Emerging Disease of the Desert: Rise of West Nile Virus Chorioretinitis in Arizona.

Purpose: To present 7 cases of West Nile virus (WNV)-related chorioretinitis in Arizona. Methods: Retina clinic charts with the terms "chorioretinitis" and "West Nile" were selected from April 1, 2012, to February 1, 2023. Results: Seven patients with initial visits between August 2019 and February 2023 were included. The majority of WNV chorioretinitis cases were seen in the last 4 years of the selected dates. Only 1 patient presented before this time but was excluded for inadequate baseline testing. All 7 patients had hospitalization for neuroinvasive disease before clinical presentation. All patients achieved a final visual acuity of 20/25 to 20/70. Conclusions: In the last 4 years of the study period, an uptrend in WNV chorioretinitis was found in our retina clinics in Arizona, reflecting the overall rise in WNV outbreaks across the state. As WNV continues to rise, the eye specialist should have high suspicion for WNV ocular disease, even in states where WNV had been an uncommon entity.

A Structured Illumination Microscopy Framework with Spatial-Domain Noise Propagation.

Biological images captured by a microscope are characterized by heterogeneous signal-to-noise ratios (SNRs) across the field of view due to spatially varying photon emission and camera noise. State-of-the-art unsupervised structured illumination microscopy (SIM) reconstruction algorithms, commonly implemented in the Fourier domain, do not accurately model this noise and suffer from high-frequency artifacts, user-dependent choices of smoothness constraints making assumptions on biological features, and unphysical negative values in the recovered fluorescence intensity map. On the other hand, supervised methods rely on large datasets for training, and often require retraining for new sample structures. Consequently, achieving high contrast near the maximum theoretical resolution in an unsupervised, physically principled manner remains a challenging task. Here, we propose Bayesian-SIM (B-SIM), an unsupervised Bayesian framework to quantitatively reconstruct SIM data, rectifying these shortcomings by accurately incorporating all noise sources in the spatial domain. To accelerate the reconstruction process for computational feasibility, we devise a parallelized Monte Carlo sampling strategy for inference. We benchmark our framework on both simulated and experimental images, and demonstrate improved contrast permitting feature recovery at up to 25% shorter length scales over state-of-the-art methods at both high- and low-SNR. B-SIM enables unsupervised, quantitative, physically accurate reconstruction without the need for labeled training data, democratizing high-quality SIM reconstruction and expands the capabilities of live-cell SIM to lower SNR, potentially revealing biological features in previously inaccessible regimes.

Two-state swimming: Strategy and survival of a model bacterial predator in response to environmental cues.

Bdellovibrio bacteriovorus is a predatory bacterium preying upon Gram-negative bacteria. As such, B. bacteriovorus has the potential to control antibiotic-resistant pathogens and biofilm populations. To survive and reproduce, B. bacteriovorus must locate and infect a host cell. However, in the temporary absence of prey, it is largely unknown how B. bacteriovorus modulate their motility patterns in response to physical or chemical environmental cues to optimize their energy expenditure. To investigate B. bacteriovorus' predation strategy, we track and quantify their motion by measuring speed distributions as a function of starvation time. While an initial unimodal speed distribution relaxing to one for pure diffusion at long times may be expected, instead we observe a bimodal speed distribution with one mode centered around that expected from diffusion and the other centered at higher speeds. What is more, for an increasing amount of time over which B. bacteriovorus is starved, we observe a progressive reweighting from the active swimming state to an apparent diffusive state in the speed distribution. Distributions of trajectory-averaged speeds for B. bacteriovorus are largely unimodal, indicating switching between a faster swim speed and an apparent diffusive state within individual observed trajectories rather than there being distinct active swimming and apparent diffusive populations. We also find that B. bacteriovorus' apparent diffusive state is not merely caused by the diffusion of inviable bacteria as subsequent spiking experiments show that bacteria can be resuscitated and bimodality restored. Indeed, starved B. bacteriovorus may modulate the frequency and duration of active swimming as a means of balancing energy consumption and procurement. Our results thus point to a reweighting of the swimming frequency on a trajectory basis rather than a population level basis.

