Modified Rankin Scale disability status at day 4 poststroke is an informative predictor of long-term day 90 outcome.

BACKGROUND: Long-term disability after stroke is standardly assessed 3 months post-onset, using the modified Rankin Scale (mRS). The value of an early, day 4 mRS assessment for projecting the 3-month disability outcome has not been formally investigated. METHODS: In this cohort of patients with acute cerebral ischemia and intracranial hemorrhage, we analyzed day 4 and day 90 mRS assessments in the NIH Field Administration of Stroke Therapy- Magnesium (FAST-MAG) Phase 3 trial. The performance of day 4 mRS, alone and as part of multivariate models, in predicting day 90 mRS was assessed using correlation coefficients, percent agreement, and the kappa statistics. RESULTS: Among the 1573 acute cerebrovascular disease (ACVD) patients, 1206 (76.7%) had acute cerebral ischemia (ACI), while 367 (23.3%) had intracranial hemorrhage. Among all 1573 ACVD patients, day 4 mRS and day 90 mRS correlated strongly, Spearman's rho=0.79, in unadjusted analysis with weighted kappa of 0.59. For dichotomized outcomes, simple carry-forward of the day 4 mRS performed fairly well in agreeing with day 90 mRS: mRS 0-1 (kappa=0.67), 85.4%; mRS 0-2 (k=0.59), 79.5%; fatal outcome, 88% (k=0.33). Correlations of 4d and 90d mRS were stronger for ACI than ICH patients, 0.76 vs 0.71. CONCLUSIONS: In this acute cerebrovascular disease patient cohort, assessment of global disability performed on day 4 is highly informative regarding long-term, 3-month mRS disability outcome, alone, and even more strongly in combination with baseline prognostic variables. The day 4 mRS is a useful measure for imputing the final patient disability outcome in clinical trials and quality improvement programs.

bHLH proneural genes as cell fate determinants of entero-endocrine cells, an evolutionarily conserved lineage sharing a common root with sensory neurons.

Entero-endocrine cells involved in the regulation of digestive function form a large and diverse cell population within the intestinal epithelium of all animals. Together with absorptive enterocytes and secretory gland cells, entero-endocrine cells are generated by the embryonic endoderm and, in the mature animal, from a pool of endoderm derived, self-renewing stem cells. Entero-endocrine cells share many structural/functional and developmental properties with sensory neurons, which hints at the possibility of an ancient evolutionary relationship between these two cell types. We will survey in this article recent findings that emphasize the similarities between entero-endocrine cells and sensory neurons in vertebrates and insects, for which a substantial volume of data pertaining to the entero-endocrine system has been compiled. We will then report new findings that shed light on the specification and morphogenesis of entero-endocrine cells in Drosophila. In this system, presumptive intestinal stem cells (pISCs), generated during early metamorphosis, undergo several rounds of mitosis that produce the endocrine cells and stem cells (ISCs) with which the fly is born. Clonal analysis demonstrated that individual pISCs can give rise to endocrine cells expressing different types of peptides. Immature endocrine cells start out as unpolarized cells located basally of the gut epithelium; they each extend an apical process into the epithelium which establishes a junctional complex and apical membrane specializations contacting the lumen of the gut. Finally, we show that the Drosophila homolog of ngn3, a bHLH gene that defines the entero-endocrine lineage in mammals, is expressed and required for the differentiation of this cell type in the fly gut.

Improving Access to Eye Care Through Community Health Screenings Using Artificial Intelligence.

PURPOSE: To the best of our knowledge, implementation of artificial intelligence (AI)-based vision screening in community health fair settings has not been previously studied. This prospective cohort study explored the incorporation of AI in a community health fair setting to improve access to eyecare. METHODS: Vision screening was implemented during a community health fair event using an AI-based non-mydriatic fundus camera. In addition, a questionnaire was provided to survey the various barriers to eyecare and assess eye health literacy. RESULTS: A total of 53 individuals were screened at this event. Notably, about 88% of participants had follow-up appointments scheduled accordingly with an approximate 62% attendance rate. The most reported barrier to eyecare was lack of health insurance followed by transportation. CONCLUSION: The addition of AI-based vision screening in community health fairs may ultimately help improve access to eye care.

Phthiriasis palpebrarum effectively treated with tea tree oil.

