Natural history of adenoviral conjunctivitis in a US-based population: Viral load, signs, and symptoms.

PURPOSE: To report the clinical signs, symptoms, and viral clearance in individuals in the United States with adenoviral conjunctivitis (Ad-Cs). METHODS: Individuals ≥ 18 years presenting within 4 days of symptoms of Ad-Cs who met eligibility criteria and tested positive with both point-of-care immunoassay antigen and quantitative polymerase chain reaction (qPCR) testing were enrolled. Patient-reported symptoms, clinician-graded signs, and qPCR viral titers were collected at baseline, days 1-2, 4 (days 3-5), 7 (days 6-10), 14 (days 11-17) and 21 (days 18-21). RESULTS: There was no detectable viral titers by the day 14 visit in 6/8 patients. By day 21, there was no detectable viral titers in the 7 participants who completed the visit; however, signs and symptoms persisted including: blurry vision (5/7), discomfort (2/7) or redness (1/7). Masked clinicians also noted conjunctival redness (4/7), follicular conjunctivitis (4/7) and bulbar edema (3/7). CONCLUSION: Many patient-reported symptoms and clinical signs persist after viral titers are no longer detectable by qPCR. Using clinical signs and symptoms to determine quarantine duration may result in patients being furloughed longer than the time that the patient is infectious.

Molecular, Epidemiological and Clinical Assessment of Adenoviral Keratoconjunctivitis in Egypt: Institutional Study.

PURPOSE: To evaluate the frequency of Human adenovirus (HAdV) and its serotypes in keratoconjunctivitis patients who attended the outpatient clinics of Mansoura Ophthalmic Center, Egypt. METHODS: Conjunctival secretions and corneal scrapings were collected from patients complaining of clinically diagnosed viral keratoconjunctivitis. The molecular method for HAdV detection was performed by polymerase chain reaction (PCR) followed by restriction enzymes (REA) determination of serotypes for hexone gene. RESULTS: HAdV infection was detected in 38% of samples. There were 4 serotypes of Human adenovirus species D (HAdV-D) isolated (4, 8, 37, 3), where HAdV-D8 was the most dominant. Contact with infected patient, follicular conjunctivitis and subepithelial corneal infiltrates are useful features for clinical diagnosis of adenoviral conjunctivitis. CONCLUSION: HAdV was significant etiological factor of acute follicular conjunctivitis. Accurate diagnosis of adenoviral conjunctivitis is essential for appropriate management, reducing permanent visual impairment and to limit the transmission of the virus within the community.

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.

COVID-19 pandemic: Impact on the rate of viral conjunctivitis.

OBJECTIVE: The COVID-19 pandemic led Spain to order a state of alert with the cessation of non-essential activities on 14 March 2020, and to implement public health interventions (such as home confinement) and other health recommendations to prevent the spread of the SARS-CoV-2 virus (hand washing and the obligation to wear face-masks). These factors could have influenced the rate of viral conjunctivitis. METHOD: In this retrospective, noninterventional, descriptive study, the incidence of viral conjunctivitis in an emergency department of a national hospital is compared over two distinct time periods: pre-COVID (13 March-30 September 2019, one year before the start of the pandemic) and COVID (13 March-30 September 2020). RESULTS: In the first period there were 436 cases of conjunctivitis, of which 168 (38.5%) were confirmed cases of viral conjunctivitis 168 (38.5%), while in the second period there were 121 recorded cases, of which the most frequent were allergic and traumatic (23 cases; 19% each group), bacterial (15 cases; 12.3%) and viral (15 cases; 12.3%). The diagnosis of viral conjunctivitis is the one that suffered the most significant relative reduction (48.5%), while other types of conjunctivitis hardly changed their relative frequency between these two periods of time. CONCLUSIONS: Viral conjunctivitis is the most frequent infectious disease of the eye and has a transmission rate similar to that of coronavirus, so the measures implemented could positively affect its incidence.

