Choroidal Invasion Research Articles

Epidemiology and clinical features of retinoblastoma: A tertiary care center's experience in India.

Introduction:Retinoblastoma (RB) is a prototype of heritable cancers. It is more common in the lower socioeconomic strata. Delayed presentation significantly reduces the overall outcome. We have analyzed the epidemiological and clinical data of children who were diagnosed with RB between the years 2009 and 2014.Aim:RB being a disease of the poor, delayed presentation is common due to lack of awareness. We have analyzed the epidemiological profile of our patients and tried to establish the link between delayed presentation and the presence of high-risk features. High-risk features are associated with higher chance of metastasis and poor rates of vision salvage in RB.Methodology:Data were collected in a retrospective manner from the patient case files retrieved from the Medical Records Department, Kidwai cancer Institute. The data were analyzed using Excel and SPSS software (IBM Corp. released 2016, IBM SPSS statistics software for Mac OS, version 24, IBM Corp., Armonk, NY).Results:A total of 53 patients were diagnosed with RB in the years 2009–2014. There was a male predominance with 1.2:1 incidence. Bilateral RB was present in 21 cases. The mean age of children with bilateral RB was 2.1 years, against 1.5 years in unilateral cases. High-risk features such as optic nerve invasion, choroidal invasion, intracranial extension, and orbital involvement were found in 12, 6, 5, and 5 eyes, respectively. Bone marrow involvement was detected in 5% and lung metastasis in 2%. Intracranial involvement was found in 10.4% and cerebrospinal fluid positivity in 15%. Children with high-risk features had a significant delay in presentation in comparison to those without high-risk features (P = 0.035).Conclusion:Incidence of metastatic disease and delayed presentation is still high in developing countries. Routine eye examination during vaccination visits can ensure early diagnosis and appropriate referral in many of these children.

Differential expression patterns of immune checkpoint markers in tumour-stromal microenvironment of primary and chemoreduced retinoblastoma

Abstract Background The goal of this study is to identify the pathological findings and expression of immune checkpoint marker (PD-1, PD-L1, and CTLA-4) in the tumor microenvironment of both primary and chemoreduced retinoblastoma and correlate with clinicopathological parameters and patient outcome. Methods Total of 262 prospective cases was included prospectively in which 144 cases underwent primary enucleation and 118 cases received chemotherapy/radiotherapy before enucleation (chemoreduced retinoblastoma). Immunohistochemistry, qRT-PCR and western blotting were performed to evaluate the expression pattern of immune checkpoint markers in primary and chemoreduced retinoblastoma. Results Tumor microenvironment was different for both primary and chemoreduced retinoblastoma. Expression of PD-1 was found in 29/144 (20.13%) and 48/118 (40.67%) in primary and chemoreduced retinoblastoma respectively, whereas PD-L1 was expressed in 46/144 (31.94%) and 22/118 (18.64%) in cases of primary and chemoreduced retinoblastoma respectively. Expression pattern of CTLA-4 protein was similar in both groups of retinoblastoma. On multivariate analysis, massive choroidal invasion, bilaterality and PD-L1 expression (p = 0.034) were found to be statistically significant factors in primary retinoblastoma whereas PD-1 expression (p = 0.015) and foamy macrophages were significant factors in chemoreduced retinoblastoma. Overall survival reduced in cases of PD-L1 (80.76%) expressed primary retinoblastoma, and PD-1 (63.28%) expressed chemoreduced retinoblastoma. Conclusion This is the first of its kind study predicting a relevant role of the immune checkpoint markers in primary and chemoreduced retinoblastoma with prognostic significance. Differential expression of these markers in both group of retinoblastoma is a novel finding and might be an interesting and beneficial target for chemoresistant tumors. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Optimal Inhibition of Choroidal Neovascularization by scAAV2 with VMD2 Promoter-driven Active Rap1a in the RPE

