Contact Lens-Related Corneal Infections - United States, 2005-2015.

Keratitis (inflammation of the cornea) can result from contact lens wear or other causes. Keratitis from all causes, including contact lens wear, results in approximately 1 million clinic and emergency department visits annually, with an estimated cost of $175 million in direct health care expenditures in 2010 (1). Approximately 41 million U.S. residents wear contact lenses, and in 2014, >99% of contact lens wearers surveyed reported at least one behavior that puts them at risk for a contact lens-related eye infection (2). The Center for Devices and Radiological Health at the Food and Drug Administration (FDA) regulates contact lenses as medical devices, and certain adverse events related to contact lenses are reported to FDA's Medical Device Report (MDR) database. To describe contact lens-related corneal infections reported to the FDA, 1,075 contact lens-related MDRs containing the terms "ulcer" or "keratitis" reported to FDA during 2005-2015 were analyzed. Among these 1,075 reports, 925 (86.0%) were reported by a contact lens manufacturer and 150 (14.0%) by an eye care provider or patient. Overall, 213 (19.8%) reports described a patient who had a central corneal scar, had a decrease in visual acuity, or required a corneal transplant following the event. Among the reports, 270 (25.1%) described modifiable factors known to be associated with an increased risk for contact lens-related corneal infections, including sleeping in contact lenses or poor contact lens hygiene; the remainder did not provide details that permitted determination of associated factors. Continued efforts to educate contact lens wearers about prevention of contact lens-related eye infections are needed.

Biomechanical and functional variation in rat sciatic nerve following cuff electrode implantation.

BACKGROUND: Nerve cuff electrodes are commonly and successfully used for stimulating peripheral nerves. On the other hand, they occasionally induce functional and morphological changes following chronic implantation, for reasons not always clear. We hypothesize that restriction of nerve mobility due to cuff implantation may alter nerve conduction. METHODS: We quantified acute changes in nerve-muscle electrophysiology, using electromyography, and nerve kinematics in anesthetized Sprague Dawley rat sciatic nerves during controlled hindlimb joint movement. We compared electrophysiological and biomechanical response in uncuffed nerves and those secured within a cuff electrode using analysis of variance (ANOVA) and regression analysis. RESULTS: Tethering resulting from cuff implantation resulted in altered nerve strain and a complex biomechanical environment during joint movement. Coincident with biomechanical changes, electromyography revealed significantly increased variability in the response of conduction latency and amplitude in cuffed, but not free, nerves following joint movement. CONCLUSION: Our findings emphasize the importance of the mechanical interface between peripheral nerves and their devices on neurophysiological performance. This work has implications for nerve device design, implantation, and prediction of long-term efficacy.

Novel applications of diagnostic X-rays in activating a clinical photodynamic drug: Photofrin II through X-ray induced visible luminescence from "rare-earth" formulated particles.

INTRODUCTION: In this communication we report on a novel non-invasive methodology in utilizing "soft" energy diagnostic X-rays to indirectly activate a photo-agent utilized in photodynamic therapy (PDT): Photofrin II (Photo II) through X-ray induced luminescence from Gadolinium Oxysulfide (20 micron dimension) particles doped with Terbium: Gd_{2}O_{2}S:Tb. Photodynamic agents such as Photo II utilized in PDT possess a remarkable property to become preferentially retained within the tumor's micro-environment. Upon the photo-agent's activation through (visible light) photon absorption, the agents exert their cellular cytotoxicity through type I and type II pathways through extensive generation of reactive oxygen species (ROS); namely, singlet oxygen ^{1}O_{2}, superoxide anion O_{2}^{-}, and hydrogen peroxide H_{2}O_{2}, within the intra-tumoral environment. Unfortunately, due to shallow visible light penetration depth (∼ 2 mm to 5 mm) in tissues, the current PDT strategy has largely been restricted to the treatment of surface tumors, such as the melanomas. Additional invasive strategies through optical fibers are currently utilized in getting the visible light into the intended deep seated targets within the body for PDT. METHODS: X-ray induced visible luminescence from Gd_{2}O_{2}S:Tb particles were spectroscopically characterized, and the potential in-vitro cellular cytotoxicity of Gd_{2}O_{2}S:Tb particles on human glioblastoma cells (due to 48 Hrs Gd_{2}O_{2}S:Tb particle exposure) was screened through the MTS cellular metabolic assay. In-vitro human glioblastoma cellular exposures in presence of Photo II with Gd_{2}O_{2}S:Tb particles were performed in the dark in sterile 96 well tissue culture plates, and the corresponding changes in the metabolic activities of the glioblastoma due to 15 minutes of (diagnostic energy) X-ray exposure was determined 48 Hrs after treatment through the MTS assay. RESULTS: Severe suppression (> 90% relative to controls) in the cellular metabolic activity of human glioblastoma was measured due to the treatment of clinically relevant concentrations of 20 µg/ml Photo II, with Gd_{2}O_{2}S:Tb particles, and (120 kVp) diagnostic X-rays. Taken together, the in-vitro findings herein provide the basis for future studies in determining the safety and efficacy of this non-invasive X-ray induced luminescence strategy in activating photo-agent in deep seated tumors.

Longitudinal neural and vascular structural dynamics produced by chronic microelectrode implantation.

Implanted microelectrode arrays sense local neuronal activity, signals which are used as control commands for brain computer interface (BCI) technology. Patients with tetraplegia have used BCI technology to achieve an extraordinary degree of interaction with their local environment. However, current microelectrode arrays for BCIs lose the ability to record high-quality neural signals in the months-to-years following implantation. Very little is known regarding the dynamic response of neurons and vasculature in the months following electrode array implantation, but loss of structural integrity near the electrode may contribute to the degradation of recording signals. Here, we use in-vivo dual-modality imaging to characterize neuronal and vasculature structures in the same animal for 3 months following electrode insertion. We find ongoing neuronal atrophy, but relative vascular stability, in close proximity to the electrode, along with evidence suggesting links between rare, abrupt hypoxic events and neuronal process atrophy.

Longitudinal vascular dynamics following cranial window and electrode implantation measured with speckle variance optical coherence angiography.

Speckle variance optical coherence angiography (OCA) was used to characterize the vascular tissue response from craniotomy, window implantation, and electrode insertion in mouse motor cortex. We observed initial vasodilation ~40% greater than original diameter 2-3 days post-surgery (dps). After 4 weeks, dilation subsided in large vessels (>50 µm diameter) but persisted in smaller vessels (25-50 µm diameter). Neovascularization began 8-12 dps and vessel migration continued throughout the study. Vasodilation and neovascularization were primarily associated with craniotomy and window implantation rather than electrode insertion. Initial evidence of capillary re-mapping in the region surrounding the implanted electrode was manifest in OCA image dissimilarity. Further investigation, including higher resolution imaging, is required to validate the finding. Spontaneous lesions also occurred in many electrode animals, though the inception point appeared random and not directly associated with electrode insertion. OCA allows high resolution, label-free in vivo visualization of neurovascular tissue, which may help determine any biological contribution to chronic electrode signal degradation. Vascular and flow-based biomarkers can aid development of novel neural prostheses.