Retinal Vasculitis and Intraocular Inflammation after Intravitreal Injection of Brolucizumab.

PURPOSE: To evaluate features and outcomes of eyes with retinal vasculitis and intraocular inflammation (IOI) after intravitreal injection (IVI) of brolucizumab 6 mg/0.05 ml for treatment of neovascular age-related macular degeneration. DESIGN: Retrospective case series. PARTICIPANTS: Fifteen eyes from 12 patients identified from 10 United States centers. METHODS: Review of patient demographics, ophthalmologic examination results, and retinal imaging findings. MAIN OUTCOME MEASURES: Baseline and follow-up visual acuity (VA), prior anti-vascular endothelial growth factor (VEGF) injections, clinical presentation, retinal findings, fluorescein angiography results, and treatment strategies. RESULTS: The number of previous anti-VEGF IVIs ranged between 2 and 80 in the affected eye before switching to brolucizumab. Retinal vasculitis and IOI were diagnosed at a mean of 30 days after brolucizumab IVI. Mean VA before brolucizumab IVI was 0.426 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, 20/53) and VA at diagnosis of retinal vasculitis was 0.981 logMAR (Snellen equivalent, 20/191; range, 20/25-20/1600; P = 0.008). All affected eyes showed IOI with variable combinations of focal or elongated segmental sheathing and discontinuity of small and large retinal arteries, sclerotic arteries, regions of vascular nonperfusion, cotton-wool spots, Kyrieleis plaques, irregular venous caliber with dilated and sclerotic segments, perivenular hemorrhages, and foci of phlebitis. Fluorescein angiography revealed delayed retinal arterial filling, retinal vascular nonperfusion, and variable dye leakage from affected vessels and the optic nerve. Systemic evaluation for embolic causes was unrevealing in 2 patients, and 3 patients showed negative laboratory assessment for uveitis. Treatment consisted of various combinations of corticosteroids (systemic, intravitreal, and topical), and 2 eyes underwent vitrectomy without improvement in vision. After a mean follow-up of 25 days, mean VA was 0.833 logMAR (Snellen equivalent, 20/136), which was reduced compared with baseline (P = 0.033). CONCLUSIONS: Retinal vasculitis and IOI after brolucizumab IVI are characterized by variable occlusion of large or small retinal arteries, or both, and perivenular abnormalities. It may span from peripheral vasculitis to occlusion of large retinal arteries around the optic nerve or macula with severe vision loss. A high index of suspicion is required because vitreous cells may obscure visualization of retinal details.

Multiple-pulse pumping for enhanced fluorescence detection and molecular imaging in tissue.

Applications of fluorescence based imaging techniques for detection in cellular and tissue environments are severely limited by autofluorescence of endogenous components of cells, tissue, and the fixatives used in sample processing. To achieve sufficient signal-to-background ratio, a high concentration of the probe needs to be used which is not always feasible. Since typically autofluorescence is in the nanosecond range, long-lived fluorescence probes in combination with time-gated detection can be used for suppression of unwanted autofluorescence. Unfortunately, this requires the sacrifice of the large portion the probe signal in order to sufficiently filter the background. We report a simple and practical approach to achieve a many-fold increase in the intensity of a long-lived probe without increasing the background fluorescence. Using controllable, well separated bursts of closely spaced laser excitation pulses, we are able to highly increase the fluorescence signal of a long-lived marker over the endogenous fluorescent background and scattering, thereby greatly increasing detection sensitivity. Using a commercially available confocal microscopy system equipped with a laser diode and time correlated single photon counting (TCSPC) detection, we are able to enhance the signal of a long-lived Ruthenium (Ru)-based probe by nearly an order of magnitude. We used 80 MHz bursts of pulses (12.5 ns pulse separation) repeated with a 320 kHz repetition rate as needed to adequately image a dye with a 380 ns lifetime. Just using 10 pulses in the burst increases the Ru signal almost 10-fold without any increase in the background signal.

