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A transocular infection has been proved as one of the main approaches that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) invades the body, and angiotensin-converting enzyme 2 (ACE2) plays a key role in this procedure. Dynamic and quantitative details on virus distribution are lacking for virus prevention and drug design. In this study, a radiotraceable pseudovirus packed with an enhanced green fluorescent protein (EGFP) gene

Background The current outbreak of COVID‐19 has spread rapidly all over the world. Respiratory droplets and contaction with infected patients are the two major transmission routes. However, the value of tear virus nucleic acid is still not clear. We dynamic detected the SARS‐CoV‐2 in eye sample of one COVID‐19 patient with obstruction of common lacrimal ducts. Methods Besides the routine examination, nasopharyngeal and eye swab were continuously measured by polymerase chain reaction assay and next‐generation sequencing (NGS). Gene detection was performed for drug use guidance, and flow cytometry was performed to analyse the lymphocyte subsets. Results Nasopharyngeal swabs were positive for 22 days, but eye swabs were still continuously positive for 2 weeks after nasopharyngeal swabs turned negative. The low level of lymphocyte and the high level IL‐6 lasted for almost 4 weeks, then became near normal. Next‐generation sequencing (NGS) confirmed the existing of SARS‐CoV‐2, HSV1 and HHV6B virus nucleic acid. The gene detection for drug use guidance showed the genetic locus ABCB1 (3435T>C) rs1045642 belonged to type CC and it mean the efficiency of lopinavir–ritonavir would be significantly decreased. The flow cytometry of lymphocyte subsets showed PD‐1+ CD95+ cells was accounting for 94.8% in CD3+ CD8+ T subset and for 94.8% in CD3+ TCRγδ+ T subset. Conclusions As obstruction of common lacrimal duct, positively detection in one eye for 2 weeks more after nasopharyngeal swab became negative. More eye swabs should be collected from COVID‐19 patients, especially from those immunocompromised, those with eye symptoms and those had a history of ocular diseases.

Ever since its outbreak in December 2019, Coronavirus disease 2019 (COVID-19) has shown a rapid spread across the globe and been declared a pandemic by the World Health Organization (WHO) on 11 March 2020 Recently published studies have shown a strong speculation that SARS-CoV-2 may be transmitted through conjunctiva In this review article, we have analyzed the dynamics of receptor modulation on the ocular surface that may be involved in the ocular transmission of the disease Coronavirus, at the moment, albeit seems to have a low risk of ocular spread, the possibility of its long-term survival and replication in the conjunctiva cannot be overlooked, emphasizing the importance of eye protection for prevention of contamination from external droplets and aerosol This article is protected by copyright All rights reserved

Purpose To investigate the ocular manifestations and clinical characteristics of COVID‐19 patients caused by SARS‐CoV‐2 in Wuhan, China. Methods A total of 535 COVID‐19 patients were recruited at Mobile Cabin Hospital and Tongji Hospital. Information on demographic characteristics, exposure history, ocular symptoms, eye drop medication, eye protections, chronic eye diseases, systemic concomitant symptoms, radiologic findings and SARS‐CoV‐2 detection in nasopharyngeal swabs by real‐time PCR was collected from questionnaires and electronic medical records. Results Of 535 patients, 27 patients (5.0%) presented with conjunctival congestion and 4 patients had conjunctival congestion as the initial symptom. The average duration of conjunctival congestion was 5.9 ± 4.5 days (mean [SD]). The other ocular symptoms, including increased conjunctival secretion, ocular pain, photophobia, dry eye and tearing, were also found in patients with conjunctival congestion. Notably, hand–eye contact was independently correlated with conjunctival congestion in COVID‐19 patients. We also found that some COVID‐19 patients had chronic eye diseases, including conjunctivitis (33, 6.2%), xerophthalmia (24, 4.5%) and keratitis (14, 2.6%). Similar to the published studies, the most common clinical symptoms were fever, cough and fatigue. A total of 343 patients (64.1%) had positive SARS‐CoV‐2 detection in nasopharyngeal swabs. Conclusions Conjunctival congestion is one of the COVID‐19‐related ocular symptoms, which could occur as the initial symptoms. Frequent hand–eye contact may be the risk factor for conjunctival congestion in COVID‐19 patients. Screening of patients with conjunctival congestion by ophthalmologists is advocated during the outbreak of COVID‐19. It is essential to provide eye‐care equipment and strengthen education on eye protection.