Age-related macular degeneration (AMD) is a multifactorial chronic disease that requires long term treatment. Gene therapy is being considered as a promising tool to treat AMD. We found that increased activation of Rap1a in the retinal pigment epithelium (RPE) reduces oxidative signaling to maintain barrier integrity of the RPE and resist neural sensory retinal angiogenesis from choroidal endothelial cell invasion. To optimally deliver constitutively active Rap1a (CARap1a) into the RPE of wild type mice, self-complementary AAV2 (scAAV2) vectors driven by two different promoters, RPE65 or VMD2, were generated and tested for optimal active Rap1a expression and inhibition of choroidal neovascularization (CNV) induced by laser injury. scAAV2-VMD2, but not scAAV2-RPE65, specifically and efficiently transduced the RPE to increase active Rap1a protein in the RPE. Mice with increased Rap1a from the scAAV2-VMD2-CARap1a had a significant reduction in CNV compared to controls. Increased active Rap1a in the RPE in vivo or in vitro inhibited inflammatory and angiogenic signaling determined by decreased activation of NF-κB and expression of VEGF without causing increased cell death or autophagy measured by increased LCA3/B. Our study provides a potential future strategy to deliver active Rap1a to the RPE in order to protect against both atrophic and neovascular AMD.

Study of Unilateral Retinoblastoma With and Without Histopathologic High-Risk Features and the Role of Adjuvant Chemotherapy: A Children's Oncology Group Study.

To prospectively determine the prevalence of high-risk histopathologic features (HRFs) in patients with unilateral retinoblastoma who undergo enucleation and to evaluate the role of chemotherapy in preventing recurrences. Children newly diagnosed with enucleated unilateral retinoblastoma were enrolled prospectively. After central histopathology review, patients with specific HRFs received chemotherapy; others were observed. Primary end points were event-free survivals (EFS). Of the 331 patients enrolled during 2005 to 2010, 321 eligible patients had central histopathologic review. Discordance between central review and contributing institutions occurred in 23% of patients with HRFs and in 17% of patients without HRFs. Postlaminar optic nerve involvement was present in 53 patients; 42 had massive posterior uveal invasion (≥ 3 mm); 15 had concomitant peripapillary 3 mm or greater choroid and postlaminar optic nerve involvement; and 15 had focal (< 3 mm) choroidal concomitant with lamina or prelamina optic nerve involvement. Two-year EFS for patients with HRFs requiring adjuvant chemotherapy was 0.96 (95% CI, 0.89 to 0.98), and 2-year EFS for patients without HRFs for which observation was indicated was 0.99 (95% CI, 0.96 to 1.0). The 2-year EFS for all patients was 0.98 (95% CI, 0.96 to 0.99). Adequate handling and interpretation of histopathology of eyes with retinoblastoma is necessary to assign metastatic risk. Concomitant less than 3 mm choroidal and any prelaminar/laminar optic nerve invasion show no recurrence and may warrant no adjuvant chemotherapy. In contrast, concomitant greater than 3 mm peripapillary choroidal invasion and 1.5 mm or greater of postlaminar optic nerve invasion have the poorest outcomes, supporting the need for a more intensive adjuvant chemotherapy regimen for this subgroup. Strict criteria for adjuvant therapy may improve outcomes of children who undergo enucleation at diagnosis and may avoid unnecessary adjuvant chemotherapy for those who are not at risk for recurrence.

An intraocular pressure predictive of high-risk histopathologic features in group e retinoblastoma eyes

To determine the intraocular pressure (IOP), with or without neovascularization of the iris (NVI), that most accurately predicts the presence of high-risk histopathologic features, including post-laminar optic nerve invasion, massive choroidal invasion, and extrascleral invasion.

Clinicopathological Findings of Retinoblastoma: A 10-Year Experience from a Tertiary Hospital in Kampala, Uganda.

