Dynamic changes in RNA-protein interactions and RNA secondary structure in mammalian erythropoiesis.

Two features of eukaryotic RNA molecules that regulate their post-transcriptional fates are RNA secondary structure and RNA-binding protein (RBP) interaction sites. However, a comprehensive global overview of the dynamic nature of these sequence features during erythropoiesis has never been obtained. Here, we use our ribonuclease-mediated structure and RBP-binding site mapping approach to reveal the global landscape of RNA secondary structure and RBP-RNA interaction sites and the dynamics of these features during this important developmental process. We identify dynamic patterns of RNA secondary structure and RBP binding throughout the process and determine a set of corresponding protein-bound sequence motifs along with their dynamic structural and RBP-binding contexts. Finally, using these dynamically bound sequences, we identify a number of RBPs that have known and putative key functions in post-transcriptional regulation during mammalian erythropoiesis. In total, this global analysis reveals new post-transcriptional regulators of mammalian blood cell development.

Factores asociados con el desprendimiento neurosensorial macular en pacientes miopes magnos con estafiloma inferior / Factors associated with serous retinal detachment in highly myopic eyes with inferior posterior staphyloma

OBJETIVO: Investigar los factores clínicos asociados con el desprendimiento neurosensorial macular en ojos de pacientes miopes magnos con estafiloma inferior. MATERIAL Y MÉTODO: Estudio transversal de 27 pacientes miopes magnos (44 ojos) con estafiloma inferior. Todos los pacientes fueron sometidos a un examen oftalmológico completo, incluyendo angiografía fluoresceína. El grosor coroideo, la interfaz vitreorretiniana y la altura del envainamiento macular se analizaron mediante el dispositivo DRI OCT Triton Swept-Source (Topcon Corp., Tokio, Japón). RESULTADOS: De los 44 ojos, 13 presentaron un desprendimiento de la retina neurosensorial y 31 carecían del mismo. No observamos diferencias estadísticamente significativas en ninguna de las variables estudiadas (edad, sexo, equivalente esférico, longitud axial, agudeza visual, tracción vitreomacular, membrana epirretiniana o desprendimiento de membrana limitante interna). Los ojos con desprendimiento de la retina neurosensorial presentaron una mayor altura del envainamiento macular (p = 0,01) y una reducción del espesor coroideo (p = 0,02). El desprendimiento neurosensorial macular siempre se produjo en el borde superior del estafiloma inferior y se caracterizó por una hiperfluorescencia granular en la angiografía fluoresceínica. CONCLUSIONES: Una mayor altura del envainamiento macular y un menor grosor coroideo podrían ser factores importantes en el desarrollo del desprendimiento neurosensorial macular en pacientes miopes magnos con estafiloma inferior

PURPOSE: To investigate the factors associated with persistent serous retinal detachment in highly myopic eyes with inferior posterior staphyloma. METHODS: A total of 27 highly myopic patients (44 eyes) with an inferior posterior staphyloma were recruited. Serous retinal detachment was investigated; 13 eyes had persistent sub-macular fluid (study group), and 31 eyes lacked sub-macular fluid (control group). All patients underwent complete ophthalmologic examinations, including axial length measurement and fluorescein angiography (FA). Triton Deep Range Imaging (DRI) optical coherence tomography (OCT) (Topcon Corp., Tokyo, Japan) scans through the fovea measured choroidal thicknesses, macular bend height, and vitreoretinal interface factors. RESULTS: Of the 44 eyes, 13 had neurosensory retinal detachment and 31 did not. No significant differences were found in any of the studied variables (age, gender, spherical equivalence, axial length, vitreomacular traction, epiretinal membrane, internal limiting membrane detachment), except a higher macular bend height (p = 0.01), and a reduced macular choroidal thickness (p = 0.02), which were associated with the risk of serous retinal detachment. No statistically significant differences in best-corrected visual acuity (BCVA) were observed between the study and control groups. Serous retinal detachment always occurred at the bisected retinal pigment epithelium of the macula corresponding to the upper edge of the staphyloma, and was characterised by multiple hyperfluorescent granular patches on fluorescein angiography. CONCLUSIONS: A higher macular bend height and a reduced macular choroidal thickness may be important factors in the development of serous retinal detachment in patients with inferior posterior staphyloma

Factors associated with serous retinal detachment in highly myopic eyes with inferior posterior staphyloma. / Factores asociados con el desprendimiento neurosensorial macular en pacientes miopes magnos con estafiloma inferior.

PURPOSE: To investigate the factors associated with persistent serous retinal detachment in highly myopic eyes with inferior posterior staphyloma. METHODS: A total of 27 highly myopic patients (44 eyes) with an inferior posterior staphyloma were recruited. Serous retinal detachment was investigated; 13 eyes had persistent sub-macular fluid (study group), and 31 eyes lacked sub-macular fluid (control group). All patients underwent complete ophthalmologic examinations, including axial length measurement and fluorescein angiography (FA). Triton Deep Range Imaging (DRI) optical coherence tomography (OCT) (Topcon Corp., Tokyo, Japan) scans through the fovea measured choroidal thicknesses, macular bend height, and vitreoretinal interface factors. RESULTS: Of the 44 eyes, 13 had neurosensory retinal detachment and 31 did not. No significant differences were found in any of the studied variables (age, gender, spherical equivalence, axial length, vitreomacular traction, epiretinal membrane, internal limiting membrane detachment), except a higher macular bend height (p = 0.01), and a reduced macular choroidal thickness (p = 0.02), which were associated with the risk of serous retinal detachment. No statistically significant differences in best-corrected visual acuity (BCVA) were observed between the study and control groups. Serous retinal detachment always occurred at the bisected retinal pigment epithelium of the macula corresponding to the upper edge of the staphyloma, and was characterised by multiple hyperfluorescent granular patches on fluorescein angiography. CONCLUSIONS: A higher macular bend height and a reduced macular choroidal thickness may be important factors in the development of serous retinal detachment in patients with inferior posterior staphyloma.

