Staphylococcus aureus is an important human pathogen that causes serious antibiotic-resistant infections. Its population structure is marked by the appearance and dissemination of successful lineages across different settings. To begin understanding the population structure of S. aureus causing ocular and otolaryngology infections, we characterized 262 isolates by antimicrobial sensitivity testing and multilocus sequence typing (MLST). Methicillin-resistant S. aureus were subjected to SCCmec typing and Panton-Valentine leukocidin (PVL) screening. Although we detected a high level of genetic diversity among methicillin-sensitive (MSSA) isolates, (63 sequence types-STs), the population was dominated by five lineages: ST30, ST5, ST8, ST15 and ST97. Resistance to penicillin, erythromycin and clindamycin was common among the major MSSA lineages, with fluctuations markedly impacted by genetic background. Isolates belonging to the predominant lineage, ST30, displayed high rates of resistance to penicillin (100%), erythromycin (71%), and clindamycin (63%). Overall, 21% of the isolates were methicillin-resistant (MRSA), with an apparent enrichment among otitis and orbital cellulitis isolates (>40%). MRSA isolates belonged to 14 STs grouped in 5 clonal complexes (CC), however, CC5 (56.1%) and CC8 (38.6%) dominated the population. Most CC5 strains were SCCmec type II, and resembled the hospital-adapted USA100 clone. CC8 strains were SCCmec type IV, and 86% were positive for the PVL toxin, common features of the community-acquired clone USA300. CC5 strains harboring a SCCmec type IV, typical for the USA800 clone, comprised 15.5% of the population. USA100 strains were highly resistant to clindamycin, erythromycin and levofloxacin (100%), while USA300 strains were frequently resistant to erythromycin (89%) but displayed lower rates of resistance to levofloxacin (39%) and clindamycin (17%). Our data demonstrate that the ocular and otolaryngology S. aureus populations are composed of strains that are commonly resistant to clinically relevant antibiotics, and are associated with the major epidemic clonal complexes of both community and hospital origins.

The Wnt signaling pathway plays a pivotal role in vascular morphogenesis in various organs including the eye. Wnt ligands and receptors are key regulators of ocular angiogenesis both during the eye development and in vascular eye diseases. Wnt signaling participates in regulating multiple vascular beds in the eye including regression of the hyaloid vessels, and development of structured layers of vasculature in the retina. Loss-of-function mutations in Wnt signaling components cause rare genetic eye diseases in humans such as Norrie disease, and familial exudative vitreoretinopathy (FEVR) with defective ocular vasculature. On the other hand, experimental studies in more prevalent vascular eye diseases, such as wet age-related macular degeneration (AMD), diabetic retinopathy (DR), retinopathy of prematurity (ROP), and corneal neovascularization, suggest that aberrantly increased Wnt signaling is one of the causations for pathological ocular neovascularization, indicating the potential of modulating Wnt signaling to ameliorate pathological angiogenesis in eye diseases. This review recapitulates the key roles of the Wnt signaling pathway during ocular vascular development and in vascular eye diseases, and pharmaceutical approaches targeting the Wnt signaling as potential treatment options.

Importance: To facilitate drug and device development for neonates, the International Neonatal Consortium brings together key stakeholders, including pharmaceutical companies, practitioners, regulators, funding agencies, scientists, and families, to address the need for objective, standardized clinical trial outcome measurements to fulfill regulatory requirements. Retinopathy of prematurity (ROP) is a disease that affects preterm neonates. The current International Classification of Retinopathy of Prematurity does not take into account all of the characteristics of ROP and does not adequately discriminate small changes in disease after treatment. These factors are critical for evaluating outcomes in clinical trials. Observations: There is need for an updated ROP acute disease activity and structure scale as well as end-stage structure and ophthalmologic outcome measures designed for use at different ages. The scale and measures, based on current diagnostic methods and treatments, could be used as a guideline for clinical intervention trials. The scale is intended to be validated against retrospective data and revised for use in future trials. An iterative revision process can be accomplished if new measures are added to clinical trials and evaluated at the end of each trial for prognostic value. The new measures would then be incorporated into a new version of the activity scale and the outcome measures revised. Conclusions and Relevance: An ROP activity scale and outcome measures to obtain the most robust and discriminatory data for clinical trials are needed. The scales should be dynamic and modified as knowledge and imaging modalities improve and then validated using data from well-documented clinical trials. This approach is relevant to improving clinical trial data quality.

Mucin glycoproteins on the ocular surface are rich in O-glycans and have important roles in the protection from physical, chemical and microbial impact. In this work, we have cultured human corneal and conjunctival epithelial cells to examine the glycosyltransferase activities that synthesize the O-glycans of mucins. The results indicate that ocular surface epithelial cells have active enzymes that synthesize O-glycans with sialylated core 1, Galβ1-3GalNAcα, and core 2, GlcNAcβ1-6(Galβ1-3)GalNAcα structures which corresponds to previous structural studies. Eye cells also have enzymes that synthesize complex N-glycans that are found on mucins. Results from treatment of eye cells with TNFα suggest that epithelial O-glycosylation changes in a dynamic fashion during inflammatory stimuli of the eye surface.