Steady State and Time Resolved Fluorescence Studies of Azadioxatriangulenium (ADOTA) Fluorophore in Silica and PVA Thin Films.

A cationic azadioxatriangulenium (ADOTA) dye was entrapped in silica thin films obtained by the sol-gel process and in poly (vinyl) alcohol (PVA) thin films. Azadioxatriangulenium is a red emitting fluorophore with a long fluorescence lifetime of ~20 ns. The fluorescent properties of azadioxatriangulenium in silica thin films and PVA films were studied by means of steady-state and time resolved fluorescence techniques. We have found that the azadioxatriangulenium entrapped in silica thin film has a wider fluorescence lifetime distribution (Lorentzian distribution), lower fluorescence efficiencies, shorter lifetimes compared to Azadioxatriangulenium in a PVA film. The local environment of azadioxatriangulenium molecules in the silica thin film is rich with water and ethanol, which creates the possibility of forming excited state aggregates due to high concentration of dye within a small confined area. In contrast to the PVA matrices, the porous silica films allow restricted rotations of Azadioxatriangulenium molecules, which result in faster and complex fluorescence anisotropy decays suggesting energy migration among dye molecules.

Surrogate headform accelerations associated with stick checks in girls' lacrosse.

Girls' lacrosse is fundamentally a different sport than boys' lacrosse, and girls are not required to wear protective headgear. Recent epidemiological studies have found that stick checks are the leading cause of concussion injury in girls' lacrosse. The purpose of this study was to determine stick check speeds and estimate the head acceleration associated with direct checks to the head. In addition, we briefly examine if commercially available headgear can mitigate the accelerations. Seven (n = 7) experienced female lacrosse players checked, with varying severity, a NOSCAE and an ASTM headform. Stick speed at impact and the associated peak linear accelerations of the headform were recorded. The NOCSAE headform was fitted with four commercially available headgear and similar stick impact testing was performed. The median stick impact speed was 8.1 m/s and 777 deg/s. At these speeds, peak linear acceleration was approximately 60g. Three out of the four headgear significantly reduced the peak linear acceleration when compared with the bare headform. These data serve as baseline for understanding the potential mechanism and reduction of concussions from stick impacts in girls' lacrosse.

Comparison of orientation and rotational motion of skeletal muscle cross-bridges containing phosphorylated and dephosphorylated myosin regulatory light chain.

Calcium binding to thin filaments is a major element controlling active force generation in striated muscles. Recent evidence suggests that processes other than Ca(2+) binding, such as phosphorylation of myosin regulatory light chain (RLC) also controls contraction of vertebrate striated muscle (Cooke, R. (2011) Biophys. Rev. 3, 33-45). Electron paramagnetic resonance (EPR) studies using nucleotide analog spin label probes showed that dephosphorylated myosin heads are highly ordered in the relaxed fibers and have very low ATPase activity. This ordered structure of myosin cross-bridges disappears with the phosphorylation of RLC (Stewart, M. (2010) Proc. Natl. Acad. Sci. U.S.A. 107, 430-435). The slower ATPase activity in the dephosporylated moiety has been defined as a new super-relaxed state (SRX). It can be observed in both skeletal and cardiac muscle fibers (Hooijman, P., Stewart, M. A., and Cooke, R. (2011) Biophys. J. 100, 1969-1976). Given the importance of the finding that suggests a novel pathway of regulation of skeletal muscle, we aim to examine the effects of phosphorylation on cross-bridge orientation and rotational motion. We find that: (i) relaxed cross-bridges, but not active ones, are statistically better ordered in muscle where the RLC is dephosporylated compared with phosphorylated RLC; (ii) relaxed phosphorylated and dephosphorylated cross-bridges rotate equally slowly; and (iii) active phosphorylated cross-bridges rotate considerably faster than dephosphorylated ones during isometric contraction but the duty cycle remained the same, suggesting that both phosphorylated and dephosphorylated muscles develop the same isometric tension at full Ca(2+) saturation. A simple theory was developed to account for this fact.