Clinical profile and prevalence of conjunctivitis in mild COVID-19 patients in a tertiary care COVID-19 hospital: A retrospective cross-sectional study.

PURPOSE: To find the clinical profile and prevalence of conjunctivitis and other ocular manifestations in mild COVID-19 positive patients in a nodal COVID-19 hospital. METHODS: A retrospective cross-sectional, single-center study conducted in 127 mild cases of COVID-19 positive patients admitted between 27th March and 19th April 2020 in a tertiary care COVID-19 hospital in north India. From the hospital records, demographic data is collected. Ocular history and ocular examinations were done by face-to-face survey during ward rounds. RESULTS: A total of 127 patients were included in the study with a median age of 38.8 years. Forty-eight (37.80%) patients had upper respiratory tract symptoms, 20 (15.75%) patients had systemic illness, 18 (14.17%) patients were using spectacles, and 50 (39.37%) patients had history of hand-eye contact. Out of 12 (9.45%) patients who had ocular complaints, 11 (8.66%) had ocular manifestation after admission. Among 11 patients, eight (6.29%) had conjunctival congestion. Three (3/8) patients had developed conjunctival congestion even before the manifestation of definite COVID-19 symptoms. Five patients (5/8) patients had no other associated ocular symptoms other than congestion. Six patients (6/8) had symptoms of upper respiratory tract infection. CONCLUSION: Mild conjunctivitis manifesting as conjunctival congestion is common and is one of the major ocular manifestations in COVID-19 positive patients even with milder disease.

The COVID-19 Pandemic from an Ophthalmologist's Perspective.

The current coronavirus disease 2019 (COVID-19) pandemic is rapidly spreading around the world. The first doctor to report this new disease was an ophthalmologist: this exemplifies the role of ophthalmologists in an infectious disease pandemic. Here we review how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects the eye and discuss implications for ophthalmologists.

A 8-year retrospective clinical analysis of 272 patients of epidemic Keratoconjunctivitis in Beijing, China.

BACKGROUND: Epidemic keratoconjunctivitis (EKC) is one of the most common eye infections worldwide. The analysis of clinical manifestations in different age groups help better know the disease. This study aims to provide more detailed analysis of 272 cases of EKC in 8 years, describe the differences of the clinical features among different age groups, and establish new clinical grading criteria. METHODS: 272 individuals were reviewed (2011-2019) in Beijing China. All the patients were classified into 3 grades according to the new grading criteria. The typical clinical signs of EKC and the photographs of the multiple subepithelial corneal infiltrates (MSI) were collected and analyzed. The number of 3 grades among and within different age groups were compared. The incidence of the typical signs among and within different age groups were compared. The proportion of each region of the cornea involved by MSI were compared. RESULTS: No significant differences were detected among the 4 groups in terms of the number of mild, moderate and severe cases, no matter in all-patients analysis (P = 0.271) nor in acute-phase-patients analysis (P = 0.203). The proportion of the severe cases was the highest among all patients (P = 0.000). Among the incidence of the typical signs, corneal involvement was the most common accounting for 69.8% (P<0.05). The probability of central region involvement was significantly higher than that of pericentral region involvement (P = 0.015) and peripheral region involvement (P = 0.000). CONCLUSIONS: Appropriate attention should be paid on EKC, because of the considerable proportion of severe cases, the high incidence of corneal lesion, and the high incidence of central region involvement of MSI.

Viral conjunctivitis: a retrospective study in an Australian hospital.

