A rare case of occlusive juxtafoveolar retinal telangiectasias associated with lesions of the central nervous system: A cerebroretinal vasculopathy like phenotype without mutations in the TREX1 gene.

PURPOSE: To report a rare case of bilateral occlusive juxtafoveolar retinal telangiectasias associated with central nervous system lesions and renal impairment. OBSERVATIONS: A 47-year-old woman presented to clinic with subjective vision loss in the right eye with best-corrected visual acuity (BCVA) 20/80. Fundoscopic examination, fluorescein angiography (FA), and optical coherence tomography with adjunct angiography (OCT/OCT-A) revealed macular microhemorrhages, enlarged foveal avascular zones (FAZ), and occlusive juxtafoveal telangiectasis with pruning of the macular capillaries in both eyes. Patient subsequently developed memory loss, dizziness, nystagmus, and diplopia secondary to intermittent exotropia. She was found to have a two-millimeter aneurysm of the proximal posterior cerebellar artery along with several scattered white matter changes on brain magnetic resonance imaging (MRI). Genetic workup revealed no mutations in the TREX1 gene. With continued surveillance over 18 months, the patient's BCVA deteriorated to 20/200 OU and she developed mild renal impairment, without further CNS complications. CONCLUSION AND IMPORTANCE: Patients who present with vision loss secondary to occlusive juxtafoveolar telangiectasias should undergo imaging of the central nervous system (CNS) for architectural abnormalities in cerebral vasculature and white matter. Further investigation of patients with the Gass-Blodi type 3 macular telangiectasia - cerebroretinal vasculopathy phenotype is required to optimize management protocols for both retinal and CNS lesions. At this time, no interventions have demonstrated clear benefit in vision preservation or recovery.

Multi-Domain Negative Capacitance Effects in Metal-Ferroelectric-Insulator-Semiconductor/Metal Stacks: A Phase-field Simulation Based Study.

We analyze the ferroelectric domain-wall induced negative capacitance (NC) effect in Metal-FE-Insulator-Metal (MFIM) and Metal-FE-Insulator-Semiconductor (MFIS) stacks through phase-field simulations by self-consistently solving time-dependent Ginzburg Landau equation, Poisson's equation and semiconductor charge equations. Considering Hf0.5Zr0.5O2 as the ferroelectric material, we study 180° ferroelectric domain formation in MFIM and MFIS stacks and their polarization switching characteristics. Our analysis signifies that the applied voltage-induced polarization switching via soft domain-wall displacement exhibits non-hysteretic characteristics. In addition, the change in domain-wall energy, due to domain-wall displacement, exhibits a long-range interaction and thus, leads to a non-homogeneous effective local negative permittivity in the ferroelectric. Such effects yield an average negative effective permittivity that further provides an enhanced charge response in the MFIM stack, compared to Metal-Insulator-Metal. Furthermore, we show that the domain-wall induced negative effective permittivity is not an intrinsic property of the ferroelectric material and therefore, is dependent on its thickness, the gradient energy coefficient and the in-plane permittivity of the underlying insulator. Similar to the MFIM stack, MFIS stack also exhibits an enhanced charge/capacitance response compared to Metal-Oxide-Semiconductor (MOS) capacitor. Simultaneously, the multi-domain state of the ferroelectric induces non-homogeneous potential in the underlying insulator and semiconductor layer. At low applied voltages, such non-homogeneity leads to the co-existence of electrons and holes in an undoped semiconductor. In addition, we show that with the ferroelectric layer being in the 180° multi-domain state, the minimum potential at the ferroelectric-dielectric interface and hence, the minimum surface potential in the semiconductor, does not exceed the applied voltage (in-spite of the local differential amplification and charge enhancement).

Room-Temperature Electrocaloric Effect in Layered Ferroelectric CuInP2S6 for Solid-State Refrigeration.

A material with reversible temperature change capability under an external electric field, known as the electrocaloric effect (ECE), has long been considered as a promising solid-state cooling solution. However, electrocaloric (EC) performance of EC materials generally is not sufficiently high for real cooling applications. As a result, exploring EC materials with high performance is of great interest and importance. Here, we report on the ECE of ferroelectric materials with van der Waals layered structure (CuInP2S6 or CIPS in this work in particular). Over 60% polarization charge change is observed within a temperature change of only 10 K at Curie temperature. Large adiabatic temperature change (|ΔT|) of 3.3 K and isothermal entropy change (|ΔS|) of 5.8 J kg-1 K-1 at |ΔE| = 142.0 kV cm-1 and at 315 K (above and near room temperature) are achieved, with a large EC strength (|ΔT|/|ΔE|) of 29.5 mK cm kV-1. The ECE of CIPS is also investigated theoretically by numerical simulation, and a further EC performance projection is provided.

A unique case of chronic myeloid leukemia presenting as monocular vision loss with unilateral retinopathy.

PURPOSE: To report a case of unilateral leukemic retinopathy secondary to chronic myeloid leukemia (CML). OBSERVATIONS: Patient presented to clinic with a visual acuity (VA) of 20/200 in the right eye (OD) after several months of progressive monocular vision loss and was found to have dense pre-retinal hemorrhage. Patient underwent 23-gauge pars plana vitrectomy to clear the preretinal hemorrhage along with a complex macula-off retinal detachment repair to address retinal tear and multilayer retinal hemorrhage. The patient was subsequently diagnosed with CML as she was found to be positive for the fusion protein of break point cluster gene (BCR) with Abelson tyrosine kinase (ABL1), BCR-ABL1, upon systemic work-up. Imatinib therapy resulted in complete hematologic and cytogenetic resolution after one month, however, the patient's vision remained unchanged six months after surgery. CONCLUSION AND IMPORTANCE: To the authors' knowledge, this is the first reported case of unilateral leukemic retinopathy secondary to low risk CML, as determined by the Sokal and Hasford prognostic scoring systems. CML should be included in the differential diagnosis of patients with progressive monocular vision loss with suspicious multi-layer retinal compromise.

