico funcional y estructural en la práctica clínica habitual. Materiales y métodos Estudio retrospectivo, observacional y unicéntrico. Se incluyeron 143 ojos de 122 pacientes diagnosticados de DMAE neovascular entre los años 2015 y 2016, que recibieron tratamiento con antiangiogénicos y con un seguimiento de dos o más años. Resultados La agudeza visual mejoró en el 45% de pacientes tras dos años de tratamiento. La disminución media de grosor macular central fue de 85 μm (p < 0,001) y el número medio de inyecciones fue de 13. Un 3,5% presentó una rotura del epitelio pigmentario. Ranibizumab fue el más utilizado como primera opción, aunque 79 pacientes (55,2%) requirieron un cambio de fármaco, pasando la mayoría a ser tratados con aflibercept. Fueron predictores de peor resultado estructural un mayor número de visitas (p < 0,001) y un menor número de inyecciones (p < 0,01). El número de visitas se asoció a mejor agudeza visual (p < 0,001). Conclusiones El tratamiento ha demostrado su eficacia mejorando la agudeza visual y el grosor macular central. Sin embargo, el número de inyecciones realizado ha sido en general superior al de otros estudios de vida real (AU)

Background The prognosis of age-related macular degeneration (AMD) has improved significantly since the advent of antiangiogenic treatments. However, several «real life» studies have shown lower number of injections and a markedly worse visual prognosis than pivotal clinical trials. Objective To assess the effectiveness and safety of the treatment of neovascular AMD and analyse clinical factors related to the functional and structural prognosis in routine clinical practice. Material and method Retrospective, observational, single-centre study that included 143 eyes of 122 patients diagnosed with neovascular AMD between the years 2015 and 2016, who received treatment with antiangiogenic drugs and were followed up for two or more years. Result Visual acuity improved in 45% of patients after two years of treatment. The mean decrease in central macular thickness was 85 microns (p < 0.001) and the mean number of injections was 13. Retinal pigment epithelium rupture was present in 3.5%. Ranibizumab was the drug most used as a first option, although 79 patients (55.2%) required a change in treatment, most being switched to aflibercept. A greater number of visits (p < 0.001) and a lower number of injections (p < 0.01) were predictors of worse structural outcome. The number of visits was associated with better visual acuity (p < 0.001). Conclusions The treatment has demonstrated its efficacy by improving visual acuity and central macular thickness. However, the number of injections performed has generally been higher than in other real-life studies (AU)

Expresión inmunohistoquímica de VEGFR1 en carcinomas de pulmón de células no pequeñas: La expresión inferior de VEGFR1 se asocia con el subtipo de carcinoma de células escamosas y los valores elevados en SUVmáx en PET de 18F-FDG / Immunohistochemical expression of VEGFR1 in non small cell lung carcinomas: Lower VEGFR1 expression is asociated with squamous cell carcinoma subtype and high max SUV values in 18F-FDG PET

Antecedentes: Estudiar la posible relación entre la expresión inmunohistoquímica del receptor 1 del factor de crecimiento endotelial vascular (VEGFR1) y el valor máximo de captación estandarizada (SUVmáx) de la PET 18F-FDG en pacientes con cáncer de pulmón de células no pequeñas.Material y métodos:El estudio incluyó 39 pacientes con NSCLC (24 carcinomas de células escamosas y 15 adenocarcinomas). Según el estadio clínico, los pacientes se distribuyeron de la siguiente manera: 8 en estadio I, 7 en estadio II, 15 en estadio III y 9 en estadio IV. Se estudió la expresión inmunohistoquímica del VEGFR1 mediante la técnica de la matriz tisular utilizando el dispositivo de arreglo de tejidos (Beecher Instruments, Sun Prairie, WI), utilizando el anticuerpo policlonal contra el VEGFR1 (Santa Cruz Biotechnology, California, EE. UU.).Resultados: Se observó una expresión inmunohistoquímica positiva del VEGFR1 en 23 casos (59%). El número de tumores positivos no se relacionó con el estadio clínico pero hubo una asociación estadísticamente significativa diferente (p: 0,0009) entre la positividad de VEGFR1 y el tipo histológico, correspondiendo los mayores porcentajes de resultados positivos a los adenocarcinomas (93,3%) frente a los carcinomas escamocelulares (37,5%). Asimismo, los valores SUVmáx fueron mayores (p: 0,039) en los carcinomas VEGFR1 negativos que en los tumores VEGFR1 positivos (r: 4-32,1; 16,4+/-6,4 [mediana 16,1] vs. r: 3-47; 14,5+/-8,6 [12,8]).Conclusiones: Nuestros resultados nos llevaron a considerar que en el CPCNP, la expresión inmunohistoquímica negativa de VEGFR1 se asocia significativamente con el subtipo de carcinomas de células escamosas y con valores SUVmáx más altos en 18F-FDG-PET (AU)