Background Retinoblastoma (RB) is one of the most common cancers occurring in young children in sub-Saharan Africa. The incidence rate reported in the literature is 9,000 new cases per year, which corresponds to 1 in 15,000 births. This study aimed at analyzing the clinicopathological findings in children with RB in Uganda. Purpose The purpose of this study was to describe and analyze the clinicopathological findings in the patients with RB. Design This was a cross-sectional analytical study involving 234 eyeball surgical specimens from 214 patients with RB diagnosed between January 2006 and December 2015. Results The mean age of the patients was 27.8 months (SD = 21.413, range: 1–132 months). More than half of the cases, 50.9%, presented with leucokoria. Invasion of choroid, sclera, anterior chamber, and optic nerve was found in 26.5% (n = 58), 51.2% (n = 88), 26.2% (n = 45), and 29.2% (n = 49), respectively. Twenty-six percent (n = 56) of the cases with intraocular tumour were at stage I and all patients with metastasis 4.7% (n = 11) had stage IV. The correlation between postlaminar optic nerve invasion and massive choroidal invasion was statistically significant (P = 0.002). Also, there was a statistical significance difference between metastasis and postlaminar invasion (P = 0.004). Conclusion The majority of children with RB in Uganda present clinically with leucokoria, and their parents or guardians seek medical intervention at a later stage. Moreover, there was a noticeably significant lag period for the patients to begin treatment after the diagnosis was done.

FEZF1-AS1 functions as an oncogenic lncRNA in retinoblastoma.

Long non-coding RNA (lncRNA) FEZF1 antisense RNA 1 (FEZF1-AS1) has been shown to be up-regulated in tumor tissues and cells, and exerts oncogenic effects on various types of malignancies. However, the expression and function of FEZF1-AS1 was still fully unclear in retinoblastoma. The purpose of our study was to investigate the expression and clinical value of FEZF1-AS1 in retinoblastoma patients, and explore the effect of FEZF1-AS1 on retinoblastoma cell proliferation, migration and invasion. In our results, levels of FEZF1-AS1 expression were elevated in retinoblastoma tissue specimens and cell lines compared with adjacent normal retina tissue specimens and human retinal pigment epithelial cell line, respectively. The correlation analysis indicated that high FEZF1-AS1 expression was significantly correlated with present choroidal invasion and optic nerve invasion. Survival analysis suggested that retinoblastoma patients in high FEZF1-AS1 expression group had obviously short disease-free survival (DFS) compared with retinoblastoma patients in low FEZF1-AS1 expression group, and high FEZF1-AS1 expression was an independent unfavorable prognostic factor for DFS in retinoblastoma patients. Loss-of-function study indicated silencing FEZF1-AS1 expression inhibited retinoblastoma cell proliferation, invasion and migration. In conclusion, FEZF1-AS1 functions as an oncogenic lncRNA in retinoblastoma.

Clinical Predictors at Diagnosis of Low-Risk Histopathology in Unilateral Advanced Retinoblastoma

Attempted eye salvage for unilateral (cT2b/group D) retinoblastoma may risk tumor spread compared with primary enucleation. Identification of clinical features predictive of low histopathologic risk support safe trial salvage. Retrospective, noncomparative single-institutional observational case series. Children with unilateral cT2b/group D retinoblastoma managed with primary enucleation at the Hospital for Sick Children, Toronto, Canada, January 2008 through February2018. Data included clinical features (intraocular pressure, optic nerve obscuration, macular involvement, tumor seeding, and serous retinal detachment [RD] >1 quadrant), timing to enucleation, histopathologic features, and follow-up. Primary outcome was low-risk (LR; pT1/pT2) versus high-risk (HR; pT3/pT4) histopathologic features with clinicopathologic correlations. Secondary outcomes were positive predictive (probability that certain clinical features would predict LR histopathologic features) and negative predictive values (probability that absence of these clinical features would predict HR histopathologic features). Thirty-eight eyes were eligible and showed vitreous seeding and normal intraocular pressure. The median diagnosis to enucleation interval was 4 days (range, 0-14 days). Histopathologic analysis diagnosed 4 (10.5%) HR and 34 (89.5%) LR eyes. High-risk eyes demonstrated massive choroidal invasion (4/38) or trans-scleral, extraocular, and postlaminar optic nerve invasion (1/38). Clinical findings included macular involvement (31/38), complete optic nerve obscuration (27/38), and RD (28/38). The proportion of eyes with HR histopathologic features was 13% (4/31; 95% confidence interval [CI], 1%-25%) with macular involvement, 15% (4/27; 95% CI, 1%-28%) with complete optic nerve obscuration, and 14% (4/28; 95% CI, 1%-27%) with RD. The predictability of LR histopathologic features was 100% with macular sparing (7/7; 95% CI, 47%-100%), optic nerve visibility (10/10; 95% CI, 63%-100%), and less than 1 quadrant of RD (10/10; 95% CI, 63%-100%). In 1 child lacking all 3 clinical LR predictive features with HR histopathologic features (pT3a), metastases developed and the patient died; other children are alive and well (mean follow-up, 65 months). Presence of macular sparing, optic nerve visibility, less than 1 quadrant of RD, or a combination thereof predicted LR histopathologic features at primary enucleation, suggesting safe trial eye salvage. No clinical sign predicted HR histopathologic features.