Phosphorylation of myosin regulatory light chain has minimal effect on kinetics and distribution of orientations of cross bridges of rabbit skeletal muscle.

Force production in muscle results from ATP-driven cyclic interactions of myosin with actin. A myosin cross bridge consists of a globular head domain, containing actin and ATP-binding sites, and a neck domain with the associated light chain 1 (LC1) and the regulatory light chain (RLC). The actin polymer serves as a "rail" over which myosin translates. Phosphorylation of the RLC is thought to play a significant role in the regulation of muscle relaxation by increasing the degree of skeletal cross-bridge disorder and increasing muscle ATPase activity. The effect of phosphorylation on skeletal cross-bridge kinetics and the distribution of orientations during steady-state contraction of rabbit muscle is investigated here. Because the kinetics and orientation of an assembly of cross bridges (XBs) can only be studied when an individual XB makes a significant contribution to the overall signal, the number of observed XBs was minimized to ∼20 by limiting the detection volume and concentration of fluorescent XBs. The autofluorescence and photobleaching from an ex vivo sample was reduced by choosing a dye that was excited in the red and observed in the far red. The interference from scattering was eliminated by gating the signal. These techniques decrease large uncertainties associated with determination of the effect of phosphorylation on a few molecules ex vivo with millisecond time resolution. In spite of the remaining uncertainties, we conclude that the state of phosphorylation of RLC had no effect on the rate of dissociation of cross bridges from thin filaments, on the rate of myosin head binding to thin filaments, and on the rate of power stroke. On the other hand, phosphorylation slightly increased the degree of disorder of active cross bridges.

Evaluating and benchmarking the EEG signal quality of high-density, dry MXene-based electrode arrays against gelled Ag/AgCl electrodes.

Objective.To evaluate the signal quality of dry MXene-based electrode arrays (also termed 'MXtrodes') for electroencephalographic (EEG) recordings where gelled Ag/AgCl electrodes are a standard.Approach.We placed 4 × 4 MXtrode arrays and gelled Ag/AgCl electrodes on different scalp locations. The scalp was cleaned with alcohol and rewetted with saline before application. We recorded from both electrode types simultaneously while participants performed a vigilance task.Main results.The root mean squared amplitude of MXtrodes was slightly higher than that of Ag/AgCl electrodes (.24-1.94 uV). Most MXtrode pairs had slightly lower broadband spectral coherence (.05 to .1 dB) and Delta- and Theta-band timeseries correlation (.05 to .1 units) compared to the Ag/AgCl pair (p< .001). However, the magnitude of correlation and coherence was high across both electrode types. Beta-band timeseries correlation and spectral coherence were higher between neighboring MXtrodes in the array (.81 to .84 units) than between any other pair (.70 to .75 units). This result suggests the close spacing of the nearest MXtrodes (3 mm) more densely sampled high spatial-frequency topographies. Event-related potentials were more similar between MXtrodes (ρ⩾ .95) than equally spaced Ag/AgCl electrodes (ρ⩽ .77,p< .001). Dry MXtrode impedance (x̄= 5.15 KΩ cm2) was higher and more variable than gelled Ag/AgCl electrodes (x̄= 1.21 KΩ cm2,p< .001). EEG was also recorded on the scalp across diverse hair types.Significance.Dry MXene-based electrodes record EEG at a quality comparable to conventional gelled Ag/AgCl while requiring minimal scalp preparation and no gel. MXtrodes can record independent signals at a spatial density four times higher than conventional electrodes, including through hair, thus opening novel opportunities for research and clinical applications that could benefit from dry and higher-density configurations.

TMS-induced phase resets depend on TMS intensity and EEG phase.

