PURPOSE: Venous thromboembolic complications have been reported in association with coronavirus disease 2019 (COVID-19) infection. We raised awareness regarding a potential temporal association between COVID-19 infection and retinal vein occlusion (RVO). DESIGN: Multicenter, retrospective, nonconsecutive case series. SUBJECTS: Patients presenting with hemi-RVO (HRVO) or central RVO (CRVO) between March 2020 and March 2021, with confirmed COVID-19 infection, were included. The exclusion criteria were as follows: age >50 years, hypertension, diabetes, glaucoma, obesity, underlying hypercoagulable states, and those requiring intubation during hospitalization. METHODS: This was a multicenter, retrospective, nonconsecutive case series including patients presenting with hemi-RVO (HRVO) or central RVO (CRVO) between March 2020 and March 2021, with confirmed COVID-19 infection. The exclusion criteria were as follows: age >50 years, hypertension, diabetes, glaucoma, obesity, underlying hypercoagulable states, and those requiring intubation during hospitalization. MAIN OUTCOME MEASURES: Ophthalmic findings, including presenting and final visual acuity (VA), imaging findings, and clinical course. RESULTS: Twelve eyes of 12 patients with CRVO (9 of 12) or HRVO (3 of 12) after COVID-19 infection were included. The median age was 32 years (range, 18-50 years). Three patients were hospitalized, but none were intubated. The median time from COVID-19 diagnosis to ophthalmic symptoms was 6.9 weeks. The presenting VA ranged from 20/20 to counting fingers, with over half (7 of 12) having a VA of ≥20/40. OCT revealed macular edema in 42% of the eyes; of these, 80% (4 of 5) were treated with anti-VEGF injections. Ninety-two percent (11 of 12) had partial or complete resolution of ocular findings at final follow-up. Four eyes (33%) had retinal thinning, as determined using OCT, by the end of the study interval. The final VA ranged from 20/20 to 20/60, with 11 of the 12 (92%) eyes achieving a VA of ≥20/40 at a median final follow-up period of 13 weeks (range, 4-52 weeks). CONCLUSIONS: Although we acknowledge the high seroprevalence of COVID-19 and that a causal relationship cannot be established, we reported this series to raise awareness regarding the potential risk of retinal vascular events due to a heightened thromboinflammatory state associated with COVID-19 infection.

Non-human primates (NHPs) are particularly relevant as preclinical models for SARS-CoV-2 infection and nuclear imaging may represent a valuable tool for monitoring infection in this species. We investigated the benefit of computed X-ray tomography (CT) and [18F]-FDG positron emission tomography (PET) to monitor the early phase of the disease in a large cohort (n = 76) of SARS-CoV-2 infected macaques. Following infection, animals showed mild COVID-19 symptoms including typical lung lesions. CT scores at the acute phase reflect the heterogeneity of lung burden following infection. Moreover, [18F]-FDG PET revealed that FDG uptake was significantly higher in the lungs, nasal cavities, lung-draining lymph nodes, and spleen of NHPs by 5 days postinfection compared to pre-infection levels, indicating early local inflammation. The comparison of CT and PET data from previous COVID-19 treatments or vaccines we tested in NHP, to this large cohort of untreated animals demonstrated the value of in vivo imaging in preclinical trials.

Three patients presented with periorbital swelling, pain with extraocular movements, and binocular diplopia 1-4 days after receiving an mRNA Coronavirus Infectious Disease-19 (COVID-19) vaccine (BNT162b2, Pfizer/BioNTech; mRNA-1273, Moderna). All patients had a normal afferent function, unilateral limitation of extraocular motility, proptosis, and periorbital inflammation. Neuroimaging of the orbits with contrast revealed inflammation and enlargement of extraocular muscles in 2 cases and the lacrimal gland in 1 case. In all 3 cases, an extensive infectious and inflammatory laboratory work-up was unremarkable and signs and symptoms of orbital inflammation rapidly improved to complete resolution after treatment with high-dose oral prednisone. This is the first reported series of orbital inflammation occurring shortly after administration of the COVID-19 vaccine. Clinicians may consider an inflammatory postvaccine etiology as an alternative to presumed idiopathic diagnosis in such cases.

Despite constant exposure to various environmental stimuli, the ocular surface remains intact and uninflamed while maintaining the transparency of the cornea and its visual function. This 'immune privilege' of the ocular surface is not simply a result of the physical barrier function of the mucosal lining but, more importantly, is actively maintained through a variety of immunoregulatory mechanisms that prevent the disruption of immune homeostasis. In this review, we focus on essential molecular and cellular players that promote immune quiescence in steady-state conditions and suppress inflammation in disease-states. Specifically, we examine the interactions between the ocular surface and its local draining lymphoid compartment, by encompassing the corneal epithelium, corneal nerves and cornea-resident myeloid cells, conjunctival goblet cells, and regulatory T cells (Treg) in the context of ocular surface autoimmune inflammation (dry eye disease) and alloimmunity (corneal transplantation). A better understanding of the immunoregulatory mechanisms will facilitate the development of novel, targeted immunomodulatory strategies for a broad range of ocular surface inflammatory disorders.