Prospective analysis of macular and optic disc changes after non-arteritic anterior ischemic optic neuropathy.

PURPOSE: To prospectively analyse macular and optic disc changes after the occurrence of non-arteritic anterior ischemic optic neuropathy (NAION) and study possible predictors of final visual outcome. METHODS: Patients with NAION underwent a complete ophthalmic examination, including spectral-domain optical coherence tomography of the macula and optic nerve head. The examination was repeated 1, 3, 6, 9 and 12 months after onset. Final visual prognosis was evaluated by visual field (VF) and best-corrected visual acuity (BCVA) at the final visit. Data within the NAION group were analysed over the course of the disease and compared to a disease-free control group at each visit. RESULTS: Twenty-two eyes with NAION and 43 eyes from a control group were included. The retinal nerve fiber layer (RNFL) was significantly thicker in NAION eyes than controls at presentation (P=0.00), and significantly decreased during the next 3 months after presentation (P=0.02). The ganglion cell+inner plexiform layer (GCIPL) was thinner in the NAION group throughout the course of the disease (all P<0.05). Although the acute NAION eyes had significantly lower cup/disc ratios and higher neuroretinal and disc sizes (all P=0.00), there were no significant differences between groups from the third month onwards (all P>0.05). The best predictors of BCVA and VF were GCIPL at 3 months of follow-up (r2=0.32; P=0.03) and RNFL at 6 months of follow-up (r2=0.41; P=0.01) respectively. CONCLUSIONS: RNFL and optic disc changes occur during the first 3 months after the onset of NAION, whereas GCIPL is affected soon after the onset of symptoms. GCIPL and RNFL are useful predictors of final visual outcome.

Estudio longitudinal de la función visual en pacientes con esclerosis múltiple remitente-recurrente con y sin antecedentes de neuritis óptica / Longitudinal study of visual function in patients with relapsing-remitting multiple sclerosis with and without a history of optic neuritis

Introducción: El examen de la sensibilidad al contraste permite determinar la calidad de la función visual en pacientes con esclerosis múltiple (EM). El objetivo de este estudio es analizar las modificaciones evolutivas de la función visual en pacientes con EM remitente-recurrente. Métodos: Estudio longitudinal de 61 pacientes clasificados en 3 grupos: a) pacientes libres de enfermedad (grupo control); b) pacientes con EM y sin antecedentes de neuritis óptica (NO), y c) pacientes con EM y antecedentes de NO unilateral. A todos los pacientes se les realizó una exploración oftalmológica que incluía agudeza visual y test de sensibilidad al contraste tipo Pelli-Robson mono y binocularmente, tanto al inicio como a los 6 años de seguimiento. Resultados: La sensibilidad al contraste monocular en pacientes con EM con y sin antecedentes de NO fue significativamente inferior al grupo control tanto al inicio (p=0,00 y p=0,01) como a los 6 años (p = 0,01 y p = 0,02), manteniéndose estable a lo largo del seguimiento excepto en el grupo de pacientes con NO en el cual existe una pérdida significativa de sensibilidad al contraste (p = 0,01). La agudeza visual y la sensibilidad al contraste binocular al inicio y a los 6 años de seguimiento fueron significativamente inferiores en el grupo de pacientes con antecedentes de NO que en el grupo control (p = 0,003 y p = 0,002; p = 0,006 y p = 0,005) y con EM sin NO (p = 0,04 y p = 0,038; p = 0,008 y p = 0,01); sin embargo, no encontramos diferencias significativas en el seguimiento (p = 0,1 y p = 0,5). Conclusiones: El test de Pelli-Robson monocular podría servir como marcador evolutivo del deterioro de la función visual en ojos con NO

Introduction: The contrast sensitivity test determines the quality of visual function in patients with multiple sclerosis (MS). The purpose of this study is to analyse changes in visual function in patients with relapsing-remitting MS with and without a history of optic neuritis (ON). Methods: We conducted a longitudinal study including 61 patients classified into 3 groups as follows: a) disease-free patients (control group); b) patients with MS and no history of ON; and c) patients with MS and a history of unilateral ON. All patients underwent baseline and 6-year follow-up ophthalmologic examinations, which included visual acuity and monocular and binocular Pelli-Robson contrast sensitivity tests. Results: Monocular contrast sensitivity was significantly lower in MS patients with and without a history of ON than in controls both at baseline (P=.00 and P=.01, respectively) and at 6 years (P=.01 and P=.02). Patients with MS and no history of ON remained stable throughout follow-up whereas those with a history of ON displayed a significant loss of contrast sensitivity (P=.01). Visual acuity and binocular contrast sensitivity at baseline and at 6 years was significantly lower in the group of patients with a history of ON than in the control group (P=.003 and P=.002 vs P=.006 and P=.005) and the group with no history of ON (P=.04 and P=.038 vs P=.008 and P=.01). However, no significant differences were found in follow-up results (P=.1 and P=.5). Conclusions: Monocular Pelli-Robson contrast sensitivity test may be used to detect changes in visual function in patients with ON

Longitudinal study of visual function in patients with relapsing-remitting multiple sclerosis with and without a history of optic neuritis. / Estudio longitudinal de la función visual en pacientes con esclerosis múltiple remitente-recurrente con y sin antecedentes de neuritis óptica.