IMPORTANCE: To update the literature on the current trends of viral conjunctivitis infections in Sydney, Australia. BACKGROUND: To find correlations between viral and patient characteristics on disease outcomes and to assess the rates of antibiotic and steroid use in patients with viral conjunctivitis prior to and after assessment by ophthalmology trainees. DESIGN: Retrospective single-centre case series. PARTICIPANTS: 368 eyes of 224 patients diagnosed with viral conjunctivitis at the Sydney Eye Hospital from 1 st January - 31 st March 2017. METHODS: Patients were identified from hospital records or polymerase chain reaction results. RESULTS: 368 eyes of 224 patients, median age 35.3 (range 7-82) and 59.8% males, were included. 152 (67.9%) patients presented already on antibiotic treatment. Most patients (83.5%) had no previous ocular history aside from 35 (15.6%) who were regular contact lens wearers. PCR was performed in 170 (75.9%) patients, with 92 (54.1%) positive for adenovirus, and 7 (4.1%) for HSV. The average duration of symptoms prior to presentation was 6.3 days. 177 (78.0%) patients presented within 1 week of symptom onset and these patients were more likely to be adenovirus positive on PCR (OR = 2.37). Patients with symptoms of longer duration were more likely to have photophobia (OR = 2.96) and have had steroid treatment (OR = 3.80). CONCLUSIONS AND RELEVANCE: Patients with viral conjunctivitis typically presented within a week of symptom onset, with bilateral disease and on topical antibiotics. Pseudomembranes and a palpable preauricular lymph node were not common. As treatments emerge for viral conjunctivitis patients may need to be encouraged to present earlier.

The Epidemic Genotypes of Human Adenovirus in Outpatient Children with Adenoviral Conjunctivitis from 2011 to 2012 in Jiangxi, China.

BACKGROUND: Human adenoviruses (HAdV) are a common cause of viral conjunctivitis, making surveillance of them from sporadic cases of conjunctivitis important. METHODS: To acquire a better understanding of the epidemic genotypes of HAdV in outpatient children with adenoviral conjunctivitis in Jiangxi Province, China (2011-2012), 179 samples from cases with a high suspicion of HAdV were analyzed by PCR. Samples confirmed to be HAdV-positive by PCR were cultured in Hep-2 cells to isolate the viruses, which were then identified through hexon gene sequencing. RESULTS: The adenoviral conjunctivitis positivity rate was 74.86% (134/179), from which 71.64% (96/134) were infections in boys, and 92.54% (124/134) were infections in children under 5 years of age. Sixty-nine HAdV strains were isolated from the positive samples and 69 sequences were obtained. Phylogenetic analysis indicated that 33 strains (47.82%) clustered with HAdV-B7, 21 (30.43%) with HAdV-B3, 6 (8.70%) with HAdV-B55, 6 (8.70%) with HAdV-E4, 1 with HAdV-B21 (1.45%), 1 with HAdV-D37 (1.45%), and 1 with HAdV-D64 (1.45%). CONCLUSIONS: This is the first identification of HAdV-B55 relating to adenoviral conjunctivitis in China. These findings provide a firm basis for future surveillance of adenoviral conjunctivitis in China or other East Asian regions.

Five-year trends in adenoviral conjunctivitis in employees of one medical center.

OBJECTIVE: To describe the 5-year findings after a policy to screen for, diagnose, and isolate medical center employees with adenoviral conjunctivitis was implemented. DESIGN: Observational report with a retrospective evaluation of a current quality improvement initiative. SETTING: Johns Hopkins Medicine, Baltimore, Maryland.ParticipantsJohns Hopkins Medicine employees. METHODS: Data were retrieved from records maintained for this initiative, in which employees with suspected adenoviral conjunctivitis were evaluated in the Occupational Health Clinic and swabbed for polymerase chain reaction (PCR) testing for adenoviral conjunctivitis. Signs, symptoms, work area, diagnoses, and disposition of employees with eye complaints as well as PCR result and adenoviral type were recorded. Five-year data were reviewed. RESULTS: From 2011 to 2016, of 10,000 full-time equivalent employees, 1,059 employees visited the Occupational Health Clinic with suspicion of adenoviral conjunctivitis. Of these, 104 (10%) were PCR positive for adenovirus. Of these PCR-positive employees, 26 (25%) had the worst clinical presentation, epidemic keratoconjunctivitis (EKC). The Outpatient Pharmacy had the highest number of adenoviral conjunctivitis cases (n=9). The proportion of red-eye employees having PCR-positive adenoviral conjunctivitis increased over 5 years (P<.005, Cochrane-Armitage test for trend) as did the proportion of employees with EKC (P<.05). The proportion of employees with EKC caused by type 37 also increased (P<.05). CONCLUSIONS: Adenoviral conjunctivitis represents 10% of employee cases clinically suspected of this infection. Employees in patient-care areas should be screened even if they have no direct patient contact. Despite increases in the proportions of adenoviral conjunctivitis and of EKC over 5 years, no outbreaks occurred. This policy helps identify incipient EKC outbreaks and guides infection control efforts.

