[Viral Conjunctivitis: Findings, Therapy, and Prophylaxis]. / Virale Bindehautentzündungen: Befunde, Therapie und Prophylaxe.

Viral conjunctivitis is one of the most common acute eye diseases. The fall and winter months are known to be the main season for viral infections which is also reflected in the ophthalmological outpatient clinics. Viral conjunctivitis is often accompanied by symptoms of the upper and lower respiratory tract, fever, chills, arthralgia or skin lesions. The spectrum of pathogens comprises DNA viruses such as Adeno-, Herpes simplex and Molluscum contagiosum as well as RNA viruses. Symptoms caused by pandemic pathogens such as SARS-CoV-2 and mpox viruses can also cause ocular manifestation. Viral conjunctivitis is often self-limiting leaving no residual symptoms, however an ophthalmologist should be consulted if there are inflammatory symptoms of the anterior eye accompanied by visual disturbance. It is particularly important to recognize the affection of corneal or even intraocular structures early to initiate an adequate and effective therapy. Affection of the cornea, vitreus or retina can result in temporary or permanent impairment of the field of vision and visual acuity. The diagnosis is usually made without further tests on the basis of the typical clinical presentation. Rapid tests or PCR diagnostics are also available for confirmation. In most patients the treatment is symptomatically with artificial tears and antibiotic eye drops in cases accompanied by secondary bacterial infections, not prophylactically. If the cornea or other ocular structures are affected by certain viruses, local as well as systemic virostatic therapy is initiated. The most important prophylactic measure is meticulous and consistent hygiene.

Evaluation of knowledge, attitude, and behaviour of ophthalmologists about adenoviral conjunctivitis transmission and treatment : An online survey for Turkish ophthalmologists.

PURPOSE: To determine the prevalence of adenoviral conjunctivitis in Turkish ophthalmologists, to provide an overview of the treatment and prophylaxis of adenoviral conjunctivitis, and to analyze the data in the context of evidence-based treatment recommendations. METHODS: An online questionnaire consisting of 20 multiple-choice questions about the characteristics of the respondents, the individual adenoviral conjunctivitis history of the ophthalmologists, their practice's approaches, and prescription preferences were emailed to Turkish ophthalmologists. RESULTS: The survey was emailed to 500 ophthalmologists; 45% of them returned the questionnaire. According to the responses, the history of adenoviral conjunctivitis infections was positive in 46.7% (n: 120), recurrent attack prevalence was 16.2% in ophthalmologists. Lubricants (67.6%) are the most preferred first-line treatment options for adenoviral conjunctivitis, followed by povidone-iodine (59.6%), topical antibiotics (51.1%), topical antivirals (29.3%), topical corticosteroids (26.7%), and topical nonsteroidal anti-inflammatory agents (19.6%). A total of 98.2% preferred to dismiss infected patients. The preferred prophylaxis options were frequent hand washing/use of gloves (97.8%), disinfection of medical devices (95.1%), isolation of infected patients (79.1%), hand hygiene with gemicides (58.7%). The percentage of single-dose eye drop selection was 46.2. CONCLUSIONS: The findings of this survey showed that most Turkish ophthalmologists generally follow international guidelines for the treatment of adenoviral conjunctivitis. The treatment algorithm is still controversial, so ophthalmologists should be aware of treatment guideline updates in line with evidence-based recommendations. Having sufficient knowledge of the basic characteristics of viruses is important to control the spread of the disease.

H9N2 avian influenza virus-induced conjunctivitis model for vaccine efficacy testing.

Clinical signs such as respiratory signs, egg drop, and mortality have been reported in field cases of low pathogenic avian influenza by H9N2 avian influenza virus (AIV) but have rarely been reproduced by the virus alone. Thus, virus reisolation rates and titers in tissues were measured for vaccine efficacy testing. In the present study, we established a clinical sign-based vaccine efficacy test by reproduction of highly frequent conjunctivitis (77.8%-90%) via binocular instillation of an H9N2 virus (01310) strain, 1 x 10(6) EID50/10 microl for each eye). Specific-pathogen-free chickens were assigned to vaccine and control groups, and the vaccine group was inoculated intramuscularly with a commercial H9N2 inactivated oil emulsion vaccine. The chickens were challenged by 01310 via binocular instillation at 2 and 4 wk postvaccination (WPV). The positive rates of conjunctivitis and virus reisolation were significantly different between the vaccine and control groups (conjunctivitis at 2 WPV, 0% vs. 77.8%, and at 4 WPV, 0% vs. 80%). Vaccine antibody was detected in tears as well as in serum samples of the vaccine group before challenge. The conjunctivitis model may be useful for efficacy testing of AI vaccine due to a clinical symptom-based read of results, but further efficacy testings with different types, doses of AI vaccines, and challenge viruses will be required to complete the evaluation of our model.

