The Role of Mitophagy in Glaucomatous Neurodegeneration.

This review aims to provide a better understanding of the emerging role of mitophagy in glaucomatous neurodegeneration, which is the primary cause of irreversible blindness worldwide. Increasing evidence from genetic and other experimental studies suggests that mitophagy-related genes are implicated in the pathogenesis of glaucoma in various populations. The association between polymorphisms in these genes and increased risk of glaucoma is presented. Reduction in intraocular pressure (IOP) is currently the only modifiable risk factor for glaucoma, while clinical trials highlight the inadequacy of IOP-lowering therapeutic approaches to prevent sight loss in many glaucoma patients. Mitochondrial dysfunction is thought to increase the susceptibility of retinal ganglion cells (RGCs) to other risk factors and is implicated in glaucomatous degeneration. Mitophagy holds a vital role in mitochondrial quality control processes, and the current review explores the mitophagy-related pathways which may be linked to glaucoma and their therapeutic potential.

Quantitative Autofluorescence in Non-Neovascular Age Related Macular Degeneration.

Quantitative autofluorescence (qAF8) level is a presumed surrogate marker of lipofuscin content in the retina. We investigated the changes in the qAF8 levels in non-neovascular AMD. In this prospective cohort study, Caucasians aged ≥50 years with varying severity of non-neovascular AMD in at least one eye and Snellen visual acuity ≥6/18 were recruited. The qAF8 levels were analysed in the middle eight segments of the Delori pattern (HEYEX software, Heidelberg, Germany). The AMD categories were graded using both the Beckman classification and multimodal imaging (MMI) to include the presence of subretinal drusenoid deposits (SDD). A total of 353 eyes from 231 participants were analyzed. Compared with the age-matched controls, the qAF8 values decreased in the eyes with AMD (adjusted % difference = -19.7% [95% CI -28.8%, -10.4%]; p < 0.001) and across the AMD categories, (adjusted % differences; Early, -13.1% (-24.4%, -1%), p = 0.04; intermediate AMD (iAMD), -22.9% (-32.3%, -13.1%), p < 0.001; geographic atrophy -25.2% (-38.1%, -10.4%), p = 0.002). On MMI, the qAF8 was reduced in the AMD subgroups relative to the controls, (adjusted % differences; Early, -5.8% (-18.9%, 8.3%); p = 0.40; iAMD, -26.7% (-36.2%, -15.6%); p < 0.001; SDD, -23.7% (-33.6%, -12.2%); p < 0.001; atrophy, -26.7% (-39.3%, -11.3%), p = 0.001). The qAF8 levels declined early in AMD and were not significantly different between the severity levels of non-neovascular AMD, suggesting the early and sustained loss of function of the retinal pigment epithelium in AMD.

Functionalization of 3D Printed Scaffolds Using Polydopamine and Silver Nanoparticles for Bone-Interfacing Applications.

The prevention of bacterial colonization and the stimulation of osseointegration are two major requirements for bone-interfacing materials to reduce the incidence of complications and promote the restoration of the patient's health. The present investigation developed an effective, two-step functionalization of 3D printed scaffolds intended for bone-interfacing applications using a simple polydopamine (PDA) dip-coating method followed by the formation of silver nanoparticles (AgNPs) after a second coating step in silver nitrate. 3D printed polymeric substrates coated with a ∼20 nm PDA layer and 70 nm diameter AgNPs proved effective in hindering Staphylococcus aureus biofilm formation, with a 3000-8000-fold reduction in the number of bacterial colonies formed. The implementation of porous geometries significantly accelerated osteoblast-like cell growth. Microscopy characterization further elucidated homogeneity, features, and penetration of the coating inside the scaffold. A proof-of-concept coating on titanium substrates attests to the transferability of the method to other materials, broadening the range of applications both in and outside the medical sector. The antibacterial efficiency of the coating is likely to lead to a decrease in the number of bacterial infections developed after surgery in the presence of these coatings on prosthetics, thus translating to a reduction in revision surgeries and improved health outcomes.

Diagnostic Yield of Electroencephalography When Seizure Is Suspected in Acute Ischemic Stroke.

INTRODUCTION: Seizures are a common complication after an ischemic stroke. Electroencephalography can assist with the diagnosis of seizures however, the diagnostic yield of its use when seizure is suspected in the setting of acute ischemic stroke is unknown. We aim to evaluate the yield and cost of EEG in the acute ischemic stroke setting. METHODS: We conducted a retrospective chart review of patients admitted to a single academic tertiary care center in the United States between September 1, 2015 to November 30, 2019 with a primary diagnosis of acute ischemic stroke and who were monitored on electroencephalography (EEG) for suspected seizures (total number of 70 patients). The primary outcome was how often EEG monitoring changed clinical management defined as starting, stopping, or changing the dose of an anti-epileptic drug. Secondary analysis was estimating the cost of EEG monitoring per change in management. RESULTS: We identified 126 patients admitted with acute ischemic stroke who underwent EEG of which 70 met all inclusion and exclusion criteria. EEG monitoring resulted in a change in management in 22 patients (31%). Predictors associated with EEG monitoring resulting in a change in management were admission to the ICU, pre-existing atrial fibrillation, and symptomatic hemorrhagic transformation. Estimated cost of EEG per change in management was $1374.96 USD. CONCLUSION: EEG monitoring resulted in a changed management in nearly one-third of patients admitted with acute ischemic stroke suspected of having seizures.