Purpose To describe the different clinical presentations of periocular molluscum contagiosum (MC) lesions and their epidemiological, clinical and histopathological features. Methods Medical records and histopathological sections of all cases of periocular MC treated at the oculoplastic clinic of the Goldschleger Eye Institute, Sheba Medical Center, Israel, between 1995 and 2016 were retrospectively reviewed. The following data were extracted: gender, age at the time of MC diagnosis, immune competency, location of the periocular lesions, number of lesions, dimensions of the lesions, clinical presentation, histopathological features, suspected clinical diagnosis before histopathological diagnosis and treatment. Results The series was composed of 41 patients (19 males, 22 females) whose mean age at presentation was 20.41 ± 21.10 years (range 1-71 years). Only one patient was immunosuppressed. The cases were classified into six proposed clinical presentations: 'umbilicated nodular', 'big/giant', 'conglomerated', 'erythematous', 'inflamed' and 'pedunculated'. Conclusion This is the first time that different clinical types of MC lesions are labelled. The current evidence also indicates that MC lesions should be suspected not only in children and in immunosuppressed adult patients but also in immunocompetent patients of all ages.

Importance To standardize initial anti-viral therapy for herpes simplex keratitis (HSK). Background To determine prescribing trends for the management of HSK and compare the trends to available clinical trial evidence. Design Retrospective review of patients at the Sydney Eye Hospital, Australia. Participants Three hundred and one eyes of 296 patients prescribed anti-virals for HSK aged 18 years and above, from 1 January 2012 to 31 December 2013. Methods Patients were identified from viral swab results, pharmacy records and International Classification of Diseases 10 (ICD-10) coding data. Main outcome measure Initial anti-viral therapy. Results Anti-viral therapy was given for therapeutic and prophylactic indications at presentation in 256 (85%) and 45 (15%) eyes, respectively. Overall, anti-virals prescribed included valaciclovir 500-1000 mg 1-3 times daily, aciclovir 200-400 mg 1-5 times daily, topical aciclovir 2-5 times daily and topical trifluorothymidine two hourly or as needed daily or combined oral and topical anti-virals. Indication and dose of prescribed anti-virals aligned with clinical evidence in 125 of 141 eyes (89%) with epithelial HSK, 2 of 22 eyes (9%) with stromal without ulceration HSK, 6 of 18 (28%) eyes with endothelial HSK and 31 of 45 (69%) eyes with HSK prophylaxis. Overall, 164 eyes (54%) received 'evidence-based' anti-viral therapy. Conclusions and relevance Prescribing patterns for anti-viral therapy to treat and prevent recurrence of HSK were diverse. Local guidelines are needed to standardize the indications and dose of initial anti-viral therapy for HSK. Implementation of these guidelines will likely improve patient care and rationalize the use of health resources.

PURPOSE To compare topical cyclosporine-A 2% eye drop (Cs-A) with prednisolone acetate 1% eye drop for treatment of herpetic stromal keratitis (HSK). METHODS In this randomized clinical trial, 38 eyes of 33 patients with HSK were randomly assigned to receive either 2% Cs-A or 1% prednisolone acetate eye drops. All subjects received oral acyclovir 400 mg twice a day. Slit-lamp examination, Scheimpflug tomography corneal optical densitometry (Pentacam®, Oculus Inc., Wetzlar, Germany), best-corrected visual acuity (BCVA), and intra-ocular pressure (IOP) were evaluated at the first visit, and 14 and 30 days after the treatment. RESULTS Within-group analysis revealed significant improvement of total cornea optical density after 30 days of treatment in both groups (30.3 ± 10.5 to 28.3 ± 9.8, p

Purpose The purpose of this study was to evaluate the involvement of human papillomavirus in the pathogenesis of primary and recurrent pterygium in northern Israel. Methods A retrospective study examined 100 randomly chosen pterygium specimens with solar elastosis, from 100 patients who underwent pterygium surgery during 2012–2013 at the Emek Medical Center. All the specimens were analysed for evidence of human papillomavirus infection by immunohistochemistry. Results Human papillomavirus was not detected in any of the 100 pterygia samples by immunohistochemistry. These used samples were taken from 100 patients with mean age of 51.5 years and a primary: recurrent ratio of 8.09:1. Conclusion We conclude from our study that human papillomavirus infection does not appear to be an important pathogenic factor of pterygium in Israel.

