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To develop an MRI-based radiomics model to predict postlaminar optic nerve invasion (PLONI) in retinoblastoma (RB) and compare its predictive performance with subjective radiologists' assessment. We retrospectively enrolled 124 patients with pathologically proven RB (90 in training set and 34 in validation set) who had MRI scans before surgery. A radiomics model for predicting PLONI was developed by extracting quantitative imaging features from axial T2W images and contrast-enhanced T1W images in the training set. The Kruskal–Wallis test, least absolute shrinkage and selection operator regression, and recursive feature elimination were used for feature selection, where upon a radiomics model was built with a logistic regression (LR) classifier. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve and the accuracy were assessed to evaluate the predictive performance in the training and validation set. The performance of the radiomics model was compared to radiologists' assessment by DeLong test. The AUC of the radiomics model for the prediction of PLONI was 0.928 in the training set and 0.841 in the validation set. Radiomics model produced better sensitivity than radiologists' assessment (81.1% vs 43.2% in training set, 82.4vs 52.9% in validation set). In all 124 patients, the AUC of the radiomics model was 0.897, while that of radiologists' assessment was 0.674 (p < 0.001, DeLong test). MRI-based radiomics model to predict PLONI in RB patients was shown to be superior to visual assessment with improved sensitivity and AUC, and may serve as a potential tool to guide personalized treatment. [ABSTRACT FROM AUTHOR]

Purpose: To measure scleral and choroidal volume in eyes of Chinese, and to assess associations with age and axial length. Methods: We histomorphometrically examined globes from infants and adults which had been enucleated due to retinoblastoma, uveal melanoma, or absolute painful glaucoma. Thickness of sclera and choroid were measured, and volumes were calculated. Results: The study included 225 globes (mean axial length: 24.6 ± 4.2 mm; range:17.0-35.7 mm; mean age: 30.4 ± 22.6 years; range: 1-83 years). Mean computed scleral volume was 648 ± 136 mm. Scleral volume in children aged <5 years significantly increased with longer axial length ( P = 0.001; correlation coefficient r: 0.42) and older age ( P = 0.003; r: 0.39) in univariate analysis. In multivariate analysis within the group of children aged ≤2 years, larger scleral volume increased with longer axial length ( P = 0.04; standardized correlation coefficient beta: 0.32; correlation coefficient B: 21.6; 95 % confidence interval (CI): 0.52, 42.7) and showed a statistically non-significant tendency to increase with older age ( P = 0.06;b eta: 0.30; B: 56.9; 95% CI: −1.5,115). In individuals aged ≥ 5 years, scleral volume was not significantly associated with axial length ( P = 0.75) or age ( P = 0.13). Mean choroidal volume as measured and calculated in 95 individuals (age: 16-81 years) was 44.1 ± 14.1 mm, and was not significantly associated with age ( P = 0.47; r: −0.08) or axial length ( P = 0.83; r: −0.02). Conclusions: This study on children eyes with retinoblastoma and adult eyes with malignant melanomas or end-stage glaucoma suggests that primary eye growth up to an age of 2 years is associated with an increase in scleral volume. After the age of 2 years, scleral volume and choroidal volume remain unchanged, leading to scleral and choroidal thinning with longer axial length, in particular at the posterior pole. [ABSTRACT FROM AUTHOR]

To characterize the spectrum of mosaic RB1 pathogenic alleles and map the distribution of mutant cells in available tissues from mosaic patients. Next-generation sequencing was performed on blood samples from 263 retinoblastoma families to identify mosaic RB1 variant alleles. A variety of available tissues were sampled to determine tissue distribution and fraction of mutant cells in five mosaic patients who consented to participate in mosaic pathogenic allele research. Twelve identified mosaic RB1 variants were all "null" pathogenic alleles and displayed reduced expressivity. The use of next-generation deep sequencing increased the sensitivity of mosaicism detection to 0.03% in the case of tissue DNA. In the five mosaic participants, we observed coherent but uneven, bilateral asymmetrical distribution of mutant cells across various tissues. They all carried early-embryonic mosaic pathogenic alleles and had significantly higher variant fractions in blood than in other tissues. Variant fractions of ipsilateral tissue samples were not concordant higher or lower compared with the contralateral side. Only ipsilateral conjunctival and oral epithelial cells showed concordance in mosaicism levels. No associations were observed between the laterality of affected eyes and variant fractions of any tissue type. NGS allows the detection of low-level mosaicism. Mosaic RB1 pathogenic alleles are prone to occur at very early stages of human embryonic development. With respect to genetic counseling, risk prediction should take into account unrecognized mosaicism. The underlying tissue distribution patterns of mosaic RB1 variant alleles remain to be determined. [ABSTRACT FROM AUTHOR]

Purpose: To explore expression and function of astrocyte elevated gene-1 (AEG-1) in human retinoblastoma (RB). Methods: The expression of AEG-1 in histological sections of human RBs and in RB cell lines was examined using immunohistochemical staining and RT-PCR and Western blotting respectively. We knocked down AEG-1 gene levels by AEG-1-siRNA lentivirus transfection of human RB cell lines SO-RB50 and Y79, and using an MTT assay, we assessed the role of AEG-1 on RB cell proliferation. The biological significance of lentivirus transfection induced AEG-1 down-regulation was examined by assessing the apoptosis rate in the transfected RB cells by Annexin V-APC staining and flow cytometry. We additionally measured the expression of Bcl-2, Bax, cleaved-caspase-3 and caspase-3, and the phosphorylation and non-phosphorylation alternation of MAPKs. Results: AEG-1 expression was detected to be strongly positive in the histological slides of 35 out of 54 (65%) patients with RB. AEG-1 expression increased significantly (P<0.05) with tumor stage. In the RB cell lines SO-RB50, Y79 and WERI-RB1 as compared with retinal pigment epithelium cells, expression of AEG-1 mRNA and AEG-1 protein was significantly higher. In AEG-1-siRNA lentivirus transfected cell cultures as compared with negative control lentivirus transfected cell cultures, levels of AEG-1 mRNA and of AEG-1 protein (P<0.05) and cell growth rates (P<0.01) were significantly lower, and apoptosis rate (P<0.001), Bax/Bcl-2 ratio and cleaved-caspase-3 protein level were significantly increased. The P-ERK/ERK ratio was significantly decreased in the AEG-1-siRNA lentivirus transfected cell lines. Conclusions: Expression of AEG-1 was associated with RB, in histological slides of patients and in cell culture experiments. Lentivirus transfection induced knockdown of AEG-1 had a tumor suppressive effect, potentially by tumor cell apoptosis induction through inhibition of ERK. [ABSTRACT FROM AUTHOR]

