Postlaminar Optic Nerve Invasion Research Articles

Optic nerve thickening on high-spatial-resolution MRI predicts early-stage postlaminar optic nerve invasion in retinoblastoma

Optic nerve thickening on high-spatial-resolution MRI predicts early-stage postlaminar optic nerve invasion in retinoblastoma

Adjuvant Chemotherapy Improves Survival for Children With Massive Choroidal Invasion of Retinoblastoma.

The purpose of this study was to investigate the effect of adjuvant chemotherapy on outcomes of children with massive choroidal invasion (MCI). In this study, we reviewed the 5-year relapse-free survival (RFS) and overall survival (OS) of children diagnosed with MCI, managed with or without adjuvant chemotherapy. Excluded were children with additional other high-risk features (post-laminar optic nerve invasion, scleral invasion, or overt extraocular disease). Of 3566 children diagnosed with retinoblastoma, 2023 had enucleation, and 60eyes of 60 children had pathology showing MCI without concomitant high-risk features. Enucleation was primary (22, 37%), or secondary (38, 63%) after failed eye salvage. Adjuvant systemic chemotherapy (median = 4, range = 1-8 cycles) was given to 48 of 60 (80%) children; 12 of 60 (20%) children had no adjuvant therapy. Five-year RFS was 88.5% (95% confidence interval [CI] = 79.7%-97.3%) and 5-year OS was 90.1% (95% CI = 81.7%-98.5%). Pre-enucleation chemotherapy did not affect RFS (89.7% vs. 75.0%; P = 0.657). Adjuvant chemotherapy improved RFS (97.2% vs. 55.6%; P < 0.001) and OS (97.2% vs. 66.7%; P < 0.001). In subgroup analysis, adjuvant chemotherapy improved RFS for both primarily enucleated (5-year RFS 100% vs. 50.0%; P = 0.002) and secondarily enucleated children (5-year RFS 95.8% vs. 60.0%; P = 0.005). The number of children treated with adjuvant chemotherapy to prevent one post-enucleation systemic relapse or death is three. Adjuvant chemotherapy significantly decreased the risk of tumor relapse and death for children with pathological MCI. For every three children treated with adjuvant chemotherapy, one systemic relapse or death could be prevented.

Can Enhancement Pattern in Normal-Sized Optic Nerves on Magnetic Resonance Imaging Better Predict Tumor Invasion in Retinoblastoma Eyes?

Introduction: Optic nerve (ON) enhancement alone without ON thickening on contrast-enhanced magnetic resonance imaging (CE-MRI) can be associated with post-laminar optic nerve invasion (PLONI) in eyes with group E retinoblastoma. A few case reports and retrospective studies in the literature show a poor correlation between ON enhancement on MRI and ON invasion on histopathological examination (HPE). There is no universal consensus on the management of such cases. It is desirable that the presence and extent of a true ON invasion be reliably picked up before planning upfront enucleation in order to avoid stage II disease. Methods: In a prospective study conducted at a tertiary eye care center in North India, all retinoblastoma patients presenting with ON enhancement on imaging were evaluated. Demographic and imaging details, histopathological findings, and treatment details were recorded. The length and pattern of enhancement noted on MRI were correlated with histopathology. Follow-up was done till the end of the study period. Results: Six group E retinoblastoma eyes were evaluated. 3 eyes (50%) showed solid enhancement, 2 eyes (33.33%) had tram track pattern and 1 eye (16.66%) showed punctate enhancement pattern on CE-MRI. On histopathology, 5 (83.33%) cases showed PLONI and all 6 (100%) had ON head infiltration. The cut end of the ON was free in all cases. On correlating MRI and HPE, all eyes with solid enhancement pattern showed PLONI, of which 2/3 (66.6%) had diffuse ON infiltration. Only 50% of eyes with tram track patterns showed PLONI. The case which showed a punctate enhancement pattern showed focal infiltration by tumor cells with vacuolated cytoplasm on HPE. At the last follow-up, all patients were alive and free of disease. Conclusion: ON enhancement patterns may make it more predictive for PLONI on HPE. Solid enhancement pattern appears to correlate better with the extent of ON invasion on HPE, and longer lengths of solid ON enhancement may be considered for neoadjuvant chemotherapy rather than upfront enucleation.