Comparison of ocular findings in patients with H1N1 influenza infection versus patients receiving influenza vaccine during a pandemic.

AIM: To evaluate ocular findings during the pandemic influenza A (H1N1) and after vaccination for the same strain. PATIENTS AND METHODS: This study was conducted on 89 patients with H1N1 influenza infection (group 1) and 28 subjects who received vaccination for H1N1 (group 2). All patients were subjected to history taking, ophthalmological examination, fundus examination, conjunctival impression cytology and conjunctival swabs. RESULTS: The patients' age ranged between 5 and 60 years (19.25 ± 11.70 years). Group 1 included 43 (48.1%) males and 46 (51.9%) females, while group 2 included 13 (46.43%) males and 15 (53.57%) females. The most common ocular finding of patients in group 1 was bilateral acute conjunctivitis in 58 cases (65.17%), while in group 2, we found 3 (10.71%) cases of mild conjunctivitis, and 2 (7.14%) cases of moderate conjunctivitis. Retinopathy, uveal affection, and optic neuritis were not statistically different between the 2 groups. Impression cytology of the conjunctiva for group 1 showed squamous metaplasia grade 3 with enlargement of epithelial cells, and fragmentation of the nucleus which is similar to virus-infected structural changes. CONCLUSION: Pandemic influenza H1N1 was able to induce different ocular manifestations including acute conjunctivitis, retinopathy, uveal effusion syndrome and optic neuritis.

Cost Savings From a Policy to Diagnose and Prevent Transmission of Adenoviral Conjunctivitis in Employees of a Large Academic Medical Center.

IMPORTANCE: Adenoviral conjunctivitis is highly contagious, can be associated with systemic infections, and can cause chronic visual impairment. It accounts for a large proportion of acute conjunctivitis. Outbreaks of epidemic keratoconjunctivitis (EKC) are costly in terms of productivity loss from work furloughs and spread to patients and have resulted in clinic and departmental closures. OBJECTIVE: To examine the institutional cost savings of a policy to diagnose adenoviral conjunctivitis and triage and furlough medical center employees with this condition to prevent outbreaks. DESIGN, SETTING, AND PARTICIPANTS: This quality improvement study assessed Johns Hopkins Medicine employees with red eye from November 1, 2011, through October 31, 2018, who were triaged at the occupational health clinic whose conditions were diagnosed using polymerase chain reaction (PCR) validated for adenoviral conjunctivitis. INTERVENTIONS: Only employees with positive PCR test results were furloughed, with furlough length tailored to subtype (a minimum of 2 weeks for EKC and 1 week otherwise). MAIN OUTCOMES AND MEASURES: Total number of furloughs avoided and cost savings associated with reducing unnecessary furloughs. RESULTS: Of 2142 employees with red eye, 1520 (71.0%) underwent PCR testing; 130 (8.6%) had positive adenoviral PCR test results, of whom 41 (31.5%) had EKC. Furloughing 130 employees with positive PCR test results vs furloughing all 1520 employees clinically suspected of having adenoviral conjunctivitis represented an estimated annual savings of $442 073, or $3 094 511 during 7 years. The cost of performing PCR on employees suspected of having adenoviral conjunctivitis was 5.0% of the cost associated with furloughing all employees with red eye. No outbreaks occurred. CONCLUSIONS AND RELEVANCE: In this quality improvement study, this policy, notable for development and use of PCR for adenoviral conjunctivitis on a large scale, resulted in substantial cost savings from fewer work furloughs compared with the number of employees who would have been furloughed based on clinical diagnosis. These results may provide impetus for policy adoption by other institutions and for development of a rapid, sensitive, and specific diagnostic test for adenoviral conjunctivitis.

Implications of COVID-19 for Ophthalmologists.

