Retinoblastoma is the most common primary intraocular tumor of childhood. Accurate diagnosis at an early stage is important to maximize patient survival, globe salvage, and visual acuity. Management of retinoblastoma is individualized based on the presenting clinical and imaging features of the tumor, and a multidisciplinary team is required to optimize patient outcomes. The neuroradiologist is a key member of the retinoblastoma care team and should be familiar with characteristic diagnostic and prognostic imaging features of this disease. Furthermore, with the adoption of intra-arterial chemotherapy as a standard of care option for globe salvage therapy in many centers, the interventional neuroradiologist may play an active role in retinoblastoma treatment. In this review, we discuss the clinical presentation of retinoblastoma, ophthalmic imaging modalities, neuroradiology imaging features, and current treatment options.

http://www.ajnr.org/content/ajnr/42/4/618.full.pdf

Retinoblastoma: What the Neuroradiologist Needs to Know.

Retinoblastoma (RB) is the most common ocular cancer, and it typically presents before the age of 5 years in over 90% of cases. In high resource countries, RB patients tend to survive and retain their sight. This is not the case in low-resource countries because of late presentation and delayed intervention arising mostly from sociocultural and socioeconomic challenges. RB has no gender or racial predilection; the incidence is estimated as 1:16,000-1:18,000 live-births or 11/1 million children under 5 years. Most of the world's RB cases are found in Asia and Africa while most RB treatment centres are in America and Europe. RB is easy to detect by caregivers as a glowing white 'cat eye reflex' at night or when captured on camera. Health workers at primary care level can detect RB in early life if red reflex test and/or squint (Hirschberg) tests are deployed as part of wellness checks done especially during routine immunisation and well-baby clinics in the first 24 months of life. In most cases of RB, biopsies for histological confirmation are not required for diagnosis and treatment decisions to be made. Clinical information, ophthalmic evaluation and imaging modalities are typically used. There have been significant changes in the management of RB using various treatment modalities such as enucleation with orbital implant, use of chemotherapy delivered through intravenous, intravitreal, periocular and intra-arterial routes and targeted treatment with laser, cryotherapy and brachytherapy. Algorithm for management and development of the national RB program within the context of a low-resource country is presented from review of data extracted from Mendeley library, PubMed library, Google Scholar and One Network; full-text articles were mostly retrieved through the American Academy of Ophthalmology.

Contemporary management of retinoblastoma in the context of a low-resource country.

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 (3 T than 1.5 T), performing fat suppression, and thinner slice thickness (< 3 mm) 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.

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

As described recently, intravenously injected gadolinium-based contrast agent (GBCA) penetrates into the anterior eye chamber (AC) and is drained from the retina to the distal optic nerve (ON) along perivascular spaces, which serves retinal homeostasis and was termed the orbital glymphatic system (GS). Independently, AC enhancement predicted ON infiltration, a major risk factor for advanced retinoblastoma (RB), in a small RB patient cohort. We aimed to review the supposed imaging biomarker for ON infiltration in a large RB cohort and with respect to the recently described orbital GS.This IRB-approved retrospective single-center study encompassed 539 orbital MRIs performed with an orbital coil and with the children under general anesthesia. Differences of signal intensity ratios (∆SIRs) of the AC to the lens were determined between non-contrast and GBCA-enhanced T1-weighted images and were correlated with histopathologic presence of ON infiltration.∆SIR of the RB eye was an independent, significant predictor for ON invasion in multivariate analysis with adjustment for tumor size (p < 0.05) and increased with infiltration level.GBCA enhancement of the AC predicts ON infiltration. This might be caused by impairment of the orbital glymphatic system, which is supposed to clear toxic metabolites from the retina to the postlaminar ON. In RB with ON infiltration, this efflux path is likely to be inhibited, which is supposed to result in disturbed retinal homeostasis, release of vascular endothelial growth factor, and iris neovascularization, which increases penetration of GBCA into the AC.• Infiltration of the optic nerve can be predicted by anterior chamber enhancement after intravenous MRI contrast agent administration. • Increased anterior chamber enhancement in retinoblastoma with optic nerve infiltration might result from dysfunction of the orbital glymphatic system with disturbance of retinal homeostasis and consecutive iris neovascularization. 