Background: To study the possible relation between immunohistochemical expression of vascular endothelial growth factor receptor 1 (VEGFR1) and the maximum standardised uptake value (maxSUV) of 18F-FDG PET in patients with non small cell lung cancer.Material and methods: The study included 39 patients with NSCLC (24 squamous cell carcinomas and 15 adenocarcinomas). According to the clinical stage, the patients were distributed as follows: 8 stage I, 7 stage II, 15 stage III and 9 stage IV. Immunohistochemical expression of VEGFR1 was studied through the technique of tissue-matrix using tissue arrayer device (Beecher Instruments, Sun Prairie, WI), using the polyclonal antibody against VEGFR1 (Santa Cruz Biotechnology, California, USA).Results: Positive VEGFR1 immunohistochemical expression was noted in 23 cases (59%). The number of positive tumours was not related with clinical stage but there was a different statistically significant association (p:.0009) between VEGFR1 positivity and histological type, corresponding the greater percentages of positive results to adenocarcinomas (93.3%) versus in squamous cell carcinomas (37.5%). Likewise, maxSUV values were higher (p: .039) in negative VEGFR1 carcinomas than in positive VEGFR1 tumors (r: 4-32.1; 16.4+/-6.4 [median 16.1] vs. r: 3-47; 14.5+/-8.6 [12.8]).Conclusions: Our results led us to consider that in NSCLC, the negative VEGFR1 immunohistochemical expression is associated significantly with squamous cell carcinomas subtype and with higher maxSUV values in 18F-FDG-PET (AU)

Shock wave and mesenchymal stem cells as treatment in the acute phase of spinal cord injury: A pilot study / Ondas de choque y células madre mesenquimales como tratamiento en la fase aguda de la lesión medular: un estudio piloto

Introduction: Spinal cord injury (SCI) is a complex pathology with thousands of patients worldwide. During the acute early phase, neural tissue shows some regenerative properties that disappear at the chronic phase. Shock Waves and Stem Cells have been proposed as a possible therapy. Methods: Here, we analyse Shock Waves’ immediate effect over spinal cord genetic response in the injured and healthy spinal cord and the effect of Shock Waves and combined Shock Waves plus Stem Cells distally grafted to treat the first month after spinal cord injury. Results: The immediate application of shock waves increases VEGF (Vascular Endothelial Growth Factor) but reduces the BDNF (Brain-Derived Growth Factor) RNA (Ribonucleic acid) response. Shock wave therapy increases GFAP (Glial fibrillary acidic protein) positive cells and vascularity during the treatment's acute phase. Conclusion: Shock wave treatment seems to be enough to produce benefits in the acute phase of spinal cord injury, with no accumulative positive effects when mesenchymal stem cell graft is applied together.(AU)

Introducción: La lesión medular es una afección compleja con miles de pacientes repartidos a lo largo del mundo. Durante la fase aguda temprana de la lesión, el tejido neural muestras ciertas propiedades regenerativas que desaparecen durante la fase crónica. Las ondas de choque y las células madre han sido propuestas como posibles terapias. Metodología: En este estudio analizamos el efecto inmediato de una sesión de ondas de choque sobre la médula espinal, tanto sana como lesionada, y si su efecto es sumatorio al que produce un tratamiento de células madre mesenquimales inyectadas distalmente, como se ha observado en estudios previos. Resultados: Se observa un efecto inmediato con las ondas de choque que promueve un incremento del efecto trófico vascular endotelial, y una disminución del factor trófico derivado del cerebro. La terapia prolongada con ondas de choque en la fase aguda incrementa la presencia de astrocitos y la vascularización local. No parece haber efecto sumatorio con el tratamiento de células madre, produciéndose efectos similares con o sin las células madre mesenquimales. Conclusiones: Las ondas de choque parecen tener un efecto positivo durante la fase aguda de una lesión medular por compresión, sin que el tratamiento distal de células madre mesenquimales parezca implicar un efecto sumatorio.(AU)

Formación atípica de agujero macular después de terapia Anti-VEGF para la degeneración macular asociada a la edad: ¿coincidencia o consecuencia? / Atypical macular hole formation after Anti-VEGF therapy for neovascular age-related macular degeneration: Coincidence or consequence?

