Detecting SARS-CoV-2 RNA in conjunctival secretions: Is it a valuable diagnostic method of COVID-19?

The main purpose of this study is to evaluate the presence of viral RNA of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in conjunctival swab specimen of coronavirus disease 2019 (COVID-19) patients with and without conjunctivitis to establish the diagnostic value of reverse transcription-polymerase chain reaction (RT-PCR) in each case and to describe its clinical characteristics. A cross-sectional study was conducted at the Hospital Clinico San Carlos of Madrid, Spain. Thirty-six subjects from the COVID admission unit with laboratory-confirmed SARS-CoV-2 infection were included. Conjunctival swabs were collected from 18 patients with conjunctivitis and 18 patients without conjunctivitis and RT-PCR was performed. Conjunctival swab was collected from both eyes of 36 patients (72 eyes), detecting SARS-CoV-2 RNA in conjunctival swab of two patients (5.5%). Among the 18 patients with conjunctivitis, only one of them (5.5%) showed positive results. Likewise, SARS-CoV-2 RNA was detected in one patient without conjunctivitis (5.5%). The mean age of the 36 patients was 67.9 years (range, 28-92 years) and the male-to-female ratio was 0.44 (16:20). The mean days since the onset of COVID-19 symptoms until conjunctivitis manifestation was 8 (range, 1-24 days). The mean duration of the conjunctivitis was 3 days (range, 1-7 days). SARS-CoV-2 RNA may be detected in conjunctival swabs of both patients with and without conjunctivitis. This study revealed the same rate of positive results amongst the group with and without conjunctivitis, suggesting that detecting SARS-CoV-2 in ocular fluids is not conditioned on the presence of conjunctivitis. The presence of SARS-CoV-2 RNA in ocular samples highlights the role of the eye as a possible route of transmission of the disease.

Ocular findings in patients with coronavirus disease 2019 (COVID-19) in an outbreak hospital.

PURPOSE: The aim of this study was to investigate the ocular findings observed in patients with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 and to present the relationship between ocular involvement, systemic findings, and laboratory results. MATERIAL AND METHODS: This cross-sectional study was carried out between 1 May and 30 June 2020. The study included 359 patients diagnosed with COVID-19 and assessed by clinical evaluation, nasopharyngeal polymerase chain reaction, and lung computed tomography. RESULTS: One hundred ninety-seven (54.9%) of the patients were male and 162 (45.1%) were female. The mean age of the patients was 58.5 years (20-91). Two hundred ninety-four (81.9%) patients were treated in the inpatient clinic and 65 (18.1%) patients were treated in the intensive care unit. Various ocular diseases were observed in 16 (4.5%) of the patients. Although the rate of ocular disease was 12 out of 294 (4.1%) in patients followed up in the inpatient clinic, this rate was 4 out of 65 (6.2%) in intensive care patients. There was no systemic problem in one patient, in whom conjunctival hyperemia was the first and only reason for admission to the hospital. Four patients followed up in the inpatient clinic had conjunctivitis at the time of admission, and conjunctivitis occurred in three patients during hospitalization. Subconjunctival hemorrhage occurred in five patients and vitreous hemorrhage in one patient. CONCLUSION: Ocular diseases are uncommon in COVID-19 patients but may occur during the first period of the disease or during follow-up. Ocular diseases may be the initial or only sign of COVID-19 infection.

Late manifestation of follicular conjunctivitis in ventilated patient following COVID-19 positive severe pneumonia.

A 65-year-old known diabetic, hypertensive, and asthmatic patient was admitted for suspected coronavirus disease 19 (COVID-19) infection following complaints of breathlessness. He tested positive for COVID-19 and was put on ventilation. He developed severe follicular conjunctivitis of the right eye while on a ventilator, which was treated conservatively. The resolution of ocular signs was noted over 2 weeks without any complications. This case highlights the timeline of events and discusses the late ophthalmic manifestations in patients with COVID-19 infection.

Serological evidence of Zika virus infection in febrile patients at Greater Accra Regional Hospital, Accra Ghana.

OBJECTIVE: Increase in the evidence of global occurrence of Zika viral infection suggests that in Africa the circulation of the virus which causes 80% of asymptomatic infection could be undetected and/or overlooked. We sought to serologically detect Zika virus infection in febrile patients at Greater Accra Regional Hospital, Ghana. RESULTS: Of the 160 patient serum samples analyzed, 33 were found to have antibodies against Zika virus infection. Among the sero-positives 30 (91%) of the cases were anti-Zika virus IgM with the 21-30-year age group recording the highest number of 8 (26%) and 2 (7%) cases being the least for the 61 years and above age group. All sero-positive febrile patients developed at least one symptom consistent with Zika virus infection: 33 (100%) fever, 25 (76%) muscle pain, 24 (73%) joint pain, and conjunctivitis 2 (6%). Digestive symptoms recorded include 16 (49%) nausea, 12 (36%) vomiting and diarrhea 18 (55%). In addition, 28 (85%) loss of appetite, 14 (75%) rapid respiration and chest pain 15 (42%) were reported by seropositive febrile patients. Our data indicates exposure to Zika virus which suggests the possible circulation of the virus among febrile patients in Ghana with a sero-prevalence rate of 20.6%.

Effect of cold atmospheric plasma (CAP) on human adenoviruses is adenovirus type-dependent.

