Whole Exome Sequencing of 20 Spanish Families: Candidate Genes for Non-Syndromic Pediatric Cataracts.

Non-syndromic pediatric cataracts are defined as opacification of the crystalline lens that occurs during the first years of life without affecting other organs. Given that this disease is one of the most frequent causes of reversible blindness in childhood, the main objective of this study was to propose new responsible gene candidates that would allow a more targeted genetic approach and expand our genetic knowledge about the disease. We present a whole exome sequencing (WES) study of 20 Spanish families with non-syndromic pediatric cataracts and a previous negative result on an ophthalmology next-generation sequencing panel. After ophthalmological evaluation and collection of peripheral blood samples from these families, WES was performed. We were able to reach a genetic diagnosis in 10% of the families analyzed and found genes that could cause pediatric cataracts in 35% of the cohort. Of the variants found, 18.2% were classified as pathogenic, 9% as likely pathogenic, and 72.8% as variants of uncertain significance. However, we did not find conclusive results in 55% of the families studied, which suggests further studies are needed. The results of this WES study allow us to propose LONP1, ACACA, TRPM1, CLIC5, HSPE1, ODF1, PIKFYVE, and CHMP4A as potential candidates to further investigate for their role in pediatric cataracts, and AQP5 and locus 2q37 as causal genes.

Type 2 diabetes-associated polymorphisms correlate with SIRT1 and TGF-ß1 gene expression.

The polymorphisms rs3758391 and rs1800470 located in SIRT1 and TGF-ß1 have been associated with type 2 diabetes in different populations but its functional effect is not clear. In this study, we evaluated their effect on the expression of SIRT1 and TGF-ß1 in peripheral blood as well as their participation in the formation of DNA-protein complexes in a pancreas-derived cell line. It has been described that SIRT1 and TGF-ß1 participate in cell growth and regulation of production and secretion of insulin in the pancreas. Anthropometric and biochemical profiles of 127 adults were measured. Genotypes for rs3758391 and rs1800470 were determined using TaqMan assays. Expression analysis of SIRT1 and TGF-ß1 were performed using real-time PCR. Gene expression of these genes increased 1.8 ± 0.6- and 1.3 ± 0.6-fold in patients carrying the TT genotype of rs3758391 and rs1800470 when compared to carriers of the CC genotype. Then, we tested whether these single-nucleotide polymorphisms (SNPs) (and rs932658, which is in linkage disequilibrium with rs3758391) are located in regulatory DNA-protein binding sites by electrophoretic mobility shift assays using nuclear extract from the pancreas-derived cell line BxPC-3. The electrophoretic mobility shift assay showed no binding of nuclear proteins to DNA. In conclusion, the genotypes of rs3758391 and rs1800470 are associated with modifications in the expression of the genes SIRT1 and TGF-ß1, respectively, but none of the tested SNPs are located in regulatory DNA-protein binding sites.

Doppler evaluation of the fetal pulmonary artery pressure.

Background The Doppler effect has allowed the characterization of several vessels in maternal-fetal circulation that have been used for practical purposes. Our review of the literature showed a paucity of information about fetal pulmonary artery pressure (FMPAP) and its behavior in regard to gestational age (GA). The objectives of the study were to evaluate a formula to calculate the main FMPAP and its correlation with GA. Methods A total of 337 fetuses without obvious pathology were studied prospectively using Doppler evaluation of the FMPAP. Using the fetal main pulmonary artery Doppler acceleration time (FMPAT), we obtained the FMPAP using the following formula: FMPAP=90 - (0.62×FMPAT). Regression analyses, Pearson's bivariate correlation and paired sample t-test were used when appropriate. Results FMPAT increases while FMPAP decreases with GA. Pearson's correlation coefficient for FMPAP and GA was -0.544 (P-value<0.001) and for FMPAT and GA was 0.556 (P-value<0.001). FMPAP and FMPAT were highly correlated (R=-0.972; P<0.001). Conclusion Pulmonary artery pressure in the fetus decreases with GA.

Pulmonary Vein Flow Impedance: An Early Predictor of Cardiac Dysfunction in Intrauterine Growth Restriction.