Introducción y objetivos La degeneración macular asociada con la edad (DMAE) es la causa primaria de ceguera en los países desarrollados, especialmente en adultos mayores. Actualmente, la inyección intravítrea del factor de crecimiento endotelial vascular (VEGF) es el tratamiento estándar para la forma neovascular de la DMAE. Existen pocos estudios que informen sobre la creación de un agujero macular (AM) después de un tratamiento anti-VEGF, y la patogénesis exacta de AM permanece en debate. El presente estudio tiene por objetivo analizar las características clínicas de los ojos que desarrollan AM después de recibir terapia anti-VEGF para la DMAE neovascular. Materiales y métodos Los pacientes fueron tratados con agentes anti-VEGF intravítreos durante al menos un año, permaneciendo estables por, al menos, seis meses. Se evaluaron la mejor agudeza visual corregida (MAVC) y los hallazgos de tomografía de coherencia óptica. Resultado Se incluyeron en el estudio 19 ojos de 18 pacientes. La edad media de los mismos fue de 77,7 años en la primera visita. Ocho eran de sexo femenino. El número medio de inyecciones antes de la formación de un AM fue de cuatro. El AM se desarrolló después de un seguimiento medio de 5,1 meses desde la última inyección. Dieciséis ojos (84,2%) exhibieron membrana coroidal neovascular sin tracción vitreomacular anormal. Once ojos (57,8%) mostraron desprendimiento del epitelio pigmentario (DEP) de la retina, dos (10,5%) tuvieron membrana epirretinal (MER) y uno (5,2%) presentó desgarro del epitelio pigmentario de la retina (PER). La media de la MAVC fue de 1,07 ± 0,48 LogMAR (0,3 a 1,8) y 1,16 ± 0,38 logMAR (0,4 a 1,8), respectivamente (AU)

Introduction and objectives Age-related macular degeneration (AMD) is the primary cause of blindness in developed countries, particularly in older adults. Anti-vascular endothelial growth factor (anti-VEGF) intravitreal injection is the current standard treatment for neovascular form of AMD. Studies reporting macular hole (MH) formation following anti-VEGF treatment are limited, and the exact pathogenesis is still under discussion. With the present study, we aim to analyse the clinical features of eyes developing MH after anti-VEGF therapy for neovascular AMD. Materials and methods Patients were treated with intravitreal anti-VEGF agents for at least one year and stable for at least six months. Best-corrected visual acuity (BCVA) and optical coherence tomography findings were evaluated. Results Nineteen eyes of 18 patients were included in this study. Patients had an average age of 77.7 years at first visit and eight were female. The average number of injections before the MH formation was four. MH developed after a mean follow-up of 5.1 months after the last injection. Sixteen eyes had (84.2%) had choroidal neovascular membrane without any abnormal vitreomacular traction. Eleven eyes (57.8%) had retinal pigment epithelium detachment (PED), two (10.5%) had an epiretinal membrane (ERM), and one (5.2%) had retinal pigment epithelium (RPE) tear. The mean first and last BCVA was 1.07 ± 0.48 LogMAR (0.3-1.8) and 1.16 ± 0.38 logMAR (0.4-1.8), respectively. Conclusions A macular hole can be observed in AMD patients receiving anti-VEGF therapy. Increased fibrovascular scar tissue due to subretinal fluid resolution, neovascular membrane contraction, and the presence of PED, RPE tear, and ERM may contribute to MH formation (AU)

Use of nimotuzumab combined with cisplatin in treatment of nasopharyngeal carcinoma and its effect on expressions of VEGF and MMP-2