An Intraocular Pressure Predictive of High-risk Histopathologic Features in Group E Retinoblastoma Eyes.

Postlaminar optic nerve invasion, massive choroidal invasion, and extrascleral invasion are histopathologic features that, when present in enucleated retinoblastoma (Rb) eyes, suggest a worse prognosis due to an increased risk for development of metastatic disease.1–6 Patients with eyes displaying these features upon postoperative histopathologic evaluation are generally recommended adjuvant chemotherapy to prevent metastasis and death.7,8 Efforts have been made to identify clinical and radiographic features associated with the presence of high-risk histopathology, which can be recognized at time of diagnosis rather than after enucleation. This gives clinicians the opportunity to recommend prompt enucleation to prevent additional growth/spread of the tumor or to suggest administration of preoperative neoadjuvant chemotherapy to achieve tumor regression and support a more targeted treatment plan.9,10 Optic nerve enhancement on magnetic resonance imaging (MRI) is a preoperative imaging finding that may be suggestive of high-risk pathology; however, thickening is more specific.10–12 In terms of clinical features, Rb eyes with glaucoma, buphthalmos, neovascularization of the iris (NVI), and an increased intraocular pressure (IOP) at diagnosis are associated with high-risk histopathologic features upon enucleation.11,13–16 Although increased IOP is already recognized as an indicator of advanced disease with high-risk pathology, it is not a clinical factor of high specificity, as many Rb patients present with elevated IOP at diagnosis, but do not display high-risk features upon enucleation. In addition, the numeric level of “elevation” is infrequently discussed in other studies; therefore, the impact of this variable is not entirely known. Secondarily, we were interested in stratifying risk for eyes with an elevated IOP based on the presence or absence of NVI. Increased IOP in Rb eyes at diagnosis can be seen with or without NVI, as the 2 most common mechanisms causing ocular hypertension in Rb are peripheral anterior synechiae formation secondary to NVI and NVI-independent angle closure due to massive exudative retinal detachment.17,18 Thus, we wanted to establish if the presence of NVI is a significant additional variable when determining an IOP cutoff value most predictive of high-risk pathology. While Group E eyes are often considered unsalvageable, there is a growing trend toward attempts at conservative treatment.19 As Group E Rb eyes have the greatest prevalence of high-risk histopathologic features,14,20–22 it is critical to stratify clinical risk for them at time of diagnosis. Therefore, this study was limited to Group E eyes at diagnosis. We hope to elucidate if there is a specific IOP value above which Rb eyes are more likely to display high-risk histopathologic features in order to equip clinicians with the most precise prognostic clinical criteria possible.

Blood Flow in Monocular Retinoblastoma Assessed by Color Doppler and Correlations With High-Risk Pathologic Features.

To use color Doppler to analyze blood flow in the retrobulbar central retinal artery (CRA) and central retinal vein (CRV) in monocular retinoblastoma. This prospective study included patients with group D and E retinoblastomas managed with only enucleation. Peak blood velocities were assessed in the CRA and CRV of tumor-containing eyes (CRAv and CRVv, respectively). The resistivity index in the CRA (RIa) and pulse index in the CRV (PIv) were calculated and related to optic nerve invasion (ONi), choroid invasion (mCHi), and tumor volume. RIa and PIv were also calculated for healthy eyes. In total, 25 patients with a mean age of 30.8-months old were included. The means (SD) for CRAv, CRVv, RIa, and PIv were 26.94 (12.32) cm/s, 16.2 (9.56) cm/s, 0.88 (0.12) and 0.79 (0.29), respectively. Tumor volume was significantly correlated with CRAv (P = 0.025) and RIa (P = 0.032). ONi was present in 19 eyes and correlated with a smaller PIv (P < 0.001). A PIv less than 0.935 had a sensitivity of 89.5% and specificity of 83.3% for predicting ONi. mCHi was not correlated with flow values. Healthy eyes had a significantly lower RIa (P < 0.001) and lower PIv than eyes with (P = 0.009) and without (P < 0.001) ONi. In advanced-stage monocular retinoblastoma, tumor volume was directly correlated with CRAv and RIa, and lower PIv was correlated with optic nerve invasion when a predictive cut-off value of less than 0.935 was applied. Comparisons with healthy eyes showed that tumor-containing eyes were associated with higher RIa and PIv values.