Resolving Molecular Heterogeneity with Single-Molecule Centrifugation.

For many classes of biomolecules, population-level heterogeneity is an essential aspect of biological function─from antibodies produced by the immune system to post-translationally modified proteins that regulate cellular processes. However, heterogeneity is difficult to fully characterize for multiple reasons: (i) single-molecule approaches are needed to avoid information lost by ensemble-level averaging, (ii) sufficient statistics must be gathered on both a per-molecule and per-population level, and (iii) a suitable analysis framework is required to make sense of a potentially limited number of intrinsically noisy measurements. Here, we introduce an approach that overcomes these difficulties by combining three techniques: a DNA nanoswitch construct to repeatedly interrogate the same molecule, a benchtop centrifuge force microscope (CFM) to obtain thousands of statistics in a highly parallel manner, and a Bayesian nonparametric (BNP) inference method to resolve separate subpopulations with distinct kinetics. We apply this approach to characterize commercially available antibodies and find that polyclonal antibody from rabbit serum is well-modeled by a mixture of three subpopulations. Our results show how combining a spatially and temporally multiplexed nanoswitch-CFM assay with BNP analysis can help resolve complex biomolecular interactions in heterogeneous samples.

Learning continuous potentials from smFRET.

Potential energy landscapes are useful models in describing events such as protein folding and binding. While single-molecule fluorescence resonance energy transfer (smFRET) experiments encode information on continuous potentials for the system probed, including rarely visited barriers between putative potential minima, this information is rarely decoded from the data. This is because existing analysis methods often model smFRET output assuming, from the onset, that the system probed evolves in a discretized state space to be analyzed within a hidden Markov model (HMM) paradigm. By contrast, here, we infer continuous potentials from smFRET data without discretely approximating the state space. We do so by operating within a Bayesian nonparametric paradigm by placing priors on the family of all possible potential curves. As our inference accounts for a number of required experimental features raising computational cost (such as incorporating discrete photon shot noise), the framework leverages a structured-kernel-interpolation Gaussian process prior to help curtail computational cost. We show that our structured-kernel-interpolation priors for potential energy reconstruction from smFRET analysis accurately infers the potential energy landscape from a smFRET binding experiment. We then illustrate advantages of structured-kernel-interpolation priors for potential energy reconstruction from smFRET over standard HMM approaches by providing information, such as barrier heights and friction coefficients, that is otherwise inaccessible to HMMs.

Inferring potential landscapes from noisy trajectories of particles within an optical feedback trap.

While particle trajectories encode information on their governing potentials, potentials can be challenging to robustly extract from trajectories. Measurement errors may corrupt a particle's position, and sparse sampling of the potential limits data in higher energy regions such as barriers. We develop a Bayesian method to infer potentials from trajectories corrupted by Markovian measurement noise without assuming prior functional form on the potentials. As an alternative to Gaussian process priors over potentials, we introduce structured kernel interpolation to the Natural Sciences which allows us to extend our analysis to large datasets. Structured-Kernel-Interpolation Priors for Potential Energy Reconstruction (SKIPPER) is validated on 1D and 2D experimental trajectories for particles in a feedback trap.

Diffraction-Limited Molecular Cluster Quantification with Bayesian Nonparametrics.