Phthiriasis palpebrarum, also known as crab lice, is a rare eyelash infestation by Pthirus pubis that is often misdiagnosed as common blepharitis, and thus mistreated. Treatment of Phthiriasis palpebrarum is widely variable. Tea tree oil is an essential oil with broad-spectrum anti-microbial therapeutic effects. Notably, however, the role of this agent in Phthiriasis palpebrarum management is unclear. The current article reports a case of phthiriasis palpebrarum effectively treated with tea tree oil.

Repeatability and Comparability of Retinal Blood Vessel Caliber Measurements by OCTA.

BACKGROUND: To investigate the repeatability in vessel caliber measurements by optical coherence tomography angiography (OCTA). METHODS: In this prospective study, 28 patients (47 eyes) underwent sequential OCTA imaging of the optic nerve head and macula. Two independent masked graders measured vessel caliber for sequential images of the optic nerve head and macula. The average vessel width was determined and variability between graders and images. RESULTS: A total of 8400 measurements of 420 vessels from 84 OCTA images were included in the analysis. Overall, inter-grader agreement was excellent (ICC 0.90). The coefficient of variation (CoV) for all repeated OCTA images was 0.10. Greater glaucoma severity, older age, macular location, and diagnosis of diabetes were associated with thinner vessels (p < 0.05). CoV was higher in the peripapillary region (0.07) as compared to the macula (0.15). ICC was high for all subgroups except for the macula (ICC = 0.72). CONCLUSIONS: Overall, the repeatability of vessel caliber measurements by OCTA was high and variability low. There was greater variability in the measurement of macular vessels, possibly due to technical limitations in acquiring accurate vessel widths for smaller macular vessels.

Modified Rankin Scale Disability Status at Day 4 Poststroke is an Informative Predictor of Long-Term Day 90 Outcome.

Background: Long-term disability after stroke is standardly assessed 3 months post-onset, using the modified Rankin Scale (mRS). The value of an early, day 4 mRS assessment for projecting the 3-month disability outcome has not been formally investigated. Methods: In this cohort of patients with acute cerebral ischemia and intracranial hemorrhage, we analyzed day 4 and day 90 mRS assessments in the NIH Field Administration of Stroke Therapy- Magnesium (FAST-MAG) Phase 3 trial. The performance of day 4 mRS, alone and as part of multivariate models, in predicting day 90 mRS was assessed using correlation coefficients, percent agreement, and the kappa statistics. Results: Among the 1573 acute cerebrovascular disease (ACVD) patients, 1206 (76.7%) had acute cerebral ischemia (ACI), while 367 (23.3%) had intracranial hemorrhage. Among all 1573 ACVD patients, day 4 mRS and day 90 mRS correlated strongly, Spearman's rho=0.79, in unadjusted analysis with weighted kappa of 0.59. For dichotomized outcomes, simple carry-forward of the day 4 mRS performed fairly well in agreeing with day 90 mRS: mRS 0-1 (k=0.67), 85.4%; mRS 0-2 (k=0.59), 79.5%; fatal outcome, 88.3% (k=0.33). Correlations of 4d and 90d mRS were stronger for ACI than ICH patients, 0.76 vs 0.71. Conclusions: In this acute cerebrovascular disease patient cohort, assessment of global disability performed on day 4 is highly informative regarding long-term, 3-month mRS disability outcome, alone, and even more strongly in combination with baseline prognostic variables. The day 4 mRS is a useful measure for imputing the final patient disability outcome in clinical trials and quality improvement programs.

Visualization of erythrocyte stasis in the living human eye in health and disease.

Blood cells trapped in stasis have been reported within the microcirculation, but their relevance to health and disease has not been established. In this study, we introduce an in vivo imaging approach that reveals the presence of a previously-unknown pool of erythrocytes in stasis, located within capillary segments of the CNS, and present in 100% of subjects imaged. These results provide a key insight that blood cells pause as they travel through the choroidal microvasculature, a vascular structure that boasts the highest blood flow of any tissue in the body. Demonstration of clinical utility using deep learning reveals that erythrocyte stasis is altered in glaucoma, indicating the possibility of more widespread changes in choroidal microvascular than previously realized. The ability to monitor the choroidal microvasculature at the single cell level may lead to novel strategies for tracking microvascular health in glaucoma, age-related macular degeneration, and other neurodegenerative diseases.

Thoracic Gut Entrapment Presenting As Intractable Hypoxia: A Case Report of Chilaiditi Syndrome.

