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.

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.

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.

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.

[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.

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.

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.

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.

[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.

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.

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.

[Study of tear function and the conjunctival surface in diabetic patients]. / Estudio de la función lagrimal y la superficie conjuntival en pacientes diabéticos.

OBJECTIVES: This study was performed to investigate whether different grades of diabetic retinopathy correlate with tear and ocular surface function in diabetic patients without subjective symptoms of dry eye. METHODS: A total of 129 eyes of 72 patients without dry eye, assessed using McMonnies questionnaire were recruited to the study. The tear film and ocular surface were evaluated using the Schirmer test, tear film break-up time (BUT), fluorescein and lissamine green staining test, and conjunctival impression cytology. The results were analysed. RESULTS: A normal Schirmer test and BUT was obtained in 51 and 67% of the eyes of diabetics patients, respectively. Fluorescein and lissamine green staining were negative in 81 and 95% of the eyes. The area and density of goblet cells was 580.46 ± 370 µm(2) and 235.58 ± 109.03 goblets cell/mm(2), respectively. CONCLUSIONS: Diabetic retinopathy patients without subjective symptoms of dry eye and normal Schirmer and BUT test showed pathological grades of squamous metaplasia.