/pdf/anterior-chamber-enhancement-predicts-optic-nerve-1wvf0i84.pdf

Anterior chamber enhancement predicts optic nerve infiltration in retinoblastoma

All national and international pediatric guidelines universally prescribe meticulous bilirubin screening for neonates as a critical measure to mitigate the incidence of acute bilirubin encephalopathy (ABE) and Kernicterus. The prevailing gold standard for jaundice detection in neonates necessitates invasive blood collection, followed by subsequent biochemical testing. While the invasive procedure provides dependable bilirubin measurements and continues to be the sole gold standard diagnostic method for assessing bilirubin concentration. There exists a pressing need to innovate non-invasive screening tools that alleviate the sampling stress endured by newborns, mitigate iatrogenic anemia, and expedite the turnaround time for obtaining results. The exploration of non-invasive modalities for bilirubin measurements is gaining momentum, driven by the overarching goal of minimizing the number of pricks inflicted upon neonates, thereby rendering screening a swift, efficient, comfortable, and dependable process. This comprehensive review article delves extensively into the array of non-invasive approaches and digital solutions that have been proposed, implemented, and utilized for neonatal bilirubin screening, with a particular emphasis on their application in low-resource settings. Within this context, the review sheds light on the existing methodologies and their practical applications, with a specific focus on transcutaneous bilirubin meters. Moreover, it underscores the prevailing open challenges in this domain and outlines potential directions for future research endeavors. Notably, the review underscores the imperative need for robust educational programs targeted at both families and healthcare personnel to expedite the process of seeking timely care for neonatal jaundice. Additionally, it underscores the necessity for the development of enhanced screening and diagnostic tools that can offer greater accuracy in clinical practice.

Demystifying non-invasive approaches for screening jaundice in low resource settings: a review

To determine the diagnostic accuracy of conventional MRI in detecting tumour invasion of advanced intraocular retinoblastoma and to correlate ADC values with high-risk prognostic parameters. The sensitivities, specificities, positive predictive values (PPV), negative predictive values (NPV) and accuracies of MRI in detecting tumour-extent parameters of 63 retinoblastomas were determined. Furthermore, ADC values were correlated with high-risk prognostic parameters. MRI detected postlaminar optic nerve with a sensitivity of 73.3% (95% CI 44.9–92.2%) and a specificity of 89.6% (77.3–96.5%), while the specificity for choroidal invasion was only 31.8% (13.9-54.9%). Likewise, MRI failed to predicted early optic nerve invasion in terms of low sensitivity and PPV. In contrast, scleral and ciliary body invasion could be correctly excluded with high NPV. ADC values were significantly lower in patients with undifferentiated tumours, large tumour size, as with optic nerve and scleral invasion (all p < 0.05). However, no correlation was found between ADC values and the degree of choroidal or ciliary body infiltration. Additionally, ADC values were negatively correlated with Ki-67 index (r = −0.62, P = 0.002). Conventional MRI has some limitations in reliably predicting microscopic infiltration, with the diagnostic efficiency showing room for improvement, whereas ADC values correlated well with certain high-risk prognostic parameters for retinoblastoma. • Conventional MRI failed to predicted microscopic infiltration of the retinoblastoma. • Scleral and ciliary body invasion could be excluded with high NPV. • ADC values correlated well with some high-risk pathological prognostic parameters.

Correlation between conventional MR imaging combined with diffusion-weighted imaging and histopathologic findings in eyes primarily enucleated for advanced retinoblastoma: a retrospective study.

Background Since most infants are usually discharged before age 48–72 hours, peak bilirubin levels will almost always occur after discharge. Parents may be the first to observe the onset of jaundice after discharge, but visual assessment is unreliable. The jaundice colour card (JCard) is a low-cost icterometer designed for the assessment of neonatal jaundice. The objective of this study was to evaluate parental use of JCard to detect jaundice in neonates. Methods We conducted a multicentre, prospective, observational cohort study in nine sites across China. A total of 1161 newborns ≥35 weeks of gestation were enrolled in the study. Measurements of total serum bilirubin (TSB) levels were based on clinical indications. The JCard measurements by parents and paediatricians were compared with the TSB. Results JCard values of parents and paediatricians were correlated with TSB (r=0.754 and 0.788, respectively). The parents’ and paediatricians’ JCard values 9 had sensitivities of 95.2% vs 97.6% and specificities of 84.5% vs 71.7% for identifying neonates with TSB ≥153.9 µmol/L. The parents’ and paediatricians’ JCard values 15 had sensitivities of 79.9% vs 89.0% and specificities of 66.7% vs 64.9% for identifying neonates with TSB ≥256.5 µmol/L. Areas under the receiver operating characteristic curves of parents for identifying TSB ≥119.7, ≥153.9, ≥205.2, and ≥256.5 µmol/L were 0.967, 0.960, 0.915, and 0.813, respectively, and those of paediatricians were 0.966, 0.961, 0.926 and 0.840, respectively. The intraclass correlation coefficient was 0.933 between parents and paediatricians. Conclusion The JCard can be used to classify different levels of bilirubin, but it is less accurate with high bilirubin levels. The JCard diagnostic performance of parents was slightly lower than that of paediatricians.

/pdf/parental-detection-of-neonatal-jaundice-using-a-low-cost-2t6qg7hj.pdf

Parental detection of neonatal jaundice using a low-cost colour card: a multicentre prospective study

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Correlation between conventional MR imaging combined with diffusion-weighted imaging and histopathologic findings in eyes primarily enucleated for advanced retinoblastoma: a retrospective study.

Parental detection of neonatal jaundice using a low-cost colour card: a multicentre prospective study