We present a rare case of a patient who had intractable hypoxia and was found to have Chilaiditi syndrome. The hypoxia and respiratory symptoms resolved after bowel decompression and relief of the mass effect of the entrapped gut in the thorax. Chilaiditi sign is the interposition of the colon between the liver and diaphragm. Colonic interposition is a common asymptomatic radiological finding, in Chilaiditi syndrome, patients experience symptoms such as abdominal pain, constipation, respiratory distress, and chest pain.

A Pilot Study Assessing Retinal Blood Flow Dysregulation in Glaucoma Using Erythrocyte Mediated Velocimetry.

Purpose: The purpose of this study was to compare autoregulation of retinal arteriolar and venular blood flow in patients with glaucoma, glaucoma suspect participants, and control participants using erythrocyte mediated velocimetry. Methods: This prospective cohort pilot study included 7 eyes of 5 participants with glaucoma, 15 eyes of 8 glaucoma suspect participants, and 11 eyes of 6 control participants. Mean erythrocyte velocity in retinal arterioles and venules was measured using erythrocyte mediated velocimetry at room air and after oxygen supplementation. Change in erythrocyte velocity was compared among all groups using generalized estimating equations. Results: In total, 64 vessels (18 with glaucoma, 31 that were glaucoma suspect, and 15 controls) of 33 eyes of 19 participants were analyzed. There was no significant difference in baseline velocities in arterioles or venules among the three groups. With induction of hyperoxia, mean arterial erythrocyte velocity decreased in glaucoma (-7.2 ± 13.7%), which differed from controls and glaucoma suspects where erythrocyte velocity increased with hyperoxia by 4.6 ± 13.3% (P = 0.002) and 7.2 ± 21.7% (P = 0.03), respectively. A higher baseline arteriolar velocity (ß = -3.9% per mm/s, P = 0.002), glaucoma diagnosis (ß = -21.1%, P = 0.03), and White race (ß = -20.0%, P = 0.01) were associated with decreased velocity in response to arterial hyperoxia. Conclusions: Hyperoxia increased erythrocyte velocity in control and glaucoma suspect participants, but decreased erythrocyte velocity in glaucoma participants, possibly due to impaired autoregulation. Baseline velocity, glaucoma diagnosis, and White race were associated with a decrease in velocity with induction of hyperoxia. Translational Relevance: The European Medicines Agency (EMA) permits precision measurements of blood flow which may aid in the development of biomarkers of glaucoma-related dysregulation of blood flow.

Ehlers-Danlos syndromes and their manifestations in the visual system.

Ehlers-Danlos syndrome (EDS) is a rare, genetically variable, heterogenous group of (currently recognized) thirteen connective tissue disorders characterized by skin hyperextensibility, tissue fragility, and generalized joint hypermobility. In addition to these commonly recognized phenotypes, recent studies have notably highlighted variable ophthalmic features in EDS. In this review, we comprehensively gather and discuss the ocular manifestations of EDS and its thirteen subtypes in the clinical setting.

Dynamic Alterations in Blood Flow in Glaucoma Measured with Laser Speckle Contrast Imaging.

PURPOSE: To assess the repeatability of blood flow velocity index (BFVi) metrics obtained with a recently Food and Drug Administration-cleared laser speckle contrast imaging device, the XyCAM RI (Vasoptic Medical, Inc), and to characterize differences in these metrics among control, glaucoma suspect, and glaucoma participants. DESIGN: Prospective, observational study. PARTICIPANTS: Forty-six participants: 20 control, 16 glaucoma suspect, and 10 glaucoma participants, 1 eye per participant. METHODS: Key dynamic BFVi metrics-mean, peak, dip, volumetric rise index (VRI), volumetric fall index (VFI), time to rise (TtR), time to fall (TtF), blow-out time (BOT), skew, and acceleration time index-were measured in the optic disc, optic disc vessels, optic disc perfusion region, and macula in 4 imaging sessions on the same day. Intrasession and intersession variability were calculated using the coefficient of variation (CV) for each metric in each region of interest (ROI). Values for each dynamic BFVi variable were compared between glaucoma, glaucoma suspect, and control participants using bivariate and multivariate analysis. Pearson correlation coefficients were used to correlate each variable in each ROI with age, intraocular pressure, cup-to-disc ratio (CDR), mean deviation, pattern standard deviation, retinal nerve fiber layer thickness, and minimum rim width. MAIN OUTCOME MEASURES: Coefficient of variation for the intrasession and intersession variability for each dynamic BFVi metric in each ROI and differences in each metric in each ROI between each diagnostic group. RESULTS: Intersession CV for mean, peak, dip, VRI, VFI, TtR, and TtF ranged from 3.2 ± 2.5% to 11.0 ± 3.8%. Age, CDR, OCT metrics, and visual field metrics showed significant correlations with dynamic BFVi variables. Peak, mean, dip, VRI, and VFI were significantly lower in patients with glaucoma than in control participants in all ROIs except the fovea. These metrics also were significantly lower in glaucoma patients than glaucoma suspect patients in the disc vessels. CONCLUSIONS: Dynamic blood flow metrics measured with the XyCAM RI are reliable, are associated with structural and functional glaucoma metrics, and are significantly different among glaucoma, glaucoma suspect, and control participants. The XyCAM RI may serve as an important tool in glaucoma management in the future.