INTRODUCTION: In intrauterine growth restriction (IUGR), increased uteroplacental vascular impedance contributes to preferential flow to left ventricle (LV), with consequent alteration of its compliance and increased left atrial (LA) pressure. Pulmonary vein pulsatility index (PVPI) reflects the increased impedance to LA filling and could be used as a cardiac monitoring parameter in IUGR. MATERIAL AND METHODS: A total of 27 IUGR fetuses (group 1), 28 fetuses with appropriate growth for gestational age from hypertensive mothers (group 2), and 28 controls (group 3) were studied. Pulsatility indices (PIs) of pulmonary veins and ductus venosus were calculated by Doppler echocardiography. Obstetric ultrasound was used to assess the PIs of uterine, umbilical, and middle cerebral arteries. Statistical analysis used analysis of variance, post-hoc Tukey, and Pearson's tests. RESULTS: Mean PVPI was higher in IUGR group (1.27 ± 0.39) when compared to groups 2 (1.02 ± 0.37; p = 0.01) and 3 (0.75 ± 0.12; p < 0.001). In group 2, moderate correlation between PVPI and ductus venosus pulsatility index (DVPI) was found but not between PVPI and cerebroplacental ratio (CPR). DISCUSSION: Higher PVPI in IUGR reflects decreased LV compliance and altered LA dynamics. As LV dysfunction precedes right ventricle, our results suggest that PVPI could be an early echocardiographic parameter of fetal diastolic function in IUGR.

JBASE: Joint Bayesian Analysis of Subphenotypes and Epistasis.

MOTIVATION: Rapid advances in genotyping and genome-wide association studies have enabled the discovery of many new genotype-phenotype associations at the resolution of individual markers. However, these associations explain only a small proportion of theoretically estimated heritability of most diseases. In this work, we propose an integrative mixture model called JBASE: joint Bayesian analysis of subphenotypes and epistasis. JBASE explores two major reasons of missing heritability: interactions between genetic variants, a phenomenon known as epistasis and phenotypic heterogeneity, addressed via subphenotyping. RESULTS: Our extensive simulations in a wide range of scenarios repeatedly demonstrate that JBASE can identify true underlying subphenotypes, including their associated variants and their interactions, with high precision. In the presence of phenotypic heterogeneity, JBASE has higher Power and lower Type 1 Error than five state-of-the-art approaches. We applied our method to a sample of individuals from Mexico with Type 2 diabetes and discovered two novel epistatic modules, including two loci each, that define two subphenotypes characterized by differences in body mass index and waist-to-hip ratio. We successfully replicated these subphenotypes and epistatic modules in an independent dataset from Mexico genotyped with a different platform. AVAILABILITY AND IMPLEMENTATION: JBASE is implemented in C++, supported on Linux and is available at http://www.cs.toronto.edu/∼goldenberg/JBASE/jbase.tar.gz. The genotype data underlying this study are available upon approval by the ethics review board of the Medical Centre Siglo XXI. Please contact Dr Miguel Cruz at mcruzl@yahoo.com for assistance with the application. CONTACT: anna.goldenberg@utoronto.ca SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Clinical management algorithm of uveitis associated with juvenile idiopathic arthritis: interdisciplinary panel consensus.

Uveitis associated with juvenile idiopathic arthritis (JIA) typically involves the anterior chamber segment, follows an indolent chronic course, and presents a high rate of uveitic complications and a worse outcome as compared to other aetiologies of uveitis. Disease assessment, treatment, and outcome measures have not been standardized. Collaboration between pediatric rheumatologists and ophthalmologists is critical for effective management and prevention of morbidity, impaired vision, and irreparable visual loss. Although the Standardization of Uveitis Nomenclature Working Group recommendations have been a great advance to help clinicians to improve consistency in grading and reporting data, difficulties arise at the time of deciding the best treatment approach in the individual patient in routine daily practice. For this reason, recommendations for a systematized control and treatment strategies according to clinical characteristics and disease severity in children with JIA-related uveitis were developed by a panel of experts with special interest in uveitis associated with JIA. A clinical management algorithm organized in a stepwise regimen is here presented.

Standard of care plus telmisartan on respiratory failure due to COVID-19 (STAR-COVID trial).