Functional clinical endpoints and their correlations in eyes with AMD with and without subretinal drusenoid deposits-a pilot study.

PURPOSE: To evaluate functional clinical endpoints and their structural correlations in AMD, with a focus on subretinal drusenoid deposits (SDD). METHODS: This prospective study enroled 50 participants (11 controls, 17 intermediate AMD (iAMD) with no SDD, 11 iAMD with SDD and 11 non-foveal atrophic AMD). Participants underwent best-corrected visual acuity (BCVA), low luminance visual acuity (LLVA), low luminance questionnaire (LLQ), scotopic thresholds, rod-intercept time (RIT), photopic flicker electroretinograms and multimodal imaging. Functional and structural relationships were assessed. RESULTS: Compared with healthy participants, BCVA, LLVA, scotopic thresholds were depressed, and RIT prolonged in iAMD patients with SDD (p = 0.028, p = 0.045, p = 0.014 and p < 0.0001 respectively). Patients with SDD also had reduced scotopic function and delayed RIT compared to iAMD without SDD (p = 0.005 and p < 0.0001). Eyes with SDD and non-foveal atrophy did not differ functionally. Nor did healthy subjects compared with iAMD without SDD. Functional parameters were significantly associated with scotopic thresholds (r = 0.39-0.64). BCVA, LLVA and scotopic thresholds correlated well with ONL volume, ONL thickness and choroidal thickness (r = 0.34-0.61). CONCLUSION: Eyes with SDD are surrogate markers of photoreceptor abnormalities comparable with non-central atrophy and should be sub-analysed in clinical trials evaluating potential prophylactic agents to decrease the progression of AMD and may even require different therapeutic interventions.

Scotopic thresholds on dark-adapted chromatic perimetry in healthy aging and age-related macular degeneration.

To evaluate the effect of aging, intra- and intersession repeatability and regional scotopic sensitivities in healthy and age-related macular degeneration (AMD) eyes. Intra- and intersession agreement and effect of age was measured in healthy individuals. The mean sensitivity (MS) and pointwise retinal sensitivities (PWS) within the central 24° with 505 nm (cyan) and 625 nm (red) stimuli were evaluated in 50 individuals (11 healthy and 39 AMD eyes). The overall intra- and intersession had excellent reliability (intraclass correlation coefficient, ICC > 0.90) and tests were highly correlated (Spearman rs = 0.75-0.86). Eyes with subretinal drusenoid deposit (SDD) had reduced PWS centrally, particularly at inferior and nasal retinal locations compared with controls and intermediate AMD (iAMD) without SDD. There was no difference in MS or PWS at any retinal location between iAMD without SDD and healthy individuals nor between iAMD with SDD and non-foveal atrophic AMD groups. Eyes with SDD have reduced rod function compared to iAMD without SDD and healthy eyes, but similar to eyes with non-foveal atrophy. Our results highlight rod dysfunction is not directly correlated with drusen load and SDD location.

Clinical impact of the first pass effect on clinical outcomes in patients with near or complete recanalization during mechanical thrombectomy for large vessel ischemic stroke.

BACKGROUND AND PURPOSE: The first pass effect has been reported as a mechanical thrombectomy (MT) success metric in patients with large vessel occlusive stroke. We aimed to compare the clinical and neuroimagign outcomes of patients who had favorable recanalization (mTICI 2c or mTICI 3) achieved in one pass versus those requiring multiple passes. METHODS: In this "real-world" multicenter study, patients with mTICI 2c or 3 recanalization were identified from three prospectively collected stroke databases from January 2016 to December 2019. Clinical outcomes were a favorable functional outcome at 90 days (modified Rankin Scale score 0-2), and the rate of symptomatic intracranial hemorrhage (ICH) any ICH, and 90-day mortality. RESULTS: Favorable recanalization was achieved in 390/664 (59%) of consecutive patients who underwent MT (age 71.2 ± 13.2 years, 188 [48.2%] women). This was achieved after a single thrombectomy pass (n = 290) or multiple thrombectomy passes (n = 100). The rate of favorable clinical outcome was higher (41% vs. 28 %, p = .02) in the first pass group with a continued trend on multivariate analysis that did not reaching statistical significance (OR 1.68 95% confidence interval [CI] 1.0-2.95, p = .07). Similarly, the odds of any ICH were significantly lower (OR 0.56 CI 0.32-0.97, p = .03). A similar trend of favorable clinical outcomes was noticed on subgroup analysis of patients with M1 occlusion (OR 1.81 CI 1.01-3.61, p = .08). CONCLUSION: The first-pass reperfusion was associated with a trend toward favorable clinical outcome and lower rates of ICH. These data suggest that the first-pass effect should be the mechanical thrombectomy procedure goal.