Objective. The phase of the electroencephalographic (EEG) signal predicts performance in motor, somatosensory, and cognitive functions. Studies suggest that brain phase resets align neural oscillations with external stimuli, or couple oscillations across frequency bands and brain regions. Transcranial Magnetic Stimulation (TMS) can cause phase resets noninvasively in the cortex, thus providing the potential to control phase-sensitive cognitive functions. However, the relationship between TMS parameters and phase resetting is not fully understood. This is especially true of TMS intensity, which may be crucial to enabling precise control over the amount of phase resetting that is induced. Additionally, TMS phase resetting may interact with the instantaneous phase of the brain. Understanding these relationships is crucial to the development of more powerful and controllable stimulation protocols.Approach.To test these relationships, we conducted a TMS-EEG study. We applied single-pulse TMS at varying degrees of stimulation intensity to the motor area in an open loop. Offline, we used an autoregressive algorithm to estimate the phase of the intrinsicµ-Alpha rhythm of the motor cortex at the moment each TMS pulse was delivered.Main results. We identified post-stimulation epochs whereµ-Alpha phase resetting and N100 amplitude depend parametrically on TMS intensity and are significantversusperipheral auditory sham stimulation. We observedµ-Alpha phase inversion after stimulations near peaks but not troughs in the endogenousµ-Alpha rhythm.Significance. These data suggest that low-intensity TMS primarily resets existing oscillations, while at higher intensities TMS may activate previously silent neurons, but only when endogenous oscillations are near the peak phase. These data can guide future studies that seek to induce phase resetting, and point to a way to manipulate the phase resetting effect of TMS by varying only the timing of the pulse with respect to ongoing brain activity.

Enhancing cognitive control with transcranial magnetic stimulation in subject-specific frontoparietal networks.

BACKGROUND: Cognitive control processes, including those involving frontoparietal networks, are highly variable between individuals, posing challenges to basic and clinical sciences. While distinct frontoparietal networks have been associated with specific cognitive control functions such as switching, inhibition, and working memory updating functions, there have been few basic tests of the role of these networks at the individual level. METHODS: To examine the role of cognitive control at the individual level, we conducted a within-subject excitatory transcranial magnetic stimulation (TMS) study in 19 healthy individuals that targeted intrinsic ("resting") frontoparietal networks. Person-specific intrinsic networks were identified with resting state functional magnetic resonance imaging scans to determine TMS targets. The participants performed three cognitive control tasks: an adapted Navon figure-ground task (requiring set switching), n-back (working memory), and Stroop color-word (inhibition). OBJECTIVE: Hypothesis: We predicted that stimulating a network associated with externally oriented control [the "FPCN-B" (fronto-parietal control network)] would improve performance on the set switching and working memory task relative to a network associated with attention (the Dorsal Attention Network, DAN) and cranial vertex in a full within-subjects crossover design. RESULTS: We found that set switching performance was enhanced by FPCN-B stimulation along with some evidence of enhancement in the higher-demand n-back conditions. CONCLUSION: Higher task demands or proactive control might be a distinguishing role of the FPCN-B, and personalized intrinsic network targeting is feasible in TMS designs.

Elimination of autofluorescence in fluorescence correlation spectroscopy using the AzaDiOxaTriAngulenium (ADOTA) fluorophore in combination with time-correlated single-photon counting (TCSPC).

Fluorescence correlation spectroscopy (FCS) is a frequently applied technique that allows for the precise and sensitive analysis of molecular diffusion and interactions. However, the potential of FCS for in vitro or ex vivo studies has not been fully realized due in part to artifacts originating from autofluorescence (fluorescence of inherent components and fixative-induced fluorescence). Here, we propose the azadioxatriangulenium (ADOTA) dye as a solution to this problem. The lifetime of the ADOTA probe, about 19.4 ns, is much longer than most components of autofluorescence. Thus, it can be easily separated by time-correlated single-photon counting methods. Here, we demonstrate the suppression of autofluorescence in FCS using ADOTA-labeled hyaluronan macromolecules (HAs) with Rhodamine 123 added to simulate diffusing fluorescent background components. The emission spectrum and decay rate of Rhodamine 123 overlap with the usual sources of autofluorescence, and its diffusion behavior is well known. We show that the contributions from Rhodamine 123 can be eliminated by time gating or by fluorescence lifetime correlation spectroscopy (FLCS). While the pairing of ADOTA and time gating is an effective strategy for the removal of autofluorescence from fluorescence imaging, the loss of photons leads to erroneous concentration values with FCS. On the other hand, FLCS eliminates autofluorescence without such errors. We then show that both time gating and FLCS may be used successfully with ADOTA-labeled HA to detect the presence of hyaluronidase, the overexpression of which has been observed in many types of cancer.