BACKGROUND: The potential influence of renin-angiotensin inhibitors on the severity of SARS-CoV-2 infection has been considered in preclinical and observational studies with contradictory results. Therefore, we investigated the effect of telmisartan in reducing lung injury among hospitalized COVID-19 patients. METHODS: The STAR-COVID trial was conducted as a prospective, parallel-group, randomized, open-label study involving hospitalized adult patients with severe COVID-19 (NCT04510662). Sixty-six patients were enrolled: 33 were assigned to the telmisartan group and 33 to the control group. The mean age of participants was 48.8 years, with 62.5% being male. Participants were randomly assigned in a 1:1 ratio to receive either telmisartan (40 mg daily for 14 days or until discharge) plus standard of care or standard of care alone. The primary outcome assessed was the initiation of mechanical ventilation within 14 days. Secondary outcomes included 30-day mortality, the need for vasopressors, hemodialysis requirements, and length of hospital stay. RESULTS: Comparison between the telmisartan group and the control group revealed no significant difference in the occurrence of mechanical ventilation at 14 days (25% with telmisartan vs. 18.7% with control, P=0.579). Additionally, there were no significant differences observed in terms of mortality (25% vs. 21.9%, P=0.768), the need for vasopressors (18.8% in both groups, P=1.000), hemodialysis requirements (6.3% vs. 3.1%, P=0.500), and length of hospital stay (median of 7 days in both groups, P=0.962). CONCLUSIONS: Compared with the standard of care, telmisartan therapy demonstrated no significant impact on respiratory failure in hospitalized patients with severe COVID-19.

Neovascular Glaucoma in Children: A case series and a review of the literature.

PURPOSE: To study the uncommon causes and treatment options for neovascular glaucoma in children. PATIENTS AND METHODS: A review of the literature on neovascular glaucoma in children was conducted and we present three cases of neovascular glaucoma in children. RESULTS: We present three cases of neovascular glaucoma: two cases were secondary to a retinal vasoproliferative tumor-one to neurofibromatosis type 1 and the other to exudative retinopathy secondary to mild retinopathy of prematurity-and one case was secondary to a central retina vein occlusion secondary to an optic nerve glioma. Vision in the affected eye was severely impaired in all the children. CONCLUSION: The diagnosis and treatment of neovascular glaucoma in children is challenging and often a complication of a systemic or late-stage ocular condition. An appropriate diagnosis and estimation of the visual potential are essential to determine the correct treatment, especially in young children.

Expanding the Phenotypic Spectrum of PAX6 Mutations: From Congenital Cataracts to Nystagmus.

BACKGROUND: Congenital aniridia is a complex ocular disorder, usually associated with severe visual impairment, generally caused by mutations on the PAX6 gene. The clinical phenotype of PAX6 mutations is highly variable, making the genotype-phenotype correlations difficult to establish. METHODS: we describe the phenotype of eight patients from seven unrelated families with confirmed mutations in PAX6, and very different clinical manifestations. RESULTS: Only two patients had the classical aniridia phenotype while the other two presented with aniridia-related manifestations, such as aniridia-related keratopathy or partial aniridia. Congenital cataracts were the main manifestation in three of the patients in this series. All the patients had nystagmus and low visual acuity. CONCLUSIONS: The diagnosis of mild forms of aniridia is challenging, but these patients have a potentially blinding hereditary disease that might present with a more severe phenotype in future generations. Clinicians should be aware of the mild aniridia phenotype and request genetic testing to perform an accurate diagnosis.

Molecular and Genetic Mechanism of Non-Syndromic Congenital Cataracts. Mutation Screening in Spanish Families.