Metastases and death rates after primary enucleation of unilateral retinoblastoma in the USA 2007–2017

Background/aimsEnucleation for retinoblastoma is performed less often in the past decade due to increasingly widespread alternative therapies, but enucleation remains an important option. There is a paucity of reports on...

Analysis of high-risk histopathologic features of 482 primarily enucleated retinoblastomas

Objective: To evaluate the high-risk histopathologic features of retinoblastoma eyes enucleated as primary treatment. Methods: Retrospective case series study. An analysis was carried out on the high-risk histopathologic features of 482 primarily enucleated retinoblastoma eyes in Beijing Tongren Eye Center during December 2011 and December 2016. The high-risk histopathologic features included post lamina cribrosa invasion, massive choroidal invasion, anterior segment invasion and extraocular invasion. According to the neovascularization of iris (NVI) in the tissue specimen, the patients were divided into the NVI positive group and negative group. The rates of high-risk histopathologic features in the NVI positive group and negative group were analyzed using the chi-square test. Results: Among 482 children with retinoblastoma, 280 (58.1%) were males and 202 (41.9%) were females. The median age at enucleation surgery was 24 months (range, 1-84 months). Of the 482 primarily enucleated eyes, 184 (38.2%) were classified as high-risk histopathologic features, including 148 (30.7%) with post lamina cribrosa invasion, 15 (3.1%) with optic nerve transection invasion, 66 (13.7%) with massive choroidal invasion, 35 (7.3%) with anterior segment invasion, and 5 (1.0%) with extraocular invasion. NVI was detected in 257 (53.3%) cases and there was a significant relation between high-risk histopathologic features and NVI. The rate of high-risk histopathologic features was significantly higher in the NVI positive group (123 cases, 47.9%) than the NVI negative group (61 cases, 27.1%) (χ(2)=21.883, P=0.001). The rate of post lamina cribrosa invasion was significantly higher in the NVI positive group (110 cases, 42.8%) than the NVI negative group (38 cases, 16.9%) (χ(2)=37.860, P=0.001). Conclusions: In this large sample of patients, about 1/3 of retinoblastoma eyes has high-risk histopathologic features. The NVI positive retinoblastoma is more likely to have high-risk histopathologic features or post lamina cribrosa invasion than the NVI negative retinoblastoma. (Chin J Ophthalmol, 2018, 54: 782-786).

Pathological Risk Factor Profile for Enucleated Retinoblastoma at Sanglah General Hospital

Retinoblastoma is a primary intraocular tumor on childhood. It has a good prognosis with early detection. Aim of this study is to know Pathological Risk Factors (PRF) profile of enucleated retinoblastoma at Sanglah General Hospital. This study is an observational retrospective study based on patient’s medical record and pathological examination. Twenty patients were included in this study, 50% were female and 50% male within age ranging from 7 month – 12 years old. Unilateral retinoblastoma was found in 18 patients (90.5%), bilateral retinoblastoma was found in 2 patients (9.5%). Majority PRF profile found that cancer cell invasions was 60% choroid infiltration and 45% of anterior segment invasion, 60% of optic nerve infiltration, and 50.1% scleral invasion. Tumor cell aggregation showed 61.9% poorly differentiated malignant cells. None of the patients had family history of retinoblastoma. This study revealed optic nerve and choroid invasion were the major PRF found in retinoblastoma, but there is a significant association between scleral infiltration and tumor cell differentiation (p = 0.025). There was no statistical difference of PRF based on age, gender, and laterality.