PURPOSE: To describe and explain the implications of coronavirus disease 2019 (COVID-19) for ophthalmologists considering the rapid developments in our understanding of the virology, transmission, and ocular involvement. DESIGN: Evidence-based perspective. METHODS: Review and synthesis of pertinent literature. RESULTS: Retrospective studies highlight that <1% of patients display COVID-19-related conjunctivitis. However, prospective studies suggest the rate is higher (~6%). Viral RNA has been identified in tears and conjunctival secretions in patients with active conjunctivitis as well as asymptomatic cases. Overall, conjunctival swabs are positive in 2.5%. Samples taken earlier in the disease course are more likely to demonstrate positive virus. Viral transmission through ocular tissues has not been substantiated. Ophthalmologists are in the high-risk category for COVID-19 infection for several reasons: high-volume clinics, close proximity with patients, equipment-intense clinics, and direct contact with patients' conjunctival mucosal surfaces. COVID-19 is predominantly contracted through direct or airborne transmission by inhalation of respiratory droplets. Evidence that aerosol transmission occurs is increasing in particularly prolonged exposure to high concentrations in a relatively closed environment. Based on the current evidence, ophthalmologists should consider measures that include social distancing, wearing masks, sterilization techniques, and managing clinic volumes. CONCLUSIONS: A major challenge to containing COVID-19 is that many infected people are asymptomatic. Droplet spread, contaminated environmental surfaces, and shared medical devices are areas that require management by ophthalmologists. More studies are required to explore the role of the conjunctiva and ocular tissues in the transmission of disease.

COVID-19 and the Eye: Ocular Manifestations, Treatment and Protection Measures.

The novel pandemic coronavirus disease 2019 (COVID-19) leading to health and economic problems worldwide is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although COVID-19 mainly occurs as a lower respiratory tract infection, there is multiorgan involvement in infected patients. The disease is transmitted from person to person through air droplets or contact with contaminated surfaces. SARS-CoV-2 leads to this systemic involvement by attaching to angiotensin-converting enzyme 2 (ACE2) receptors located on several human cells. Since SARS-CoV-2 RNA has been found in tears of infected patients, ocular surface may allow the virus to transmit to nasopharynx via the nasolacrimal duct. This narrative review aims to sum up all segmental ocular complications, ocular adverse effects of COVID-19 treatment, and preventive measures suggested to minimize the SARS-CoV-2 transmission between patients and ophthalmologists by reviewing currently available literature.

Precaution and prevention of coronavirus disease 2019 infection in the eye.

Although current studies suggested that conjunctivitis is not a common presentation of coronavirus disease 2019 (COVID-19), several studies have reported the presence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in ocular secretions. Coronavirus had not yet been successfully cultured from tears or conjunctival swabs in humans, neither SARS-CoV-2 nor SARS-CoV. However, live feline coronavirus has been isolated from conjunctival swabs. In addition, infection of COVID-19 through unprotected eye exposure had been suspected in several articles. Reports of ophthalmologists and otolaryngologists died of COVID-19 also raised concern on ocular transmission. As a result, we strongly suggest that personal protective equipment (PPE) should cover the mouth, nose, and eyes of ophthalmologists, especially when conjunctivitis caused by SARS-CoV-2 is clinically indistinguishable from other viral follicular conjunctivitis.

COVID-19 and ophthalmology: an underappreciated occupational hazard.

The proximity required of a thorough biomicroscopic slit-lamp examination may put ophthalmologists at increased risk for respiratory-borne infection with SARS-CoV-2. Conjunctivitis has been described in a few patients with COVID-19 and other coronavirus syndromes. Although SARS-CoV-2 has been detected in the conjunctival secretions or tears of patients with COVID-19 and conjunctivitis, transmission of infection through respiratory droplets to ophthalmologists without eye protection or masks may be the bigger concern.

Natural protection of ocular surface from viral infections - A hypothesis.