Our purpose was to identify mutations responsible for non-syndromic congenital cataracts through the implementation of next-generation sequencing (NGS) in our center. A sample of peripheral blood was obtained from probands and willing family members and genomic DNA was extracted from leukocytes. DNA was analyzed implementing a panel (OFTv2.1) including 39 known congenital cataracts disease genes. 62 probands from 51 families were recruited. Pathogenic or likely pathogenic variants were identified in 32 patients and 25 families; in 16 families (64%) these were de novo mutations. The mutation detection rate was 49%. Almost all reported mutations were autosomal dominant. Mutations in crystallin genes were found in 30% of the probands. Mutations in membrane proteins were detected in seven families (two in GJA3 and five in GJA8). Mutations in LIM2 and MIP were each found in three families. Other mutations detected affected EPHA2, PAX6, HSF4 and PITX3. Variants classified as of unknown significance were found in 5 families (9.8%), affecting CRYBB3, LIM2, EPHA2, ABCB6 and TDRD7. Mutations lead to different cataract phenotypes within the same family.

CYP1B1 mutations in Spanish patients with primary congenital glaucoma: phenotypic and functional variability.

PURPOSE: To analyze the contributions of cytochrome P4501B1 (CYP1B1) mutations to primary congenital glaucoma (PCG) in Spanish patients. METHODS: We analyzed, by polymerase chain reaction (PCR) DNA sequencing, the presence of promoter (-1 to -867) and exon CYP1B1 mutations in 38 unrelated Spanish probands affected by PCG. Functional analysis of nine identified mutations was performed measuring ethoxyresorufin O-deethylation activity and CYP1B1 stability in transiently transfected human embryonic kidney 293T (HEK-293-T) cells. RESULTS: We found a total of 16 different mutations in 13 (34.2%) index cases. The identified mutations included nine missense and three nonsense nucleotide changes, three small deletions, and a short duplication. Eleven probands were compound heterozygotes and two were heterozygotes. Six of the identified mutations were novel (A106D, E173X, F261L, E262X, W341X, and P513_K514del). Mutations T404fsX30 and R355fsX69 were the most prevalent among index cases and were detected in six (23.0%) and three (11.5%) patients, respectively. Functional analysis showed that the three nonsense mutants assayed (E173X, E262X, and W341X) and F261L were null alleles. Of the remaining mutants, four (P52L, G61E, Y81N, and E229K) showed catalytic activities ranging from 20% to 40% of wild-type CYP1B1 and high protein instability. Mutation P400S showed normal catalytic activity and moderate instability. These five mutants were classified as hypomorphic alleles. Patients carrying two null alleles showed severe phenotypes featured by very early PCG onset usually at birth or in the first month of life (0.6+/-0.9 months). Incomplete penetrance was detected in patients carrying hypomorphic alleles. CONCLUSIONS: Our data indicate that approximately one-third of Spanish patients with PCG carry loss-of-function CYP1B1 and show that null alleles are associated with the most severe phenotypes. Hypomorphic alleles may contribute to some cases of incomplete penetrance.

Fulcro cardíaco de Trainini en el corazón fetal / Trainini cardiac fulcrum in the fetal heart

RESUMEN Demostrar mediante la disección de piezas anatómicas y de imágenes ultrasonográficas prenatales del corazón fetal la presencia del fulcro cardíaco como estructura de fijación que sirve de soporte a la banda miocárdica helicoidal. Se disecaron 6 corazones de fetos entre las 20 y 24 semanas de edad gestacional productos de abortos espontáneos, logrando encontrar el fulcro cardíaco en la proximidad de la aorta y conexiones con fibras miocárdicas. En 50 embarazos simples con fetos entre las 18 y 37 semanas de gestación, mediante ultrasonografía cardíaca fetal se obtuvieron las modalidades 2D, Doppler, color y tridimensión, STIC, HD Flow y speckle tracking, imágenes, medidas del fulcro y su cinética. Con la estrategia descrita se identificó y demostró la presencia del fulcro cardíaco o palanca miocárdica, estableciendo sus características anatómicas, conexiones con fibras miocárdicas del asa cardíaca y la biometría según la edad gestacional. Se formula una hipótesis sobre la biomecánica o cinética del fulcro durante el ciclo cardíaco. Para que el corazón cumpla su función de bomba aspirante e impelente debe poseer un punto de apoyo, una palanca o fulcro, que constituye una especie de unidad músculo-tendinosa. Dicha palanca presenta desplazamientos mixtos durante la torsión y detorsión del miocardio. Sus diámetros aumentan progresivamente a medida que avanza la gestación.