Correlating somatic copy number alteration in aqueous humour cfDNA with chemotherapy history, eye salvage and pathological features in retinoblastoma

BackgroundThis study determined to probe the potential association between somatic copy number alteration (SCNA) in retinoblastoma (RB) aqueous humour (AH) and pathological high-risk factors, clinical features and previous chemotherapy history.MethodsSingle-centre...

A comparison of high risk pathological features between primary and secondary enucleation for retinoblastoma.

To compare the risk and pattern of High-Risk Pathologic Features (HRPF) in retinoblastoma between primary and secondary enucleation. A retrospective analysis of 121 eyes from 118 patients who underwent enucleation at the King Hussein Cancer Center (KHCC) Amman, Jordan, between November 2009 and January 2020. Demographic information, tumor stage, time from diagnosis-to-enucleation, results of pathology, metastasis, and mortality were retrieved. Patients in the secondary group (49/121 eyes, 40%) were considerably younger at diagnosis (p = 0.0014), had bilateral disease (p = 0.0001), and had less-progressed disease at presentation (p = 0.016) compared to the primary enucleation. Primarily enucleated eyes were more-likely to have massive choroidal invasion (p = 0.0315) and post-laminar optic nerve invasion (p = 0.027), in spite of the finding that the overall prevalence of HRPF was similar between the two groups (35.5 percent vs. 37.5 percent; p = 0.585). The likelihood of anterior chamber invasion, was considerably higher in secondary enucleated eyes (p = 0.013). We evaluated primary and secondary enucleation for each subgroup (D and E) of the International Intraocular Retinoblastoma Classification (IIRC) and found the prevalence of HRPF was comparable (p = 0.58, 1.0, respectively). The difference in time between diagnosis-to-enucleation in secondary enucleation did not predict HRPF (p = 0.50). There was no discernible difference between primary and secondary enucleated eyes in terms of metastasis or survival (p = 0.156 and 0.44, respectively). Systemic chemotherapy has the ability to reduce the extent of tumor expansion that has been pathologically identified. Primary and secondary enucleated eyes are comparable in low metastatic risk only when strict examination and management guidelines are followed.

Association of choroidal invasion with retinoblastoma survival rates

To assess the impact of varying levels of choroidal invasion on survival from retinoblastoma. A retrospective nationwide analysis of retinoblastoma cases diagnosed between 2004-2016 using the Surveillance, Epidemiology, and End Results database was conducted. Overall survival, cause-specific survival, and all-cause mortality risk were assessed as primary outcomes. A total of 393 retinoblastoma patients were included, of whom 268 (68.2%) had no choroidal invasion, 91 (23.2%) had focal choroidal invasion, and 34 (8.7%) had massive choroidal invasion on enucleation. A total of 6 deaths occurred throughout an average follow-up period of 72.2 ± 47.1 months: 4 deaths were cancer related. Adjusted Cox regression demonstrated higher all-cause mortality in patients with massive choroidal invasion (HR, 41.29; 95% CI, 4.05-420.49; P = 0.002) relative to those without choroidal invasion; however, those with focal choroidal invasion (HR, 2.69; 95% CI, 0.17-43.09; P = 0.484) demonstrated no difference in all-cause mortality. On further stratification by level of optic nerve invasion (ONI), all cancer-related deaths (4/4) were found to have occurred in patients with massive choroidal invasion and concomitant postlaminar ONI (PLONI). Patients with massive choroidal invasion without PLONI demonstrated 5-year overall and cause-specific survival of 100%, whereas patients with massive choroidal invasion and PLONI demonstrated 5-year overall and cause-specific survival of 80.2%. All retinoblastoma-related deaths occurred in patients with both massive choroidal invasion and PLONI. These findings could not establish that massive choroidal invasion is an independent risk factor for poor outcome.