Elimination of autofluorescence background from fluorescence tissue images by use of time-gated detection and the AzaDiOxaTriAngulenium (ADOTA) fluorophore.

Sample autofluorescence (fluorescence of inherent components of tissue and fixative-induced fluorescence) is a significant problem in direct imaging of molecular processes in biological samples. A large variety of naturally occurring fluorescent components in tissue results in broad emission that overlaps the emission of typical fluorescent dyes used for tissue labeling. In addition, autofluorescence is characterized by complex fluorescence intensity decay composed of multiple components whose lifetimes range from sub-nanoseconds to a few nanoseconds. For these reasons, the real fluorescence signal of the probe is difficult to separate from the unwanted autofluorescence. Here we present a method for reducing the autofluorescence problem by utilizing an azadioxatriangulenium (ADOTA) dye with a fluorescence lifetime of approximately 15 ns, much longer than those of most of the components of autofluorescence. A probe with such a long lifetime enables us to use time-gated intensity imaging to separate the signal of the targeting dye from the autofluorescence. We have shown experimentally that by discarding photons detected within the first 20 ns of the excitation pulse, the signal-to-background ratio is improved fivefold. This time-gating eliminates over 96 % of autofluorescence. Analysis using a variable time-gate may enable quantitative determination of the bound probe without the contributions from the background.

Two Photon Induced Luminescence of BSA Protected Gold Clusters.

In this short letter, we have synthesized the BSA protected Au25 nanoclusters and studied their two photon luminescence behavior. We demonstrate that BSA Au25 nanoclusters can be used as a probe with two photon excitation capability. Our results show a quadratic relation between excitation power and emission intensity whereas with one photon excitation shows a linear dependence. The emission spectrum of BSA Au25 nanoclusters with one photon and two photon excitation shows no appreciable change. Due to its long wavelength emission (650 nm) and two photon excitation, BSA Au25 can be potentially used as a probe for deep tissue imaging.

EEG Phase Can Be Predicted with Similar Accuracy across Cognitive States after Accounting for Power and Signal-to-Noise Ratio.

EEG phase is increasingly used in cognitive neuroscience, brain-computer interfaces, and closed-loop stimulation devices. However, it is unknown how accurate EEG phase prediction is across cognitive states. We determined the EEG phase prediction accuracy of parieto-occipital alpha waves across rest and task states in 484 participants over 11 public datasets. We were able to track EEG phase accurately across various cognitive conditions and datasets, especially during periods of high instantaneous alpha power and signal-to-noise ratio (SNR). Although resting states generally have higher accuracies than task states, absolute accuracy differences were small, with most of these differences attributable to EEG power and SNR. These results suggest that experiments and technologies using EEG phase should focus more on minimizing external noise and waiting for periods of high power rather than inducing a particular cognitive state.

Alerting attention is sufficient to induce a phase-dependent behavior that can be predicted by frontal EEG.