ABSTRACT To demonstrate by dissection of anatomical specimens and prenatal ultrasonographic images of the fetal heart the presence of the cardiac fulcrum as a fixation structure supporting the helical myocardial band. Six hearts of fetuses between 20-24 weeks of gestational age resulting from spontaneous abortions were dissected, finding the cardiac fulcrum in the proximity of the aorta and connections with myocardial fibers. In 50 singleton pregnancies with fetuses between 18-37 weeks of gestation, fetal cardiac ultrasonography was used to obtain 2D, Doppler, color and three-dimensional modalities, STIC, HD Flow and speckle tracking, images, fulcrum measurements and its kinetics. With the described strategy, the presence of the cardiac fulcrum or myocardial lever was identified and demonstrated, establishing its anatomical characteristics, connections with myocardial fibers of the cardiac loop and the biometry according to gestational age. A hypothesis on the biomechanics or kinetics of the fulcrum during the cardiac cycle is formulated. In order for the heart to fulfill its function as an aspirating and impelling pump, it must have a support point, a lever or fulcrum, which constitutes a sort of muscle-tendon unit. This lever presents mixed displacements during myocardial torsion and detorsion. Its diameters increase progressively as gestation advances.

Pars planitis in children: epidemiologic, clinical, and therapeutic characteristics.

PURPOSE: To report the demographics and clinical characteristics, therapy logarithm, and prognosis of children with pars planitis. PATIENTS AND METHODS: The medical records were reviewed of all patients diagnosed with pars planitis between June 1995 and December 2005 in the Department of Pediatric Ophthalmology at Hospital Universitario La Paz, Madrid, Spain. A retrospective, descriptive, and longitudinal study of 30 eyes in 16 children was performed. RESULTS: Pars planitis was bilateral in 87.5% and more frequent in males (68.8%). Average age at onset was 9.2 years. The main ophthalmologic findings recorded were snowballs (96.7%) and vitritis (93.3%). Cataract formation was the most prevalent complication (36.7%). Mean initial and final best-corrected visual acuities were 0.640 and 0.840, respectively. Periocular corticosteroids were used in 33.3% of cases and cryotherapy or laser photocoagulation in 16.7%. Complications requiring surgical management occurred in 4 eyes (13.3%). CONCLUSION: Pars planitis treated with adequate medical and surgical procedures has a good prognosis in most cases.

Índice de rendimiento biventricular del corazón fetal

Objetivo. Proponer un índice de rendimiento biventricular basado en los valores promedio de la duración del ciclo cardíaco de cada uno de los ventrículos, determinar la variable incluida en el estudio con la correlación estadística más significativa, establecer valores de referencia que permitan identificar el trabajo de cada ventrículo en función de dicha variable y obtener un índice de gasto biventricular equilibrado. Metodología. Estudio prospectivo y transversal en fetos de 168 gestantes, en embarazos entre las 16 y 38 semanas sin patologías materno-fetales. Se obtuvieron ondas de velocidad de flujo de ambas válvulas atrioventriculares y el tiempo total del ciclo sístole-diástole se calculó en milisegundos para cada válvula. Se calcularon promedios, desviación estándar y puntuación Z del tiempo sistólico-diastólico para cada ventrículo y el índice de rendimiento ventricular individual dividiendo el valor obtenido entre la frecuencia cardiaca fetal. Se obtuvo el valor promedio de ambos y este, al ser dividido por la frecuencia cardíaca, permitió obtener el índice de rendimiento biventricular para establecer la correlación entre este, la frecuencia cardiaca fetal y la edad de gestación. Resultados. Se halló valores de tiempo sistólico-diastólico en milisegundos para el ventrículo derecho de 420,8 (DE ±28,3) y para el ventrículo izquierdo de 418,8 (DE ±26,3), sin diferencias estadísticamente significativas (p=0,371). La correlación con la frecuencia cardíaca fetal resultó negativa para ambos ventrículos (-0,491 y -0,553; p<0,05). El tiempo promedio biventricular fue de 418,37 ms (± 20,59) y la correlación con la edad gestacional de 0,48 (p<0,05); la correlación con la frecuencia cardiaca fetal fue negativa, -0,50 (p<0,05). El índice de rendimiento biventricular mostró valores de 2,8 (extremos 2,4 (P5) y 3,4 (P95)). La correlación entre el índice de rendimiento biventricular y la frecuencia cardiaca fetal fue 0,78 (p<0,05), de menor grado (0,27) con la edad gestacional. Conclusiones. Se demostró que los tiempos sistólico-diastólicos de cada ventrículo no difirieron entre sí y se correlacionaron de manera negativa con la frecuencia cardiaca fetal. Se comprobó que es posible evaluar el ciclo cardíaco fetal de cada ventrículo mediante el índice de rendimiento ventricular, así como calificar con el índice de rendimiento biventricular el gasto cardíaco combinado como equilibrado.