Risk factors for poor outcomes in patients with open-globe injuries.

PURPOSE: The aim of this study was to identify the risk factors that are predictive of poor outcomes in penetrating globe trauma. PATIENTS AND METHODS: This retrospective case series evaluated 103 eyes that had been surgically treated for an open-globe injury from 2007 to 2010 at the eye clinic of the University of Virginia. A total of 64 eyes with complete medical records and at least 6 months of follow-up were included in the study. Four risk factors (preoperative best-corrected visual acuity [pre-op BCVA], ocular trauma score [OTS], zone of injury [ZOI], and time lapse [TL] between injury and primary repair) and three outcomes (final BCVA, monthly rate of additional surgeries [MRAS], and enucleation) were identified for analysis. RESULTS: Pre-op BCVA was positively associated with MRAS, final BCVA, and enucleation. Calculated OTS was negatively associated with the outcome variables. No association was found between TL and ZOI with the outcome variables. Further, age and predictor variable-adjusted analyses showed pre-op BCVA to be independently positively associated with MRAS (P=0.008) and with final BCVA (P<0.001), while the calculated OTS was independently negatively associated with final BCVA (P<0.001), but not uniquely associated with MRAS (P=0.530). CONCLUSION: Pre-op BCVA and OTS are best correlated with prognosis in open-globe injuries. However, no conventional features reliably predict the outcome of traumatized eyes.

Undetected intraocular metallic foreign body causing hyphema in a patient undergoing MRI: a rare occurrence demonstrating the limitations of pre-MRI safety screening.

The case reported is of a 47-year-old man with an undetected ferromagnetic metallic intraocular foreign body in the right eye who underwent elective MR examinations for chronic neck and low back pain. The patient underwent the MR scans and subsequently developed blurred vision in his right eye caused by a hyphema associated with an anterior chamber metallic foreign body. Case reports of orbital injuries in patients with intraocular metallic foreign bodies undergoing MRI are rare, with only one prior report in the radiology literature. While the incidence of intraocular foreign bodies causing injury in patients undergoing MRI is likely rare even among patients with foreign bodies, this case demonstrates that complications from an IMFB can potentially have a subtle presentation. Our case also illustrates potential limitations of pre-MRI safety questionnaires, particularly pertaining to a patient's understanding of the thoroughness of foreign body removal.

A hardware-algorithm co-design approach to optimize seizure detection algorithms for implantable applications.

Implantable neural prostheses that deliver focal electrical stimulation upon demand are rapidly emerging as an alternate therapy for roughly a third of the epileptic patient population that is medically refractory. Seizure detection algorithms enable feedback mechanisms to provide focally and temporally specific intervention. Real-time feasibility and computational complexity often limit most reported detection algorithms to implementations using computers for bedside monitoring or external devices communicating with the implanted electrodes. A comparison of algorithms based on detection efficacy does not present a complete picture of the feasibility of the algorithm with limited computational power, as is the case with most battery-powered applications. We present a two-dimensional design optimization approach that takes into account both detection efficacy and hardware cost in evaluating algorithms for their feasibility in an implantable application. Detection features are first compared for their ability to detect electrographic seizures from micro-electrode data recorded from kainate-treated rats. Circuit models are then used to estimate the dynamic and leakage power consumption of the compared features. A score is assigned based on detection efficacy and the hardware cost for each of the features, then plotted on a two-dimensional design space. An optimal combination of compared features is used to construct an algorithm that provides maximal detection efficacy per unit hardware cost. The methods presented in this paper would facilitate the development of a common platform to benchmark seizure detection algorithms for comparison and feasibility analysis in the next generation of implantable neuroprosthetic devices to treat epilepsy.

The design and hardware implementation of a low-power real-time seizure detection algorithm.

Epilepsy affects more than 1% of the world's population. Responsive neurostimulation is emerging as an alternative therapy for the 30% of the epileptic patient population that does not benefit from pharmacological treatment. Efficient seizure detection algorithms will enable closed-loop epilepsy prostheses by stimulating the epileptogenic focus within an early onset window. Critically, this is expected to reduce neuronal desensitization over time and lead to longer-term device efficacy. This work presents a novel event-based seizure detection algorithm along with a low-power digital circuit implementation. Hippocampal depth-electrode recordings from six kainate-treated rats are used to validate the algorithm and hardware performance in this preliminary study. The design process illustrates crucial trade-offs in translating mathematical models into hardware implementations and validates statistical optimizations made with empirical data analyses on results obtained using a real-time functioning hardware prototype. Using quantitatively predicted thresholds from the depth-electrode recordings, the auto-updating algorithm performs with an average sensitivity and selectivity of 95.3 +/- 0.02% and 88.9 +/- 0.01% (mean +/- SE(alpha = 0.05)), respectively, on untrained data with a detection delay of 8.5 s [5.97, 11.04] from electrographic onset. The hardware implementation is shown feasible using CMOS circuits consuming under 350 nW of power from a 250 mV supply voltage from simulations on the MIT 180 nm SOI process.