Recent studies suggest that attention is rhythmic. Whether that rhythmicity can be explained by the phase of ongoing neural oscillations, however, is still debated. We contemplate that a step toward untangling the relationship between attention and phase stems from employing simple behavioral tasks that isolate attention from other cognitive functions (perception/decision-making) and by localized monitoring of neural activity with high spatiotemporal resolution over the brain regions associated with the attentional network. In this study, we investigated whether the phase of electroencephalography (EEG) oscillations predicts alerting attention. We isolated the alerting mechanism of attention using the Psychomotor Vigilance Task, which does not involve a perceptual component, and collected high resolution EEG using novel high-density dry EEG arrays at the frontal region of the scalp. We identified that alerting attention alone is sufficient to induce a phase-dependent modulation of behavior at EEG frequencies of 3, 6, and 8 Hz throughout the frontal region, and we quantified the phase that predicts the high and low attention states in our cohort. Our findings disambiguate the relationship between EEG phase and alerting attention.

Randomized Phase IIb Study of Brimonidine Drug Delivery System Generation 2 for Geographic Atrophy in Age-Related Macular Degeneration.

PURPOSE: To evaluate the safety and efficacy of repeat injections of Brimonidine Drug Delivery System (Brimo DDS) Generation 2 (Gen 2) containing 400-µg brimonidine in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). DESIGN: A phase IIb, randomized, multicenter, double-masked, sham-controlled, 30-month study (BEACON). PARTICIPANTS: Patients diagnosed with GA secondary to AMD and multifocal lesions with total area of > 1.25 mm2 and ≤ 18 mm2 in the study eye. METHODS: Enrolled patients were randomized to treatment with intravitreal injections of 400-µg Brimo DDS (n = 154) or sham procedure (n = 156) in the study eye every 3 months from day 1 to month 21. MAIN OUTCOME MEASURES: The primary efficacy endpoint was GA lesion area change from baseline in the study eye, assessed with fundus autofluorescence imaging, at month 24. RESULTS: The study was terminated early, at the time of the planned interim analysis, because of a slow GA progression rate (∼ 1.6 mm2/year) in the enrolled population. Least squares mean (standard error) GA area change from baseline at month 24 (primary endpoint) was 3.24 (0.13) mm2 with Brimo DDS (n = 84) versus 3.48 (0.13) mm2 with sham (n = 91), a reduction of 0.25 mm2 (7%) with Brimo DDS compared with sham (P = 0.150). At month 30, GA area change from baseline was 4.09 (0.15) mm2 with Brimo DDS (n = 49) versus 4.52 (0.15) mm2 with sham (n = 46), a reduction of 0.43 mm2 (10%) with Brimo DDS compared with sham (P = 0.033). Exploratory analysis showed numerically smaller loss over time in retinal sensitivity assessed with scotopic microperimetry with Brimo DDS than with sham (P = 0.053 at month 24). Treatment-related adverse events were usually related to the injection procedure. No implant accumulation was observed. CONCLUSIONS: Multiple intravitreal administrations of Brimo DDS (Gen 2) were well tolerated. The primary efficacy endpoint at 24 months was not met, but there was a numeric trend for reduction in GA progression at 24 months compared with sham treatment. The study was terminated early because of the lower-than-expected GA progression rate in the sham/control group. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosures may be found after the references.

Properties of coatings on RFID p-Chips that support plasmonic fluorescence enhancement in bioassays.

Microtransponders (RFID p-Chips) derivatized with silver island film (SIF) have previously seen success as a platform for the quantification of low-abundance biomolecules in nucleic acid based assays and immunoassays. In this study, we further characterized the morphology of the SIF as well as the polymer matrix enveloping it by scanning electron microscopy (SEM). The polymer was a two-layer silane-based matrix engulfing the p-Chip and SIF. Through a series of SEM and confocal fluorescence microscopy experiments, we found the depth of the polymer matrix to be 1-2 µm. The radiative effects of the SIF/polymer layer were assessed by fluorescence lifetime imaging (FLIM) of p-Chips coated with the polymer to which a fluorophore (Alexa Fluor 555) was conjugated. FLIM images showed an 8.7-fold increase in fluorescence intensity and an increased rate of radiative decay, the latter of which is associated with improved photostability and both of which are linked to plasmonic enhancement by the SIF. Plasmonic enhancement was found to extend uniformly across the p-Chip and, interestingly, to a depth of about 1.2 µm. The substantial depth of enhancement suggests that the SIF/polymer layer constitutes a three-dimensional matrix that is accessible to solvent and small molecules such as fluorescent dyes. Finally, we confirmed that no surface-enhanced Raman scattering is seen from the SIF/polymer combination. The analysis provides a possible mechanism by which the SIF/polymer-coated p-Chips allow a highly sensitive immunoassay and, as a result, leads to an improved bioassay platform.

