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Purpose: To determine whether a low-technology novel virtual vision screening protocol can reliably screen pediatric visual acuity. Methods: Give Kids Sight Day (GKSD), an annual out-reach program, aims to provide free vision screening and ophthalmic care to underserved children in Philadelphia, Pennsylvania. Children were screened virtually through the low-technology protocol. Based on screening results, 152 children were provided in-person eye examinations. Data from in-person examinations were compared to data from virtual screenings for 151 children who were seen in-person. Results: Of 475 children screened virtually, 152 children were seen in-person for examination, and 151 children were included in the analysis. Results from 151 children (mean age: 10.7 years, age range: 5 to 18 years, 43% female, 28% speaking a non-English language) were reviewed. There was a moderate correlation ( R = .64, P < .0001; n = 100 children) between screening and in-person visual acuity without refractive correction and a strong correlation ( R = 0.82, P < .0001; n = 18 children) between screening and in-person visual acuity with refractive correction. Of the 140 children who were seen in-person, 133 children were provided glasses prescriptions. Seventeen children required a referral to a pediatric ophthalmologist for evaluation of ophthalmic conditions, most commonly strabismus (5.3%) and amblyopia (4%). Conclusions: The GKSD virtual visual acuity testing demonstrated good correlation with in-person visual acuity testing, supporting the virtual screening approach as a useful tool for future applications in widespread community vision outreach programs. Further studies are needed to refine virtual ophthalmic screening to optimize its applications in bridging the gaps in ophthalmic care. [ J Pediatr Ophthalmol Strabismus . 20XX;X(X):XX–XX.]

Diabetic retinopathy (DR) is the leading cause of blindness in working-age adults. Severe visual loss in DR is primarily due to proliferative diabetic retinopathy, characterized by pathologic preretinal angiogenesis driven by retinal ischemia. Microglia, the resident immune cells of the retina, have emerged as a potentially important regulator of pathologic retinal angiogenesis. Corticosteroids including triamcinolone acetonide (TA), known for their antiangiogenic effects, are used in treating retinal diseases, but their use is significantly limited by side effects including cataracts and glaucoma. Generation-4 hydroxyl polyamidoamine dendrimer nanoparticles are utilized to deliver TA to activated microglia in the ischemic retina in a mouse model of oxygen-induced retinopathy (OIR). Following intravitreal injection, dendrimer-conjugated TA (D-TA) exhibits selective localization and sustained retention in activated microglia in disease-associated areas of the retina. D-TA, but not free TA, suppresses inflammatory cytokine production, microglial activation, and preretinal neovascularization in OIR. In addition, D-TA, but not free TA, ameliorates OIR-induced neuroretinal and visual dysfunction. These results indicate that activated microglia are a promising therapeutic target for retinal angiogenesis and neuroprotection in ischemic retinal diseases. Furthermore, dendrimer-based targeted therapy and specifically D-TA constitute a promising treatment approach for DR, offering increased and sustained drug efficacy with reduced side effects.

A 32-year-old female with a history of bipolar disorder and schizophrenia was transported to our tertiary-care hospital after swallowing a large toilet paper holder bracket. Removal of the large foreign body required coordination between anesthesiology, otolaryngology, and trauma surgery. A tracheostomy airway was established, and the object was removed transorally. The object was found to be a toilet paper holder bracket measuring 7.5 cm × 5.4 cm × 5.4 cm with a 2.6 cm screw protruding from the end. A review of articles describing the removal of foreign bodies from the upper aerodigestive tract found our object to be the largest foreign body ingestion described in literature. One report suggested that 18% of adult patients with foreign body ingestions had primary neuropsychiatric disorders. Our patient’s psychiatric disorder was a major underlying factor leading to the ingestion, with our patient reporting hallucinations instructing her to ingest household objects.

Spinal cord injury (SCI) often leads to impaired motor and sensory functions, partially because the injury-induced neuronal loss cannot be easily replenished through endogenous mechanisms.In vivoneuronal reprogramming has emerged as a novel technology to regenerate neurons from endogenous glial cells by forced expression of neurogenic transcription factors. We have previously demonstrated successful astrocyte-to-neuron conversion in mouse brains with injury or Alzheimer's disease by overexpressing a single neural transcription factor NeuroD1. Here we demonstrate regeneration of spinal cord neurons from reactive astrocytes after SCI through AAV NeuroD1-based gene therapy. We find that NeuroD1 converts reactive astrocytes into neurons in the dorsal horn of stab-injured spinal cord with high efficiency (~95%). Interestingly, NeuroD1-converted neurons in the dorsal horn mostly acquire glutamatergic neuronal subtype, expressing spinal cord-specific markers such as Tlx3 but not brain-specific markers such as Tbr1, suggesting that the astrocytic lineage and local microenvironment affect the cell fate after conversion. Electrophysiological recordings show that the NeuroD1-converted neurons can functionally mature and integrate into local spinal cord circuitry by displaying repetitive action potentials and spontaneous synaptic responses. We further show that NeuroD1-mediated neuronal conversion can occur in the contusive SCI model with a long delay after injury, allowing future studies to further evaluate thisin vivoreprogramming technology for functional recovery after SCI. In conclusion, this study may suggest a paradigm shift from classical axonal regeneration to neuronal regeneration for spinal cord repair, usingin vivoastrocyte-to-neuron conversion technology to regenerate functional new neurons in the gray matter.