If homonymous hemianopia develops in childhood it is frequently accompanied by strabismus. In some of these cases the strabismus increases the size of the binocular visual field. We determined how prevalent visual-field-expanding strabismus is in children who have homonymous hemianopia. Medical records were examined from 103 hemianopic patients with exotropia (XT) or esotropia (ET). For each participant, we determined whether their strabismus was in a direction that resulted in visual field expansion (i.e. left exotropia with left homonymous hemianopia). Ages at which hemianopia and strabismus were first noted were compared to determine which developed first. The prevalence of XT (24%) and ET (9%) with homonymous hemianopia were both much higher than in the general population (1.5% and 5%, respectively). More strabismic eyes pointed to the blind than seeing side (62 vs 41, 60% vs. 40%, p = 0.02). Exotropic eyes were five times more likely to point to the blind side than esotropic eyes (85% vs 15%). Strabismus, especially exotropia, is much more common in pediatric homonymous hemianopia than in the general population. The strabismus is significantly more often in a visual field-expanding direction. These results support an adaptive role for the strabismus. Patients with HH and exotropia or esotropia should be aware that their visual field could be reduced by strabismus surgery.

Objective: Otologic methicillin-resistant (MRSA) infection has historically been rare, but given the rise in community-acquired MRSA carriage and infection at other body sites, prevalence rates may be changing. The goal of this study was to determine the prevalence of MRSA in recent otologic cultures from patients with acute otitis externa (AOE). Study design: Retrospective review of an institutional microbiologic database. Methods: A retrospective analysis was performed on serial culture isolates taken from the ear at a quaternary care hospital from January 2014 to April 2016. The causative pathogen and antibiotic sensitivity was determined by culture isolation and end point mean inhibitory concentration (MIC) testing. Medical records were reviewed to document patient characteristics, chronicity of infection, symptomatology, and previous treatments. Results: Over the study period, 173 patients were diagnosed with AOE and underwent otologic cultures of the ear. Fifty-three (30.6%) of cultures grew (SA). Of SA infections, 15 (28.3%) were identified as MRSA. MRSA patients were typically older than patients with methicillin-sensitive SA (MSSA) (mean age 46.7 ± 17.9 29 ± 19.4,  = 0.003) and had more medical comorbidities (4 1.7,  = 0.001). Compared to patients with MSSA, patients with MRSA were significantly more likely to have had prior ototopical antibiotic exposure (37% 73%,  = 0.019). Conclusion: Contemporary ear culture isolates at quaternary care center show higher rates of MRSA compared to historical reports in the literature. Clinicians should consider ear cultures to identify MRSA AOE. Level of Evidence: IV.

The original publication of this article [1] was missing the below author that made contributions to the research and the published article.

Despite advances in therapy for rheumatic diseases, hydroxychloroquine remains almost universally recommended for the treatment of systemic lupus erythematosus (SLE), and is often used in the management of other rheumatic diseases such as rheumatoid arthritis (RA). However, the major dose-limiting toxicity of hydroxychloroquine is retinopathy that can lead to loss of vision. New highly sensitive screening methods can identify early stages of retinopathy, and studies that include these modalities have indicated a substantially higher prevalence of hydroxychloroquine retinopathy than was previously recognized, resulting in revisions to ophthalmology guidelines and the recommendation of a low dose of hydroxychloroquine for many patients. However, the efficacy of low-dose hydroxychloroquine for treating SLE and other rheumatic diseases is unknown. Further studies are required to establish the effectiveness and retinal safety of the latest hydroxychloroquine treatment recommendations.

Purpose: Sjögren syndrome is an autoimmune disease that occurs primarily in women, and is associated with lacrimal gland inflammation and aqueous-deficient dry eye. We hypothesize that sex-associated differences in lacrimal gland gene expression are very important in promoting lymphocyte accumulation in this tissue and contribute to the onset, progression, and/or severity of the inflammatory disease process. To test our hypothesis, we explored the nature and extent of sex-related differences in gene expression in autoimmune lacrimal glands. Methods: Lacrimal glands were collected from age-matched, adult, male and female MRL/MpJ-Tnfrsf6lpr (MRL/lpr) and nonobese diabetic/LtJ (NOD) mice. Glands were processed for the analysis of differentially expressed mRNAs by using CodeLink Bioarrays and Affymetrix GeneChips. Data were evaluated with bioinformatics and statistical software. Results: Our results show that sex significantly influences the expression of thousands of genes in lacrimal glands of MRL/lpr and NOD mice. The immune nature of this glandular response is very dependent on the Sjögren syndrome model. Lacrimal glands of female, as compared with male, MRL/lpr mice contain a significant increase in the expression of genes related to inflammatory responses, antigen processing, and chemokine pathways. In contrast, it is the lacrimal tissue of NOD males, and not females, that presents with a significantly greater expression of immune-related genes. Conclusions: These data support our hypothesis that sex-related differences in gene expression contribute to lacrimal gland disease in Sjögren syndrome. Our findings also suggest that factors in the lacrimal gland microenvironment are critically important in mediating these sex-associated immune effects.