Personalized treatment planning in eye brachytherapy for ocular melanoma: Dosimetric analysis on ophthalmic structure at risk

Purpose: To evaluate the impact on dose distribution to eye organs-at-risk (eOARs) of a computed tomography (CT)-based treatment planning in eye plaque brachytherapy (EPB) treatment. Methods: We analyzed 19 ocular melanoma patients treated with ruthenium-106 plaques to a total dose of 100 Gy to tumor apex using conventional central-axis-point dose calculation. Treatments were re-planned using the Plaque Simulator (PS) software implementing two different strategies: a personalized CT-eye-model (CT-PS) and a standard-eye-model (SEM-PS) defined by Collaborative Ocular Melanoma Study. Dice coefficient and Hausdorff distance evaluated the concordance between eye-bulb-models. Mean doses (Dmean) to tumor and eOARs were extracted from Dose-Volume-Histograms and Retinal-Dose-Area-Histogram. Differences between planning approaches were tested by Wilcoxon signed-rank test. Results: In the analyzed cohort, 8 patients (42%) had posterior tumor location, 8 (42%) anterior, and 3 (16%) equatorial. The SEM did not accurately described the real CT eye-bulb geometry (median Hausdorff distance 0.8 mm, range: (0.4–1.3) mm). Significant differences in fovea and macula Dmean values were found (p = 0.04) between CT-PS and SEM-PS schemes. No significant dosimetric differences were found for tumor and other eOARs. The planning scheme particularly affects the OARs closest to the tumor with a general tendency of SEM-PS to overestimate the doses to the OARs closest to the tumor. Conclusion: The dosimetric accuracy achievable with CT-PS EPB treatment planning may help to identify ocular melanoma patients who could benefit the most from a personalized eye dosimetry for an optimal outcome in terms of tumor coverage and eOARs sparing. Further research and larger studies are underway

Distinct gene expression in demyelinated white and grey matter areas of patients with multiple sclerosis

Demyelination of the central nervous system is a prominent pathological hallmark of multiple sclerosis and affects both white and grey matter. However, demyelinated white and grey matter exhibit clear pathological differences, most notably the presence or absence of inflammation and activated glial cells in white and grey matter, respectively. In order to gain more insight into the differential pathology of demyelinated white and grey matter areas, we micro-dissected neighbouring white and grey matter demyelinated areas as well as normal-appearing matter from leucocortical lesions of human post-mortem material and used these samples for RNA sequencing. Our data show that even neighbouring demyelinated white and grey matter of the same leucocortical have a distinct gene expression profile and cellular composition. We propose that, based on their distinct expression profile, pathological processes in neighbouring white and grey matter are likely different which could have implications for the efficacy of treating grey matter lesions with current anti-inflammatory-based multiple sclerosis drugs

The current clinically relevant findings on COVID-19 pandemic

The emergence of a novel coronavirus and coronavirus disease 2019 (COVID-19) represents a challenge to global healthcare. In the past 20 years, this is the third coronavirus that jumped the species barrier and infected humans. It is highly contagious but associated with low pathogenicity. First identified in Wuhan, China, a city of over 11 million, the disease has since spread to every continent except Antarctica. About 15 to 20 of all cases may be called severe, and it is believed many cases are asymptomatic. The average age of a person with COVID has been reported as 49 years. Worse outcomes are associated with geriatric populations and those with un-derlying diseases such as cardiovascular, respiratory disorders, and/or diabetes. The coronavirus, like other coronaviruses, is highly contagious and has a latency period of about 14 days. Most patients present with fever and a dry cough, but fever may be absent. Differential diagnosis can be challenging since influenza may present with similar symptoms. Chest radiography or computed to-mography may be used to find evidence of secondary pneumonia. Nosocomial infection is of concern, and it has been reported that 3.8 of all cases with COVID-19 in that country involve healthcare workers in China. Most patients have mild disease, and supportive care suffices. A variety of repurposed and investigational drugs are being evaluated. There are currently no antiviral therapies or vaccines, even if many therapies are proposed. Hand hygiene, social distancing, and scientifically sound information are the best strategies at the moment to combat this epidemic. © 2020, Author(s)

Astrocyte-Derived Tissue Transglutaminase Interacts with Fibronectin: A Role in Astrocyte Adhesion and Migration?