Ocular Symptoms and Signs of Chikungunya Fever in Puerto Rico.

OBJECTIVE: To determine what ocular symptoms and signs are most common and if there are any associations with comorbid conditions in patients with Chikungunya fever. METHODS: A retrospective data review and analysis of the ocular symptomatology of 139 patients with Chikungunya fever who visited a local emergency room from August through September 2014. Frequencies were calculated, and Pearson's chisquare test employed. All the patients were confirmed as having Chikungunya with IgM (ELISA) before admittance into the study. RESULTS: Of the 139 patients, 42 (30.2%) had red eyes, 27 (19.4%) had conjunctivitis, and 13 (9.4%) had symptoms related to anterior uveitis, such as unilateral red eye, ciliary flush, or irregular pupil(s). Patients with a history of diabetes, hypertension, or cancer were more likely to have both red eyes (p = 0.033) and the symptomatology of anterior uveitis (p = 0.006), while patients with nausea or vomiting were more likely to have red eyes only (p = 0.001). CONCLUSIONS AND RELEVANCE: Red eyes, conjunctivitis, and anterior uveitis occur frequently in patients with Chikungunya fever. Systemic diseases, such as diabetes, hypertension, and cancer, may increase the risk of such ocular manifestations. Routine ophthalmic evaluation is warranted in patients with these medical conditions. The relevance of this study lies in the fact that this disease remains an important public health issue, since such ocular sequelae as may be present can range from mild to severe, either as an acute or a delayed manifestation.

Molecular epidemiology of circulating human adenovirus types in acute conjunctivitis cases in Chandigarh, North India.

Human adenovirus (HAdV) is a major cause of viral conjunctivitis. The various serotypes implicated in the causation are 3, 4, 8, 19 and 37. The present study aimed to know the circulating types of HAdV causing acute conjunctivitis in North India. A total of 23 conjunctival swabs were collected from patients with clinically suspected acute viral conjunctivitis during 2014-2015. The HAdV was implicated in the etiology in 65.2% of cases. The sequencing of representative samples using hexon gene suggests the presence of serotype 8 and 4. The serotype eight sequences showed 99%-100% similarity with other Indian strains. The phylogenetic analysis showed that the current circulating serotypes, responsible for conjunctivitis, belonged to epidemic keratoconjunctivitis strains.

ADenoVirus Initiative Study in Epidemiology (ADVISE): Results of a multicentric epidemiology study in Spain. / ADenoVirus Initiative Study in Epidemiology (ADVISE): resultados de un estudio epidemiológico multicéntrico en España.