Exploratory Study on Visual Acuity and Patient-Perceived Visual Function in Patients with Subretinal Drusenoid Deposits.

PURPOSE: To investigate the value of visual acuity and patient-perceived visual function test when subretinal drusenoid deposits (SDD) are incorporated into the classification of age-related macular degeneration (AMD). A total of 50 participants were recruited into the study in these groups: healthy ageing (n = 11), intermediate AMD (iAMD) with no SDD (n = 17), iAMD with SDD (n = 11) and non-foveal atrophic AMD (n = 11) confirmed by two retinal imaging modalities. Best-corrected visual acuity (BCVA) and low luminance visual acuity (LLVA) were measured and low luminance deficit (LLD) was calculated. Participants were also interviewed with the low luminance questionnaire (LLQ). Linear regression was used to assess function-function relations. Compared with healthy participants, BCVA and LLVA scores were significantly reduced in the atrophic AMD group (p < 0.0001 and p = 0.00016, respectively) and in patients with SDD (p = 0.028 and p = 0.045, respectively). Participants with atrophy also had reduced BCVA (p = 0.001) and LLVA (p = 0.009) compared with the iAMD no SDD group. However, there were no differences in visual function tests between healthy aging and iAMD without SDD and between iAMD with SDD and atrophic AMD groups. The LLD score did not differ between groups. BCVA and LLVA correlated well. The LLQ did not correlate with visual function tests. This study shows that LLD is not a marker of disease severity as assessed clinically. Although LLQ is a good marker for disease severity using the current AMD classification, it does not differentiate between eyes with and without SDD. Eyes with non-macular geographic atrophy and SDD had lower function than eyes with no SDD and healthy controls.

Optically Improved Mitochondrial Function Redeems Aged Human Visual Decline.

The age spectrum of human populations is shifting toward the older with larger proportions suffering physical decline. Mitochondria influence the pace of aging as the energy they provide for cellular function in the form of adenosine triphosphate (ATP) declines with age. Mitochondrial density is greatest in photoreceptors, particularly cones that have high energy demands and mediate color vision. Hence, the retina ages faster than other organs, with a 70% ATP reduction over life and a significant decline in photoreceptor function. Mitochondria have specific light absorbance characteristics influencing their performance. Longer wavelengths spanning 650->1,000 nm improve mitochondrial complex activity, membrane potential, and ATP production. Here, we use 670-nm light to improve photoreceptor performance and measure this psychophysically in those aged 28-72 years. Rod and cone performance declined significantly after approximately 40 years of age. 670-nm light had no impact in younger individuals, but in those around 40 years and older, significant improvements were obtained in color contrast sensitivity for the blue visual axis (tritan) known to display mitochondrial vulnerability. The red visual axis (protan) improved but not significantly. Rod thresholds also improved significantly in those >40 years. Using specific wavelengths to enhance mitochondrial performance will be significant in moderating the aging process in this metabolically demanding tissue.

COVID-19: Neurology residents' perspective.

Throughout this pandemic, neurology resident education and service has, and will continue to be, affected during this unprecedented time. Balancing the safety of our residents as well as the anticipated inpatient service demands, we have, and continue to, make changes to meet the needs of our community. Education certainly has been affected but we have made great effort to maintain normalcy. We are leveraging web-based technologies to continue formal didactics. The American Academy of Neurology has provided program directors with various tools to share to provide high-yield academic education. AAN Synapse, distance learning modules, and podcasts are a few examples. Each residency training program will likely face different challenges depending on location and community structure. We have an obligation to help all of our colleagues in the hospital in providing quality and compassionate care during this time of need. Our training and education will only benefit from this experience teaching us lessons on adaptability, the importance of teamwork, and self-sacrifice.

A Pilot Study Evaluating the Effects of 670 nm Photobiomodulation in Healthy Ageing and Age-Related Macular Degeneration.

Limited evidence suggests that the application of 670 nm of red light alters the course of aged decline. A previous report on 18 patients showed regression of drusen and improvement in visual functions in patients with intermediate age-related macular degeneration (AMD) by 12 months. We evaluated the functional and structural effects of applying 670 nm light to 31 patients with intermediate AMD and 11 people aged 55 years or above with normal retina. The study eyes were treated daily in the morning with a 670 nm hand-held light source housed in a torch-like tube that emitted energy equivalent to 40 mW/cm2 or 4.8J/ cm2 for 2 min at the viewing aperture. Visual function in terms of best-corrected visual acuity, low luminance visual acuity, scotopic thresholds and rod-intercept time were compared between baseline and 1, 3, 6 and 12 months. Structural changes on optical coherence tomography OCT and colour photographs were also assessed. Five withdrew consent voluntarily due to the intensity of the study visit assessments and two developed neovascular AMD and were excluded from further treatment and the analysis. In normal ageing, there was an improvement in scotopic thresholds in the group with no AMD by 1.77dB (p = 0.03) and no other parameters showed any clinically significant change. In eyes with intermediate AMD, there was no significant improvement in any functional or structural changes at any time point up to 12 months although the compliance was good. This pilot study shows that photobiomodulation with 670 nm has no effect in patients who have already progressed to intermediate AMD.