Imaging techniques for ocular neoplasia

Background: Novel ocular imaging modalities have greatly impacted the diagnosis and management of different types of ocular neoplasia. In this narrative review, we summarize the practical features of popular and novel imaging modalities for ocular tumors.&#x0D; Methods: Four databases, including PubMed/MEDLINE, Web of Science, Scopus, and Google Scholar, were searched from January 1, 2000 to August 31, 2022. Articles reporting different imaging modalities for diagnosing or monitoring treatment responses of ocular tumors were extracted using various combinations of the following keywords: ocular neoplasia, positron emission tomography or PET, single-photon emission computed tomography or SPECT, optical coherence tomography or OCT, OCT angiography or OCTA, computed tomography or CT, ultrasonography or US, ultrasound biomicroscopy or UBM, and magnetic resonance imaging or MRI.&#x0D; Results: Various ocular imaging modalities had different accuracies as adjunctive tools for detecting or managing ocular tumors. Anterior ultra-high-resolution optical coherence tomography (OCT) could be used to evaluate images with &lt; 5-µm resolution. OCT angiography provided deeper insight into retinal vascular changes associated with the malignant transformation of choroidal melanoma. OCT in children altered the diagnosis of suspicious retinoblastoma in 3% of the cases and treatment plan in 11% of the cases. While positron-emission tomography (PET)/computed tomography (CT) allowed the detection of metastatic lesions of choroidal melanoma by full-body scanning, single-photon emission CT was more sensitive compared to PET in detecting choroidal melanoma. Ultrasound biomicroscopy, with an accuracy exceeding 92.5%, could detect retinal calcification in lesions measuring 2–3 mm. Magnetic resonance imaging (MRI) had better contrast compared to ultrasound biomicroscopy and higher sensitivity compared to CT in detecting post-laminar optic nerve invasion. However, MRI had a lower spatial resolution compared to OCT. Further development of imaging modalities and their application in drug development would improve the treatment of ocular tumors.&#x0D; Conclusions: Although diagnosing ocular tumors depend on clinical characteristics, innovations in ocular imaging have enabled early diagnosis and timely, appropriate management of ocular neoplasia, which are conducive to favorable visual outcomes and increased life expectancy. Further systematic reviews and meta-analyses of primary studies focusing on a specific imaging modality in ocular neoplasia could precisely determine the diagnostic accuracy of each imaging modality to better guide eye practitioners with efficient diagnostic or therapeutic approaches for these sight- or life-threatening entities. Imaging modalities may play a major role in drug development in the future.

Diffusion-Weighted MR Imaging of the Optic Nerve Can Improve the Detection of Post-Laminar Optic Nerve Invasion from Retinoblastoma.

Post-laminar optic nerve invasion (PLONI) is a high-risk factor for the metastasis of retinoblastoma (RB). Unlike conventional MRI, diffusion-weighted imaging (DWI) reflects histopathological features, and may aid the assessment of PLONI. To determine the value of conventional MRI plus DWI in detecting PLONI in RB patients. Retrospective. Eighty-three RB patients, including 28 with histopathologically proven PLONI and 55 without PLONI. 3.0 T, precontrast axial T1-weighted and T2-weighted imaging, DWI, and postcontrast axial, coronal, and oblique-sagittal T1-weighted imaging. PLONI was assessed using post-enucleation histology and preoperative MRI features (optic nerve signal intensity, enlargement, and enhancement on conventional MRI, and apparent diffusion coefficient [ADC] of the optic nerve on DWI) evaluated by three observers. MRI features suggesting the presence of PLONI were identified using univariable and multivariable analyses. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to analyze diagnostic performance. Optic nerve enhancement and low ADC of the optic nerve were significant indicators of PLONI. ROC curve analysis showed that the AUC of the combination of these two features for detecting PLONI was 0.87 (95% confidence interval [CI]: 0.78-0.93). The diagnostic performance of this model was significantly superior to that of optic nerve enhancement alone (0.76, 95% CI: 0.65-0.85) and marginally superior to that of the ADC of the affected optic nerve (0.78, 95% CI: 0.68-0.87, P=0.051). Conventional MRI combined with DWI can improve the detection of PLONI in RB patients over conventional MRI alone. 3 Technical Efficacy: Stage 2.

High-Risk Histopathologic Features of Retinoblastoma Treated at a Tertiary Hospital in West Java, Indonesia

Purpose: To evaluate the histopathological characteristics of clinically advanced retinoblastoma (RB) and its relationship with tumor differentiation. Methods: This was a cross-sectional study of primary enucleated group D/E intraocular RB using medical records from 2017 to 2020 in a tertiary referral hospital. Cases with incomplete histopathological results were excluded. Tumors were classified into well, moderately, and poorly differentiated and undifferentiated. High-risk histopathological features were classified as per Thaung and Karaa [Community Eye Health. 2018;31(101):17–3]. Results: This study included 121 patients (129 eyes), of which 32.2% were diagnosed at 25–36 months. High-risk features (HRFs) were found in 100/129 eyes, and of 73 complete histopathological results, the 2 most common HRFs were postlaminar optic nerve invasion and massive choroidal invasion. RB was poorly differentiated in 69.9% and well differentiated in 12.3% of eyes. There was no statistically significant association between any HRFs and tumor differentiation, with age >2 years associated with tumor differentiation (p < 0.05). Conclusion: The frequency of HRFs is 77.5% of primary enucleated eyes, mainly poorly and undifferentiated cells, particularly in children aged >2 years old.