OBJECTIVE: Non-interventional, observational, epidemiology study to assess clinical characteristics and frequency of adenovirus conjunctivitis diagnosed by AdenoPlus® in patients who presented with signs and symptoms of acute conjunctivitis. Safety aspects during use of the test were analyzed as well. METHOD: This analysis presents the data obtained from the 386 patients enrolled in Spain. Patients had to present with acute signs and symptoms of conjunctivitis ≤7days. The minimum age was 1year old. Patients who had already used local antiviral therapies, topical steroids or immuno-modulators were not allowed to enter the study. A standardized questionnaire was used to collect patient's ocular history and test results. RESULTS: A total of 386 patients were recruited in 22 sites, being analyzed 329 patients. Among them, the percentage of "AdenoPlus® positive" was 36,2% (119/329). Before the test was performed, in 84,1% of the cases, investigators believed that the conjunctivitis was of viral origin but only 50,3% of the investigators had their clinical assessment confirmed by the test. Patients who tested positive for adenoviral conjunctivitis presented higher percentages of signs and symptoms than the rest of the patients. CONCLUSIONS: None of the signs or symptoms could be qualified as pathognomonic of the disease, being difficult for the clinicians to perform an accurate diagnosis. AdenoPlus® test is an antigen based immunoassay test that detects the presence of adenovirus directly from tears, and it can be an useful tool to help early differential diagnosis in patients with conjunctivitis signs and symptoms lasting for less than or equal to 7days.

Outbreaks of epidemic keratoconjunctivitis caused by human adenovirus type 8 in the Tibet Autonomous Region of China in 2016.

From April to November 2016, two outbreaks of epidemic keratoconjunctivitis (EKC) occurred successively at primary and middle schools in the Tibet Autonomous Region of China, and a total of 197 clinically diagnosed cases were reported. Real-time PCR analyses confirmed that human adenovirus (HAdV) infection was related to these outbreaks. Further studies involving sequence determination and phylogenetic analysis based on the penton base, hexon, and fiber genes indicated that human adenovirus type 8 (HAdV-8), belonging to species D, was responsible for the outbreaks. This is the first report of a HAdV-8 associated EKC outbreak in mainland of China, and the results of this study are expected to provide support for future research into HAdV-8 in China.

Α molecular epidemiological analysis of adenoviruses from excess conjunctivitis cases.

BACKGROUND: Τo perform a molecular epidemiological analysis of viral conjunctivitis among excess conjunctivitis cases recorded at the University Hospital of Patras, Greece, for the period March to June 2012. METHODS: A structured questionnaire containing demographic and clinical data was developed in order to collect retrospective data on the cases. Eye swab specimens were collected and molecular detection of adenoviruses was performed by nested PCR. Positive results were confirmed by sequencing. To determine the relatedness between the isolated sequences, a phylogenetic analysis was conducted. RESULTS: The epidemiological analysis (including retrospective data) included 231 conjunctivitis cases (47.1% male, and 52.8% female). Based on clinical features 205 of the cases were diagnosed of viral origin (46.3% male and 53.7% female), 4 of bacterial origin (50% male and 50% female) while 22 were undefined conjunctivitis. The outbreak excess cases (included 156 cases) affected all age groups regardless gender predilection. For the positive samples indicated that 29 samples (72.5%) were AdV17, and 5 (12.5%) as AdV54. CONCLUSIONS: Molecular analysis could define the cause of viral conjunctivitis, while epidemiological data contributed to the assessment of the risk factors and underlined possible preventive measures. This study is one of the very few on viral conjunctivitis in Greece. This outbreak underscores the need for a national surveillance system for acute infectious conjunctivitis outbreaks. The epidemiological as well as molecular investigation on HAdV ocular infections is rather absent in Greece, which has no surveillance system for viral conjunctivitis.

[Senegalese experience with acute viral conjunctivitis]. / Expérience sénégalaise des conjonctivites virales aiguës.