Purpose This paper aims to observe the expressions of VEGF and MMP-2 in patients with nasopharyngeal carcinoma treated by nimotuzumab combined with cisplatin. Methods Altogether, 104 patients with nasopharyngeal carcinoma treated in our hospital from April 2014 to August 2016 were selected as research subjects. Among them, 50 patients treated with cisplatin were divided into a control group and 54 patients treated with nimotuzumab combined with cisplatin were divided into an observation group. The two groups of patients were compared in terms of efficacy after treatment and incidence of adverse reactions. Changes of serum VEGF and MMP-2 concentrations before and after treatment were detected using enzyme-linked immunosorbent assay (ELISA), and the 3-year overall survival (OS) of patients was observed. Results Compared with the control group, patients in the observation group had significantly higher total remission rate (RR) (P < 0.05) and significantly lower incidence of adverse reactions (P < 0.05). Before treatment, there was no significant difference between the observation and control groups in the concentrations of VEGF and MMP-2 (P > 0.05). After treatment, the concentrations in the two groups were significantly lower than those before treatment (P < 0.05), and the concentrations in the observation group were significantly lower than those in the control group (P < 0.05). There was no significant difference in the 3-year OS between the observation and control groups (P > 0.05). Conclusions Nimotuzumab combined with cisplatin could improve the conditions of patients with nasopharyngeal carcinoma. After treatment, the expression of VEGF and MMP-2 decreased significantly. We speculated that it improves the survival rate of patients by reducing the expression of VEGF and MMP-2 (AU)

Prognostic value of the immunohistochemical expression of vascular endothelial growth factors in malignant salivary gland neoplasms: a systematic review and meta-analysis / Valor pronóstico de la expresión inmunohistoquímica de vascular. Factores de crecimiento endotelial en neoplasias malignas de glándulas salivales: una revisión sistemática y un metanálisis

Background: The immunohistochemical expression of vascular endothelial growth factor is a prognostic markerin several cancer types. In salivary gland tumors, the association between vascular endothelial growth factor andprognosis remains unclear. The purpose of this study was to perform a systematic review and meta-analysis to as-sess whether the immunohistochemical expression of vascular endothelial growth factor in patients with salivarygland neoplasms presents prognostic value.Material and Methods: Immunohistochemical studies assessing the predictive value of vascular endothelialgrowth factor in salivary gland neoplasms were systematically reviewed using PubMed, Scopus, Embase, Co-chrane Library, and Web of Science databases. It was assessed any survival rates. The fixed-effect model withan adjusted hazard ratio (HR) and 95% confidence intervals (95% CI) as effect measures were performed in themeta-analysis. The Quality in Prognosis Studies (QUIPS) tool was used to assess the quality of the included stud-ies, and the evidence quality was assessed by the Grading of Recommendation, Assessment, Development, andEvaluation (GRADE) system.Results: The immunohistochemical overexpression of vascular endothelial growth factor in patients with salivarygland neoplasms was associated with shortened survival (HR=5.37, 95% CI: 2.67-10.83, P = 0.00001). In addition,the presence of vascular endothelial growth factor was tightly associated with tumor size, lymph node metastasis,clinical stage, perineural invasion, vascular invasion, poor local control of the disease, and recurrence.Conclusions: The immunohistochemical overexpression of vascular endothelial growth factor in patients withsalivary gland neoplasms has prognostic value and was associated with decreased survival time. However, moreprimary well-designed studies are necessary to increase the level of evidence.(AU)

Implicación de la isoforma antiangiogénica VEGF-A165b en la angiogénesis y la función sistólica tras un infarto de miocardio reperfundido / Role of antiangiogenic VEGF-A165b in angiogenesis and systolic function after reperfused myocardial infarction

Introducción y objetivos La angiogénesis participa en la restauración de la microcirculación después de un infarto agudo de miocardio (IAM). El objetivo de este estudio es explorar el papel que juega la isoforma anti-angiogénica del factor de crecimiento endotelial vascular (VEGF)-A165b y explorar su potencial como terapia coadyuvante a la reperfusión coronaria. Métodos Se realizaron dos modelos murinos de IAM: a) ligadura permanente de la arteria coronaria (IAM no reperfundido) y b) oclusión transitoria durante 45 minutos de la arteria coronaria seguida de reperfusión (IAM reperfundido); en ambos modelos, se realizó a los animales una ecocardiografía previa a la eutanasia el día 21 pos-IAM. Se determinaron los niveles séricos y miocárdicos de VEGF- A165b. En ambos modelos experimentales se evaluó la implicación funcional y estructural del bloqueo de esta isoforma. En una cohorte de 104 pacientes con IAM con elevación del segmento ST se cuantificaron los niveles circulantes de VEGF-A165b y se estudió su asociación con la fracción de eyección del ventrículo izquierdo determinada mediante resonancia magnética cardiaca a los 6 meses del IAM, así como con la aparición de eventos adversos (muerte, insuficiencia cardiaca o reinfarto) durante el seguimiento. Resultados En ambos modelos, los niveles séricos y tisulares de VEGF-A165b habían aumentado a los 21 días de la inducción del IAM. Además, existía una correlación negativa entre los valores circulantes de VEGF-A165b y la función sistólica evaluada mediante ecocardiografía. El bloqueo in vivo de VEGF-A165b se relacionó con una mayor densidad microvascular, menor tamaño de infarto y mejor fracción de eyección en el modelo de IAM reperfundido, pero no en el modelo de IAM no reperfundido. En la cohorte de pacientes, aquellos con unos niveles séricos elevados de VEGF-A165b presentaron una fracción de eyección deprimida y una mayor tasa de eventos adversos. Conclusiones ... (AU)

