Continuous saline bladder irrigation for two hours following transurethral resection of bladder tumors in patients with non-muscle invasive bladder cancer does not prevent recurrence or progression compared with intravesical Mitomycin-C.

BackgroundIntravesical Mitomycin-C (MMC) following transurethral resection of bladder tumor (TURBT), while efficacious, is associated with side effects and poor utilization. Continuous saline bladder irrigation (CSBI) has been examined as an alternative. In this study we sought to compare the rates of recurrence and/or progression in patients with NMIBC who were treated with either MMC or CSBI after TURBT.MethodsWe retrospectively reviewed records of patients with NMIBC at our institution in 2012-2015. Perioperative use of MMC (40 mg in 20 mL), CSBI (two hours), or neither were recorded. Primary outcome was time to recurrence or progression. Descriptive statistics, chi-squared analysis, Kaplan-Meier survival analysis, and Cox multivariable regression analyses were performed.Results205 patients met inclusion criteria. Forty-five (22.0%) patients received CSBI, 71 (34.6%) received MMC, and 89 (43.4%) received no perioperative therapy. On survival analysis, MMC was associated with improved DFS compared with CSBI (p = 0.001) and no treatment (p = 0.0009). On multivariable analysis, high risk disease was associated with increased risk of recurrence or progression (HR 2.77, 95% CI: 1.28-6.01), whereas adjuvant therapy (HR 0.35, 95% CI: 0.20-0.59) and MMC (HR 0.43, 95% CI: 0.25-0.75) were associated with decreased risk.ConclusionsPostoperative MMC was associated with improved DFS compared with CSBI and no treatment. The DFS benefit seen with CSBI in other studies may be limited to patients receiving prolonged irrigation. New intravesical agents being evaluated may consider saline as a control given our data demonstrating that short-term CSBI is not superior to TURBT alone

Pupillometry evaluation of melanopsin retinal ganglion cell function and sleep-wake activity in pre-symptomatic Alzheimer's disease

BACKGROUND: Melanopsin-expressing retinal ganglion cells (mRGCs), intrinsically photosensitive RGCs, mediate the light-based pupil response and the light entrainment of the body's circadian rhythms through their connection to the pretectal nucleus and hypothalamus, respectively. Increased awareness of circadian rhythm dysfunction in neurological conditions including Alzheimer's disease (AD), has led to a wave of research focusing on the role of mRGCs in these diseases. Postmortem retinal analyses in AD patients demonstrated a significant loss of mRGCs, and in vivo measurements of mRGC function with chromatic pupillometry may be a potential biomarker for early diagnosis and progression of AD. METHODS: We performed a prospective case-control study in 20 cognitively healthy study participants: 10 individuals with pre-symptomatic AD pathology (pre-AD), identified by the presence of abnormal levels of amyloid \u3b242 and total Tau proteins in the cerebrospinal fluid, and 10 age-matched controls with normal CSF amyloid \u3b242 and Tau levels. To evaluate mRGC function, we used a standardized protocol of chromatic pupillometry on a Ganzfeld system using red (640 nm) and blue (450 nm) light stimuli and measured the pupillary light response (PLR). Non-invasive wrist actigraphy and standardized sleep questionnaires were also completed to evaluate rest-activity circadian rhythm. RESULTS: Our results did not demonstrate a significant difference of the PLR between pre-AD and controls but showed a variability of the PLR in the pre-AD group compared with controls on chromatic pupillometry. Wrist actigraphy showed variable sleep-wake patterns and irregular circadian rhythms in the pre-AD group compared with controls. CONCLUSIONS: The variability seen in measurements of mRGC function and sleep-wake cycle in the pre-AD group suggests that mRGC dysfunction occurs in the pre-symptomatic AD stages, preceding cognitive decline. Future longitudinal studies following progression of these participants can help in elucidating the relationship between mRGCs and circadian rhythm dysfunction in AD