An important neuropathological feature of neuroinflammatory processes that occur during e.g. Multiple Sclerosis (MS) is the formation of an astroglial scar. Astroglial scar formation is facilitated by the interaction between astrocytes and extracellular matrix proteins (ECM) such as fibronectin. Since there is evidence indicating that glial scars strongly inhibit both axon growth and (re)myelination in brain lesions, it is important to understand the factors that contribute to the interaction between astrocytes and ECM proteins. Tissue Transglutaminase (TG2) is a multifunctional enzyme with an ubiquitous tissue distribution, being clearly present within the brain. It has been shown that inflammatory cytokines can enhance TG2 activity. In addition, TG2 can mediate cell adhesion and migration and it binds fibronectin with high affinity. We therefore hypothesized that TG2 is involved in astrocyte-fibronectin interactions. Our studies using primary rat astrocytes show that intracellular and cell surface expression and activity of TG2 is increased after treatment with pro-inflammatory cytokines. Astrocyte-derived TG2 interacts with fibronectin and is involved in astrocyte adhesion onto and migration across fibronectin. TG2 is involved in stimulating focal adhesion formation which is necessary for the interaction of astrocytes with ECM proteins. We conclude that astrocyte-derived TG2 contributes to the interaction between astrocytes and fibronectin. It might thereby regulate ECM remodeling and possibly glial scarring

Optical coherence tomography angiography in contractile morning glory syndrome

This study describes the optical coherence tomography and optical coherence tomography angiography features of three eyes of three patients affected by contractile morning glory syndrome. Optical coherence tomography angiography scans of the peripapillary retina revealed a dense microvascular network without any vascular difference between the superficial vascular plexus and the deep vascular plexus around the optic nerve. These optical coherence tomography angiography findings confirm that the contractile movement could be due to the presence of an autonomic cholinergic muscular mechanism in the posterior part of the globe. In fact in our cases, the contractile movement seemed to be induced by massage of the eyeball. Optical coherence tomography angiography is a valid, non-invasive, dyeless, and reliable method that could shed light on the pathogenesis of this rare disease of the optic disk

Correlation between the optic nerve pial diameter and radial peripapillary vascular changes in primary open-angle glaucoma

Purpose: To assess the optic nerve pial diameter (ONPD) in patients with primary open-angle glaucoma (POAG) using standardized A-scan ultrasound and to evaluate the correlation between the ONPD and structural, vascular optic nerve head features and visual field parameters in glaucomatous eyes. Methods: In this prospective study, we enrolled 126 eyes of 63 POAG patients and 124 eyes of 62 healthy controls. In all subjects, the ONPD was evaluated by means of A-scan ultrasound. Spectral domain (SD)-OCT was used to assess ganglion cell complex (GCC), retinal nerve fiber layer (RNFL), thicknesses, and the optic nerve head (ONH) morphology. OCTA measured the vessel density (VD) of radial peripapillary capillary (RPC) plexus. Results: The ONPD showed a statistically significant reduction in POAG group with respect to controls (p < 0.001). SD-OCT and OCTA parameters showed a significant impairment in patient group with respect to controls (p < 0.001). The ONH analysis revealed significantly lower values in rim area (p = 0.009) and an increased cup-to-disc area ratio (p = 0.013) and cup volume (p < 0.001) in patients with respect to controls. Significant correlations were shown in POAG group between ONPD and RPC plexus (p = 0.006). Moreover, significant correlation was also found between ONPD and structural SD-OCT parameters (p = 0.001) and between ONPD and visual field parameters (p = 0.001). Conclusions: The standardized A-scan ultrasound measurements of the ONPD showed a significant correlation with structural and vascular glaucomatous changes measured by means of SD-OCT and OCTA. These results confirm the diagnostic reliability of the ultrasound evaluation in glaucoma optic neuropathy. [Figure not available: see fulltext.