Introduction and objectives Angiogenesis helps to reestablish microcirculation after myocardial infarction (MI). In this study, we aimed to further understand the role of the antiangiogenic isoform vascular endothelial growth factor (VEGF)-A165b after MI and to explore its potential as a coadjuvant therapy to coronary reperfusion. Methods Two mice MI models were formed: a) permanent coronary ligation (nonreperfused MI); b) transient 45-minute coronary occlusion followed by reperfusion (reperfused MI); in both models, animals underwent echocardiography before euthanasia at day 21 after MI induction. We determined serum and myocardial VEGF-A165b levels. In both experimental MI models, we assessed the functional and structural role of VEGF-A165b blockade. In a cohort of 104 ST-segment elevation MI patients, circulating VEGF-A165b levels were correlated with cardiovascular magnetic resonance-derived left ventricular ejection fraction at 6 months and with the occurrence of adverse events (death, heart failure, and/or reinfarction). Results In both models, circulating and myocardial VEGF-A165b levels were increased 21 days after MI induction. Serum VEGF-A165b levels inversely correlated with systolic function evaluated by echocardiography. VEGF-A165b blockade increased capillary density, reduced infarct size, and enhanced left ventricular function in reperfused, but not in nonreperfused, MI experiments. In patients, higher VEGF-A165b levels correlated with depressed ejection fraction and worse outcomes. Conclusions In experimental and clinical studies, higher serum VEGF-A165b levels are associated with worse systolic function. Their blockade enhances neoangiogenesis, reduces infarct size, and increases ejection fraction in reperfused, but not in nonreperfused, MI experiments. Therefore, VEGF-A165b neutralization represents a potential coadjuvant therapy to coronary reperfusion. (AU)

Nailfold Videocapillaroscopy Findings in Bradykinin-Mediated Angioedema

Background: Hereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) and acquired angioedema related to angiotensin-converting enzyme (ACE) inhibitors (ACEI-AAE) are types of bradykinin-mediated angioedema without wheals characterized by recurrent swelling episodes. Recent evidence suggests that a state of “vascular preconditioning” predisposes individuals to attacks, although no data are available on possible structural alterations of the vessels. Objective: This study aims to compare the features of nailfold capillaries to highlight possible structural anomalies between patients affected by C1-INH-HAE and controls and between patients with ACEI-AAE and hypertensive controls.Methods: We used nailfold videocapillaroscopy (NVC) to assess the following: apical, internal, and external diameter; loop length; intercapillary distance; and capillary density, distribution, and morphology. Plasma levels of vascular endothelial growth factor (VEGF) A, VEGF-C, angiopoietin (Ang) 1, and Ang2 were also measured. Results: Compared with healthy controls (n=28), C1-INH-HAE patients (n = 34) were characterized by significant structural alterations of the capillaries, such as greater intercapillary distance (216 vs 190 μm), increased apical, internal, and external diameter (28 vs 22 μm; 22 vs 20 μm; and 81 vs 65 μm, respectively), decreased density (4 vs 5 capillaries/mm2), more irregular capillary distribution, and more tortuous morphology. Apical diameter was enlarged in patients with ≥12 attacks per year. In ACEI-AAE patients, NVC showed no alterations with respect to hypertensive controls. NVC performed in 2 C1-INH-HAE patients during attacks showed no changes compared with the remission phase. Conclusions: We detected major structural capillary alterations in C1-INH-HAE patients, thus confirming the involvement of microcirculation in the pathogenesis of angioedema (AU)