Retinal Imaging in Alzheimer’s Disease

Identifying biomarkers of Alzheimer's disease (AD) will accelerate the understanding of its pathophysiology, facilitate screening and risk stratification, and aid in developing new therapies. Developments in non-invasive retinal imaging technologies, including optical coherence tomography (OCT), OCT angiography and digital retinal photography, have provided a means to study neuronal and vascular structures in the retina in people with AD. Both qualitative and quantitative measurements from these retinal imaging technologies (eg, thinning of peripapillary retinal nerve fibre layer, inner retinal layer, and choroidal layer, reduced capillary density, abnormal vasodilatory response) have been shown to be associated with cognitive function impairment and risk of AD. The development of computer algorithms for respective retinal imaging methods has further enhanced the potential of retinal imaging as a viable tool for rapid, early detection and screening of AD. In this review, we present an update of current retinal imaging techniques and their potential applications in AD research. We also discuss the newer retinal imaging techniques and future directions in this expanding field

Retinal nerve fiber layer thickness predicts CSF amyloid/tau before cognitive decline

Background: Alzheimer's disease (AD) pathology precedes symptoms and its detection can identify at-risk individuals who may benefit from early treatment. Since the retinal nerve fiber layer (RNFL) is depleted in established AD, we tested whether its thickness can predict whether cognitively healthy (CH) individuals have a normal or pathological cerebrospinal fluid (CSF) A f42 (A) and tau (T) ratio. Methods: As part of an ongoing longitudinal study, we enrolled CH individuals, excluding those with cognitive impairment and significant ocular pathology. We classified the CH group into two sub-groups, normal (CH-NAT, n = 16) or pathological (CH-PAT, n = 27), using a logistic regression model from the CSF AT ratio that identified >85% of patients with a clinically probable AD diagnosis. Spectral-domain optical coherence tomography (OCT) was acquired for RNFL, ganglion cell-inner plexiform layer (GC-IPL), and macular thickness. Group differences were tested using mixed model repeated measures and a classification model derived using multiple logistic regression. Results: Mean age (\ub1 standard deviation) in the CH-PAT group (n = 27; 75.2 \ub1 8.4 years) was similar (p = 0.50) to the CH-NAT group (n = 16; 74.1 \ub1 7.9 years). Mean RNFL (standard error) was thinner in the CH-PAT group by 9.8 (2.7) \u3bcm; p < 0.001. RNFL thickness classified CH-NAT vs. CH-PAT with 87% sensitivity and 56.3% specificity. Conclusions: Our retinal data predict which individuals have CSF biomarkers of AD pathology before cognitive deficits are detectable with 87% sensitivity. Such results from easy-to-acquire, objective and non-invasive measurements of the RNFL merit further study of OCT technology to monitor or screen for early AD pathology

Choroidal thickness and the retinal ganglion cell complex in chronic Leberʼs hereditary optic neuropathy: a prospective study using swept-source optical coherence tomography

Background/Objectives: Choroidal thinning has been suggested in Leber�s hereditary optic neuropathy (LHON). No study has been conducted of the choroid in relation to the retinal ganglion cell-inner plexiform layer (RGC-IPL). We sought to measure choroidal thickness in chronic LHON and to correlate thickness changes with the RGC-IPL. Subjects/Methods: Chronic LHON, 11778 mitochondrial DNA (mtDNA) mutation, patients (26 eyes; mean age: 35.1 ± 16.1 years) were prospectively recruited at Doheny Eye Center, University of California Los Angeles from March 2016 to July 2017. Age-matched healthy controls (27 eyes; mean age: 32.4 ± 11.1 years) were enroled for comparison. Swept-source optical coherence tomography (SS-OCT) imaging was performed in chronic LHON patients and compared with age-matched healthy controls. Results: The macular choroid was significantly thinner in chronic LHON (250.5 ± 62.2 μm) compared with controls (313.9 ± 60.2 μm; p < 0.0001). The peripapillary choroid was also significantly thinner in chronic LHON (135.7 ± 51.4 μm) compared with controls (183.0 ± 61.8 μm, p < 0.001). Choroidal thickness strongly correlated with retinal nerve fibre layer (RNFL) thickness in both the macular (R2 = 0.72; 95 CI, 0.57�0.84) and peripapillary regions (R2 = 0.53; 95 CI, 0.31�0.70). Choroidal thickness was also significantly correlated with macular RGC-IPL thickness (R2 = 0.51; 95 CI, 0.26�0.73). Conclusions: Choroidal thinning in chronic LHON correlated strongly with both RNFL and RGC-IPL thicknesses. These findings may suggest a pathophysiological mechanism involving vascular pathology of the choroid in relation to the retinal ganglion cell complex in LHON. © 2019, The Author(s), under exclusive licence to The Royal College of Ophthalmologists

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

Parry–Romberg Syndrome with Uhthoff’s Phenomena: A Spectrum of Autoimmune Disease?

