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The following is a case of vitreoretinal lymphoma masquerading as central serous chorioretinopathy (CSCR). A 74-year-old man presented with blurred vision in the left eye with unilateral subretinal fluid in the setting of exogenous corticosteroid use, which was diagnosed as CSCR and resolved with corticosteroid cessation. He later experienced a similar self-limited episode in the right eye. Subsequently, he developed bilateral vitritis with yellow-white subretinal pigment epithelial infiltrates. Vitreous biopsy confirmed a diagnosis of large B-cell lymphoma. Vitreoretinal lymphoma can masquerade as a number of ocular pathologies, including CSCR. [Ophthalmic Surg Lasers Imaging Retina 2024;55:467–470.] [ABSTRACT FROM AUTHOR]

This case report describes a 74-year-old woman who developed a crystalline retinopathy following intravitreal injection of clindamycin. The patient presented with ocular toxoplasmosis in the left eye but was allergic to sulfa medications, so she was treated with intravitreal clindamycin. Subsequently, fine refractile yellow-white crystals were observed on examination of the left macula. Optical coherence tomography localized the crystals to the posterior hyaloid. Intravitreal clindamycin should be considered in the differential diagnosis of crystalline retinopathy. [Ophthalmic Surg Lasers Imaging Retina 2024;55:168–170.] [ABSTRACT FROM AUTHOR]

Introduction: The current standard of care for newly diagnosed glioblastoma (GBM) is maximum surgical resection followed by concurrent treatment with temozolomide (TMZ) and radiotherapy (RT) and then six to twelve cycles of maintenance TMZ. RRx-001, an NLRP3 inhibitor and nitric oxide (NO) donor with chemoradiosensitizing, vascular normalizing and macrophage repolarizing properties, is currently in a Phase III trial for small cell lung cancer (SCLC). The purpose of this non-randomized trial was to establish the safety and look for a signal of clinical activity of RRx-001 as an add-on to RT and TMZ in patients with newly diagnosed glioblastoma. Methods: In this non-randomized, open-label, two part trial called G-FORCE-1 (NCT02871843), the first four cohorts of adult patients with histologically confirmed high grade gliomas received fractionated radiotherapy (60 Gy in 30 fractions over 6 weeks), daily 75 mg/m2 temozolomide and escalating doses of once weekly RRx-001 from 0.5 mg to 4 mg according to a 3+3 design followed by a 6 week no treatment interval and then standard maintenance TMZ (150 mg/ m2 Cycle 1 and 200 mg/m2 in subsequent cycles) until disease progression. The second two cohorts of patients received fractionated radiotherapy (60 Gy in 30 fractions over 6 weeks), daily 75 mg/m2 temozolomide and once weekly RRx001 4 mg followed by a 6 week no treatment interval and then two different maintenance schedules until disease progression according to the same 3+ 3 design: 1. 0.5 mg RRx-001 once weekly + 100 mg/m2 TMZ 5 days/week for up to 6 cycles of therapy; 2. 4 mg RRx-001 once weekly + 100 mg/m2 TMZ 5 days/ week for up to 6 cycles of therapy. The primary endpoint was the recommended dose/maximally tolerated dose of the combination of RRx-001, TMZ and RT. Secondary endpoints were overall survival, progression free survival, objective response rate, duration of response and clinical benefit response. Results: A total of 16 newly diagnosed glioblastoma patients were enrolled. No dose limiting toxicities were observed and no MTD was reached. The recommended dose is 4 mg. After 24 months of follow up the median OS was 21.9 months (95% CI: 11.7 – NA). PFS median was 8 months (95% CI: 5 – NA). The overall response rate was 18.8% (3 PR out of 16) and the disease control rate was 68.8% (3 PR, 8 SD out of 16). Conclusions: The addition of RRx-001 to TMZ and RT and to TMZ during maintenance was safe and well-tolerated and deserves further study. [ABSTRACT FROM AUTHOR]