INTRODUCTION: The contrast sensitivity test determines the quality of visual function in patients with multiple sclerosis (MS). The purpose of this study is to analyse changes in visual function in patients with relapsing-remitting MS with and without a history of optic neuritis (ON). METHODS: We conducted a longitudinal study including 61 patients classified into 3 groups as follows: a) disease-free patients (control group); b) patients with MS and no history of ON; and c) patients with MS and a history of unilateral ON. All patients underwent baseline and 6-year follow-up ophthalmologic examinations, which included visual acuity and monocular and binocular Pelli-Robson contrast sensitivity tests. RESULTS: Monocular contrast sensitivity was significantly lower in MS patients with and without a history of ON than in controls both at baseline (P=.00 and P=.01, respectively) and at 6 years (P=.01 and P=.02). Patients with MS and no history of ON remained stable throughout follow-up whereas those with a history of ON displayed a significant loss of contrast sensitivity (P=.01). Visual acuity and binocular contrast sensitivity at baseline and at 6 years was significantly lower in the group of patients with a history of ON than in the control group (P=.003 and P=.002 vs P=.006 and P=.005) and the group with no history of ON (P=.04 and P=.038 vs P=.008 and P=.01). However, no significant differences were found in follow-up results (P=.1 and P=.5). CONCLUSIONS: Monocular Pelli-Robson contrast sensitivity test may be used to detect changes in visual function in patients with ON.

Domain-focused CRISPR screen identifies HRI as a fetal hemoglobin regulator in human erythroid cells.

Increasing fetal hemoglobin (HbF) levels in adult red blood cells provides clinical benefit to patients with sickle cell disease and some forms of ß-thalassemia. To identify potentially druggable HbF regulators in adult human erythroid cells, we employed a protein kinase domain-focused CRISPR-Cas9-based genetic screen with a newly optimized single-guide RNA scaffold. The screen uncovered the heme-regulated inhibitor HRI (also known as EIF2AK1), an erythroid-specific kinase that controls protein translation, as an HbF repressor. HRI depletion markedly increased HbF production in a specific manner and reduced sickling in cultured erythroid cells. Diminished expression of the HbF repressor BCL11A accounted in large part for the effects of HRI depletion. Taken together, these results suggest HRI as a potential therapeutic target for hemoglobinopathies.

[Analysis of the quantitative differences in the thickness of the retinal nerve fibre layer between time-domain and spectral-domain optical coherence tomography in patients with relapsing-remitting multiple sclerosis]. / Analisis de las diferencias cuantitativas en el grosor de la capa de fibras nerviosas retiniana entre la tomografia de coherencia optica de dominio-tiempo y de dominio-espectral en pacientes con esclerosis multiple remitente recurrente.

INTRODUCTION: Optical coherence tomography (OCT) is a tool that is increasingly more commonly used in the study of neuro-degenerative diseases. AIMS: To analyse and correlate the thickness of the retinal nerve fibre layer (RNFL) by means of time-domain and spectral-domain OCT in patients with relapsing-remitting multiple sclerosis (MS), with and without a history of optic neuritis (ON). SUBJECTS AND METHODS: We conducted a cross-sectional study of the thickness (mean and by quadrants) of the RNFL of 15 disease-free subjects, 28 with MS with no prior history of ON and 18 with a history of ON. The full ophthalmologic examination included measurement of the RNFL by means of time-domain and spectral-domain tomography. RESULTS: Statistically significant differences are found between the two tomography scans on comparing the mean thickness of the RNFL of the control group (p = 0.000), the group with a history of ON (p = 0.000) and the group without ON (p = 0.000). We obtained a strong, statistically significant and directly proportional correlation between the mean thickness of the RNFL measured with the two types of tomography in the control group (rho = 0.842; p = 0.000), and the groups of eyes without ON (rho = 0.91; p = 0.000) and with ON (rho = 0.902; p = 0.000). CONCLUSIONS: There is a strong correlation between the two tomography scans in the measurement of the thickness of the RNFL in patients with MS, with and without a history of ON. Time-domain OCT quantifies greater thicknesses, and therefore both types of tomography have proven to be effective in the study of MS, although the results cannot be interchanged or extrapolated.