Postoperative complications of Ab-Interno XEN implantation in primary angle closure glaucoma.

The XEN Gel Stent offers a unique Ab-interno approach for managing glaucoma and has shown a favorable risk profile relative to traditional trabeculectomy. XEN implantation has almost exclusively been reported in patients with open angle glaucoma and data in patients with angle closure glaucoma is limited. We report a postoperative complication of the XEN Gel Stent in a patient with primary angle closure glaucoma. An 86-year-old man with primary angle closure glaucoma underwent combined phacoemulsification and XEN implantation. After approximately two months, intraocular pressure was elevated and the stent was occluded by iris pigmentary deposits, traversing from the proximal to the distal conjunctival ends of the stent. Using an Ab-interno approach, the implant was successfully explanted, and the patient's intraocular pressure was notably lowered.

Quantification of Retinal Ganglion Cell Morphology in Human Glaucomatous Eyes.

Purpose: To characterize retinal ganglion cell morphological changes in patients with primary open-angle glaucoma associated with hemifield defect (HD) using adaptive optics-optical coherence tomography (AO-OCT). Methods: Six patients with early to moderate primary open-angle glaucoma with an average age of 58 years associated with HD and six age-matched healthy controls with an average age of 61 years were included. All participants underwent in vivo retinal ganglion cell (RGC) imaging at six primary locations across the macula with AO-OCT. Ganglion cell layer (GCL) somas were manually counted, and morphological parameters of GCL soma density, size, and symmetry were calculated. RGC cellular characteristics were correlated with functional visual field measurements. Results: GCL soma density was 12,799 ± 7747 cells/mm2, 9370 ± 5572 cells/mm2, and 2134 ± 1494 cells/mm2 at 3°, 6°, and 12°, respectively, in glaucoma patients compared with 25,058 ± 4649 cells/mm2, 15,551 ± 2301 cells/mm2, and 3891 ± 1105 cells/mm2 (P < 0.05 for all locations) at the corresponding retinal locations in healthy participants. Mean soma diameter was significantly larger in glaucoma patients (14.20 ± 2.30 µm) compared with the health controls (12.32 ± 1.94 µm, P < 0.05 for all locations); symmetry was 0.36 ± 0.32 and 0.86 ± 0.13 in glaucoma and control cohorts, respectively. Conclusions: Glaucoma patients had lower GCL soma density and symmetry, greater soma size, and increased variation of GCL soma reflectance compared with age-matched control subjects. The morphological changes corresponded with HD, and the cellular level structural loss correlated with visual function loss in glaucoma. AO-based morphological parameters could be potential sensitive biomarkers for glaucoma.

Retinal ganglion cell dysfunction in preclinical Alzheimer's disease: an electrophysiologic biomarker signature.

The current study evaluated retinal function using electroretinography (ERG) in cognitively healthy (CH) participants with preclinical Alzheimer's disease (AD), as classified by cerebral spinal fluid (CSF) Aß42/Tau ratio. Individuals with normal retinal morphology ascertained by spectral-domain optical coherence tomography were enrolled. Full-field ERG, pattern PERG, and photopic negative response (PhNR) were performed in 29 adult participants (58 eyes). Amplitude and implicit times of the ERG wave components were analyzed. Preclinical AD participants showed marked retinal ganglion cell dysfunction relative to controls. The PhNR was significantly diminished in preclinical AD relative to controls. PhNR amplitude and N95 implicit time differentiated CH individuals with CSF biomarkers of AD pathology with 87% sensitivity and 82% specificity. These quantitative electrophysiologic findings expand our understanding of early retinal functional changes that precede cognitive decline in AD. Retinal ganglion cell dysfunction, as detected by ERG, may be a clinically useful, non-invasive in vivo biomarker for early disease detection, which is necessary for ultimately pursuing early intervention.