Objectives: To propose a biventricular performance index based on the average values of the duration of the cardiac cycle of each of the ventricles, to determine the variable included in the study with the most significant statistical correlation, to establish reference values that allow the work of each ventricle to be identified according to this variable, and to obtain a balanced biventricular output index. Methodology: Prospective and cross-sectional study in fetuses of 168 pregnant women, in pregnancies between 16 and 38 weeks without maternal-fetal pathologies. Flow velocity waves were obtained from both atrioventricular valves and the total systole-diastole cycle time was calculated in milliseconds for each valve. Averages, standard deviation, and Z-score were calculated of the systolic-diastolic time for each ventricle and the individual ventricular performance index (VPI) were calculated by dividing the value obtained by the fetal heart rate (FHR). The average value of both was obtained and this, when divided by the heart rate, made it possible to obtain the biventricular performance index (BPI) to establish the correlation between this, the fetal heart rate and gestational age. Results: Systolic-diastolic time values in milliseconds for the right ventricle were 420.8 (SD ±28.3) and for the left ventricle 418.8 (SD ±26.3), with no statistically significant differences (p<0.371). The correlation with the FHR was negative for both ventricles: (-0.491 and -0.553; p<0.05). The mean biventricular time was 418.37 ms (±20.59) and the correlation with gestational age was 0.48 (p<0.05); the correlation with FHR was negative, -0.50 (p<0.05).The BPI showed values of 2.8 (extremes 2.4 (P5) and 3.4 (P95)). The correlation between BPI and FHR was 0.78 (p<0.05) and of lesser degree with gestational age (0.27; p<0.05). Conclusions: It was demonstrated that the systolic-diastolic times of each ventricle did not differ from each other and were negatively correlated with fetal heart rate. It was shown that it is possible to evaluate the fetal cardiac cycle of each ventricle by means of the ventricular performance index as well as to qualify with the biventricular performance index the combined cardiac output as balanced.

[Splenic rupture secondary to abscess: Rare cause of pneumoperitoneum. Case report]. / Rotura esplénica secundaria a absceso, causa poco común de neumoperitoneo. Reporte de un caso.

BACKGROUND: Splenic abscesses are rare entities; reports are commonly described in immunocompromised patients (72%) as: hematologic diseases, diabetes, endocarditis, acquired immunodeficiency syndrome, transplant patients and subjects who had abdominal trauma or splenic infarction. The main and most serious complication is the abscess rupture into the peritoneal cavity or adjacent organs (stomach or colon), which determines hemodynamic instability or septic state. CLINICAL CASE: Fifty-year-old man, who was admitted at Emergency Room due eight days' progressive, oppressive, and current pain; intensity 4/10, irradiated at hemi-back, which was higher intensity during the standing and decreased at supine position. It was accompanied by nausea and vomiting in two occasions. LABORATORY RESULTS: Hemoglobin 15.1g/dl, hematocrit 45.2%, platelets 176×103, 23.1×103 leukocytosis, neutrophils 92%. Simple abdominal radiographic studies revealed in 'ground glass' and radiopaque imagines. CONCLUSIONS: At presence of free air inside the abdominal cavity, is usually to think of a complicated diverticular disease, intestinal perforation or perforated peptic ulcer. The actual medical literature described very few cases of splenic abscess with pneumoperitoneum as cardinal manifestation. In our case, the splenic abscess was detected during exploratory laparotomy and only in retrospective the imaging studies were interpreted.

Intravitreal Bevacizumab for Zone II Retinopathy of Prematurity.