HIGH-RISK INTRAOCULAR RETINOBLASTOMA: Comparison Between Asian Indians and Americans From Two Major Referral Centers.

To identify the differences in the clinical and histopathologic features in eyes with advanced intraocular retinoblastoma in a developing country (India) versus a developed country (USA). Retrospective study. Of 524 patients with retinoblastoma who underwent primary enucleation, 331 were from India, and 193 were from the USA. Asian Indians were older at presentation (35 months vs. 29 months; P = 0.02), had thicker tumors (13.8 mm vs. 12.4 mm; P = 0.0001) compared with Americans. High-risk intraocular retinoblastoma was more common in Asian Indians with a 2-fold greater risk compared with Americans (35% vs. 23%; odds ratio = 1.83; P = 0.003). Statistically significant differences in the histopathologic features (Asian Indians vs. Americans) included massive (≥3 mm) choroidal infiltration (17% vs. 6%; P = 0.0003) and optic nerve infiltration (48% vs. 15%; P = 0.0001). Asian Indians had a 5-fold greater risk of having optic nerve invasion (odds ratio = 5.45; P < 0.0001) and 3-fold greater risk of massive choroidal invasion (odds ratio = 2.80; P < 0.0001) compared with Americans. With appropriate use of adjuvant systemic chemotherapy, the difference in the rates of systemic metastasis (5% vs. 2%, P = 0.67) and related death in both countries (5% vs. 0%, P = 0.14) were not statistically significant. High-risk intraocular retinoblastoma is more common in Asian Indians compared with Americans.

Expression of multidrug-resistance associated proteins in human retinoblastoma treated by primary enucleation.

To reveal the expression of multidrug-resistance associated proteins: glutathione-S-transferase π (GSTπ), P-glycoprotein (P-gp) and vault protein lung resistance protein (LRP) in retinoblastoma (RB) without any conservative treatment before primary enucleation and to correlate this expression with histopathological tumor features. A total of 42 specimens of RB undergone primary enucleation were selected for the research. Sections from the formalin-fixed, paraffin-embedded specimens were stained with HE and immunohistochemistry to detect the expression of GSTπ, P-gp and LRP. GSTπ was expressed in 39/42 (92.86%) RBs and in 9/9 (100%) well-differentiated RBs. P-gp/GSTπ was found in 30 (71.42%) of 42 RBs. Totally 9 (21.43%) tumors were well differentiated and 33 (78.57%) were poorly differentiated. Totally 15 (35.71%) eyes had optic nerve (ON) tumor invasion, 36 (85.71%) had choroidal tumor invasion, and 14 (33.33%) had simultaneous choroidal and ON invasion. There was no statistically significant relationship between P-gp, GSTπ, LRP positivity and the degree of ocular layer tumor invasion and ON tumor invasion (P>0.05). RB intrinsically expresses GSTπ, P-gp and LRP. GSTπ expression is positive in 100% well-differentiation ones, so in which way it is correlated with differentiation. But the other two proteins expressions are not related to tumor differentiation and to the degree of tumor invasion. GSTπ may be a new target of chemotherapy in RB.

Correlations between claudin-1 and PIGF expressions in retinoblastoma.