Life's fundamental processes involve multiple molecules operating in close proximity within cells. To probe the composition and kinetics of molecular clusters confined within small (diffraction-limited) regions, experiments often report on the total fluorescence intensity simultaneously emitted from labeled molecules confined to such regions. Methods exist to enumerate total fluorophore numbers (e.g., step counting by photobleaching). However, methods aimed at step counting by photobleaching cannot treat photophysical dynamics in counting nor learn their associated kinetic rates. Here we propose a method to simultaneously enumerate fluorophores and determine their individual photophysical state trajectories. As the number of active (fluorescent) molecules at any given time is unknown, we rely on Bayesian nonparametrics and use specialized Monte Carlo algorithms to derive our estimates. Our formulation is benchmarked on synthetic and real data sets. While our focus here is on photophysical dynamics (in which labels transition between active and inactive states), such dynamics can also serve as a proxy for other types of dynamics such as assembly and disassembly kinetics of clusters. Similarly, while we focus on the case where all labels are initially fluorescent, other regimes, more appropriate to photoactivated localization microscopy, where fluorophores are instantiated in a non-fluorescent state, fall within the scope of the framework. As such, we provide a complete and versatile framework for the interpretation of complex time traces arising from the simultaneous activity of up to 100 fluorophores.

Resolution of Optic Disc Pit Maculopathy Following Posterior Vitreous Detachment.

Purpose: This work presents a case of significant improvement of optic pit disc maculopathy following an acute posterior vitreous detachment (PVD) and discusses the possible mechanisms of this phenomenon. Methods: A case report and review of the literature are presented. Results: A 56-year-old man presenting with progressive visual decline in his left eye was found to have an optic disc pit with optical coherence tomography (OCT) evidence of severe intraretinal edema and maculoschisis. His visual acuity and macular anatomy on OCT improved dramatically in the months following a PVD. Conclusions: This report presents an interesting case of spontaneous improvement of optic disc pit-related maculopathy following PVD. We discuss the cause of the retinal fluid accumulation in optic disc pit maculopathy and consider that the OCT findings in our case lend credence to the theory that this fluid originates from the vitreous humor.

CHOROIDAL NEOVASCULARIZATION IN NORTH CAROLINA MACULAR DYSTROPHY RESPONSIVE TO ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY.

PURPOSE: To report a new family with North Carolina macular dystrophy including a patient with choroidal neovascularization (CNV). METHODS: Diagnostic modalities included fundus imaging, fluorescein angiography, optical coherence tomography, and genetic testing. The CNV was treated with intravitreal anti-vascular endothelial growth factor according to a treat-and-extend protocol in both eyes. RESULTS: A 60-year-old man presented with North Carolina macular dystrophy with decreasing vision in the left eye and persistently deceased central vision in the right eye. Optical coherence tomography examination showed intraretinal and subretinal fluid consistent with CNV. Genetic testing was performed. Examination of family members showed no signs of CNV. The visual acuity improved from 20/400 to 20/150 in the right eye and from 20/100 to 20/40 in the left eye after intravitreal bevacizumab treatment for CNV. Molecular analysis of the PRDM13 gene revealed a pathogenic heterozygous point mutation. CONCLUSION: Recognition and treatment of CNV in North Carolina macular dystrophy can result in improved vision. Genetic testing of the PRDM13 gene can confirm a molecular diagnosis for North Carolina macular dystrophy.

ACUTE MACULAR EDEMA WITH SEROUS RETINAL DETACHMENT AFTER CATARACT SURGERY IN A VITRECTOMIZED EYE: A CASE REPORT.

PURPOSE: To present the first case of acute macular edema with serous retinal detachment after cataract surgery in a vitrectomized eye. METHODS: A 63-year-old female patient, with history of pars plana vitrectomy and epiretinal membrane removal, underwent uneventful phacoemulsification surgery with injection of standard intracameral dose of cefuroxime (1 mg/0.1 mL of solution) at the end of the procedure. RESULTS: First day after cataract surgery, visual acuity did not correlate with anterior segment findings, and funduscopic eye examination revealed acute macular edema with serous retinal detachment, which was confirmed by spectral domain optical coherence tomography. Fluorescein angiography showed no retinal or choroidal hyperpermeability. At 2-week follow-up visit, visual acuity had significantly improved, and there was complete resolution of macular edema and subretinal fluid. CONCLUSION: The current case suggests that acute macular edema with serous retinal detachment after cataract surgery with standard cefuroxime prophylaxis can occur even in vitrectomized eyes. A high level of suspicious is needed when visual acuity does not correlate with anterior segment findings immediately after cataract surgery. Similar to reports from nonvitrectomized eyes, visual prognosis was favorable.