PURPOSE: To study the epidemiological and clinical aspects of acute enteroviral and adenoviral conjunctivitis. PATIENTS AND METHODS: A prospective study was conducted between January 1st and October 31st, 2015, jointly between two Ophthalmology services and a virology laboratory, which identified 51 patients. Were included all patients who presented a painful red eye without loss of visual acuity associated with secretions,evolving for less than 4weeks RESULTS: The mean age was 32 years, and the sex ratio 1:1. Over half of our patients (61%) came from populous districts. A history of the virus "going around" was reported by 30 patients (59% of cases). Virological testing was positive in 35 patients (68.7% of cases). Over 90% of samples collected during the first week of clinical signs were positive. CONCLUSION: Viral conjunctivitis is a contagious condition, the spread of which is favored by promiscuity. Adenovirus and enterovirus are the main causative agents. They are present on an endemic scale in Senegal; thus, the need for better epidemiological surveillance in order to limit spread.

[The virological and epidemiological aspects of human adenoviral conjunctivitis in Tunisia]. / Aspects épidémiologiques et virologiques de la conjonctivite à adénovirus en Tunisie.

Human adenoviruses (HAdV) are the main cause of viral conjunctivitis. In Tunisia and North Africa more generally, there is no regular nationwide surveillance program that monitors viruses causing conjunctivitis and keratoconjunctivitis. In this study, we report the results of HAdV screening in conjunctival samples collected for over 14 years in Tunisia. A total of 282 conjunctival samples received between 2000 and 2013 were investigated. Detection and identification of genotype were performed by PCR-sequencing at the hexon gene; 64.5% of samples (n=182) revealed positive by PCR detection without correlation noted between infection, age, sex, social class or clinical manifestations of viral conjunctivitis. HAdV-D8 was the largely predominant genotype in Tunisia, representing 81.3% of all isolates, and was detected continuously from 2000 to 2013. Minor co-circulating genotypes were also identified - HAdV-E4, HAdV-B3, B55 and HAdV-B7 - accounting for 10.7%, 4.9%, 1.9% and 0.9% of isolates, respectively. In conclusion, this work reports epidemiological data on adenoviral conjunctivitis from a region where such information is very scarce and contributes to a better knowledge of the worldwide distribution of causative genotypes. It also presents an approach for the identification of circulating HAdV in the country and demonstrates the importance of molecular tools for both detection and identification of genotypes, which allow rapid virological investigation, especially during epidemics.

Identification and molecular characterization of adenovirus types (HAdV-8, HAdV-37, HAdV-4, HAdV-3) in an epidemic of keratoconjunctivitis occurred in Pune, Maharashtra, Western India.

Epidemic keratoconjunctivitis (EKC) is a highly contagious infectious disease of the ocular surface and is caused mainly due to adenoviruses species D, B, and E. The present study was carried out to identify and characterize the viral etiological agents associated with the keratoconjunctivitis cases reported from Pune (Maharashtra), Western India between November-December 2013 and January, October-November 2014. Conjunctival swab specimens (n = 23) obtained from keratoconjunctivitis patients were subjected to detection of Adenovirus (AdV) and Enterovirus (EV) by PCR/RT-PCR using hexon and 5' NCR gene specific primers, respectively. Molecular typing of AdV and EV positive specimens was carried out by amplifying penton, fiber, and VP1 genes, respectively followed by sequencing and phylogenetic analysis. In this study, human adenovirus (HAdV) was identified as an etiological agent. None of the clinical specimens were found positive for enterovirus. AdV positivity in keratoconjunctivitis cases was found to be 60.9% (14/23). Fourteen of the HAdV positive strains, all of them were amplified by hexon gene, nine strains by fiber gene, and all 14 strains by penton gene specific primers. Sequencing of all HAdV positive samples revealed the presence of HAdV-8, HAdV-37, HAdV-3, and HAdV-4. All Indian strains showed highest nucleotide identity with the reference strains reported worldwide. The study revealed the circulation of HAdV-8 (78.6%) as predominant AdV strain followed by HAdV-37, HAdV-3, and HAdV-4 (7.2%) identified in the epidemic keratoconjunctivitis. Multiple types of AdVs in EKC reported for the first time in Western India. J. Med. Virol. 88:2100-2105, 2016. © 2016 Wiley Periodicals, Inc.