Neuroretinal Biomarkers for Schizophrenia Spectrum Disorders.

Purpose: We evaluated the patient-control differences and predictive value of the retina as potential biomarkers for schizophrenia. Methods: The institutional study included both eyes of 58 schizophrenia spectrum disorder (SSD) patients (age 37.2 ± 12.3 years) and 35 controls (age 41.1 ± 15.2 years). Retinal nerve fiber layer (RNFL), ganglion cell-inner plexiform layer, outer retinal photoreceptor complex, and total macula thicknesses were measured by optical coherence tomography (OCT). Anterior segment parameters including central corneal thickness, anterior chamber depth, and axial length were measured to rule out confounds on the retinal measures. Results: The peripapillary RNFL was overall significantly thinner in SSD relative to controls (F = 3.97, P = 0.049), most pronounced in the temporal (5.2 µm difference, F = 6.95, P = 0.010) and inferior quadrants (12.1 µm difference, F = 7.32, P = 0.009). There were no significant group differences in thickness for the macular RNFL, ganglion, or photoreceptor cell related measures (P > 0.05). Peripapillary RNFL, central macula, and outer photoreceptor complex thicknesses were together able to classify SSD patients with 80% sensitivity and 71% specificity; area under the curve = 0.82 (95% confidence interval, 0.75-0.88). Conclusions: SSD patients exhibited significant RNFL thinning relative to controls. Notably, retinal thickness measures including both peripapillary and macular data exhibited improved diagnostic accuracy for SSD as compared to these regions alone. Translational Relevance: This is the first study to evaluate the predictive value of both the inner and outer retina in SSD. OCT retinal thickness measures including peripapillary data in conjunction with macular data may provide an informative, noninvasive in vivo ocular biomarker for schizophrenia.

Past, present and future role of retinal imaging in neurodegenerative disease.

Retinal imaging technology is rapidly advancing and can provide ever-increasing amounts of information about the structure, function and molecular composition of retinal tissue in humans in vivo. Most importantly, this information can be obtained rapidly, non-invasively and in many cases using Food and Drug Administration-approved devices that are commercially available. Technologies such as optical coherence tomography have dramatically changed our understanding of retinal disease and in many cases have significantly improved their clinical management. Since the retina is an extension of the brain and shares a common embryological origin with the central nervous system, there has also been intense interest in leveraging the expanding armamentarium of retinal imaging technology to understand, diagnose and monitor neurological diseases. This is particularly appealing because of the high spatial resolution, relatively low-cost and wide availability of retinal imaging modalities such as fundus photography or OCT compared to brain imaging modalities such as magnetic resonance imaging or positron emission tomography. The purpose of this article is to review and synthesize current research about retinal imaging in neurodegenerative disease by providing examples from the literature and elaborating on limitations, challenges and future directions. We begin by providing a general background of the most relevant retinal imaging modalities to ensure that the reader has a foundation on which to understand the clinical studies that are subsequently discussed. We then review the application and results of retinal imaging methodologies to several prevalent neurodegenerative diseases where extensive work has been done including sporadic late onset Alzheimer's Disease, Parkinson's Disease and Huntington's Disease. We also discuss Autosomal Dominant Alzheimer's Disease and cerebrovascular small vessel disease, where the application of retinal imaging holds promise but data is currently scarce. Although cerebrovascular disease is not generally considered a neurodegenerative process, it is both a confounder and contributor to neurodegenerative disease processes that requires more attention. Finally, we discuss ongoing efforts to overcome the limitations in the field and unmet clinical and scientific needs.

OCTA in neurodegenerative optic neuropathies: emerging biomarkers at the eye-brain interface.

OCTA imaging in optic neuropathies.

Corneal Endotheliitis Associated with a Methicillin Resistant Pyogenic Liver Abscess.

Endotheliitis is the inflammation of the corneal endothelium resulting in edema and subsequent loss of vision. Bacterial causes of corneal inflammation primarily of the epithelium with subsequent, secondary involvement of the endothelium have previously been described. Notably, however, there are no reports of isolated endotheliitis related to a bacterial pathogen. We report, for the first time, a case of corneal endotheliitis associated with a pyogenic liver abscess caused by methicillin resistant Staphylococcus aureus (MRSA). Treatment targeting the underlying source of infection led to visual recovery in our patient.