Objective To determine whether the use of fibrin sealant tissue adhesives during lateral neck dissections is associated with a change in postoperative outcomes. Study Design Retrospective cohort. Setting Institutionally affiliated tertiary care center. Methods Various demographic, disease, and surgical data were collected for patients who underwent lateral neck dissections. Univariate regression analysis was performed with the following outcomes: total drain output and duration of drain placement, as well as incidence of postoperative infection, hematoma, seroma, chyle leak, and salivary leak. Results A total of 133 patients underwent lateral neck dissections. Fibrin sealant was used in 35% of cases (n = 46). Its use was not associated with differences in total drain output ( P = .77) or the number of days that the drains were in place ( P = .83). On secondary analysis, the use of fibrin sealant was not associated with a difference in postoperative incidence of hematoma ( P = .65), seroma ( P = .68), chyle leak ( P = .42), or salivary leak ( P = .73). These results were consistent when stratified by the presence of intraoperative complications. Its use accompanied an average cost of $674 per case. Conclusions Fibrin sealant use during lateral neck dissections was not associated with a reduction in drain output or days that the drains remained in situ. Although the current study was limited by sample size, fibrin sealant use was not associated with a decreased risk of postoperative adverse events. The evidence in this report suggests that the routine use of these products adds cost without clear benefit.

PURPOSE To quantitate corneal haze and analyze the postoperative time course of corneal haze after transepithelial corneal collagen cross-linking (TECXL) in patients with keratoconus. METHODS Patients underwent TECXL and were randomized into 2 groups. One group received intraoperative riboflavin 0.10% every minute, and the second group received riboflavin 0.10% every 2 minutes during ultraviolet exposure. Scheimpflug densitometry was measured preoperatively, and at 1, 3, 6, and 12 months to assess the postoperative time course. Densitometry measurements were also correlated with visual acuity, pachymetry, and topography outcomes. RESULTS Fifty-nine eyes of 43 patients with keratoconus were analyzed. Preoperative mean corneal densitometry was 20.45 ± 2.79. Mean densitometry increased at 1 month (22.58 ± 3.79; P < 0.001), did not significantly change between 1 and 3 months (22.64 ± 3.83; P = 0.8), and significantly improved between 3 and 12 months postoperatively (mean6 21.59 ± 3.39; P = 0.002, mean12 20.80 ± 3.27; P = 0.002). There was no difference between preoperative and 1-year densitometry measurements (P = 0.21). There was no significant difference between the 1-minute and 2-minute subgroups. In addition, corneal densitometry at either 3 months or 1 year did not correlate with uncorrected distance visual acuity (P = 0.4), corrected distance visual acuity (P = 0.1), or maximum keratometry (P = 0.5), 1 year after corneal collagen cross-linking (CXL). CONCLUSIONS After TECXL, corneal haze increased slightly at 1 month, plateaued between 1 and 3 months, and returned to baseline between 3 and 12 months. In general, corneal haze in this study was substantially less than the haze previously reported for the standard cross-linking procedure. CXL-associated corneal haze did not correlate with the postoperative visual or topographic outcomes 1 year after CXL.

Ischemic retinopathies are major causes of blindness worldwide. Local hypoxia created by loss of vascular supply leads to tissue injury and aberrant neovascularization in the retina. There is a great need for therapies that enhance revascularization of hypoxic neuroretinal tissue. To test the therapeutic feasibility of human-induced pluripotent stem cell–derived endothelial cells (hiPSC-ECs) for the treatment of ischemic retinopathies, we compared the angiogenic potential of hiPSC-ECs with mature human retinal endothelial cells (HRECs) in response to hypoxia. hiPSC-ECs formed more robust and complex vascular networks in collagen gels, whereas HRECs displayed minimal sprouting. The cells were further tested in the mouse oxygen-induced retinopathy (OIR) model. Retinas with hiPSC-EC injection showed colocalization with host vessels, whereas HRECs lacked such responses. hiPSC-ECs markedly reduced vaso-obliteration and pathological neovascularization. This beneficial effect of hiPSC-ECs was explained by the stromal cell–derived factor-1a (SDF1a)/CXCR4 axis; hiPSC-ECs exhibited much higher cell-surface expression of CXCR4 than HRECs and greater chemotaxis toward SDF1a-embedded 3D collagen hydrogel. Furthermore, treatment with neutralizing antibody to CXCR4 abolished recruitment of hiPSCs in the OIR model. These findings suggest superior angiogenic potential of hiPSC-ECs under hypoxia and underscore the importance of SDF1a/CXCR4 in the reparative function of hiPSC-ECs in ischemic diseases.

