An Optical Coherence Tomography-Based Measure as an Independent Estimate of Retinal Function in Retinitis Pigmentosa.

Background: With the clinical advances in the field of gene therapy, the development of objective measures of visual function of patients with inherited retinal dystrophies (IRDs) is of utmost importance. Here, we propose one such measure.

Methods: We retrospectively analyzed data from a cohort of 194 eyes of 97 genetically diagnosed patients with retinitis pigmentosa (RP), the most common IRD, followed at the UPMC Vision Institute.

Tuned to Tremor: Increased Sensitivity of Cortico-Basal Ganglia Neurons to Tremor Frequency in the MPTP Nonhuman Primate Model of Parkinson's Disease.

Rest tremor is one of the most prominent clinical features of Parkinson's disease (PD). Here, we hypothesized that cortico-basal ganglia neurons tend to fire in a pattern that matches PD tremor frequency, suggesting a resonance phenomenon. We recorded spiking activity in the primary motor cortex (M1) and globus pallidus external segment of 2 female nonhuman primates, before and after parkinsonian state induction with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

Current Status of Clinical Trials Design and Outcomes in Retinal Gene Therapy.

With the rapid expansion of methods encompassed by the term gene therapy, new trials exploring the safety and efficacy of these methods are initiated more frequently. As a result, important questions arise pertaining the design of these trials and patient participation. One of the most important aspects of any clinical trial is the ability to measure the trial's outcome in a manner that will reflect the effect of the treatment and allow its quantification, whether the trial is aimed at preservation or restoration of retinal cells (photoreceptors and others), vision, or both.

Batch-balanced focal loss: a hybrid solution to class imbalance in deep learning.

Purpose: To validate the effectiveness of an approach called batch-balanced focal loss (BBFL) in enhancing convolutional neural network (CNN) classification performance on imbalanced datasets.

Materials And Methods: BBFL combines two strategies to tackle class imbalance: (1) batch-balancing to equalize model learning of class samples and (2) focal loss to add hard-sample importance to the learning gradient. BBFL was validated on two imbalanced fundus image datasets: a binary retinal nerve fiber layer defect (RNFLD) dataset () and a multiclass glaucoma dataset ().

Coagulase-negative staphylococcal endophthalmitis: clinical severity and outcomes based on speciation.

Objective: To identify characteristics and visual outcomes of coagulase-negative staphylococcal (CoNS) endophthalmitis in the era after the Endophthalmitis Vitrectomy Study.

Design: Single-centre retrospective analysis.

Participants: Forty-two samples from 40 patients with documented CoNS endophthalmitis.

Lifting the iron curtain of vision.

Ocular and specifically retinal toxicities of systemic medications are prevalent and encompass many disease modalities. For many of these pharmaceuticals, established follow-up protocols are in place to ensure timely detection and cessation of therapy. However, while for some disorders, cessation of therapy is a viable option due to existing treatment alternatives, for some others cessation of treatment can be life threatening and/or shorten the patient's life expectancy.

Identification of autosomal recessive novel genes and retinal phenotypes in members of the solute carrier (SLC) superfamily.

Purpose: This study aimed to investigate the clinical and genetic aspects of solute carrier (SLC) genes in inherited retinal diseases (IRDs).

Methods: Exome sequencing data were filtered to identify pathogenic variants in SLC genes. Analysis of transcript and protein expression was performed on fibroblast cell lines and retinal sections.

Autoimmune retinopathy: clinical, electrophysiological, and immunological features in nine patients with long-term follow-up.

Purpose: We aim to report on the clinical, imaging, immunological, and electrophysiological features of patients with autoimmune retinopathy (AIR) with long-term follow-up.

Methods: Single-center, retrospective study of a consecutive group of AIR patients treated in a tertiary academic medical center.

Results: Included were nine patients with a mean ± SD age at presentation of 65 ± 13 years and a median follow-up of 63 months (range 18-120).

Broadening INPP5E phenotypic spectrum: detection of rare variants in syndromic and non-syndromic IRD.

Pathogenic variants in INPP5E cause Joubert syndrome (JBTS), a ciliopathy with retinal involvement. However, despite sporadic cases in large cohort sequencing studies, a clear association with non-syndromic inherited retinal degenerations (IRDs) has not been made. We validate this association by reporting 16 non-syndromic IRD patients from ten families with bi-allelic mutations in INPP5E.

How do the blind 'see'? The role of spontaneous brain activity in self-generated perception.

Spontaneous activity of the human brain has been well documented, but little is known about the functional role of this ubiquitous neural phenomenon. It has previously been hypothesized that spontaneous brain activity underlies unprompted (internally generated) behaviour. We tested whether spontaneous brain activity might underlie internally-generated vision by studying the cortical visual system of five blind/visually-impaired individuals who experience vivid visual hallucinations (Charles Bonnet syndrome).

Surface Modification by Nano-Structures Reduces Viable Bacterial Biofilm in Aerobic and Anaerobic Environments.

Bacterial biofilm formation on wet surfaces represents a significant problem in medicine and environmental sciences. One of the strategies to prevent or eliminate surface adhesion of organisms is surface modification and coating. However, the current coating technologies possess several drawbacks, including limited durability, low biocompatibility and high cost.

The combination of whole-exome sequencing and clinical analysis allows better diagnosis of rare syndromic retinal dystrophies.