This paper describes the influence of the Physical, Executive, Developmental and Systems (PEDS) framework on the delivery of community-based child neuropsychological rehabilitation and how it has been enhanced by the proliferation of neuroscientific, neuropsychological and psychosocial research and evidence-base in childhood brain injury and rehabilitation over the past decade. The paper signposts to some of the key models, theories and concepts currently shaping service delivery. Application of the PEDS framework in a clinical case is described. [ABSTRACT FROM AUTHOR]

Cells derived from pluripotent sources in vitro must resemble those found in vivo as closely as possible at both transcriptional and functional levels in order to be a useful tool for studying diseases and developing therapeutics. Recently, differentiation of human pluripotent stem cells (hPSCs) into brain microvascular endothelial cells (ECs) with blood-brain barrier (BBB)-like properties has been reported. These cells have since been used as a robust in vitro BBB model for drug delivery and mechanistic understanding of neurological diseases. However, the precise cellular identity of these induced brain microvascular endothelial cells (iBMECs) has not been well described. Employing a comprehensive transcriptomic metaanalysis of previously published hPSC-derived cells validated by physiological assays, we demonstrate that iBMECs lack functional attributes of ECs since they are deficient in vascular lineage genes while expressing clusters of genes related to the neuroectodermal epithelial lineage (Epi-iBMEC). Overexpression of key endothelial ETS transcription factors (ETV2, ERG, and FLI1) reprograms Epi-iBMECs into authentic endothelial cells that are congruent with bona fide endothelium at both transcriptomic as well as some functional levels. This approach could eventually be used to develop a robust human BBB model in vitro that resembles the human brain EC in vivo for functional studies and drug discovery. [ABSTRACT FROM AUTHOR]

BACKGROUND AND PURPOSE: Glioblastomas (GBMs) that involve the subventricular zone (SVZ) have a poor prognosis, possibly due to recruitment of neural stem cells. The purpose of this study was to evaluate whether SVZ involvement by lower grade gliomas (LGG), WHO grade II and III, similarly predicts poorer outcomes. We further assessed whether tumor genetics and cellularity are associated with SVZ involvement and outcomes. METHODS: Forty‐five consecutive LGG patients with preoperative imaging and next generation sequencing were included in this study. Regional SVZ involvement and whole tumor apparent diffusion coefficient (ADC) values, as a measure of cellularity, were assessed on magnetic resonance imaging. Progression was determined by RANO criteria. Kaplan‐Meier curves and Cox regression analyses were used to determine the hazard ratios (HR) for progression and survival. RESULTS: Frontal, parietal, temporal, and overall SVZ involvement and ADC values were not associated with progression or survival (P ≥.05). However, occipital SVZ involvement, seen in two patients, was associated with a higher risk of tumor progression (HR = 6.6, P =.016) and death (HR = 31.5, P =.015), CDKN2A/B mutations (P =.03), and lower ADC histogram values at the 5th (P =.026) and 10th percentiles (P =.046). Isocitrate dehydrogenase, phosphatase and tensin homolog, epidermal growth factor receptor, and cyclin‐dependent kinase 4 mutations were also prognostic (P ≤.05). CONCLUSIONS: Unlike in GBM, overall SVZ involvement was not found to strongly predict poor prognosis in LGGs. However, occipital SVZ involvement, though uncommon, was prognostic and found to be associated with CDKN2A/B mutations and tumor hypercellularity. Further investigation into these molecular mechanisms underlying occipital SVZ involvement in larger cohorts is warranted. [ABSTRACT FROM AUTHOR]

A mechanics-based mathematical model of retinal detachment due to the geometric changes of the eye associated with the evolution of myopia is developed. This includes deformation of the retina due to biological growth of the retina, as well as elastic deformation imposed on the retina by the myopic change in shape of the much stiffer choroid and sclera. The problem is formulated as a propagating boundary value problem in the calculus of variations, which yields self-consistent governing equations, boundary conditions, and transversality conditions that establish the location of the propagating boundaries that correspond to equilibrium configurations of the detaching ocular system. Axisymmetric conditions are considered, and exact, analytical solutions to the corresponding boundary value problem are obtained for detaching retinas with and without a tear. Based upon application of the model presented herein to the emmetropic retina, a value of the bond energy of the retina to retinal pigment epithelium interface is estimated using material properties found in the literature. Simulations based on the analytical solutions are performed for a detachment in the retina located at either the posterior or superior pole of the eye. The results support the clinical finding of an increased prevalence of retinal detachment in myopic eyes and provide insight into the potential causation for the increased prevalence. [ABSTRACT FROM AUTHOR]