Purpose To evaluate outcomes of corneal crosslinking (CXL) using a transepithelial technique for the treatment of keratoconus. Setting Cornea and refractive surgery subspecialty practice. Design Prospective case series. Methods Transepithelial CXL was performed in keratoconic eyes using riboflavin 0.1% and topical anesthetic containing benzalkonium chloride to facilitate riboflavin diffusion through the epithelium. Eyes were randomized to receive riboflavin administration either every 1 minute or every 2 minutes during ultraviolet-A exposure at 3mW/cm2. The principal outcome was change in maximum keratometry (K) and secondary outcomes included uncorrected (UDVA) and corrected (CDVA) distance visual acuities, mean K, and comparison of randomized groups. Results Eighty-two eyes of 56 patients were treated. At 1 year, maximum K decreased significantly by 0.45 diopters (D) ± 1.94 (SD); it improved by 2.0 D or more in 11 eyes (13%) and worsened by 2.0 D or more in 4 eyes (5%). The mean UDVA significantly improved by 0.7 lines, whereas the CDVA improved by 0.2 lines. Two eyes showed both continued progression with loss of CDVA. Only the 1-minute subgroup showed significant improvements in maximum K (−0.73 D) and UDVA. Transient corneal erosion and epitheliopathy were reported in 21% of eyes. Conclusions Transepithelial CXL resulted in significant improvements in maximum K and UDVA over 1 year. There was a suggestion that increased riboflavin dosing might improve procedure outcomes. Further study is required to determine the relative advantages and disadvantages of different transepithelial approaches to the standard CXL protocol with epithelial removal.

The Nrf2-Keap1 pathway regulates transcription of a wide array of antioxidant and cytoprotective genes and offers critical protection against oxidative stress. This pathway has demonstrated benefit for a variety of retinal conditions. Retinal ischemia plays a pivotal role in many vision threatening diseases. Retinal vascular endothelial cells are an important participant in ischemic injury. In this setting, Nrf2 provides a protective pathway via amelioration of oxidative stress and inflammation. In this study, we investigated a potent small molecule inhibitor of the Nrf2-Keap1 protein-protein interaction (PPI), CPUY192018, for its therapeutic potential in retinal cells and retinal ischemia-reperfusion injury. In human retinal endothelial cells (HREC), treatment with CPUY192018 increased Nrf2 protein levels and nuclear translocation, stimulated Nrf2-ARE-induced transcriptional capacity, and induced Nrf2 target gene expression. Furthermore, CPUY192018 protected HREC against oxidative stress and inflammatory activation. CPUY192018 also activated Nrf2 and suppressed inflammatory response in macrophages. In the retinal ischemia-reperfusion (I/R) model, administration of CPUY192018 induced Nrf2 target gene activation in the retina. Both systemic and topical treatment with CPUY192018 rescued visual function after ischemia-reperfusion injury. Taken together, these findings indicate that small molecule Keap1-Nrf2 PPI inhibitors can activate the Nrf2 pathway in the retina and provide protection against retinal ischemic and inflammatory injury, suggesting Keap1-Nrf2 PPI inhibition in the treatment of retinal conditions.

Objective We aimed to find new methods to detect and quantify hemolysis and icterus which may cause assay biases. These methods need to determine each of these interferents in the presence of various other interferents. They also need to have less stringent requirements in development and implementation than those conventional analyzers currently must satisfy. Design and methods We developed two spectral analysis methods that obtain absorption signals of interest by background subtraction or by calculating the spectral curvatures near the peaks of interest. We optimized and tested the performance of these methods using a plasma sample set with permutations of the levels of hemolysis, icterus, and lipemia (using 510 samples in total). Results The processed signals correlated well with concentrations of hemoglobin and bilirubin, indicators of hemolysis and icterus, respectively. Through iterations of randomly splitting the samples for calibration and testing, the two new methods performed as well as those used on conventional analyzers. We demonstrated that the two methods can lessen the application requirements of 1) prior knowledge of the absorption spectra of individual interferents, 2) calibration over a wide concentration range for each interferent, and 3) the need for full-range spectrophotometers spanning most of the ultraviolet/visible spectrum. We also proposed a hardware setup to detect and quantify hemolysis or icterus with a camera and two optical filters. Conclusions This work indicates that new methods of spectral analysis can reduce practical constraints in the development of interference screening systems. These methods could also benefit other assays that rely on reading spectral signals.

Controllable gene delivery via vector-based systems remains a formidable challenge in mammalian synthetic biology and a desirable asset in gene therapy applications. Here, we introduce a methodology to control the copies and residence time of a gene product delivered in host human cells but also selectively disrupt fragments of the delivery vehicle. A crucial element of the proposed system is the CRISPR protein Cas9. Upon delivery, Cas9 guided by a custom RNA sequence cleaves the delivery vector at strategically placed targets thereby inactivating a co-expressed gene of interest. Importantly, using experiments in human embryonic kidney cells, we show that specific parameters of the system can be adjusted to fine-tune the delivery properties. We envision future applications in complex synthetic biology architectures, gene therapy and trace-free delivery.