Antecedentes: Tanto el angioedema hereditario con deficiencia de inhibidor del C1 (C1-INH-HAE) como el angioedema adquiridorelacionado con los inhibidores de la ECA (ACEI-AAE), son dos tipos de angioedema mediados por bradicinina que cursan con episodiosde inflamación recurrente sin acompañarse de habones. Existe evidencia de la existencia de un estado de "preacondicionamiento vascular"que predispone a estos pacientes a los ataques, pero no hay datos disponibles sobre las posibles alteraciones estructurales de los vasos.Objetivo: Este estudio tiene como objetivo el evaluar las características de los capilares de la base ungueal para identificar posiblesanomalías estructurales en los pacientes afectados por C1-INH-HAE en comparación con la población sana, y en los pacientes con ACEIAAE en comparación con controles con hipertensión arterial.Métodos: Mediante videocapilaroscopia de la base ungueal (NVC), se evaluaron: los diámetros apical, interno y externo, la longitud delasa, la distancia intercapilar, la densidad capilar, su distribución y su morfología. También se midieron los niveles plasmáticos del factorde crecimiento endotelial vascular (VEGF)-A, VEGF-C, angiopoyetina (Ang)1 y Ang2.Resultados: En los pacientes con C1-INH-HAE (n = 34) se observaron alteraciones estructurales de los capilares significativas, en comparacióncon los controles sanos (n = 28): mayor distancia intercapilar (216 frente a 190 µm), aumento del diámetro apical, interno y externo(28 frente a 22 µm; 22 frente a 20 µm; y 81 frente a 65 µm, respectivamente), disminución de la densidad (4 frente a 5 capilares/mm2),distribución capilar más irregular y una morfología más tortuosa. El diámetro apical fue mayor en aquellos pacientes con ≥12 ataques/año. En los pacientes con ACEI-AAE, las NVC no mostraron alteraciones al ser comparadas con las de los controles hipertensos. Las NVC realizadas en dos pacientes ...(AU)

Manejo de la membrana neovascular coroidea secundaria a toxoplasmosis ocular / Management of the neovascular choroidal membrane secondary to ocular toxoplasmosis

Paciente de 12 años diagnosticado de toxoplasmosis congénita sin tratamiento sistémico en el momento actual que acude por disminución de la agudeza visual (AV) en su ojo izquierdo (OI). A la exploración se objetiva una AV en su OI de 0,05 y al examen funduscópico un foco de coriorretinitis adyacente a una cicatriz macular pigmentada y una gran hemorragia subretiniana asociada. Tras confirmar el diagnóstico de membrana neovascular coroidea (MNVC) secundaria a toxoplasmosis ocular, se inicia tratamiento con fármacos anti-toxoplásmicos sistémicos y 2 dosis de anti-VEGF intravítreos separadas por un mes de diferencia. Finalmente, alcanza una AV en el OI de 0,4, y se logra una reabsorción de la hemorragia quedando una cicatriz pigmentada macular inactiva. El uso de anti-VEGF intravítreos en cuadros de toxoplasmosis ocular se han asociado a la reactivación de antiguas lesiones, por lo que se recomienda el uso profiláctico de fármacos anti-toxoplásmicos orales en estos casos

A 12-year-old patient diagnosed with congenital toxoplasmosis, with no systemic treatment at the time, who presented with a decreased visual acuity (VA) in his left eye (LE). On examination, VA in the LE was 0.05 and the fundus examination revealed a focus of chorioretinitis adjacent to a pigmented macular scar, as well as a large associated subretinal haemorrhage. After confirming the diagnosis of choroidal neovascular membrane secondary to ocular toxoplasmosis, treatment was started with systemic anti-toxoplasmosis drugs and two anti-VEGF intravitreal injections separated by one month. Finally, the patients had a VA in LE of 0.4, with reabsorption of the haemorrhage, leaving an inactive pigmented macular scar. The use of anti-VEGF intravitreal injections in cases of ocular toxoplasmosis has been associated with a reactivation of old lesions, so the prophylactic use of oral anti-toxoplasmosis drugs is recommended in these cases

Regulación por micro RNA de la respuesta angiogénica en la retina diabética / Micro-RNA regulation of the angiogenic response in the diabetic retina

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