Objectives: Texture analysis performed on MRI images can provide additional quantitative information that is invisible to human assessment. This study aimed to evaluate the feasibility of texture analysis on preoperative conventional MRI images in predicting early malignant transformation from low- to high-grade glioma and compare its utility to histogram analysis alone.Methods: A total of 68 patients with low-grade glioma (LGG) were included in this study, 15 of which showed malignant transformation. Patients were randomly divided into training (60%) and testing (40%) sets. Texture analyses were performed to obtain the most discriminant factor (MDF) values for both training and testing data. Receiver operating characteristic (ROC) curve analyses were performed on MDF values and 9 histogram parameters in the training data to obtain cutoff values for determining the correct rates of discrimination between two groups in the testing data.Results: The ROC analyses on MDF values resulted in an area under the curve (AUC) of 0.90 (sensitivity 85%, specificity 84%) for T2w FLAIR, 0.92 (86%, 94%) for ADC, 0.96 (97%, 84%) for T1w, and 0.82 (78%, 75%) for T1w + Gd and correctly discriminated between the two groups in 93%, 100%, 93%, and 92% of cases in testing data, respectively. In the astrocytoma subgroup, AUCs were 0.92 (88%, 83%) for T2w FLAIR and 0.90 (92%, 74%) for T1w + Gd and correctly discriminated two groups in 100% and 92% of cases. The MDF outperformed all 9 of the histogram parameters.Conclusion: Texture analysis on conventional preoperative MRI images can accurately predict early malignant transformation of LGGs, which may guide therapeutic planning.Key Points: • Texture analysis performed on MRI images can provide additional quantitative information that is invisible to human assessment. • Texture analysis based on conventional preoperative MR images can accurately predict early malignant transformation from low- to high-grade glioma. • Texture analysis is a clinically feasible technique that may provide an alternative and effective way of determining the likelihood of early malignant transformation and help guide therapeutic decisions. [ABSTRACT FROM AUTHOR]

Background and Purpose: Telomerase reverse transcriptase (TERT) promoter mutations are associated with worse prognosis in glioblastoma. The purpose of this study was to evaluate whether TERT mutation status was associated with specific morphologic and quantitative imaging features.Methods: Twenty-nine patients with isocitrate dehydrogenase 1/2-wildtype glioblastoma (13 TERT-wildtype, 16 TERT-mutated), who underwent preoperative magnetic resonance (MR) imaging were included in this retrospective study. Qualitative imaging phenotypes were evaluated using the Visually Accessible Rembrandt Images (VASARIs) feature set. Histogram analysis of apparent diffusion coefficient (ADC) and dynamic contrast-enhanced MR perfusion values were performed on enhancing tumor volumes-of-interest, and differences between TERT-wildtype and TERT-mutated tumors were assessed.Results: VASARI analysis demonstrated that the majority of morphologic features were not significantly different between TERT-wildtype and TERT-mutated tumors, although a higher proportion of TERT-wildtype tumors featured nonenhancing tumor crossing midline (P = .014). TERT-mutated tumors demonstrated lower median rate constant kep (.38 vs. .76, P = .03) and lower median volume transfer coefficient Ktrans (.13 vs. .31, P = .02). There was no significant difference in median plasma volume vp (P = .92) or ADC values (P = .66) between the two groups. We further found a significant interaction between median kep and Ktrans and TERT status, respectively, suggesting greater risk of death with increasing blood-brain barrier dysfunction in TERT-mutated but not in TERT-wildtype tumors.Conclusion: Our study demonstrates evidence of altered permeability metrics associated with TERT mutation in glioblastoma, laying the foundation for future prospective studies assessing implications for therapeutic management and clinical outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Molecular data has become an essential part of the updated World Health Organization (WHO) grading of central nervous system tumors. However, stereotactic needle biopsies provide only small volume specimens and limit the extent of histologic and molecular testing that can be performed. We assessed the use of a tubular retractor-based minimally invasive biopsy technique to provide improved tissue yield and diagnostic data compared to needle biopsy.Methods: Eighteen patients underwent an open transtubular biopsy compared to 146 stereotactic biopsies during the years of 2010-2018.Results: Tubular biopsies resulted in a higher volume of tissue provided to the pathologist than needle biopsies (1.26 cm3 vs. 0.3 cm3; p < 0.0001). There was a higher rate of non-diagnostic sample with stereotactic compared to transtubular biopsy (13% vs. 0%; p = 0.13). Six patients who underwent stereotactic biopsy required reoperation for diagnosis, while no transtubular biopsy patient required reoperation in order to obtain a diagnostic specimen. Postoperative hematoma was the most common post-operative complication in both groups.Conclusions: Stereotactic transtubular biopsies are a viable alternative to stereotactic needle biopsies with excellent rates of diagnostic success and acceptable morbidity relative to the needle biopsy technique. As molecular data begins to increasingly drive treatment decisions, additional biopsy techniques that afford large tissue volumes may be necessary to adapt to the new needs of pathologists and treating oncologists. [ABSTRACT FROM AUTHOR]

