Retinoblastoma Survival Following Primary Enucleation by AJCC Staging

Primary enucleation of the eye with retinoblastoma is a widely accessible, life-saving treatment for retinoblastoma. This study evaluated the survival of patients following primary enucleation based on AJCC 8th edition staging. Included were 700 consecutive patients (700 eyes) treated with primary enucleation at 29 Chinese treatment centers between 2006 and 2015. Excluded were patients with less than one year follow-up, bilateral retinoblastoma, clinical evidence of extraocular disease at diagnosis, or prior focal or systemic therapy. The 5-year overall survival was 95.5%, and 5-year disease-specific survival (DSS) was 95.7%. Survival was better when enucleation was <26 days from diagnosis than delayed >26 days (96.1% vs. 86.9%; p = 0.017). Patients with eyes presenting with raised intraocular pressure with neovascularization and/or buphthalmos (cT3c) had worse 5-year DSS (87.1%) than those without (cT2b, 99.1%; cT3b, 98.7%; cT3d, 97.2%) (p < 0.05). The 5-year DSS based on pathological staging was pT1 (99.5%), pT2a (95.5%), pT3a (100%), pT3b (93.0%), pT3c/d (92.3%), and pT4 (40.9%). Patients with pT3 pathology who received six cycles of adjuvant chemotherapy had better 5-year DSS (97.7%) than those with no chemotherapy (88.1%; p = 0.06) and those who underwent 1–3 cycles (86.9%, p = 0.02) or 4–5 cycles (89.3%, p = 0.06). Patients with pT4 pathology who received six cycles of chemotherapy had better 5-year DSS than those with 0–5 cycles (63.6% vs. 16.7%; p = 0.02). Prompt primary enucleation yielded high long-term survival for children with retinoblastoma. The AJCC 8th edition staging is predictive of survival.

Characterization of The Portuguese Population Diagnosed With Retinoblastoma

PurposeThe purpose of this study is to characterize demographically and genetically the Portuguese population with retinoblastoma; to report the clinical stage at presentation and its impact on survival and ocular preservation rate and, finally, to assess the incidence of retinoblastoma in Portugal.MethodsCohort retrospective observational study including children consecutively diagnosed with retinoblastoma at the Portuguese National Referral Center of Intraocular Tumors, between October 2015 and October 2020ResultsTwenty-eight children were diagnosed with retinoblastoma at our center, 15 hereditary from which 12 presented with bilateral retinoblastoma and 3 were unilateral. The overall mean age at diagnosis was 13.6 ± 11.1 months with hereditary retinoblastomas diagnosed slightly earlier at 9.6 ± 6.3 months. A familial history of retinoblastoma was found in only 4 (14.3%) of the cases. A pathogenic mutation in the RB1 gene was found in 13 (46.4%) of the children. The most frequent sign at referral was leukocoria in 71.4% of patients. Considering the ICRB classification of the tumors, 84.6% of non-hereditable hereditary retinoblastomas were referred to our center in advanced stages. In the group of hereditable retinoblastomas 86.7% presented with one of the eyes with advanced intraocular retinoblastoma. Fourteen children had one eye enucleated due to retinoblastoma. No deaths were registered during the study period. Considering the incidence analysis, we registered a year-of-birth controlled incidence analysis of 4.04 per 100.000 living births (IC 95% 1.59 – 6.49).Conclusion This is the first characterization of the Portuguese Population diagnosed with Retinoblastoma in the National Reference Center.

Inter-eye genomic heterogeneity in bilateral retinoblastoma via aqueous humor liquid biopsy

Germline alterations in the RB1 tumor suppressor gene predispose patients to develop retinoblastoma (RB) in both eyes. While similar treatment is given for each eye, there is often a variable therapeutic response between the eyes. Herein, we use the aqueous humor (AH) liquid biopsy to evaluate the cell-free tumor DNA (ctDNA) from each eye in a patient with bilateral RB. Despite the same predisposing germline RB1 mutation, AH analysis identified a different somatic RB1 mutation as well as separate and distinct chromosomal alterations in each eye. The longitudinal alterations in tumor fraction (TFx) corresponded to therapeutic responses in each eye. This case demonstrates that bilateral RB tumors develop separate genomic alterations, which may play a role in tumorigenesis and prognosis for eye salvage. Identifying these inter-eye differences without the need for enucleated tumor tissue may help direct active management of RB, with particular usefulness in bilateral cases.

A Rare Case of Acute Hemorrhagic Retinopathy Following Intravitreal Melphalan Injection for Persistent Vitreous Seeds in Retinoblastoma

Purpose: This report describes a case of acute occlusive hemorrhagic complication after intravitreal melphalan for vitreous seeds in retinoblastoma. Methods: A case report is presented. Results: Intravitreal melphalan has been used extensively for vitreous seeds in retinoblastoma. Although melphalan is relatively safe at optimal doses, it can sometimes cause inadvertent complications like hemorrhagic events if the drug is administered close to the retina or in more pigmented eyes. We report a case of a 5-month-old patient with bilateral retinoblastoma who underwent enucleation of the right eye and 2 intravitreal melphalan injections in the left eye (20 µg/0.02 mL) at a 1-month interval for persistent vitreous seeds. After the second injection, there was a sudden decrease in the child’s visual acuity in the left eye, and the retina showed multiple intraretinal hemorrhages and diffuse chorioretinal atrophy. Conclusion: Intravitreal melphalan may cause acute hemorrhagic complications after intravitreal use for retinoblastoma seeds, especially in pigmented eyes.

Bioinformatics analysis of key biomarkers for retinoblastoma

Objective To identify key genes involved in occurrence and development of retinoblastoma. Methods The microarray dataset, GSE5222, was downloaded from the gene expression omnibus (GEO) database. Differentially expressed genes (DEGs) between unilateral and bilateral retinoblastoma were identified and functional enrichment analysis performed. The protein–protein interaction (PPI) network was constructed and analysed by STRING and Cytoscape. Results DEGs were mainly associated with activation of cysteine-type endopeptidase activity involved in apoptotic process and small molecule catabolic process. Seven genes (WAS, GNB3, PTGER1, TACR1, GPR143, NPFF and CDKN2A) were identified as HUB genes. Conclusion Our research provides more understanding of the mechanisms of the disease at a molecular level and may help in the identification of novel biomarkers for retinoblastoma.

Bilateral Retinoblastoma Presenting in an in vitro Fertilization Infant with Retinopathy of Prematurity

Retinopathy of prematurity (ROP) and retinoblastoma (RB) are well-described entities in premature babies. Although their pathogeneses are different, with ROP representing a disorder of interrupted development and RB a genetic disease, a few co-occurring cases have been reported, raising the possibility that the 2 conditions. Here, we report the sixth such case of co-occurring ROP and RB in an 8-month-old infant conceived by in vitro fertilization (IVF) who developed bilateral retinoblastoma a few months after treatment for advanced-stage ROP. While the ROP was initially adequately managed, bilateral RB necessitated bilateral enucleation. This case raises a number of important questions about whether IVF, ROP, and RB are causally related. Although the associations between IVF, ROP, and RB are likely to be coincidental, this case nevertheless highlights that ROP patients require regular follow-up for early diagnosis and treatment of ocular sequelae including RB.