TITLE: Analisis de las diferencias cuantitativas en el grosor de la capa de fibras nerviosas retiniana entre la tomografia de coherencia optica de dominio-tiempo y de dominio-espectral en pacientes con esclerosis multiple remitente recurrente.Introduccion. La tomografia de coherencia optica (OCT) es una herramienta cada vez mas extendida en el estudio de las enfermedades neurodegenerativas. Objetivos. Analizar y correlacionar el grosor de la capa de fibras nerviosas retiniana (CFNR) mediante OCT de dominio-tiempo y dominio-espectral en pacientes con esclerosis multiple (EM) remitente recurrente, con y sin antecedente de neuritis optica (NO). Sujetos y metodos. Estudio transversal del grosor medio y por cuadrantes de la CFNR en 15 sujetos libres de enfermedad, 28 con EM sin historia previa de NO y 18 con antecedentes de NO. La exploracion oftalmologica completa incluia la medicion de la CFNR mediante tomografos de dominio-tiempo y dominio-espectral. Resultados. Existen diferencias estadisticamente significativas entre ambos tomografos al comparar el grosor medio de la CFNR en el grupo control (p = 0,000), el grupo con antecedentes de NO (p = 0,000) y el grupo sin NO (p = 0,000). Hemos obtenido una fuerte correlacion, estadisticamente significativa y directamente proporcional entre el grosor medio de la CFNR medido con ambos tomografos en el grupo control (rho = 0,842; p = 0,000), y los grupos de ojos sin NO (rho = 0,91; p = 0,000) y con NO (rho = 0,902; p = 0,000). Conclusiones. Existe una fuerte correlacion en la medicion del grosor de la CFNR entre ambos tomografos en pacientes con EM, con y sin antecedente de NO. La OCT de dominio-tiempo cuantifica grosores mayores, por lo que ambos tomografos se demuestran eficaces en el estudio de la EM, aunque los resultados no son intercambiables ni extrapolables.

Análisis del grosor macular y de capa de fibras nerviosas en pacientes con esclerosis múltiple en relación con su nivel de gravedad y antecedentes previos de neuritis óptica / Analysis of macular and nerve fiber layer thickness in multiple sclerosis patients according to severity level and optic neuritis episodes

Introducción: Evaluar cuantitativamente el grosor macular y de la capa de fibras nerviosas en pacientes con esclerosis múltiple en relación con la escala expandida del estado de discapacidad (EDSS) con o sin antecedentes previos de neuritis óptica. Métodos: Sesenta y dos pacientes diagnosticados de esclerosis múltiple (53 remitente recidivante y 9 secundariamente progresiva) y 12 libres de enfermedad fueron reclutados para el estudio. Se les realizó una exploración oftalmológica, incluyendo el análisis cuantitativo de la capa de fibras nerviosas retinianas y el grosor macular mediante tomografía óptica de coherencia. Los pacientes fueron clasificados según la escala EDSS en: A: inferior a 1,5; B: entre 1,5 y 3,5, y C: superior a 3,5. Resultados: El grosor medio ± desviación estándar de la capa de fibras nerviosas en los grupos control, A, B y C fue de 103,35 ± 12,62, 99,04 ± 14,35, 93,59 ± 15,41 y 87,36 ± 18,75 μm, respectivamente, con diferencias estadísticamente significativas (p < 0,05). En pacientes sin una historia previa de neuritis, o con un episodio de esta patología entre 3 y 6 meses de evolución o anterior a 6 meses, el grosor medio fue de 99,25 ± 13,71, 93,92 ± 13,30, 80,07 ± 15,91 μm, respectivamente, con diferencias significativas (p < 0,05). El grosor macular medio en el grupo control, A, B y C se situó en 220,01 ± 12,07, 217,78 ± 20,02, 217,68 ± 20,77 y 219,04 ± 24,26 μm, respectivamente. Las diferencias observadas entre grupos no fueron estadísticamente significativas. Conclusiones: El grosor medio de la capa de fibras nerviosas en pacientes con esclerosis múltiple se relaciona con el nivel en la escala EDSS. Los pacientes con historia previa de neuritis óptica cursan con una disminución del grosor de esta capa respecto a aquellos sin antecedentes de neuritis. El grosor macular no se relaciona con el grado de afectación en la EDSS

Introduction: Quantitative assessment of macular and nerve fibre layer thickness in multiple sclerosis patients with regard to expanded disability status scale (EDSS) and presence or absence of previous optic neuritis episodes. Methods: We recruited 62 patients with multiple sclerosis (53 relapsing-remitting and 9 secondary progressive) and 12 disease-free controls. All patients underwent an ophthalmological examination, including quantitative analysis of the nerve fibre layer and macular thickness using optical coherence tomography. Patients were classified according to EDSS as A (lower than 1.5), B (between 1.5 and 3.5), and C (above 3.5). Results: Mean nerve fibre layer thickness in control, A, B, and C groups was 103.35 ± 12.62, 99.04 ± 14.35, 93.59 ± 15.41, and 87.36 ± 18.75 μm respectively, with statistically significant differences (P < .05). In patients with no history of optic neuritis, history of episodes in the last 3 to 6 months, or history longer than 6 months, mean nerve fibre layer thickness was 99.25 ± 13.71, 93.92 ± 13.30 and 80.07 ± 15.91 μm respectively; differences were significant (P < .05). Mean macular thickness in control, A, B, and C groups was 220.01 ± 12.07, 217.78 ± 20.02, 217.68 ± 20.77, and 219.04 ± 24.26 μm respectively. Differences were not statistically significant. Conclusions: The mean retinal nerve fibre layer thickness in multiple sclerosis patients is related to the EDSS level. Patients with previous optic neuritis episodes have a thinner retinal nerve fibre layer than patients with no history of these episodes. Mean macular thickness is not correlated to EDSS leve