Intratumoral heterogeneity at the genetic, epigenetic, transcriptomic, and morphologic levels is a commonly observed phenomenon in many aggressive cancer types. Clonal evolution during tumor formation and in response to therapeutic intervention can be predicted utilizing reverse engineering approaches on detailed genomic snapshots of heterogeneous patient tumor samples. In this study, we developed an extensive dataset for a GBM case via the generation of polyclonal and monoclonal glioma stem cell lines from initial diagnosis, and from multiple sections of distant tumor locations of the deceased patient's brain following tumor recurrence. Our analyses revealed the tissue-wide expansion of a new clone in the recurrent tumor and chromosome 7 gain and chromosome 10 loss as repeated genomic events in primary and recurrent disease. Moreover, chromosome 7 gain and chromosome 10 loss produced similar alterations in mRNA expression profiles in primary and recurrent tumors despite possessing other highly heterogeneous and divergent genomic alterations between the tumors. We identified ETV1 and CDK6 as putative candidate genes, and NFKB (complex), IL1B, IL6, Akt and VEGF as potential signaling regulators, as potentially central downstream effectors of chr7 gain and chr10 loss. Finally, the differences caused by the transcriptomic shift following gain of chromosome 7 and loss of chromosome 10 were consistent with those generally seen in GBM samples compared to normal brain in large-scale patient-tumor data sets. [ABSTRACT FROM AUTHOR]

Background/Aims. To evaluate the impact of back-illuminated and nonilluminated electronic reading devices on reading speed and comfort in patients with decreased vision. Methods. A prospective study involving a convenience sample of 167 patients at a single retina practice from January 2011 to December 2012. Participants were asked to read five different excerpts on five different media in a randomly assigned order. Media included a printed book at 12-point font (12PF), iPad2 at 12PF, iPad2 at 18-point font (18PF), Kindle2 at 12PF, and Kindle2 at 18PF. Reading speed in words per minute (WPM) and medium preference were recorded and stratified by visual acuity (VA). Results. Mean reading speeds in WPM: iPad2 at 18PF (217.0), iPad2 at 12PF (209.1), Kindle2 at 18PF (183.3), Kindle2 at 12PF (177.7), and printed book at 12PF (176.8). Reading speed was faster on back-illuminated media compared to nonilluminated media. Text magnification minimized losses in reading performance with worsening patient VA. The majority of participants preferred reading on the iPad2 at 18PF. Conclusions. Back-illuminated devices may increase reading speed and comfort relative to nonilluminated devices and printed text, particularly in patients with decreased VA. [ABSTRACT FROM AUTHOR]