Purpose: To identify the accurate clinical diagnosis of rare syndromic inherited retinal diseases (IRDs) based on the combination of clinical and genetic analyses.

Methods: Four unrelated families with various autosomal recessive syndromic inherited retinal diseases were genetically investigated using whole-exome sequencing (WES).

Results: Two affected subjects in family MOL0760 presented with a distinctive combination of short stature, developmental delay, congenital mental retardation, microcephaly, facial dysmorphism and retinitis pigmentosa (RP).

CASE REPORT OF SEVERE PROLIFERATIVE RETINOPATHY IN A PATIENT WITH CONGENITAL LIPODYSTROPHY.

Purpose: A case report of a patient with severe proliferative retinopathy due to congenital lipodystrophy.

Methods: We reviewed the medical history, imaging, and surgical procedures of a 25-year-old woman with a history of congenital lipodystrophy, presenting with bilateral combined tractional and exudative retinal detachment, poorly controlled diabetes mellitus, and extreme dislipidemia.

Results: The patient underwent retinal detachment repair surgery both eyes.

Ketamine induced converged synchronous gamma oscillations in the cortico-basal ganglia network of nonhuman primates.

-methyl-d-aspartate (NMDA) antagonists are widely used in anesthesia, pain management, and schizophrenia animal model studies, and recently as potential antidepressants. However, the mechanisms underlying their anesthetic, psychotic, cognitive, and emotional effects are still elusive. The basal ganglia (BG) integrate input from different cortical domains through their dopamine-modulated connections to achieve optimal behavior control.

Trends of Bacterial Keratitis Culture Isolates in Jerusalem; a 13- Years Analysis.

Purpose: To describe the trends in pathogens and antibacterial resistance of corneal culture isolates in infectious keratitis during a period of 13 years at Hadassah-Hebrew University Medical Center.

Methods: A Retrospective analysis of bacterial corneal isolates was performed during the months of January 2002 to December 2014 at Hadassah Hebrew University Medical Center. Demographics, microbiological data and antibiotic resistance and sensitivity were collected.

Genetics and Disease Expression in the CNGA3 Form of Achromatopsia: Steps on the Path to Gene Therapy.

Purpose: Achromatopsia (ACHM) is a congenital, autosomal recessive retinal disease that manifests cone dysfunction, reduced visual acuity and color vision, nystagmus, and photoaversion. Five genes are known causes of ACHM. The present study took steps toward performing a trial of gene therapy in ACHM by characterizing the genetics of ACHM in Israel and the Palestinian Territories and analyzing retinal function and structure in CNGA3 ACHM patients from the Israeli-Palestinian population and US patients with other origins.

Closed-loop deep brain stimulation is superior in ameliorating parkinsonism.

Continuous high-frequency deep brain stimulation (DBS) is a widely used therapy for advanced Parkinson's disease (PD) management. However, the mechanisms underlying DBS effects remain enigmatic and are the subject of an ongoing debate. Here, we present and test a closed-loop stimulation strategy for PD in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) primate model of PD.

Neighboring Pallidal Neurons Do Not Exhibit more Synchronous Oscillations than Remote Ones in the MPTP Primate Model of Parkinson's Disease.

In the healthy primate, neurons of the external and internal segments of the globus pallidus (GP) present a primarily irregular firing pattern, and a negligible level of synchrony is observed between pairs of neurons. This holds even for neighboring cells, despite their higher probability to receive common inputs and to innervate each other via lateral connectivity. In the Parkinsonian primate, this changes drastically, and many pairs of GP cells show synchronous oscillations.

Encoding of probabilistic rewarding and aversive events by pallidal and nigral neurons.

Previous studies have rarely tested whether the activity of high-frequency discharge (HFD) neurons of the basal ganglia (BG) is modulated by expectation, delivery, and omission of aversive events. Therefore the full value domain encoded by the BG network is still unknown. We studied the activity of HFD neurons of the globus pallidus external segment (GPe, n=310), internal segment (GPi, n=149), and substantia nigra pars reticulata (SNr, n=145) in two monkeys during a classical conditioning task with cues predicting the probability of food, neutral, or airpuff outcomes.

Physiology and pathophysiology of the basal ganglia-thalamo-cortical networks.

Low-frequency resting tremor is one of the cardinal signs of Parkinson's disease (PD) and occurs also in some of its animal models. Current physiological studies and models of the basal ganglia indicate that changes of discharge pattern and synchronization of basal ganglia neurons rather than modification in their discharge rate are crucial to the pathophysiology of PD. However, parkinsonian tremor is not strictly correlated with the synchronous oscillations in the basal ganglia networks.

Low-pass filter properties of basal ganglia cortical muscle loops in the normal and MPTP primate model of parkinsonism.

Oscillatory bursting activity is commonly found in the basal ganglia (BG) and the thalamus of the parkinsonian brain. The frequency of these oscillations is often similar to or higher than that of the parkinsonian tremor, but their relationship to the tremor and other parkinsonian symptoms is still under debate. We studied the frequency dependency of information transmission in the cortex-BG and cortex-periphery loops by recording simultaneously from multiple electrodes located in the arm-related primary motor cortex (MI) and in the globus pallidus (GP) of two vervet monkeys before and after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment and induction of parkinsonian symptoms.