To investigate the expressions of claudin-1 and placental growth factor (PlGF) proteins in retinoblastoma (RB) and their relationships with the differentiation of RB, the infiltration of optic nerve and choroid and clinical stages. Immunohistochemical (IHC) method was used to detect the expressions of claudin-1 and PlGF proteins in 56 cases of RB paraffin-embedded tissue samples. The x2-test and Fisher exact test were used to compare the qualitative variables. The Pearson correlation coefficient was used to detect the correlation of the expression of claudin-1 with that of PlGF in RB tissues. 1) Among RB tissues, the positive expression rates of claudin-1 in clinical stage I tumors and clinical stage III tumors were 69.2% and 38.9%, respectively, and claudin-1 was not expressed in all clinical stage II tumors (p=0.002). In case of optic nerve invasion, the lowly positive expression of claudin-1 was detected, and the difference was significant (p=0.001). 2) The positive expression rate of PlGF proteins in RB was 73.8%, which was higher in tumors with optic nerve invasion than in tumors without the invasion; the expression was significantly different (p=0.001). In addition, the positive expression rate of PlGF in tumors with choroidal invasion was 74.1%. 3) The expression of claudin-1 in RB was negatively correlated with the presence of choroidal invasion (r=0.52, p≤0.0001) and optic nerve infiltration (r=0.49, p=0.0003). There was a significant positive correlation between the expression of PlGF and the presence of optic nerve invasion (r=0.30, p=0.009). In addition, there was a significant positive correlation between the expression of claudin-1 and that of PlGF (r=0.41, p=0.006). The expression level of claudin-1 is negatively correlated with the differentiation of RB cells, optic nerve infiltration and clinical stages, while the expression of PlGF was positively correlated with the optic nerve infiltration and clinical stages of RB. The role of claudin-1 may be opposite to that of matrix metalloproteinase-2 (MMP-2) in the development of RB.

The predictive value of magnetic resonance imaging of retinoblastoma for the likelihood of high-risk pathologic features.

To evaluate the predictive value of magnetic resonance imaging in retinoblastoma for the likelihood of high-risk pathologic features. A retrospective study of 64 eyes enucleated from 60 retinoblastoma patients. Contrast-enhanced magnetic resonance imaging was performed before enucleation. Main outcome measures included demographics, laterality, accuracy, sensitivity, and specificity of magnetic resonance imaging in detecting high-risk pathologic features. Optic nerve invasion and choroidal invasion were seen microscopically in 34 (53%) and 28 (44%) eyes, respectively, while they were detected in magnetic resonance imaging in 22 (34%) and 15 (23%) eyes, respectively. The accuracy of magnetic resonance imaging in detecting prelaminar invasion was 77% (sensitivity 89%, specificity 98%), 56% for laminar invasion (sensitivity 27%, specificity 94%), 84% for postlaminar invasion (sensitivity 42%, specificity 98%), and 100% for optic cut edge invasion (sensitivity100%, specificity 100%). The accuracy of magnetic resonance imaging in detecting focal choroidal invasion was 48% (sensitivity 33%, specificity 97%), and 84% for massive choroidal invasion (sensitivity 53%, specificity 98%), and the accuracy in detecting extrascleral extension was 96% (sensitivity 67%, specificity 98%). Magnetic resonance imaging should not be the only method to stratify patients at high risk from those who are not, eventhough it can predict with high accuracy extensive postlaminar optic nerve invasion, massive choroidal invasion, and extrascleral tumor extension.

LncRNA AFAP1-AS1 is a prognostic biomarker and serves as oncogenic role in retinoblastoma.

The actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) has been found to serve as an oncogenic long noncoding RNA (lncRNA) in most types of human cancer. The role of AFAP1-AS1 in retinoblastoma remains unknown. The purpose of the present study is to explore the clinical significance and biological function of AFAP1-AS1 in retinoblastoma. Levels of AFAP1-AS1 expression were measured in retinoblastoma tissues and cell lines. Loss-of-function study was performed to observe the effects of AFAP1-AS1 on retinoblastoma cell proliferation, cell cycle, migration, and invasion. In our results, AFAP1-AS1 expression was elevated in retinoblastoma tissues and cell lines, and associated with tumor size, choroidal invasion, and optic nerve invasion. Moreover, high expression of AFAP1-AS1 was an independent unfavorable prognostic factor in retinoblastoma patients. The experiment in vitro suggested down-regulation of AFAP1-AS1 inhibited retinoblastoma cell proliferation, migration and invasion, and blocked cell cycle. In conclusion, AFAP1-AS1 functions as an oncogenic lncRNA in retinoblastoma.

Clinicopathologic Correlation of Choroidal Invasion in Retinoblastoma

Clinicopathologic Correlation of Choroidal Invasion in Retinoblastoma

Choroidal Invasion in Retinoblastoma Treated with Intrarterial Chemotherapy

Choroidal Invasion in Retinoblastoma Treated with Intrarterial Chemotherapy