Grosor coroideo macular en la neuropatía óptica isquémica anterior no arterítica / Macular choroidal thickness in non-arteritic ischemic optic neuropathy

OBJETIVO: Analizar el grosor coroideo macular (GCM) en la neuropatía óptica isquémica anterior no arterítica (NOIA-NA). MATERIAL Y MÉTODOS: Un total de 22 pacientes diagnosticados de NOIA-NA (22 ojos) y 42 sujetos sanos (42 ojos) fueron estudiados usando tomografía de coherencia óptica con técnica Enhanced Depth Imaging (EDI-OCT). Se realizó un escáner de una línea horizontal centrado en la fóvea 3 meses después del inicio de NOIA-NA. Se tomaron 3 medidas desde la parte posterior del epitelio pigmentario hasta la unión esclerocoroidea a intervalos de 500 μm en las 1.500 μm centrales de la mácula. Los resultados fueron analizados estadísticamente comparando la media de GCM entre grupos y correlacionando el GCM con otros parámetros oculares y sistémicos. RESULTADOS: Excepto en el error refractivo (p = 0,01), no hubo diferencias significativas en longitud axial (p = 0,53), edad (p = 0,88) ni en otros parámetros oculares ni epidemiológicos entre grupos. La media de GCM en la NOIA-NA y en el grupo control fue 236,21 ± 63,29 μm y 269,13 ± 52,28, respectivamente. La media del GCM fue significativamente más delgada en ojos con NOIA-NA que en sanos (p = 0,03). El adelgazamiento del GCM estuvo asociado con el diagnóstico de NOIA-NA después de ajustar por error refractivo (p = 0,04). CONCLUSIONES: Los ojos afectos con NOIA-NA mostraron un GCM significativamente más adelgazado que en sujetos sanos, después de ajustar por error refractivo

OBJECTIVE: To analyse macular choroidal thickness (MCT) in non-arteritic ischaemic optic neuropathy (NAION). MATERIALS AND METHODS: An analysis was made on 22 patients diagnosed with NAION (22 eyes) and 42 healthy controls (42 eyes) using enhanced-depth imaging of spectral-domain optical coherence tomography. A horizontal raster scan centred on the fovea was obtained per eye 3 months after the onset of NAION. Three measurements of MCT were obtained from the posterior edge of the retinal pigment epithelium to the choroid-sclera junction at 500 μm intervals. Statistical analysis was used to compare the mean MCT and to correlate MCT with other ocular and systemic parameters. RESULTS: Except for refractive error (P=.01), there were no statistically significant differences between both groups in axial length (P=.53), age (P=.88) and other epidemiological and ocular parameters. Mean MCT in NAION eyes and control group was 236.21 ± 63.29 μm and 269.13 ± 52.28, respectively. Mean MCT was significantly thinner in NAION eyes than in healthy eyes (P=.03). Thinner MCT, adjusted for refractive error, was associated with the diagnosis of NAION (P=.04). CONCLUSIONS: Eyes affected by NAION showed significantly thinner MCT compared with healthy control eyes after adjusting for refractive error

Implante intravítreo de dexametasona como terapéutica del edema macular persistente en la retinocoroidopatía de Birdshot / Dexamethasone intravitreal implant for treatment of persistent macular oedema in Birdshot retinochoroidopathy

CASO CLÍNICO: Presentamos el caso clínico de un paciente varón de 32 años de edad con edema macular quístico y desprendimiento seroso del neuroepitelio en ambos ojos secundario a una retinocoroidopatía de Birdshot. Tras la respuesta parcial del edema macular a corticoides orales y subtenonianos, se inició tratamiento mediante un implante intravítreo de 0,7 mg de dexametasona (Ozurdex®, Allergan) en ambos ojos, obteniéndose una mejoría anatómica y funcional que se mantuvo durante los 6 meses de seguimiento. Discusión: En pacientes con edema macular secundario a la enfermedad de Birdshot, bien por ineficacia, bien por intolerancia a terapias previas, los implantes intravítreos de dexametasona pueden ser una opción terapéutica

CLINICAL CASE: The case is reported of a 32 year-old man with a bilateral cystoid macular oedema and serous macular detachment due to birdshot retinochoroidopathy. An intravitreal implant of 0.7 mg dexamethasone (Ozurdex®, Allergan) was performed on both eyes, after a partial response of the macular oedema to oral and subtenon corticosteroids. Anatomical and visual improvements were observed and maintained after six months of follow up. DISCUSSION: Intravitreal dexamethasone implant may be a good therapeutic option in patients with macular oedema due to Birdshot retinochoroidopathy, and who were refractory or had intolerance to previous therapies

Macular choroidal thickness in non-arteritic ischemic optic neuropathy. / Grosor coroideo macular en la neuropatía óptica isquémica anterior no arterítica.