Parry–Romberg syndrome (PRS) is a rare disorder characterized by unilateral facial atrophy. Currently, the pathogenesis of PRS is poorly understood and no definitive treatment is available. This article reports the case of a 51-year-old woman with progressive hemifacial atrophy following herpes zoster infection, who presented with a concomitant chronic history of heat-induced diplopia. Magnetic resonance imaging showed unilateral cerebral white matter, periventricular, and medial longitudinal fasciculus lesions. The patient’s diplopia resolved following treatment with valacyclovir. Infection has been previously considered as potential cause of PRS. However, herpes-induced PRS with ophthalmologic manifestations of Uhthoff’s phenomena has not previously been reported. The present case suggests that PRS may possibly have an autoimmune etiology resembling that of multiple sclerosis

Value of medical history in ophthalmology: A study of diagnostic accuracy.

PURPOSE: This study aimed to demonstrate the value of the chief compliant and patient history to accurately diagnose patient pathology without requiring ocular examination or imaging in an outpatient neuro-ophthalmology clinic. METHODS: We prospectively evaluated 115 consecutive patients at our institution from January to April 2009. The attending neuro-ophthalmologist committed to a single most likely diagnosis while solely being exposed to patient demographic information (age, gender, race) and chief complaint, but was otherwise blinded to ocular examination or imaging. The validity of the initial diagnosis was assessed by further acquiring subjective and objective findings and the percentage of correct diagnoses was determined. RESULTS: Patient cases were categorized based on the neuro-ophthalmologic localization of the final diagnoses: afferent nervous system, central nervous system (CNS), efferent nervous system, orbital system, and pupillary system. Correct diagnoses by chief complaint and patient history were 84%, 100%, 86%, 80%, 50% and 100% for afferent, central, efferent, orbit, pupil, and other neuro-ophthalmic diseases, respectively. Over half the cases were correctly diagnosed by chief complaint alone, which improved to 88% when combined with the patient history. CONCLUSIONS: A simple combination of patient history and chief complaint predicts an overall diagnostic accuracy in approximately 90% of cases. Our study demonstrates the remarkable diagnostic value of patient history in neuro-ophthalmologic clinic practice

Value of medical history in ophthalmology: A study of diagnostic accuracy

Purpose: This study aimed to demonstrate the value of the chief compliant and patient history to accurately diagnose patient pathology without requiring ocular examination or imaging in an outpatient neuro-ophthalmology clinic. Methods: We prospectively evaluated 115 consecutive patients at our institution from January to April 2009. The attending neuro-ophthalmologist committed to a single most likely diagnosis while solely being exposed to patient demographic information (age, gender, race) and chief complaint, but was otherwise blinded to ocular examination or imaging. The validity of the initial diagnosis was assessed by further acquiring subjective and objective findings and the percentage of correct diagnoses was determined. Results: Patient cases were categorized based on the neuro-ophthalmologic localization of the final diagnoses: afferent nervous system, central nervous system (CNS), efferent nervous system, orbital system, and pupillary system. Correct diagnoses by chief complaint and patient history were 84%, 100%, 86%, 80%, 50% and 100% for afferent, central, efferent, orbit, pupil, and other neuro-ophthalmic diseases, respectively. Over half the cases were correctly diagnosed by chief complaint alone, which improved to 88% when combined with the patient history. Conclusions: A simple combination of patient history and chief complaint predicts an overall diagnostic accuracy in approximately 90% of cases. Our study demonstrates the remarkable diagnostic value of patient history in neuro-ophthalmologic clinic practice. Keywords: Diagnostic accuracy, Patient history, Neuro-ophthalmolog