Membrane nanotubes (MNTs) are newly discovered cellular extensions that are either blind-ended or can connect widely separated cells. They have predominantly been investigated in cultured isolated cells, however, previously we were the first group to demonstrate the existence of these structures in vivo in intact mammalian tissues. We previously demonstrated the frequency of both cell-cell or bridging MNTs and blind-ended MNTs was greatest between major histocompatibility complex (MHC) class II(+) cells during corneal injury or TLR ligand-mediated inflammation. The present study aimed to further explore the dynamics of MNT formation and their size, presence in another tissue, the dura mater, and response to stress factors and an active local viral infection of the murine cornea. Confocal live cell imaging of myeloid-derived cells in inflamed corneal explants from Cx(3)cr1(GFP) and CD11c(eYFP) transgenic mice revealed that MNTs form de novo at a rate of 15.5 μm/min. This observation contrasts with previous studies that demonstrated that in vitro these structures originate from cell-cell contacts. Conditions that promote formation of MNTs include inflammation in vivo and cell stress due to serum starvation ex vivo. Herpes simplex virus-1 infection did not cause a significant increase in MNT numbers in myeloid cells in the cornea above that observed in injury controls, confirming that corneal epithelium injury alone elicits MNT formation in vivo. These novel observations extend the currently limited understanding of MNTs in live mammalian tissues.

Objective To describe clinical and virological findings of an outbreak of ocular disease attributed to naturally-acquired primary canine herpesvirus-1 (CHV-1) infection in a closed domestic dog colony. Animals studied Twenty-seven 10- to 16-week-old laboratory Beagles. Procedure Complete ophthalmic examinations were performed and ocular samples collected for CHV-1 polymerase chain reaction and virus isolation. Results The prevalence of ocular morbidity was 100% in examined dogs. Lesions were restricted to the ocular surface and included bilateral conjunctivitis (100% of dogs); punctate, dendritic, or geographic ulcerative keratitis (26% of dogs); and non-ulcerative keratitis (19% of dogs). Conjunctival petechiae were detected in 22% of dogs. Punctate and dendritic corneal ulcers were frequently organized into discrete groups or linear arrangements. Non-ulcerative keratitis appeared clinically as a perilimbal ring of superficial corneal vascularization and leukocyte infiltration. CHV-1 was detected in ocular samples by polymerase chain reaction or virus isolation in all dogs sampled. Conclusions In susceptible populations of domestic dogs, CHV-1 may be associated with outbreaks of highly contagious ocular infection in the absence of concurrent overt systemic disease. This naturally-acquired outbreak of CHV-1 infection provides an opportunity to report the spectrum and prevalence of ocular lesions associated with primary ocular CHV-1 infection in dogs. Conjunctivitis was the most frequent ocular lesion detected. Ulcerative and non-ulcerative keratitis were less prevalent and of variable clinical appearance. Dendritic ulcerative keratitis, a classic and relatively specific ocular lesion associated with alphaherpesvirus infection, was detected in

Serum and tear IgA, IgG and IgM levels were studied in patients with bacterial, fungal and viral corneal ulcers. In patients with viral corneal ulcers serum IgA and IgG levels were found to be significantly raised, while IgM concentration remained unaltered. In bacterial and mycotic ulcerations, serum IgA, IgG and IgM levels remained unaltered. All three immunoglobulins were found to be raised in tears of patients with viral corneal ulcers, while only IgA levels were found to be increased in bacterial and mycotic ulcerations.