Accuracy of Computed Tomography and Magnetic Resonance Imaging for Detection of Pathologic Risk Factors in Patients Diagnosed with Retinoblastoma

ABSTRACT Aim: To assess and compare the diagnostic accuracy of magnetic resonance imaging (MRI) and computed tomography (CT) for detecting the extent of tumor invasion in eyes with advanced retinoblastoma prior to enucleation using histopathologic analysis as a reference. Methods: A total of 56 patients (68 eyes) enucleated for retinoblastoma were reviewed. Eyes with complete data (CT 28, MRI 16) were included for analysis. Imaging data were reviewed by a pediatric radiologist, blinded to histopathology results. Four high-risk factors which included scleral, choroidal, anterior eye segment invasion, and postlaminar optic nerve invasion were assessed. Results: For CT, the diagnostic odds ratio (DOR), sensitivity, and specificity for detecting postlaminar optic nerve invasion were 1.7%, 25%, and 83.3%. Choroidal invasion was correctly identified in only 2 of 10 eyes (DOR 0.5, sensitivity 20%, specificity 66.7%). For scleral invasion, CT showed a diagnostic ratio of 1.5%, sensitivity 40%, specificity 69.6% whereas for anterior segment invasion DOR was 9.2%, sensitivity 100%, and specificity 65.4%. MRI showed a higher DOR for detecting postlaminar optic nerve invasion of 39%, sensitivity 77.8%, and specificity 100%. Choroidal and scleral invasion on MRI had a DOR of 6.5% (sensitivity 25%, specificity 100%) and 6% (sensitivity 33.3%, specificity 92.3%) respectively while DOR for anterior segment invasion was 1.3% (sensitivity 50%, specificity 57.1%). Conclusion: CT showed a poor diagnostic accuracy for all four high-risk factors in advanced retinoblastoma and therefore may not be a useful tool for assessment of tumor extension. For MRI, detection of postlaminar optic nerve invasion was moderately accurate although less accurate for detection of other risk factors. Decision-making for each child should not be based on any single parameter but rather on consideration of clinical factors in combination with radiologic findings.

Adjuvant therapy of histopathological risk factors of retinoblastoma in Europe: A survey by the European Retinoblastoma Group (EURbG).

Advanced intraocular retinoblastoma can be cured by enucleation, but spread of retinoblastoma cells beyond the natural limits of the eye is related to a high mortality. Adjuvant therapy after enucleation has been shown to prevent metastasis in children with risk factors for extraocular retinoblastoma. However, histological criteria and adjuvant treatment regimens vary and there is no unifying consensus on the optimal choice of treatment. Data on guidelines for adjuvant treatment in European retinoblastoma referral centres were collected in an online survey among all members of the European Retinoblastoma Group (EURbG) network. Extended information was gathered via personal email communication. Data were collected from 26 centres in 17 countries. Guidelines for adjuvant treatment were in place at 92.3% of retinoblastoma centres. There was a consensus on indication for and intensity of adjuvant treatment among more than 80% of all centres. The majority of centres use no adjuvant treatment for isolated focal choroidal invasion or prelaminar optic nerve invasion. Patients with massive choroidal invasion or postlaminar optic nerve invasion receive adjuvant chemotherapy, while microscopic invasion of the resection margin of the optic nerve or extension through the sclera are treated with combined chemo- and radiotherapy. Indications and adjuvant treatment regimens in European retinoblastoma referral centres are similar but not uniform. Further biomarkers in addition to histopathological risk factors could improve treatment stratification. The high consensus in European centres is an excellent foundation for a common European study with prospective validation of new biomarkers.