Dark adaptation (DA) refers to the slow recovery of visual sensitivity in darkness following exposure to intense or prolonged illumination, which bleaches a significant amount of the rhodopsin. This natural process also offers an opportunity to understand cellular function in the outer retina and evaluate for presence of disease. How our eyes adapt to darkness can be a key indicator of retinal health, which can be altered in the presence of certain diseases, such as age-related macular degeneration (AMD). A specific focus on clinical aspects of DA measurement and its significance to furthering our understanding of AMD has revealed essential findings underlying the pathobiology of the disease. The process of dark adaptation involves phototransduction taking place mainly between the photoreceptor outer segments and the retinal pigment epithelial (RPE) layer. DA occurs over a large range of luminance and is modulated by both cone and rod photoreceptors. In the photopic ranges, rods are saturated and cone cells adapt to the high luminance levels. However, under scotopic ranges, cones are unable to respond to the dim luminance and rods modulate the responses to lower levels of light as they can respond to even a single photon. Since the cone visual cycle is also based on the Muller cells, measuring the impairment in rod-based dark adaptation is thought to be particularly relevant to diseases such as AMD, which involves both photoreceptors and RPE. Dark adaptation parameters are metrics derived from curve-fitting dark adaptation sensitivities over time and can represent specific cellular function. Parameters such as the cone-rod break (CRB) and rod intercept time (RIT) are particularly sensitive to changes in the outer retina. There is some structural and functional continuum between normal aging and the AMD pathology. Many studies have shown an increase of the rod intercept time (RIT), i.e., delays in rod-mediated DA in AMD patients with increasing disease severity determined by increased drusen grade, pigment changes and the presence of subretinal drusenoid deposits (SDD) and association with certain morphological features in the peripheral retina. Specifications of spatial testing location, repeatability of the testing, ease and availability of the testing device in clinical settings, and test duration in elderly population are also important. We provide a detailed overview in light of all these factors.

ABSTRACT: Ocular surface disease can be difficult to manage, causing patients discomfort and vision loss. Therapeutic contact lenses are an important treatment option that is often neglected because it is conventional wisdom that eyes that are dry or irritated are not good candidates for contact lens. In this focused review, we consider the substantial literature on the use of bandage soft contact lenses (BSCL), scleral lenses, and customized prosthetic devices in the management of ocular graft-vs-host disease. Reports on BSCLs for recurrent corneal erosion are reviewed, as is literature on scleral lenses and prosthetic replacement of the ocular surface ecosystem treatment for Stevens-Johnson syndrome. Clinical pearls for fitting BSCLs are presented, and the issue of antibiotic prophylaxis is considered.

OBJECTIVE: To perform a bibliometric analysis in the field of ocular drug delivery research to characterize the current international trends and to present visual representations of the past and emerging trends on ocular drug delivery research over the past decade. METHOD: In this cross-sectional study, a bibliometric analysis of data retrieved and extracted from the Web of Science Core Collection (WoSCC) database was performed to analyze evolution and theme trends on ocular drug delivery research from January 1, 2001, to December 31, 2020. A total of 4334 articles on ocular drug delivery were evaluated for specific characteristics, such as publication year, journals, authors, institutions, countries/regions, references, and keywords. Co-authorship analysis, co-occurrence analysis, co-citation analysis, and network visualization were constructed by VOSviewer. Some important subtopics identified by bibliometric characterization were further discussed and reviewed. RESULTS: From 2001 to 2020, the annual global publications increased by 746.15%, from 52 to 440. International Journal of Pharmaceutics published the most manuscripts (250 publications) and produced the highest citations (9509 citations), followed by Investigative Ophthalmology & Visual Science (202 publications) and Journal of Ocular Pharmacology and Therapeutics (136 publications). The United States (1289 publications, 31,512 citations), the University of Florida (82 publications, 2986 citations), and Chauhan, Anuj (52 publications, 2354 citations) were the most productive and impactful institution, country, and author respectively. The co-occurrence cluster analysis of the top 100 keywords form five clusters: (1) micro/nano ocular drug delivery systems; (2) the treatment of inflammation and posterior diseases; (3) macroscopic ocular drug delivery systems/devices; (4) the characteristics of drug delivery systems; (5) and the ocular drug delivery for glaucoma treatment. Diabetic macular edema, anti-VEGF, ranibizumab, bevacizumab, micelles and latanoprost, were the latest high-frequency keywords, indicating the emerging frontiers of ocular drug delivery. Further discussions into the subtopics were provided to assist researchers to determine the range of research topics and plan research direction. CONCLUSIONS: Over the last two decades there has been a progressive increase in the number of publications and citations on research related to ocular drug delivery across many countries, institutions, and authors. The present study sheds light on current trends, global collaboration patterns, basic knowledge, research hotspots, and emerging frontiers of ocular drug delivery. Novel solutions for ocular drug delivery and the treatment of inflammation and posterior diseases were the major themes over the last 20 years.