PURPOSE: To evaluate the treatment outcomes of intravitreal bevacizumab injections as monotherapy in type 1 retinopathy of prematurity (ROP). METHODS: A retrospective chart review was performed for patients with type 1 ROP who had intravitreal bevacizumab injections between November 2013 and January 2015 at La Paz University Hospital in Madrid, Spain. Gestational age at birth, birth weight, sex, ROP zone, ROP stage, mean age at treatment, and follow-up period were recorded. The final clinical status of the retina was noted for each patient. The primary outcome measures included ROP recurrences requiring re-treatment, complete or incomplete peripheral vascularization, mean age at complete vascularization, and refractive errors. RESULTS: From 14 patients enrolled with type 1 ROP, 28 eyes were included. The mean gestational age at birth was 25.9 ± 2.34 weeks (range: 23.6 to 32.4 weeks) and the median birth weight was 694 g (range: 487 to 1,740 g). All eyes showed zone II ROP: 18 eyes (64.3%) had anterior zone II ROP and 10 eyes (35.7%) had posterior zone II ROP. One week after intravitreal bevacizumab injection, 14 eyes (50%) had achieved complete regression of ROP, and a partial regression of ROP was observed in 10 eyes (35.7%). Twenty-two eyes (78.6%) obtained complete vascularization during the follow-up. The median time to complete vascularization was 134 ± 21.45 days. The mean spherical equivalent at last visit was 1.99 diopters. CONCLUSIONS: Intravitreal bevacizumab injection used as a monotherapy is an effective treatment approach in patients with zone II ROP. [J Pediatr Ophthalmol Strabismus. 2016;53(6):375-382.].

Topical carbonic anhydrase inhibitors in macular edema associated with Alström syndrome.

BACKGROUND: Alström syndrome is a rare genetic ciliopathy caused by a mutation in the ALMS1 gene. The syndrome is characterized by cone-rod dystrophy, dilated myocardiopathy, childhood obesity and sensorineural hearing loss. To date, cystoid macular edema has not been reported. METHODS: A female affected by Alström syndrome developed bilateral cystoid macular edema evidenced by optical coherence tomography. A topical carbonic anhydrase inhibitor was prescribed. RESULTS: Complete resolution of the cystoid macular edema was achieved, though visual acuity did not improve. CONCLUSIONS: Topical carbonic anhydrase inhibitors may have a role in the treatment of macular edema in syndromic retinal dystrophies such as Alström syndrome.

Obesity is associated with the Arg389Gly ADRB1 but not with the Trp64Arg ADRB3 polymorphism in children from San Luis PotosÍ and León, México.

This research was designed to analyze the possible associations of Arg389Gly ADRB1 and Trp64Arg ADRB3 polymorphisms in children with obesity. A cross-sectional study included 1,046 school-age Mexican participants (6-12 years old) from the cities of San Luis PotosÍ and León. Children were classified as non-obese or obese according to their body mass index (BMI) percentile; obese children had a BMI≥95th percentile for sex and age. Biochemical data were collected. Polymorphisms were detected using TaqMan qPCR assay. A logistic regression analysis was used to calculate the risk of obesity based on genotypes. Differences were found between groups where obese children had a significant increase in systolic and diastolic blood pressure, fasting plasma glucose, insulin, HOMA-IR, LDL-cholesterol, triglycerides, and lower HDL-cholesterol compared with the normal weight group (P<0.05). The distribution of allele frequency in the population was Arg= 87.4 and Gly= 12.6 (Hardy Weinberg equilibrium c2 = 3.16 , P = 0.07 ); Trp= 81.5 and Arg= 18.5 (Hardy Weinberg equilibrium c2 = 2.2, P = 0.14 ) for ADRB1 and ADRB3, respectively. Even though no different frequencies of Arg389Gly polymorphism between groups were found (P = 0.08), children carriers of one Gly389 ADRB1 allele had a risk for obesity of OR=1.40 (95%CI, 1.03-1.90, P = 0.03) after adjustment for age and gender. No other association was found for Trp64Arg ADRB3 polymorphism. Only the Arg389Gly ADRB1 polymorphism was associated with risk for obesity in Mexican children.