Fluorescent Polyelectrolyte Capped Silver Nanoclusters: Optimization and Spectroscopic Evaluation.

In the present work, we have synthesized water soluble Ag nanoclusters using PMAA as a template with different Ag+: COO-ratios, to optimize it for highest brightness using less UV exposure time. Fluorescence polarization was 0.30 for and was found to vary with excitation and emission wavelength with few hundred picoseconds average fluorescence lifetime. Fluorescence Correlation Spectroscopy data depicts slower diffusion at red excitation compared to blue excitation in confocal volume than conventionally synthesized colloids proving presence of multiple sizes. The optical properties of the particles are dependent upon the excitation wavelength used and the emission wavelength collected.

Non-excitonic defect-assisted radiative transitions are responsible for new D-type blinking in ternary quantum dots.

This work addresses the issue of dark states formation in QDs by cooperative excitonic and intrinsic defect-assisted radiative transitions. Here we refer to the observed blinking as D-type to distinguish it from purely excitonic types. It is shown experimentally that defect-assisted radiative relaxations in a single I-III-VI QD result in atypical blinking characteristics that cannot be explained on the basis of charged exciton models. In addition to the excitonic channel, it has been proposed that defect-assisted kinetics can also form blinking patterns. Two conditions for the formation of dark states have been identified which are related to correlation and competition when considering photons emitted from bright defects. Two transition schemes have therefore been proposed. The first transition scheme includes time-correlated trapping of more than one electron at a single trap centre. This is used to simulate variations in the defect's charge state and switching between radiative/nonradiative transitions. The latter scheme, on the other hand, involves uncorrelated trapping and radiative relaxations from two different types of defects (competition). Both schemes are seen to play an equal role in radiative processes in I-III-VI QDs. Considered together, the proposed models can reflect the experimental data with very good accuracy, providing a better understanding of the underlying physics. An important implication of these schemes is that dark states formation doesn't have to be limited to mechanisms that involve charged excitons, and it may also be observed for independent defect assisted kinetics. This is especially valid for highly defected or multinary QDs.

Treatment of choroidal neovascularization associated with Best's disease in children.

The development of secondary choroidal neovascularization in Best's disease is rare in the pediatric population. A retrospective review of pediatric patients with choroidal neovascularization secondary to Best's disease was performed. The patients' courses and treatments were recorded. Three patients with choroidal neovascularization were identified. All had decreased vision and were treated in an individual manner. Vision improved after treatment in all patients. Treatment may hasten resolution of choroidal neovascularization and improve vision.

Infectious scleritis after retinal surgery.

PURPOSE: To report a series of patients in whom infectious scleritis developed after vitreoretinal surgery. DESIGN: Interventional case series of four patients. METHODS: Medical records of patients at a single institution in whom infectious scleritis developed after vitreoretinal surgery were reviewed. RESULTS: In three patients, infectious scleritis developed after 20-gauge pars plana vitrectomy, and in one patient, infectious scleritis developed after a scleral buckling procedure. Three cases were had positive culture results; the identified organisms were Pseudomonas aeruginosa in two cases and methicillin-resistant Staphylococcus aureus in one. The fourth patient did not have culture results but responded rapidly to empiric treatment with moxifloxacin. In one patient, surgically induced necrotizing scleritis subsequently developed. CONCLUSIONS: Although infectious scleritis is an uncommon complication after vitreoretinal surgery, it should be a considered cause in patients with persistent postoperative pain and inflammation.