Retinal Manifestations of Incontinentia Pigmenti: A Case Series of 14 Patients Highlighting the Importance of Intravenous Fluorescein Angiography and the Benefits of Early Laser Photocoagulation.

Purpose: This case series describes the nature and frequency of retinal manifestations in patients with incontinentia pigmenti (IP). Methods: This is a retrospective single-center case series of all known patients with IP who presented to Associated Retina Consultants (Phoenix, AZ) between May 2016 and April 2019. Twenty-eight eyes of 14 patients with a dermatologic diagnosis of IP were included (n = 28). Most patients underwent examination under anesthesia with fundus photographs and intravenous fluorescein angiography (IVFA). Results: Of the 28 eyes, 8 (28.6%) had abnormal retinal findings on fundus examination. Of the 26 eyes that had IVFA, 10 (38.5%) had abnormal findings: Seven eyes (26.9%) had peripheral ischemia, 2 (7.7%) had previous peripheral laser scarring, and 2 (7.7%) had active peripheral neovascularization. Three eyes with normal examination results were found to have mild ischemia by IVFA. Patients with ischemia confirmed by IVFA were treated with laser photocoagulation. During follow-up, 4 previously treated eyes received additional laser photocoagulation. No patients showed vision loss, vitreous hemorrhage, retinal detachment, or adverse effects of treatment. No patients required vitreoretinal surgery. Conclusions: IP is a potentially blinding disease. Our case series demonstrates the efficacy of early treatment and the importance of ancillary testing with IVFA and fundus photography.

Inferring effective forces for Langevin dynamics using Gaussian processes.

Effective forces derived from experimental or in silico molecular dynamics time traces are critical in developing reduced and computationally efficient descriptions of otherwise complex dynamical problems. This helps motivate why it is important to develop methods to efficiently learn effective forces from time series data. A number of methods already exist to do this when data are plentiful but otherwise fail for sparse datasets or datasets where some regions of phase space are undersampled. In addition, any method developed to learn effective forces from time series data should be minimally a priori committal as to the shape of the effective force profile, exploit every data point without reducing data quality through any form of binning or pre-processing, and provide full credible intervals (error bars) about the prediction for the entirety of the effective force curve. Here, we propose a generalization of the Gaussian process, a key tool in Bayesian nonparametric inference and machine learning, which meets all of the above criteria in learning effective forces for the first time.

Bilateral ischemic maculopathy in acquired immune deficiency syndrome.

BACKGROUND: This brief report aims to report a case of bilateral macular ischemia as a cause of sudden decreased vision in a patient with acquired immune deficiency syndrome (AIDS). FINDINGS: A 26-year-old male with disseminated cryptococcal meningitis, Candida thrush, Pneumocystis jiroveci pneumonia, and positive human immunodeficiency virus (HIV) infection with CD4 count of 4 cells/µl complained of sudden blurred vision in both eyes while on treatment with systemic antiviral, antifungal, and antibiotic medications. Ocular examination revealed HIV retinopathy changes with significant macular ischemia in both eyes, which was confirmed by fluorescein angiography. One dose of intravitreal foscarnet (1.2 mg/0.1 cc) was injected in both eyes. Laboratory work-up of serum and vitreous samples showed negative cytomegalovirus (CMV) titers. At 2 weeks of follow-up, he was started on treatment with atripla, a combination anti-retroviral therapy for AIDS. At 6 weeks of follow-up, there was an improvement in visual acuity and clinical findings. CONCLUSIONS: Noninfectious HIV retinopathy in AIDS is common, but bilateral macular ischemia is a rare presentation. It is important to rule out CMV retinitis as it is a major cause of visual morbidity among AIDS patients.

Vitreoretinal lymphoma: changing trends in diagnosis and local treatment modalities at a single institution.

