Case Report: Acute Retinal Necrosis after a Cervical Epidural Steroid Injection.

SIGNIFICANCE: Acute retinal necrosis is a rare, sight-threatening condition typically found in immunocompromised patients and is most commonly caused by varicella zoster virus. Because of the poor prognosis and rapid progression of the disease course, prompt antiviral management is paramount. PURPOSE: A case report of acute retinal necrosis in a patient with herpes virus infection after a cervical epidural corticosteroid injection was performed. Extensive laboratory work and frequent follow-ups are necessary for management. This case report outlines the clinical signs of acute retinal necrosis and discusses the appropriate referrals and treatment needed to improve prognosis. CASE REPORT: A 63-year-old man presented to our eye clinic with symptoms of pain and light sensitivity. Examination revealed anterior uveitis, vitritis, optic disc edema, macular edema, vasculitis, and retinitis of the left eye. The serum antibody test results showed abnormal ranges for varicella zoster virus and herpes simplex virus type 1, and the patient was diagnosed with acute retinal necrosis. Treatment prescribed by a retina specialist included oral valacyclovir and later oral prednisolone, for which the patient responded well before developing the common complication of retinal detachment. CONCLUSIONS: The progressive nature of acute retinal necrosis is usually debilitating to vision, even when managed properly. Because prognosis is often poor, it is important to make proper diagnoses combined with a complete review of the patient's medical history and immune status to prevent further vision loss.

Case Report: Vitamin A Deficiency and Nyctalopia in a Patient with Chronic Pancreatitis.

SIGNIFICANCE: Vitamin A deficiency is a known concern in developing countries, but it is often overlooked in developed regions. A history of conditions causing alimentary malabsorption should be considered when patients present with complaints of nyctalopia. PURPOSE: A case of vitamin A deficiency with nyctalopia in a patient with chronic pancreatitis including pertinent diagnostic testing, treatment, and management is presented. The intent is to draw attention to the condition as a differential diagnosis for nyctalopia due to increased prevalence of conditions causing malabsorption. CASE REPORT: A patient with a history of chronic pancreatitis and pancreatic tumor presented with symptoms of nyctalopia and xerophthalmia. Given his systemic history, testing was ordered to determine serum vitamin A levels and retinal function. After results had confirmed depleted vitamin A levels and diminished retinal function, treatment with both oral and intramuscular vitamin A supplementation was initiated to normalize vitamin A levels and improve retinal photoreceptor function. Subjective improvement in symptoms was reported shortly after beginning supplementation, and ultimately, vitamin A levels and retinal function showed improvement after intramuscular treatment. CONCLUSIONS: Detailed case history and a careful review of systems along with serum vitamin A testing and, if available, electroretinography to assess retinal function can help to make a definitive diagnosis. With appropriate comanagement with the patient's primary care physician, it is possible for those with nyctalopia to begin vitamin A supplementation and regain retinal function.

Molecular heterogeneity of C. elegans glia across sexes.

A comprehensive description of nervous system function, and sex dimorphism within, is incomplete without clear assessment of the diversity of its component cell types, neurons and glia. C. elegans has an invariant nervous system with the first mapped connectome of a multicellular organism and single-cell atlas of component neurons. Here we present single nuclear RNA-seq evaluation of glia across the entire adult C. elegans nervous system, including both sexes. Machine learning models enabled us to identify both sex-shared and sex-specific glia and glial subclasses. We have identified and validated molecular markers in silico and in vivo for these molecular subcategories. Comparative analytics also reveals previously unappreciated molecular heterogeneity in anatomically identical glia between and within sexes, indicating consequent functional heterogeneity. Furthermore, our datasets reveal that while adult C. elegans glia express neuropeptide genes, they lack the canonical unc-31/CAPS-dependent dense core vesicle release machinery. Thus, glia employ alternate neuromodulator processing mechanisms. Overall, this molecular atlas, available at www.wormglia.org, reveals rich insights into heterogeneity and sex dimorphism in glia across the entire nervous system of an adult animal.

In Vitro CRISPR/Cas9-Directed Gene Editing to Model LRRK2 G2019S Parkinson's Disease in Common Marmosets.

Leucine-rich repeat kinase 2 (LRRK2) G2019S is a relatively common mutation, associated with 1-3% of Parkinson's disease (PD) cases worldwide. G2019S is hypothesized to increase LRRK2 kinase activity. Dopaminergic neurons derived from induced pluripotent stem cells of PD patients carrying LRRK2 G2019S are reported to have several phenotypes compared to wild type controls, including increased activated caspase-3 and reactive oxygen species (ROS), autophagy dysfunction, and simplification of neurites. The common marmoset is envisioned as a candidate nonhuman primate species for comprehensive modeling of genetic mutations. Here, we report our successful use of CRISPR/Cas9 with repair template-mediated homology directed repair to introduce the LRRK2 G2019S mutation, as well as a truncation of the LRRK2 kinase domain, into marmoset embryonic and induced pluripotent stem cells. We found that, similar to humans, marmoset LRRK2 G2019S resulted in elevated kinase activity. Phenotypic evaluation after dopaminergic differentiation demonstrated LRRK2 G2019S-mediated increased intracellular ROS, decreased neuronal viability, and reduced neurite complexity. Importantly, these phenotypes were not observed in clones with LRRK2 truncation. These results demonstrate the feasibility of inducing monogenic mutations in common marmosets and support the use of this species for generating a novel genetic-based model of PD that expresses physiological levels of LRRK2 G2019S.