Purpose: To describe 8 cases of reversible reticular corneal epithelial edema of the cornea that developed after use of the topical Rho-kinase inhibitor netarsudil. Methods: This is a retrospective chart review case series of 8 patients treated with netarsudil at an academic medical center. Observations: Patients had predisposing corneal conditions including penetrating keratoplasty, corneal decompensation after trabeculectomy-associated endophthalmitis, congenital glaucoma with Haab striae, aphakic bullous keratopathy, history of Ahmed valve and silicone oil, and Fuchs endothelial corneal dystrophy undergoing Descemet stripping only. One patient did not have clear predisposing corneal disease other than low endothelial cell density and a history of trabeculectomy. All patients developed reticular corneal epithelial edema, which appeared as collections of moderate sized superficial epithelial bullae arranged in a reticular pattern resembling a honeycomb. Most developed these changes within weeks of initiating netarsudil, but unique to this series are 2 cases in which netarsudil was tolerated by the cornea for months before developing reticular corneal epithelial edema after diode laser cyclophotocoagulation. In cases which underwent anterior segment optical coherence tomography, the imaging demonstrated that the corneal stroma was not edematous, and the reticular corneal epithelial edema involved both host and donor corneal epithelium in cases of penetrating keratoplasty. This fully resolved in all cases upon cessation of netarsudil, and this series is the first to document resolution via a pattern in which the individual bullae become smaller and more widely spaced apart. Conclusion: Netarsudil can cause a reversible reticular corneal epithelial edema.

Enterococci are a part of human microbiota and a leading cause of multidrug resistant infections. Here, we identify a family of Enterococcus pore-forming toxins (Epxs) in E. faecalis, E. faecium, and E. hirae strains isolated across the globe. Structural studies reveal that Epxs form a branch of β-barrel pore-forming toxins with a β-barrel protrusion (designated the top domain) sitting atop the cap domain. Through a genome-wide CRISPR-Cas9 screen, we identify human leukocyte antigen class I (HLA-I) complex as a receptor for two members (Epx2 and Epx3), which preferentially recognize human HLA-I and homologous MHC-I of equine, bovine, and porcine, but not murine, origin. Interferon exposure, which stimulates MHC-I expression, sensitizes human cells and intestinal organoids to Epx2 and Epx3 toxicity. Co-culture with Epx2-harboring E. faecium damages human peripheral blood mononuclear cells and intestinal organoids, and this toxicity is neutralized by an Epx2 antibody, demonstrating the toxin-mediated virulence of Epx-carrying Enterococcus.

PURPOSE: To evaluate differences between autorefraction measurements with and without cycloplegia among school-aged individuals and to explore factors associated with significant differences. DESIGN: Cross-sectional, retrospective study. PARTICIPANTS: Individuals between 3 and 22 years of age evaluated at the Illinois College of Optometry from September 2016 through June 2019 who underwent same-day noncycloplegic and cycloplegic autorefraction of the right eye. METHODS: Demographic information including age, sex, and race or ethnicity were collected during the eye examination. Autorefraction was performed before and after cycloplegia. Myopia, defined as at least -0.50 diopter (D) spherical equivalent (SE), hyperopia, defined as at least +0.50 D SE, and astigmatism of at least 1.00 D cylinder were determined using noncycloplegic and cycloplegic autorefractions. Factors associated with at least 1.00 D more myopic SE or at least 0.75 D cylindrical difference by noncycloplegic autorefraction were assessed using logistic regression models. MAIN OUTCOME MEASURES: Differences between noncycloplegic and cycloplegic autorefraction measurements. RESULTS: The mean age was 10.8 ± 4.0 years for the 11 119 individuals; 52.4% of participants were female. Noncycloplegic SE measured 0.65 ± 1.04 D more myopic than cycloplegic SE. After adjusting for demographic factors and refractive error, individuals with at least 1.00 D of more myopic SE refraction by noncycloplegic autorefraction (25.9%) were more likely to be younger than 5 years (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.18-1.79) and 5 to younger than 10 years (OR, 1.32; 95% CI, 1.18-1.48) than those 10 to younger than 15 years. This difference of at least 1.00 D of more myopic SE was more likely to be observed in Hispanic people (OR, 1.23; 95% CI, 1.10-1.36) and those with hyperopia (OR range, 4.20-13.31). Individuals with 0.75 D or more of cylindrical difference (5.1%) between refractions were more likely to be younger than 5 years, to be male, and to have mild-moderate-high myopia or moderate-high hyperopia. CONCLUSIONS: Three quarters of school-aged individuals had < 1 D of myopic SE difference using noncycloplegic compared with cycloplegic autorefraction. Understanding measurement differences obtained for refractive error and associated factors may provide useful information for future studies or programs involving refraction in school-aged children.