A pandemic outbreak of a viral respiratory infection (COVID-19) caused by a coronavirus (SARS-CoV-2) prompted a multitude of research focused on various aspects of this disease. One of the interesting aspects of the clinical manifestation of the infection is an accompanying ocular surface viral infection, viral conjunctivitis. Although occasional reports of viral conjunctivitis caused by this and the related SARS-CoV virus (causing the SARS outbreak in the early 2000s) are available, the prevalence of this complication among infected people appears low (~1%). This is surprising, considering the recent discovery of the presence of viral receptors (ACE2 and TMPRSS2) in ocular surface tissue. The discrepancy between the theoretically expected high rate of concurrence of viral ocular surface inflammation and the observed relatively low occurrence can be explained by several factors. In this work, we discuss the significance of natural protective factors related to anatomical and physiological properties of the eyes and preventing the deposition of large number of virus-loaded particles on the ocular surface. Specifically, we advance the hypothesis that the standing potential of the eye plays an important role in repelling aerosol particles (microdroplets) from the surface of the eye and discuss factors associated with this hypothesis, possible ways to test it and its implications in terms of prevention of ocular infections.

Personal protective equipment and risk for avian influenza (H7N3).

An outbreak of avian influenza (H7N3) among poultry resulted in laboratory-confirmed disease in 1 of 103 exposed persons. Incomplete use of personal protective equipment (PPE) was associated with conjunctivitis and influenza-like symptoms. Rigorous use of PPE by persons managing avian influenza outbreaks may reduce exposure to potentially hazardous infected poultry materials.

[Inflammation of the conjunctiva]. / Bindehautentzündung.

Inflammations of the conjunctiva represent some of the most frequent eye diseases in general and ophthalmologic practice. Etiologically multiple diseases can be identified. A group of infectious conjunctivites contrasts with a very hereogeneous non-infectious group. Neoplastic processes such as low grade epithelial dysplasias and lymphomas may mascarade conjunctivitis. The differentiation of the various clinical pictures may be challenging for the practitioner. This article reviews the methodology of patient history and clinical work up as well as the symptomatology and treatment options for the most important conjunctivites in clinical practice.

Multivalent sialic acid conjugates inhibit adenovirus type 37 from binding to and infecting human corneal epithelial cells.

Adenovirus type 37 is one of the main causative agents of epidemic keratoconjunctivitis. In a series of publications, we have reported that this virus uses sialic acid as a cellular receptor. Here we demonstrate in vitro that on a molar basis, multivalent sialic acid conjugated to human serum albumin prevents adenovirus type 37 from binding to and infecting human corneal epithelial cells 1000-fold more efficiently than monosaccharidic sialic acid. We also demonstrate that the extraordinary inhibitory effect of multivalent sialic acid is due to the ability of this compound to aggregate virions. We conclude that multivalent sialic acid may be a potential new antiviral drug, for use in the treatment of epidemic keratoconjunctivitis caused by the adenoviruses that use sialic acid as cellular receptor.

Efficacy of topical cobalt chelate CTC-96 against adenovirus in a cell culture model and against adenovirus keratoconjunctivitis in a rabbit model.

BACKGROUND: Adenovirus (Ad), associated with significant morbidity, has no topical treatment. A leading CTC compound (CTC-96), a Co(III) chelate, was found to have potent in vitro and in vivo antiviral efficacy against herpes viruses. In this study CTC-96 is being tested for possible anti-Adenovirus activity. METHODS: The biological anti-adenovirus activity of CTC-96 in concentrations from 5 to 250 ug/ml, was evaluated initially by viral inactivation (viral exposure to CTC-96 followed by dilution and inoculation of cells), virucidal (viral exposure to CTC-96 and inoculation of cells without dilution) and antiviral (effect of CTC-96 on previously adsorbed virus) plaque assays on HeLa (human cervical carcinoma), A549 (human lung carcinoma) and SIRC (rabbit corneal) cells. After verifying the antiviral activity, New Zealand White rabbits were infected with Ad-5 into: 1) the anterior cul-de-sac scarifying the conjunctiva (Group "C+"); 2) the anterior cul-de-sac scarifying the conjunctiva and cornea (Group "CC+"); 3) the stroma (Group "CI+"). Controls were sham-infected ("C-", "CC-", "CI-"). Other rabbits, after "CC", were treated for 21 days with: 1) placebo, 9x/day ("-"); 2) CTC-96, 50 ug/ml, 9x/day ("50/9"); CTC-96, 50 ug/ml, 6x/day ("50/6"); CTC-96, 25 ug/ml, 6x/day ("25/6"). All animals were monitored via examination and plaque assays. RESULTS: In vitro viral inactivation, virucidal and antiviral assays all demonstrated CTC-96 to be effective against Adenvirus type 5 (ad-5). The in vivo model of Ad keratoconjunctivitis most similar to human disease and producing highest viral yield was "CC". All eyes (6/6) developed acute conjunctivitis. "CI" yielded more stromal involvement (1/6) and iritis (5/6), but lower clinical scores (area x severity). Infection via "C" was inconsistent (4/6). Fifty (50) ug/ml was effective against Ad-5 at 6x, 9x dosings while 25 ug/ml (6x) was only marginally effective. CONCLUSION: CTC-96 demonstrated virucidal activity against Ad5 in tissue culture with HeLa, A549 and SIRC cell lines. Animal Model Development: 1) "CC" produced conjunctival infection with occasional keratitis similar to human disease; "CI" yielded primarily stromal involvement; 2) "C" consistently produced neither conjunctivitis nor keratitis.CTC Testing: 1) Conjunctivitis in all eyes; 2) Resolution fastest in "50/9" ("50/9". "50/6" > "25/6" > "-"); 3) Efficacy in "50/6" was not statistically different than "50/9"; 4) Conjunctival severity was lower in treatment groups then controls; 5) Little corneal or intra-ocular changes were noted.