The significance of retinal image contrast and spatial frequency composition for eye growth modulation in young chicks.

PURPOSE: This study sought further insight into the stimulus dependence of form deprivation myopia, a common response to retinal image degradation in young animals. METHODS: Each of 4 Bangerter diffusing filters (0.6, 0.1, <0.1, and LP (light perception only)) combined with clear plano lenses, as well as plano lenses alone, were fitted monocularly to 4-day-old chicks. Axial ocular dimensions and refractive errors were monitored over a 14-day treatment period, using high frequency A-scan ultrasonography and an autorefractor, respectively. RESULTS: Only the <0.1 and LP filters induced significant form deprivation myopia; these filters induced similarly large myopic shifts in refractive error (mean interocular differences+/-SEM: -9.92+/-1.99, -7.26+/-1.60 D, respectively), coupled to significant increases in both vitreous chamber depths and optical axial lengths (p<0.001). The other 3 groups showed comparable, small changes in their ocular dimensions (p>0.05), and only small myopic shifts in refraction (<3.00 D). The myopia-inducing filters eliminated mid-and-high spatial frequency information. CONCLUSIONS: Our results are consistent with emmetropization being tuned to mid-spatial frequencies. They also imply that form deprivation is not a graded phenomenon.

Developing Bayesian adaptive methods for estimating sensitivity thresholds (d') in Yes-No and forced-choice tasks.

Motivated by Signal Detection Theory (SDT), we developed a family of novel adaptive methods that estimate the sensitivity threshold-the signal intensity corresponding to a pre-defined sensitivity level (d' = 1)-in Yes-No (YN) and Forced-Choice (FC) detection tasks. Rather than focus stimulus sampling to estimate a single level of %Yes or %Correct, the current methods sample psychometric functions more broadly, to concurrently estimate sensitivity and decision factors, and thereby estimate thresholds that are independent of decision confounds. Developed for four tasks-(1) simple YN detection, (2) cued YN detection, which cues the observer's response state before each trial, (3) rated YN detection, which incorporates a Not Sure response, and (4) FC detection-the qYN and qFC methods yield sensitivity thresholds that are independent of the task's decision structure (YN or FC) and/or the observer's subjective response state. Results from simulation and psychophysics suggest that 25 trials (and sometimes less) are sufficient to estimate YN thresholds with reasonable precision (s.d. = 0.10-0.15 decimal log units), but more trials are needed for FC thresholds. When the same subjects were tested across tasks of simple, cued, rated, and FC detection, adaptive threshold estimates exhibited excellent agreement with the method of constant stimuli (MCS), and with each other. These YN adaptive methods deliver criterion-free thresholds that have previously been exclusive to FC methods.

Ethnic differences in dry eye symptoms: effects of corneal staining and length of contact lens wear.

PURPOSE: To explore the relationships among length of contact lens (CL) wear, degree of corneal staining and severity of dryness symptoms, and to determine whether these relationships differ between Asians and non-Asians. METHODS: Adapted soft CL wearers (n=395; 180 Asian, 215 non-Asian) were required to discontinue CL wear for at least 24h and report to the University of California, Berkeley Clinical Research Center (UCB-CRC). Fluorescein corneal staining was graded according to Brien Holden Vision Institute scales. Length of CL wear was reported by subjects and subjective dryness ratings were collected using the UCB-CRC Dry Eye Flow Chart (DEFC). RESULTS: More Asian CL wearers exhibited corneal staining compared to non-Asians, and Asian CL wearers had a higher mean grade of corneal staining (p<0.001), as well as a higher mean DEFC classification (p<0.001). The difference between Asians and non-Asians in grades of corneal staining extent and depth were significant (p<0.001). Among non-Asian CL wearers, dryness symptoms decreased with more years of CL wear and increased in the presence of corneal staining, which was not the case for Asian CL wearers. CONCLUSIONS: Asian soft CL wearers reported more severe dryness symptoms and demonstrated more severe corneal staining overall compared to non-Asians. Among non-Asians, dryness symptoms were less severe on average with increased years of CL wear and more severe in the presence of corneal staining. Dryness severity does not appear to be related to years of CL wear or corneal staining among Asians.