Evaluation the risk of optic nerve invasion associated with optic nerve obscuration in advanced retinoblastoma

Objective: To evaluate the potential association between optic nerve invasion and optic nerve obscuration during treatment of advanced retinoblastoma. Methods: Retrospective case series study. Medical records of 77 patients (77 eyes) with advanced retinoblastoma (Group D/E) who were treated with primary or secondary enucleation in the Ophthalmology Department of Peking University People's Hospital from January 1st 2012 to December 31th 2015 were retrospectively reviewed. RetCam photographs under general anesthesia at diagnosis and each subsequent follow-up were evaluated for complete obscuration of the optic nerve. The primary endpoints included prelaminar invasion, postlaminar invasion and optic nerve transection invasion. Group difference was calculated with chi-square. Results: There were 46 boys and 31 girls in the study. The mean age at the first diagnosis was (27.1±22.1) months. The optic nerve was obscured in 62 eyes (80.5%) at the first diagnosis and 61 eyes (79.2%) at the last ocular examination prior to enucleation. Twenty-nine eyes (37.7%) underwent primary enucleation. Forty-eight eyes (62.3%) were treated with eye-preserving therapy, followed by enucleation. Fourteen eyes (18.2%) were in Group D and 63 eyes (81.8%) were in Group E. Histopathologic analysis of enucleated eyes without optic nerve obscuration (16 eyes) showed prelaminar invasion in 7 eyes, postlaminar invasion in 2 eyes and optic nerve transection invasion in 0 eyes. Histopathologic analysis of enucleated eyes with optic nerve obscuration (61 eyes) showed prelaminar invasion in 26 eyes, postlaminar invasion in 9 eyes and optic nerve transection invasion in 4 eyes. The difference between two groups did not achieve statistical significance (P=0.935, 1.000, 0.296). Histopathologic analysis of enucleated eyes with persistent complete obscuration of the optic nerve showed a high risk factor in 10 eyes (10/40), while in 1 eye (1/8) the optic nerve was visible at the initial presentation and obscured before secondary enucleation (P=0.529). Conclusion: Optic nerve obscuration at the last examination prior to enucleation may not be associated with postlaminar optic nerve invasion in advanced retinoblastoma. (Chin J Ophthalmol, 2020, 56: 681-687).

Diagnostic performance of MRI of post-laminar optic nerve invasion detection in retinoblastoma: A systematic review and meta-analysis.

Preoperative MRI detection of post-laminar optic nerve invasion (PLONI) offers guidance in assessing the probability of total tumor resection, an estimation of the extent of surgery, and screening of candidates for eye-preserving therapies or neoadjuvant chemotherapies in the patients with retinoblastoma (RB). The purpose of this systematic review and meta-analysis was to evaluate the diagnostic performance of MRI for detecting PLONI in patients with RB and to demonstrate the factors that may influence the diagnostic performance. Ovid-MEDLINE and EMBASE databases were searched up to January 11, 2020, for studies identifying the diagnostic performance of MRI for detecting PLONI in patients with RB. The pooled sensitivity and specificity of all studies were calculated followed by meta-regression analysis. Twelve (1240 patients, 1255 enucleated globes) studies were included. The pooled sensitivity was 61%, and the pooled specificity was 88%. Higgins I2 statistic demonstrated moderate heterogeneity in the sensitivity (I2= 72.23%) and specificity (I2= 78.11%). Spearman correlation coefficient indicated the presence of a threshold effect. In the meta-regression, higher magnetic field strength (3T than 1.5T), performing fat suppression, and thinner slice thickness (< 3mm) were factors causing heterogeneity and enhancing diagnostic power across the included studies. MR imaging was demonstrated to have acceptable diagnostic performance in detecting PLONI in patients with RB. The variation in the magnetic field strength and protocols was the main factor behind the heterogeneity across the included studies. Therefore, there is room for developing and optimizing the MR protocols for patients with RB.

