Neurofilament Light Chain in Aqueous Humor as a Marker of Neurodegeneration in Glaucoma.

Purpose: Neurofilament light chain (NfL) is a neuronal cytoskeletal protein that has been identified as a marker of neurodegeneration in diseases of the central nervous system. In this study, we investigated whether NfL in the aqueous humor (AH) can serve as a marker of neurodegeneration in glaucoma in a racially diverse North American population. Design: Single-center, case-control study. Participants: We enrolled patients with various types and stages of glaucoma undergoing planned ophthalmic surgery as part of their routine care and compared them with patients without glaucoma undergoing phacoemulsification for age-related cataract. Methods: We collected AH from 39 glaucoma patients and 10 patients without glaucoma. AH NfL was quantified using the Single-Molecule Array (Simoa)® NF-light assay (Quanterix). Demographic information, such as age, body mass index, sex, and self-reported race, as well as clinical information, such as pre-operative intraocular pressure (IOP), maximum IOP, and number of pre-operative glaucoma medications, was obtained by reviewing the medical record. Main Outcome Measures: Levels of AH NfL. Results: In a model controlling for age and body mass index (BMI), NfL was significantly elevated in AH from glaucoma patients (mean: 429 pg/mL; standard deviation [SD]: 1136 pg/mL) compared to AH from patients without glaucoma (mean: 3.1 pg/mL; SD: 1.9 pg/mg): P = 0.002. Higher AH NfL was associated with higher maximum IOP (R = 0.44, P = 0.005), higher pre-operative IOP (R = 0.46, P = 0.003), and more pre-operative glaucoma medications (Rs = 0.61, P < 0.001). There was no association between AH NfL and Humphrey visual field mean deviation (R = -0.20, P = 0.220), retinal nerve fiber layer thickness as measured with optical coherence tomography (R = 0.07, P = 0.694), or glaucoma stage (Rs = 0.015, P = 0.935). Conclusion: Our findings suggest that AH NfL may have clinical utility as a marker of glaucomatous neurodegeneration.

Clusters of substance use and mental health variables with emergency room visits in U.S. adults: The 2020 National Survey on Drug Use and Health.

BACKGROUND: This study evaluated the prevalence of emergency room (ER) visits, given numerous substance use and mental health variables in the past year. METHODS: Data from 5206 emergency room visits out of 27,170 adults were extracted from the 2020 National Survey on Drug Use and Health. Oblique principal component cluster analysis was used to classify 39 substance use and mental health variables into disjoint clusters. RESULTS: In 2020, the overall prevalence of ER visits was 21.9 %. Being female, age above 65 years, with insurance, low income and low education levels, and being African American increased the risk of ER visit. Nine clusters were made out of 39 substance use and mental health variables. Multivariate stepwise logistic regression analysis showed 15 substance use and mental health variables were significantly associated with ER visits including heavy alcohol use past 30 days in cluster 3, nicotine dependence and cigarettes use in cluster 4, major depressive episode, serious psychological distress, and suicidal plans in past year in cluster 5, any psychotherapeutics use in cluster 7, tranquilizers use and lorazepam products use in cluster 8, and any pain reliever, pain reliever misuse, hydrocodone products use, oxycodone products use, tramadol products use, and codeine products use in cluster 9. CONCLUSIONS: Several substance use and mental health problems, including nicotine dependence, illicit drugs, and serious mental health problems were among the common reasons for ER visits. These findings suggest the effective use of ER as the venue to implement interventions for substance use and mental health.

Neurodegeneration Markers Galectin-3 and Apolipoprotein E Are Elevated in the Aqueous Humor of Eyes With Glaucoma.

Purpose: Galectin-3 (Gal-3) and apolipoprotein E (APOE) are markers of activated microglia in neurodegenerative diseases of the central nervous system, whose targeting is protective in mouse models of glaucoma. In this study, we examined levels of Gal-3 and APOE in human aqueous humor (AH) and defined their clinical associations with glaucoma. Methods: We collected AH from 59 glaucoma patients and 15 controls at the start of planned ophthalmic surgery. Gal-3 and APOE levels were quantified by enzyme-linked immunosorbent assay. Total protein in AH was quantified by bicinchoninic acid assay. Significant associations between Gal-3, APOE, and clinical covariates were defined using univariate and multivariate linear regression models. Results: Gal-3 and APOE levels were significantly elevated in the AH of glaucoma patients compared to controls (P = 0.004 and P < 0.001, respectively). Gal-3 and APOE were positively correlated across the entire cohort (r = 0.65, P = 6.2E-9). No association was observed between Gal-3 and total protein or APOE and total protein (P = 0.35 and P = 0.50, respectively), indicating that their levels were not increased in glaucomatous AH due to nonspecific protein accumulation. Multivariate linear regression modeling revealed significant associations between Gal-3 and maximum recorded intraocular pressure (P = 0.009) and between APOE and number of past ophthalmic surgeries (P = 0.031). Conclusions: We demonstrate that Gal-3 and APOE are significantly elevated in the AH of eyes with glaucoma and are associated with a history of poorly controlled disease. Translational Relevance: Gal-3 and APOE in AH may inform clinical decision-making as quantifiable readouts of microglial activation in eyes with glaucoma.

Long-term response to fractionated radiotherapy of presumed optic nerve sheath meningioma.

BACKGROUND/AIMS To review the long-term results of treatment of optic nerve sheath meningiomas (ONSMs) with conformal radiotherapy. METHODS Eleven patients with presumed ONSM were treated with fractionated conformal radiotherapy using 45-54 Gy in 25-30 fractions and followed for more than 5 years. Affected eye visual acuity in logMAR notation, colour vision, threshold perimetry, mean deviation (dB) and imaging were studied before and after treatment. ANALYSIS Included adverse effects of treatment and the frequency of affected eye maintained or improved vision. RESULTS There were nine women and two men with a mean age of 45.3. Vision or field loss was the most common presentation. All had abnormal MR imaging. The follow-up period after radiotherapy was 61-156 months (mean 89.6). Visual acuity was unchanged or improved in 10 patients (91%). The average difference between pretreatment and final logMAR visual acuity was 0.08, while the average difference in visual-field mean deviation was -4.63 dB. The radiographic appearance of the tumours was stable in size in nine patients and decreased in two. No major side effects from radiation were seen. CONCLUSIONS Vision, MRI and complication outcomes are favourable for using fractionated conformal radiotherapy for ONSM.

Design principles for developing an efficient clinical anatomy course.

The exponential growth of medical knowledge presents a challenge for the medical school curriculum. Because anatomy is traditionally a long course, it is an attractive target to reduce course hours, yet designing courses that produce students with less understanding of human anatomy is not a viable option. Faced with the challenge of teaching more anatomy with less time, we set out to understand how students employ instructional media to learn anatomy inside and outside of the classroom. We developed a series of pilot programs to explore how students learn anatomy and, in particular, how they combine instructional technology with more traditional classroom and laboratory-based learning. We then integrated what we learned with principles of effective instruction to design a course that makes the most efficient use of students' in-class and out-of-class learning. Overall, we concluded that our new anatomy course needed to focus on transforming how medical students think, reason, and learn. We are currently testing the hypothesis that this novel approach will enhance the ability of students to recall and expand their base of anatomical knowledge throughout their medical school training and beyond.