Objective: To assess the characteristics of retinoblastomas enucleated from Chinese children aged 5-14 years. Methods: This retrospective hospital-based study included all eyes with retinoblastomas consecutively enucleated in the Beijing Tongren Hospital between August 2003 and July 2013. Results: Out of 1,205 patients, 47 (3.9%) were 5 years or older. All tumors in this age group occurred unilaterally, the patients had a negative family history, and the tumors were detected at an age of 6.9 ± 1.8 years (range: 5-14). The main clinical features at the time of examining the as yet untreated children aged 5-7 years (n = 30) or >7-14 years (n = 10) were leukocoria, strabismus, pseudohypopyon, hypertension, vitreous seeds ('snowballs'), and calcifications. In 12 patients (26%), the retinoblastoma had not initially been diagnosed as a tumor. Histopathology revealed tumor invasion into nonretinal tissue in 19 eyes (40%). Therapy included enucleation only (n = 22; 47%), adjuvant systemic chemotherapy (n = 24; 51%), and additional orbital exenteration (n = 1). After a mean follow-up of 3.0 ± 2.1 years (range: 0.2-9.8), which was done for 40 children, none of these children showed a tumor recurrence. Conclusions: Of the children undergoing enucleation for retinoblastoma in Beijing, 3.9% were aged 5 years or more. As in Western countries, the tumor occurrence was unilateral, their family history was negative, and the survival rate was relatively high in these children. In 1 out of 4 children, the tumor had initially been misdiagnosed due to a masquerade syndrome. Retinoblastoma should be considered in the differential diagnosis of any unclear intraocular situation in children. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Extracted from the traditional Chinese medicine of Kushen, matrine is an alkaloid with potential anti-neoplastic and anti-inflammatory effects. Here, we examined the effect of matrine on proliferation and apoptosis of cultured retinoblastoma cells. Methods: The retinoblastoma cell lines Y79, WERI-RB1 and SO-RB50 were treated with matrine in increasing concentrations from 0.2-1.1 mg/ml for 24 hours, and the cell proliferation rate was measured. The cells were exposed to matrine at 50% inhibition concentration (IC50) for 12, 24 and 48 hours. Cell cycle was analyzed by flow cytometry, concentration of proteins regulating cell cycle and apoptosis was determined by Western blot, apoptosis rate was measured by TUNEL staining, and cell morphology was assessed by electron transmission microscopy. Results: The retinoblastoma cell lines Y79, WERI-RB1 and SO-RB50 showed an increased inhibition of cell proliferation with increasing matrine concentrations. Applying the IC50 concentration of matrine, the alteration of the cell cycle, including a reduced percentage of the S phase, was significantly ( P < 0.01) associated with a longer treatment time by matrine. Correspondingly, the cell-cycle-associated proteins P21 and P27 were up-regulated and the protein cyclinD1 was down-regulated. The apoptosis-associated protein Bcl-2 was down-regulated, and Bax was up-regulated. In a similar manner, the apoptosis rate was significantly increased with longer treatment time. Conclusions: Matrine added to cultures of immortalized retinoblastoma cells led to a reduced tumor cell proliferation, decreased rate of mitosis and an increased tumor cell apoptosis, paralleled by corresponding changes in the proteins regulating the cell cycle or apoptosis. [ABSTRACT FROM AUTHOR]

Purpose: Retinoblastoma is the most frequent primary intraocular tumour and is rapidly gaining importance in Asia. As the survival is markedly dependent on early diagnosis and as information on that is not available from East Asia, we assessed the time interval between symptoms detection and therapy of children treated in the Beijing TongRen Eye Hospital. Methods: The retrospective study consisted of all patients who were treated in the study period from January 1987 to November 2006 in the Beijing TongRen Hospital and for whom the data on delay in diagnosis, age, clinical appearance and histological tumour features were available. Results: The inclusion criteria were met by 572 patients (326 boys) with a mean age of 2.6 ± 1.8. Mean interval between first detection of symptoms and clinical diagnosis and therapy was 4.1 ± 5.9 months (range: 3-36 months). A diagnostic delay of 2 months or >6 months was found for 337 (59%) children and 98 (17%) children, respectively. Diagnostic delay was significantly (p < 0.001) the longest in the 2- to 4-year-old group (5.5 ± 7.4 months). It decreased from the study period 1987-1991 to the period 2002-2006 (p < 0.001). It was significantly associated with the clinical appearance (p = 0.001) and histological finding (p = 0.008). Conclusions: Delay in the diagnosis of retinoblastoma depended on the age of the children, study period, and clinical and histological stage. Because the prognosis is markedly influenced by tumour stage, further improvements in the alertness of parents, family doctors and paediatricians and in the medical infrastructure in China may be addressed. [ABSTRACT FROM AUTHOR]