OBJECTIVE: To analyse macular choroidal thickness (MCT) in non-arteritic ischaemic optic neuropathy (NAION). MATERIALS AND METHODS: An analysis was made on 22 patients diagnosed with NAION (22 eyes) and 42 healthy controls (42 eyes) using enhanced-depth imaging of spectral-domain optical coherence tomography. A horizontal raster scan centred on the fovea was obtained per eye 3 months after the onset of NAION. Three measurements of MCT were obtained from the posterior edge of the retinal pigment epithelium to the choroid-sclera junction at 500µm intervals. Statistical analysis was used to compare the mean MCT and to correlate MCT with other ocular and systemic parameters. RESULTS: Except for refractive error (P=.01), there were no statistically significant differences between both groups in axial length (P=.53), age (P=.88) and other epidemiological and ocular parameters. Mean MCT in NAION eyes and control group was 236.21±63.29µm and 269.13±52.28, respectively. Mean MCT was significantly thinner in NAION eyes than in healthy eyes (P=.03). Thinner MCT, adjusted for refractive error, was associated with the diagnosis of NAION (P=.04). CONCLUSIONS: Eyes affected by NAION showed significantly thinner MCT compared with healthy control eyes after adjusting for refractive error.

Dexamethasone intravitreal implant for treatment of persistent macular oedema in Birdshot retinochoroidopathy.

CLINICAL CASE: The case is reported of a 32 year-old man with a bilateral cystoid macular oedema and serous macular detachment due to birdshot retinochoroidopathy. An intravitreal implant of 0.7 mg dexamethasone (Ozurdex®, Allergan) was performed on both eyes, after a partial response of the macular oedema to oral and subtenon corticosteroids. Anatomical and visual improvements were observed and maintained after six months of follow up. DISCUSSION: Intravitreal dexamethasone implant may be a good therapeutic option in patients with macular oedema due to Birdshot retinochoroidopathy, and who were refractory or had intolerance to previous therapies.

Analysis of macular and nerve fiber layer thickness in multiple sclerosis patients according to severity level and optic neuritis episodes. / Análisis del grosor macular y de capa de fibras nerviosas en pacientes con esclerosis múltiple en relación con su nivel de gravedad y antecedentes previos de neuritis óptica.

INTRODUCTION: Quantitative assessment of macular and nerve fibre layer thickness in multiple sclerosis patients with regard to expanded disability status scale (EDSS) and presence or absence of previous optic neuritis episodes. METHODS: We recruited 62 patients with multiple sclerosis (53 relapsing-remitting and 9 secondary progressive) and 12 disease-free controls. All patients underwent an ophthalmological examination, including quantitative analysis of the nerve fibre layer and macular thickness using optical coherence tomography. Patients were classified according to EDSS as A (lower than 1.5), B (between 1.5 and 3.5), and C (above 3.5). RESULTS: Mean nerve fibre layer thickness in control, A, B, and C groups was 103.35±12.62, 99.04±14.35, 93.59±15.41, and 87.36±18.75µm respectively, with statistically significant differences (P<.05). In patients with no history of optic neuritis, history of episodes in the last 3 to 6 months, or history longer than 6 months, mean nerve fibre layer thickness was 99.25±13.71, 93.92±13.30 and 80.07±15.91µm respectively; differences were significant (P<.05). Mean macular thickness in control, A, B, and C groups was 220.01±12.07, 217.78±20.02, 217.68±20.77, and 219.04±24.26µm respectively. Differences were not statistically significant. CONCLUSIONS: The mean retinal nerve fibre layer thickness in multiple sclerosis patients is related to the EDSS level. Patients with previous optic neuritis episodes have a thinner retinal nerve fibre layer than patients with no history of these episodes. Mean macular thickness is not correlated to EDSS level.

Relación entre el test de sensibilidad al contraste y el nivel de gravedad en pacientes con esclerosis múltiple / Relationship between contrast sensitivity test and disease severity in multiple sclerosis patients

OBJETIVO: Evaluar la utilidad de la prueba de sensibilidad al contraste Pelli-Robson en pacientes con esclerosis múltiple, dependiendo de la escala expandida del estado de discapacidad (EDSS). MATERIAL Y MÉTODOS: Estudio retrospectivo de 62 pacientes diagnosticados de esclerosis múltiple y remitidos desde el Servicio de Neurología a la Unidad de Neurooftalmología del Hospital Virgen de la Victoria. Los pacientes fueron clasificados según la escala EDSS en 3 grupos: A) inferior a 1,5; B) entre 1,5 y 3,5 y C) superior a 3,5. Se determinó la agudeza visual y la sensibilidad al contraste monocular y binocular mediante las pruebas de Snellen y Pelli-Robson, respectivamente. Un total de 12 pacientes libres de enfermedad fueron reclutados como grupo control. Se analizaron estadísticamente los resultados obtenidos. RESULTADOS: El tiempo medio de evolución de la enfermedad fue de 81,54 ± 35,32 meses. Los valores medios del Pelli-Robson monocular y binocular en el grupo control fueron 1,82 ± 0,10 y 1,93 ± 0,43, mientras que en los pacientes con esclerosis múltiple fueron 1,61 ± 0,29 y 1,83 ± 0,19 respectivamente, siendo estas diferencias estadísticamente significativas en el análisis monocular para un nivel de significación de p < 0,05. Respecto al nivel de gravedad, los valores medios monoculares y binoculares de la prueba de Pelli-Robson fueron en el grupo A: 1,66 ± 0,24 y 1,90 ± 0,98; en el grupo B: 1,64 ± 0,21 y 1,82 ± 0,16 y en el grupo C: 1,47 ± 0,45 y 1,73 ± 0,32, respectivamente. Las diferencias entre grupos mostraron una significación estadística para ambas pruebas: p = 0,05 y p = 0,027. CONCLUSIONES: La sensibilidad al contraste, monocular y binocular, analizada mediante la prueba de Pelli-Robson disminuye significativamente según aumenta el nivel de gravedad medida con la escala EDSS en pacientes con esclerosis múltiple