Long-term acyclovir use to prevent recurrent ocular herpes simplex virus infection.

OBJECTIVE: To evaluate the effectiveness of more than 12 months of oral acyclovir therapy in reducing recurrences of ocular herpes simplex virus. METHODS: We retrospectively compared ocular herpes simplex virus recurrence in 2 groups of patients. In group 1, patients used oral acyclovir for at least 12 months and then discontinued the treatment. In group 2, patients received the treatment for at least 18 months. We compared recurrences when both groups were using acyclovir (period 1) and when only group 2 was receiving the drug (period 2). Statistical analysis was performed with the t test, chi2 test, and Kaplan-Meier method. RESULTS: Group 1 had 18 patients and a mean +/- SD follow-up of 45.2 +/- 22.2 months. Group 2 had 22 patients and a mean +/- SD follow-up of 42.4 +/- 30.2 months. Six patients (33%) in group 1 and 4 patients (18%) in group 2 had recurrence in period 1 (P =.3). In period 2, 14 patients (78%) in group 1 and 8 patients (36%) in group 2 had recurrence (P =.01). Mean +/- SD recurrence-free survival in period 2 was 15.3 +/- 5.5 months in group 1 and 37.3 +/- 6.3 months in group 2 (P =.001). CONCLUSIONS: Long-term oral acyclovir use seems to remain effective in decreasing the number of ocular herpes simplex virus recurrences beyond 12 months.

The effects of corticosteroids of adenoviral replication.

OBJECTIVE: To evaluate the effects of Pred Forte (prednisolone acetate; Allergan Pharmaceutical, Irvine, Calif) on the replication of different adenoviral serotypes in vitro and in the adenovirus type 5/New Zealand rabbit ocular model. METHODS: The 50% inhibitory doses of Pred Forte and its components were determined for common ocular serotypes. The effects of continuous topical treatment with Pred Forte for 18 days were evaluated (eg, conjunctivitis, subepithelial immune infiltrates, and serial ocular viral titers) in the adenovirus 5/New Zealand rabbit ocular model. RESULTS: Pred Forte and prednisolone acetate inhibited adenoviruses 1, 5, 8, and 19 in vitro. In vivo, 1% Pred Forte significantly reduced conjunctivitis (P = .04) and subepithelial infiltrates (P = .02), but enhanced viral replication (P = .01) on days 9 to 21 and increased the duration of viral shedding (P < .001). CONCLUSIONS: Despite demonstrated anti-inflammatory and anti-immune effects, prolonged treatment of acute adenoviral infections with topical Pred Forte is not recommended because of the enhanced risks of viral transmission and community epidemics.

Conjunctivitis of the newborn.

Infectious conjunctivitis of the newborn is caused by a wide variety of microorganisms. The ocular findings may be part of a widespread systemic infection. Clinical presentations are not diagnostic of the cause, and a microbiologic work-up with cytology, cultures, and microbial sensitivities is mandatory. The selection of specific antimicrobial therapy is based on the findings of laboratory studies. Prophylaxis with silver nitrate solution, 1.0% tetracycline, or 0.05% erythromycin ointment is effective for the prevention of gonococcal and chlamydial conjunctivitis in the newborn.