Retinoblastoma management in 13q deletion syndrome patients using super-selective chemotherapies and other cancer-directed interventions.

BACKGROUND: This study aimed to identify best practices for treating 13q deletion syndrome (13q-) patients with retinoblastoma in the era of super-selective ophthalmic artery chemosurgery (OAC) and intravitreal injection therapy (IVIT). METHODS: Retrospective study of 21 eyes from 14 patients with retinoblastoma and 13q- who were treated at Memorial Sloan Kettering Cancer Center (MSKCC) between May 2006 and May 2020, with a mean follow up of 3.7 years. Ocular survival, patient survival, and treatment toxicities were assessed. RESULTS: Nine of the 12 eyes that underwent OAC/IVIT at MSKCC have been progression free for at least 1 year since their last treatments. Fifteen out of 26 OAC cycles resulted in grade 3-4 hematologic toxicity. There was one death from sepsis in the setting of intravenous chemotherapy (IVC) for metastatic disease that occurred after OAC/IVIT therapy. The 2-year Kaplan-Meier ocular survival estimate for the whole cohort was 75% and for the eyes that received OAC or IVIT at MSKCC 83%. For OAC hematologic toxicities, one platelet transfusion and two filgrastim doses were administered, and one patient was hospitalized for neutropenic fevers. CONCLUSIONS: The majority of 13q- eyes treated with OAC/IVIT-based regimens can be cured, and there were no deaths related to complications from OAC or IVIT. 13q- Patients did have increased risk of systemic treatment complications, even from super-selective chemotherapies. Despite these toxicities, only one patient developed febrile neutropenia, one patient required a blood product transfusion, and two patients received filgrastim for both OAC and IVC complications. PRÉCIS: Children with 13q deletion syndrome with retinoblastoma managed with intra-arterial and intravitreal chemotherapy have excellent patient and ocular survival with acceptable toxicity.

Trends in Geographic Distribution of Visual Disability - United States, 2010-2019.

PURPOSE: We aimed to describe changes in the geographic distribution of self-reported visual impairment (VI) over the last decade (2010-2019) in the U.S. METHODS: Our study was an analysis of publicly available data collected between 2010 and 2019 from the Census Bureau American Community Survey. RESULTS: The mean overall prevalence of self-reported VI from 2010 to 2019 was 2.31% in the United States, and there was a significant increase in VI over the past decade from 2.25% in 2010-2014 to 2.37% in 2015-2019 (p < .001). VI was significantly higher in rural counties (3.58%), compared to urban (3.10%) or metropolitan counties (2.18%) (p < .001). In terms of geographic region, the South of the United States had the highest rate of VI (2.63%) (p < .001). For age groups > 17-years-old in the 2010-2019 data, women had higher rates of VI compared to men. CONCLUSIONS: Prevalence of self-reported visual impairment has risen and disproportionately affects certain communities. This includes individuals living in the South, in rural counties, and women.

Premature Emulsification of Silicone Oil After Retinal Detachment Repair in the Setting of High-Intensity Exercise.

PURPOSE: To describe a rare case of silicone oil emulsification which occurred only three months postoperatively. We discuss the implications for postoperative counseling. METHODS: Retrospective chart review of a single patient. RESULTS: 39-year-old female who presented with a right eye macula-on retinal detachment which was repaired with scleral buckle, vitrectomy, and silicone oil tamponade. Her course was complicated by extensive silicone oil emulsification within 3 months postoperatively, most likely due to shear forces induced by her daily CrossFit exercise regimen. CONCLUSION: Typical postoperative precautions after a retinal detachment repair include no heavy lifting or strenuous activity for one week. These restrictions may need to be more stringent and long-term for patients with silicone oil to prevent early emulsification.

Accuracy and Utility of Internet Image Search as a Learning Tool for Retinal Pathology.

Purpose Ophthalmology residency training heavily relies on visual and pattern recognition-based learning. In parallel with traditional reference texts, online internet search via Google Image Search (GIS) is commonly used and offers an accessible fund of reference images for ophthalmology trainees seeking rapid exposure to images of retinal pathology. However, the accuracy and quality of this tool within this context is unknown. We aim to evaluate the accuracy and quality of GIS images of selected retinal pathologies. Methods A cross-sectional study was performed of GIS of 15 common and 15 rare retinal diseases drawn from the American Academy of Ophthalmology residency textbook series. A total of 300 evaluable image results were assessed for accuracy of images and image source accountability in consultation with a vitreoretinal surgeon. Results A total of 377 images were reviewed with 77 excluded prior to final analysis. A total of 288 (96%) search results accurately portrayed the retinal disease being searched, whereas 12 (4%) were of an erroneous diagnosis. More images of common retinal diseases were from patient education Web sites than were images of rare diseases ( p < 0.01). Significantly more images of rare retinal diseases were found in peer-reviewed sources ( p = 0.01). Conclusions GIS search results yielded a modest level of accuracy for the purposes of ophthalmic education. Despite the ease and rapidity of accessing multimodal retinal imaging examples, this tool may best be suited as a supplementary resource for learning among residents due to limited accuracy, lack of sufficient supporting information, and the source Web site's focus on patient education.

Non-canonical Wnt Signaling through Ryk Regulates the Generation of Somatostatin- and Parvalbumin-Expressing Cortical Interneurons.

GABAergic interneurons have many important functions in cortical circuitry, a reflection of their cell diversity. The developmental origins of this diversity are poorly understood. Here, we identify rostral-caudal regionality in Wnt exposure within the interneuron progenitor zone delineating the specification of the two main interneuron subclasses. Caudally situated medial ganglionic eminence (MGE) progenitors receive high levels of Wnt signaling and give rise to somatostatin (SST)-expressing cortical interneurons. By contrast, parvalbumin (PV)-expressing basket cells originate mostly from the rostral MGE, where Wnt signaling is attenuated. Interestingly, rather than canonical signaling through ß-catenin, signaling via the non-canonical Wnt receptor Ryk regulates interneuron cell-fate specification in vivo and in vitro. Indeed, gain of function of Ryk intracellular domain signaling regulates SST and PV fate in a dose-dependent manner, suggesting that Ryk signaling acts in a graded fashion. These data reveal an important role for non-canonical Wnt-Ryk signaling in establishing the correct ratios of cortical interneuron subtypes.

Clonally Related Forebrain Interneurons Disperse Broadly across Both Functional Areas and Structural Boundaries.

The medial ganglionic eminence (MGE) gives rise to the majority of mouse forebrain interneurons. Here, we examine the lineage relationship among MGE-derived interneurons using a replication-defective retroviral library containing a highly diverse set of DNA barcodes. Recovering the barcodes from the mature progeny of infected progenitor cells enabled us to unambiguously determine their respective lineal relationship. We found that clonal dispersion occurs across large areas of the brain and is not restricted by anatomical divisions. As such, sibling interneurons can populate the cortex, hippocampus striatum, and globus pallidus. The majority of interneurons appeared to be generated from asymmetric divisions of MGE progenitor cells, followed by symmetric divisions within the subventricular zone. Altogether, our findings uncover that lineage relationships do not appear to determine interneuron allocation to particular regions. As such, it is likely that clonally related interneurons have considerable flexibility as to the particular forebrain circuits to which they can contribute.