Herpesviruses are involved in the pathogenesis of acute retinal necrosis syndrome (ARN). A rapid and accurate diagnosis of herpetic infections is crucial for prompt administration of a specific antiviral therapy. The purpose of this study was to evaluate a polymerase chain reaction (PCR)-based assay to detect herpesvirus DNA in the aqueous humor of clinical samples from ten patients with uveitis and clinical suspicion of ARN. Samples were assayed for herpes simplex virus type 1-2 (HSV 1-2), varicella zoster virus (VZV) and cytomegalovirus (CMV). Clinical suspicion of ARN was confirmed for four patients. Two patients (one with bilateral ARN) tested PCR-positive for VZV DNA and the other two were positive for HSV 1-2 DNA. CMV DNA was not detected in any of the samples, and no sample was positive for DNA from more than one virus. The remaining patients did not show any evidence of herpesvirus DNA in their aqueous samples. Our findings demonstrate that the use of PCR for detecting herpesvirus DNA in aqueous humor of uveitic subjects may be a valuable tool for early diagnosis of acute retinal necrosis syndrome and for timely administration of a suitable therapy.

Low levels of tear lysozyme were observed in patients with infective corneal ulcers, when compared with controls. Lowest levels were seen in patients with bacterial corneal ulcers. The levels of tear lysozyme showed a corresponding decrease with the increase in Schirmer test values; meaning thereby, that in ocular conditions associated with increased rate of tear flow, the lysozyme content in tears tends to be low.

Purpose: To investigate the role of human papillomavirus (HPV) types 6, 11, 16 and 18 in corneal and conjunctival carcinoma, we examined 88 dysplastic corneal and conjunctival specimens and 66 controls that had been formalin-fixed and paraffin-embedded. Methods: Sections were graded for histological abnormality by light microscopy and the presence of HPV DNA was determined by polymerase chain reaction using LI consensus primers. Results: Human papillomavirus DNA was detected in 34 (39%) dysplasias and in five (7.5%) controls. Of dysplasias that were HPV-positive, 20 (59%) contained either types 16 or 18, 13 (38%) contained only types 6/11, while combinations of HPV types were present in 11 (32%). A histological correlation was found with HPV positivity (all genotypes) and unusually large (‘epithelioid’) dysplastic cells. Conclusion: The present study demonstrates a lower incidence of HPV in corneal and conjunctival carcinoma than previously reported, but shows an unexpectedly high incidence of HPV 6/11 in conjunctival carcinomas.

Adenoviruses are associated with endemic and epidemic acute conjunctivitis, large nosocomial outbreaks reflecting virus transmission on unwashed hands or inadequately sterilised ophthalmic instruments. The polymerase chain reaction (PCR) proved more sensitive than antigen detection by immune dot-blot test for the rapid diagnosis of ocular adenovirus infection (sensitivities in a retrospective study 112/123 (91%) versus 72/123 (59%), P < 0.001). Indeed, in a prospective comparison, DNA amplification and virus isolation generated similar numbers of positive results (34 versus 32), though five PCR positive results were possibly false positives. The sensitivity of the PCR was largely independent of adenovirus subgenus or serotype, though reduced sensitivity with subgenus B strains could not be excluded. Specimen preparation for DNA amplification using a simple lysis buffer proved more effective than phenol-chloroform extraction. The immune dot-blot test gave unavoidable false positive results, but with the PCR this problem could be minimized by technical modifications. The PCR could replace antigen detection and virus isolation as the initial test for adenoviruses in conjunctival swabs, with cell culture only being retained for adenovirus serotyping in PCR positive specimens and for other viruses such as herpes simplex. © 1995 wiIey-Liss, Inc.

A 17-year-old youth presented with bilateral follicular conjunctivitis and nummular subepithelial corneal infiltrates. Failure of this to settle in an outpatient setting led to corneal scraping with microscopy and culturing for bacteria, fungi, Herpes simplex, adenovirus and Acanthamoeba as an inpatient. Polymerase chain reaction analysis of corneal cells was positive for adenovirus, and culture on live Escherichia coli- coated agar plates was positive for Acanthamoeba by phase contrast microscopy on day two. We conclude that Acanthamoeba infection can complicate adenoviral keratoconjunctivitis. This observation is in keeping with previously reported modes of infection by Acanthamoeba, whereby any epithelial breach seems to allow inoculation of the eye by this opportunistic organism.

In a patient with a 5-month history of chronic relapsing keratoconjunctivitis, herpes simplex virus antigen was disclosed by immunofluorescence test in material obtained by conjunctival scraping, and the symptoms resolved following acyclovir (Zovirax) treatment. The diagnostic difficulties with patients presenting without symptoms suggestive of herpes simplex virus may be responsible for the lack of similar reports.