UNLABELLED: In this retrospective study on vitreoretinal lymphoma, there was significant change in diagnosis and treatment trends over 17 years at a single institution. Fine needle aspiration biopsy had replaced vitrectomy to collect vitreous sample and external beam radiotherapy in combination with systemic chemotherapy was replaced by intravitreal methotrexate and rituximab, which regressed vitreoretinal lymphoma (VRL) with no relapses or major ocular complications. INTRODUCTION: The purpose of this study was to report the changing trends in treatment (external beam radiotherapy [EBRT] and intravitreal chemotherapy) of VRL and treatment outcomes at a single institution. MATERIALS AND METHODS: A retrospective chart review of vitreous biopsy proven patients was performed. The data analysis included demographics, systemic lymphoma status, ocular symptoms, clinical and immunocytological findings, treatment methods, and response (intravitreal methotrexate 300 µg/0.05 mL, 1000 µg/0.1 mL of rituximab and EBRT 36-45 Gy) and ocular and systemic lymphoma outcomes at last follow-up. RESULTS: Twelve eyes of 8 patients had intraocular B-cell lymphoma (median age, 61 years; range, 50-83). Central nervous system non-Hodgkin's lymphoma (CNS-NHL) was present in 7 of 8 patients. Most common ocular symptoms were diminution of vision in 4 and floaters in 3 patients. Iritis and uveitis were found in 6 eyes and vitritis in 11 eyes. Retinal infiltrates were present in 8 eyes. Immunocytology revealed elevated levels of interleukin (IL)-10 (12,783.5 pg/mL), IL-6 (26.7 pg/mL), and IgH gene rearrangement. Three patients were treated with EBRT, 6 eyes with intravitreal methotrexate (median, 9.5; range, 2-15), and 2 eyes with intravitreal rituximab injections (median, 4; range, 2-6). Two patients developed marked keratitis because of methotrexate toxicity. At median follow-up of 33.5 months (range, 4-96), VRL had resolved in 7 eyes and persistent in 5 eyes. One patient died because of advanced CNS-NHL. CONCLUSION: Intravitreal chemotherapy provided good control rates for VRL patients in our limited series. Patients with associated CNS-NHL had poorer outcomes.

Laser pointer induced macular damage: case report and mini review.

To report laser pointer induced damage to retina and choroid and briefly review literature. A case report of a 13-year old Caucasian boy developed blurry central vision and central scotoma in right eye (OD). He was exposed for one minute to class IIIA green laser pointer of 650 nm wavelength and 5 mW power. Clinical examination showed a grayish lesion in foveal region. Ancillary testing revealed disruption of the retinal pigment epithelial (RPE) layer in foveal region and indocyanine green angiography demonstrated evidence of choroidal hypofluorescence suggestive of choroidal infarction in OD. Visual acuity improved from 20/100 to 20/60 in one day and he was treated with tapering doses of oral prednisolone (40 mg) for 3 weeks. Laser pointer with a power of >5 mW caused damage to RPE in the macula. Children should not be given laser pointers as toys especially those with label of danger instructions.

Pegaptanib combined with intravitreal injection of moxifloxacin as treatment of wet macular degeneration.

PURPOSE: To evaluate the effectiveness of pegaptanib combined with intravitreal injection of moxifloxacin as treatment of wet macular degeneration. METHODS: This retrospective review included patients who received pegaptanib combined with 165 microg of moxifloxacin every 6 weeks. Ophthalmic examination was performed, and adverse events were recorded at each visit; additional assessments (e.g., optical coherence tomography) were performed when indicated. RESULTS: Eighty eyes of 65 patients were identified; the median length of follow-up was 13.2 months (range, 10-16 months), and eyes received an average of 6 injections (range, 4-9 months). Seventy eyes of 80 patients have been followed for >or=1 year; 80% (65/70) had stable or improved vision, and 97% (68/70) lost <15 letters of vision. CONCLUSION: Pegaptanib combined with intravitreal injection of moxifloxacin appears to be effective treatment of wet macular degeneration.