OBJECTIVE: To assess the importance of the Pelli-Robson contrast sensitivity test in multiple sclerosis patients according to the Expanded Disability Status Scale (EDSS). MATERIAL AND METHODS: A total of 62 patients with multiple sclerosis were included in a retrospective study. Patients were enrolled from the Neurology Department to Neuroophthalmology at Virgen de la Victoria Hospital. Patients were classified into 3 groups according to EDSS: group A) lower than 1.5, group B) between 1.5 and 3.5 and group C) greater than 3.5. Visual acuity and monocular and binocular contrast sensitivity were performed with Snellen and Pelli-Robson tests respectively. Twelve disease-free control participants were also recruited. Correlations between parameter changes were analyzed. RESULTS: The mean duration of the disease was 81.54 ± 35.32 months. Monocular and binocular Pelli-Robson mean values in the control group were 1.82 ± 0.10 and 1.93 ± 0.43 respectively, and 1.61 ± 0.29 and 1.83 ± 0.19 in multiple sclerosis patients. There were statistically significant differences in the monocular analysis for a level of significance P<0.05. Mean monocular and binocular Pelli-Robson values in relation to gravity level were, in group A: 1.66 ± 0.24 and 1.90 ± 0.98, group B: 1.64 ± 0.21 and 1.82 ± 0.16, and group C: 1.47 ± 0.45 and 1.73 ± 0.32 respectively. Group differences were statistically significant in both tests: P=0.05 and P=0.027. CONCLUSIONS: Monocular and binocular contrast discrimination analyzed using the Pelli-Robson test was found to be significantly lower when the severity level, according EDSS, increases in multiple sclerosis patients

Crecimiento neovascular en un modelo experimental de quemadura corneal por álcali / Neovascular growth in an experimental alkali corneal burn model

OBJETIVOS: Analizar la longitud y área corneal ocupada por neovasos, así como la localización de estos, en un modelo experimental de neovascularización corneal por quemadura con álcali. MÉTODOS: Se utilizaron 91 ratas Sprague-Dawley en las que se realizó una quemadura en el centro de la córnea del ojo derecho utilizando un lápiz de nitrato de plata. Los animales fueron divididos en 7 grupos que fueron sacrificados a los 2, 4, 6, 8, 10, 12 y 14 días posquemadura, siendo perfundidos mediante una mezcla de tinta china y PBS (tampón fosfato salino). Las córneas fueron procesadas «a plano» y divididas en 4 cuadrantes. Se analizaron diferentes parámetros del crecimiento neovascular corneal (longitud y área), así como la localización de dichos neovasos de forma enmascarada. Los resultados fueron analizados estadísticamente. RESULTADOS: A partir del 2.° día se observa un crecimiento neovascular que alcanza su pico máximo a los 12 días posquemadura, tanto en longitud como en área. A partir de esta fecha se produce un débil retroceso del crecimiento neovascular. Los neovasos se localizan inicialmente en el tercio medio del estroma, tendiendo a situarse, a medida que transcurre el experimento, en el tercio anterior. CONCLUSIÓN: La neovascularización se observó al 2° día posquemadura en todos los sectores de la superficie corneal. El crecimiento neovascular fue uniforme durante todo el experimento. Los neovasos se localizaron en el tercio medio y anterior de la córnea

OBJECTIVE: To review the scientific literature about the relationship between impairment on smooth pursuit eye movements and schizophrenia. METHODS: Narrative review that includes historical articles, reports about basic and clinical investigation, systematic reviews, and meta-analysis on the topic. RESULTS: Up to 80% of schizophrenic patients have impairment of smooth pursuit eye movements. Despite the diversity of test protocols, 65% of patients and controls are correctly classified by their overall performance during this pursuit. The smooth pursuit eye movements depend on the ability to anticipate the target's velocity and the visual feedback, as well as on learning and attention. The neuroanatomy implicated in smooth pursuit overlaps to some extent with certain frontal cortex zones associated with some clinical and neuropsychological characteristics of the schizophrenia, therefore some specific components of smooth pursuit anomalies could serve as biomarkers of the disease. Due to their sedative effect, antipsychotics have a deleterious effect on smooth pursuit eye movements, thus these movements cannot be used to evaluate the efficacy of the currently available treatments. CONCLUSION: Standardized evaluation of smooth pursuit eye movements on schizophrenia will allow to use specific aspects of that pursuit as biomarkers for the study of its genetics, psychopathology, or neuropsychology

Bevacizumab intravítreo como tratamiento de las telangiectasias yuxtafoveales idiopáticas tipo I / Intravitreal bevacizumab in the treatment of idiopathic juxtafoveal telangiectasis type I