High Resolution MR Imaging guidelines in retinoblastoma: prospective study correlated with histopathological results

BackgroundRetinoblastoma is the commonest intraocular pediatric neoplasm. With the recent scope of shifting to eye preserving therapies, preoperative MRI is becoming the primary noninvasive diagnostic method to confirm the diagnosis, assess the ocular coats and optic nerve, and detect extraocular tumor extension and intracranial primitive neuroectodermal tumor associated with retinoblastoma as funduscopy and ultrasound have limitations. Diffusion-weighted images (DWIs) detect abnormalities based on differences in tissue cellularity. Echoplanar-based (EP) DWI results in susceptibility artifacts and geometric distortions, which make DWI of the orbit a challenging technique. The purpose of our study is to evaluate preoperative magnetic resonance (MR) imaging diagnostic merits and indices in patients with retinoblastoma.ResultsFifty-eight eyes were prospectively reviewed in 30 girls and 27 boys (mean age at diagnosis was 23 months ± 18.9) with retinoblastoma by two radiologists on T1-weighted images, fat saturated T2-weighted images, DWIs, ADC, and postcontrast T1-weighted MR images with and without fat suppression. All patients included were primarily treated by surgical enucleation; one girl had bilateral enucleation. MRI shows accuracy, sensitivity, specificity, NPV, and PPV; 86.2%, 95.3%, 60%, 81.8%, and 87.2% respectively for choroidal invasion; 75.8%, 58.8%, 82.9%, 83%, and 58.8% in prelaminar optic nerve invasion; and 86.2%, 85.2%, 87%, 87%, and 85% in postlaminar optic nerve invasion (PLONI) respectively. For sclera and extrascleral tumor invasion, MRI show accuracy, sensitivity, specificity, NPV, and PPV of 93%, 55.6%, 100%, 92.5%, 100%, and 98.3%, 100%, 98%,100%, 80% respectively. On DWIs, the vital solid tumor shows hyperintense signal compared to the vitreous. The difference between the mean ADC value of the solid enhancing tumor (0.3[0.12–0.8] × 10−3 s/mm2) and nonenhancing necrotic parts (1.4[1.0–1.8] × 10−3 s/mm2) was statistically significant (p < 0.001). No correlation was found between the ADC values and high risk features for metastasis. Abnormal anterior chamber enhancement shows no statistically significant correlation with main MRI and histopathology findings. Maximum tumor diameter in mm show statistically significant correlation with postlaminar optic nerve invasion (ρ = .002) and choroidal invasion (ρ = .007). Sensitivity and specificity of different tumor size cutoff values are calculated using the ROC analysis.ConclusionHigh-resolution ocular MR imaging can reliably detect postlaminar optic nerve invasion, choroid, and extrascleral invasion; meanwhile, it shows low sensitivity in prelaminar optic nerve, ciliary body, and sclera invasion. Significantly lower ADC values in viable tumor than necrotic parts are recorded.

Diagnosis of Postlaminar Optic Nerve Invasion in Retinoblastoma With MRI Features.

Retinoblastomas (RBs) with postlaminar optic nerve invasion (PLONI) increases the risk of local recurrence or systemic metastasis. Most MRI studies on PLONI focused on optic nerve enhancement and tumor size, with reported relatively high specificity (84-98%) but low sensitivity (37-78%), which shows room for improvement, especially with regard to sensitivity. To evaluate the diagnostic performance for detecting PLONI with RB using MRI features. Retrospective. Fifty patients with histopathologic PLONI and 70 patients without PLONI of RB. 1.5T and 3.0T, precontrast axial T1 -weighted and T2 -weighted, postcontrast axial, coronal and oblique-sagittal T1 -weighted. The eyes were histopathologically analyzed and the preoperative MRI features of the eyes were independently evaluated by three observers. MRI features suggesting the presence of PLONI were identified by univariate and multivariable analysis. Receiver operating characteristic curve (ROC) and the area under the curve (AUC) were used to analyze diagnostic performance. Significant independent diagnostic factors for PLONI include: 1: Bilateral tumor (odds ratio [OR], 15.32; 95% confidence interval [CI]: 1.63-143.51); 2: Tumor with total coverage of the optic disk (OR, 6.43; 95% CI: 1.04-39.79); and 3: Optic nerve enhancement (OR, 8.43; 95% CI: 3.50-20.31). On the other hand, isointense signal of tumor on T2 WI (OR, 0.30; 95% CI: 0.12-0.75) was an independent diagnostic factor in excluding PLONI. ROC analysis showed AUC of 0.84 (95% CI: 0.77-0.91, P < 0.0001) for PLONI. Based on the cutoff of maximum Youden index, the sensitivity, specificity, and accuracy were 82%, 73%, and 77%, respectively. MRI features of RB showed a strong association with PLONI. The model of MRI features demonstrated promising diagnostic performance in detecting PLONI. 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:1045-1052.

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.

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.