CASO CLÍNICO: Se presenta el caso clínico de un paciente varón de 42 años de edad con edema macular quístico secundario a telangiectasias yuxtafoveales idiopáticas tipo I. Se inicia tratamiento con bevacizumab intravítreo (1,25 mg en 0,05 ml) cada cuatro semanas hasta un total de tres inyecciones, obteniéndose una mejoría funcional y anatómica que se mantiene durante el primer año de seguimiento. DISCUSIÓN: Actualmente no existe consenso en el tratamiento de las telangiectasias yuxtafoveales idiopáticas. Entre las opciones terapéuticas se encuentra la fotocoagulación con láser en rejilla, la corticoterapia, la terapia fotodinámica con verteforfirino (Visudyne) o la terapia antiangiogénica. En nuestro caso clínico observamos un beneficio tanto funcional como anatómico tras la inyección de bevacizumab que se mantiene durante los 12 primeros meses de seguimiento

CLINICAL CASE: We report a case of a 42 year-old male with a macular edema due to idiopathic juxtafoveal retinal telangiectasis type I, treated with 3 sequential injections of intravitreal bevacizumab (1.25 mg in 0.05 ml). Anatomical improvements were observed after one year of follow up. DISCUSSION: There is currently no general consensus regarding the treatment of unilateral idiopathic juxtafoveal telangiectasis. The therapeutic options are, grid laser photocoagulation, intravitreal triamcinolone, verteporfin photodynamic therapy, or anti-VEGF. Visual acuity and anatomical improvements were observed in this case after intravitreal bevacizumab. Thus, intravitreal bevacizumab seems to be effective to treat macular edema in idiopathic juxtafoveal telangiectasis type I

Relationship between contrast sensitivity test and disease severity in multiple sclerosis patients.

OBJECTIVE: To assess the importance of the Pelli-Robson contrast sensitivity test in multiple sclerosis patients according to the Expanded Disability Status Scale (EDSS). MATERIAL AND METHODS: A total of 62 patients with multiple sclerosis were included in a retrospective study. Patients were enrolled from the Neurology Department to Neuroophthalmology at Virgen de la Victoria Hospital. Patients were classified into 3 groups according to EDSS: group A) lower than 1.5, group B) between 1.5 and 3.5 and group C) greater than 3.5. Visual acuity and monocular and binocular contrast sensitivity were performed with Snellen and Pelli-Robson tests respectively. Twelve disease-free control participants were also recruited. Correlations between parameter changes were analyzed. RESULTS: The mean duration of the disease was 81.54±35.32 months. Monocular and binocular Pelli-Robson mean values in the control group were 1.82±0.10 and 1.93±0.43 respectively, and 1.61±0.29 and 1.83±0.19 in multiple sclerosis patients. There were statistically significant differences in the monocular analysis for a level of significance P<.05. Mean monocular and binocular Pelli-Robson values in relation to gravity level were, in group A: 1.66±0.24 and 1.90±0.98, group B: 1.64±0.21 and 1.82±0.16, and group C: 1.47±0.45 and 1.73±0.32 respectively. Group differences were statistically significant in both tests: P=.05 and P=.027. CONCLUSIONS: Monocular and binocular contrast discrimination analyzed using the Pelli-Robson test was found to be significantly lower when the severity level, according EDSS, increases in multiple sclerosis patients.

Neovascular growth in an experimental alkali corneal burn model.

OBJECTIVE: To analyse the length and area of corneal surface occupied by vessels, and their location in an experimental model of alkali burn-induced corneal neovascularization. METHODS: An injury to the central cornea of the right eye in 91 Sprague-Dawley rats was induced using a silver nitrate pencil. The rats were divided in 7 groups that were sacrificed 2, 4, 6, 8, 10, 12 and 14 days post-injury, and then perfused with a mixture of Chinese ink in PBS -phosphate buffer saline-. Corneas were flat-mounted processed and divided in 4 quadrants. Corneal neovascular growth parameters (length and area) and the location of these vessels were performed blind. The results were statistically analysed. RESULTS: Neovascular growth was observed from day 2, reaching its maximum peak in length and area on the 12th day post-injury. A slight reduction in corneal neovascularization was observed after this day. The vessels were initially located in the middle third of the stroma and tended to be observed in the anterior third during the course of the experiment. CONCLUSIONS: Neovascularisation was observed on day 2 post-injury in all sectors of corneal surface. Neovascular growth was uniform during the experiment. Neovessels were located in the middle and anterior third of the cornea.

[Intravitreal bevacizumab in the treatment of idiopathic juxtafoveal telangiectasis type I]. / Bevacizumab intravítreo como tratamiento de las telangiectasias yuxtafoveales idiopáticas tipo i.

CLINICAL CASE: We report a case of a 42 year-old male with a macular edema due to idiopathic juxtafoveal retinal telangiectasis type i, treated with 3 sequential injections of intravitreal bevacizumab (1.25 mg in 0.05 ml). Anatomical improvements were observed after one year of follow up. DISCUSSION: There is currently no general consensus regarding the treatment of unilateral idiopathic juxtafoveal telangiectasis. The therapeutic options are, grid laser photocoagulation, intravitreal triamcinolone, verteporfin photodynamic therapy, or anti-VEGF. Visual acuity and anatomical improvements were observed in this case after intravitreal bevacizumab. Thus, intravitreal bevacizumab seems to be effective to treat macular edema in idiopathic juxtafoveal telangiectasis type i.