More than 70 human adenovirus types were identified divided into 7 different species (A-G). Diseases caused by human adenoviruses are type-dependent and can range from mild to severe respiratory infections, gastrointestinal infections or eye infections such as epidemic keratoconjunctivitis. Unfortunately there is no specific anti-adenovirus therapy available. Here we addressed the question whether treatment with cold atmospheric plasma (CAP) for anti-adenoviral therapy such as virus-mediated ulcerations may be feasible. CAP has already been explored for the treatment of dermatological diseases such as chronic wounds. To investigate whether CAP is an effective antiviral tool, purified human adenovirus types derived from different human adenovirus species (HAdV -4, -5, -20, -35, -37, -50) tagged with luciferase were treated with defined dosages of plasma. The CAP treatment was varied by incrementally increasing the time span of CAP treatment. After CAP treatment, the virus containing solution was added to eukaryotic cells and the viral load was determined by measurement of luciferase expression levels. Through the plasma treatment the adenovirus driven luciferase expression directly correlating with adenovirus transduction efficiencies could be reduced for HAdV-5 and HAdV-37. Plasma treatment had no influence on adenovirus derived luciferase expression levels for HAdV-4 and HAdV-50 and it even had a positive effect on luciferase expression levels for HAdV-20 and HAdV-35. These results suggest that CAP has a type dependent effect on adenoviruses and that infectivity can be even increased for certain adenovirus types. Further studies should address the mechanisms behind this phenomenon. In summary we demonstrate that CAP may represent an interesting option for antiviral treatment in a virus type dependent manner.

Distinguishing Zika and Dengue Viruses through Simple Clinical Assessment, Singapore.

Dengue virus and Zika virus coexist in tropical regions in Asia where healthcare resources are limited; differentiating the 2 viruses is challenging. We showed in a case-control discovery cohort, and replicated in a validation cohort, that the diagnostic indices of conjunctivitis, platelet count, and monocyte count reliably distinguished between these viruses.

Randomized, Controlled, Phase 2 Trial of Povidone-Iodine/Dexamethasone Ophthalmic Suspension for Treatment of Adenoviral Conjunctivitis.

PURPOSE: To evaluate the efficacy/safety of an ophthalmic suspension of povidone-iodine (PVP-I) 0.6% and dexamethasone 0.1% in patients with acute adenoviral conjunctivitis. DESIGN: Multicenter, randomized, vehicle-controlled, double-masked trial. METHODS: Adults with a positive Rapid Pathogen Screening Adeno-Detector Plus test were randomized 1:1:1 to PVP-I 0.6%/dexamethasone 0.1%, PVP-I 0.6%, or vehicle, bilaterally 4 times daily for 5 days (days 1-5). Patients were evaluated on days 3, 6, and 12 (+1-day window). Efficacy measures included clinical resolution and adenoviral eradication. RESULTS: Overall, 144 patients were included in the efficacy analysis (PVP-I/dexamethasone, n = 48; PVP-I, n = 50; vehicle, n = 46). The proportion of patients with clinical resolution (primary study eye with last observation carried forward [LOCF]) at the day 6 visit was higher with PVP-I/dexamethasone (31.3%) than with vehicle (10.9%; P = .0158) and PVP-I (18.0%; P = nonsignificant). The proportion with adenoviral eradication (primary study eye with LOCF) was higher with PVP-I/dexamethasone than with vehicle at the day 3 (35.4% vs 8.7%; P = .0019) and day 6 (79.2% vs 56.5%; P = .0186) visits and vs PVP-I (day 3 visit, 32.0%; day 6 visit, 62.0%; each P = nonsignificant). Treatment-emergent adverse events (AEs) occurred in 69.0% (vehicle), 62.7% (PVP-I), and 53.4% (PVP-I/dexamethasone) of patients in the safety dataset. Discontinuation owing to AEs occurred in 37 patients (vehicle, n = 16; PVP-I, n = 12; PVP-I/dexamethasone, n = 9). CONCLUSION: PVP-I/dexamethasone appeared safe and well tolerated, and significantly improved clinical resolution and adenoviral eradication in patients with acute adenoviral conjunctivitis.

The eyes have it: influenza virus infection beyond the respiratory tract.

Avian and human influenza A viruses alike have shown a capacity to use the eye as a portal of entry and cause ocular disease in human beings. However, whereas influenza viruses generally represent a respiratory pathogen and only occasionally cause ocular complications, the H7 virus subtype stands alone in possessing an ocular tropism. Clarifying what confers such non-respiratory tropism to a respiratory virus will permit a greater ability to identify, treat, and prevent zoonotic human infection following ocular exposure to influenza viruses; especially those within the H7 subtype, which continue to cause avian epidemics on many continents.

Prevalence of Ocular Manifestations and Visual Outcomes in Patients With Herpes Zoster Ophthalmicus.

PURPOSE: To investigate the prevalence of ocular manifestations and visual outcomes in patients with herpes zoster ophthalmicus (HZO). METHODS: Consecutive cases diagnosed with HZO who attended 2 hospitals between July 1, 2011, and June 30, 2015, were retrospectively reviewed. Patient demographics, clinical presentations, and management were reviewed. The logistic regression model was used to estimate the odds ratio of visual loss with ocular manifestations. RESULTS: A total of 259 patients were included. Of these, 110 (42.5%) patients were <60 years old and 149 patients (57.5%) were ≥60 years old. None of the patients had received zoster vaccination before presentation. Ocular manifestations were present in 170 (65.6%) patients with no difference between both age groups (P = 0.101). Conjunctivitis was the most common ocular manifestation, followed by anterior uveitis and keratitis. After resolution of HZO, 58.7% of patients had a visual acuity of 6/12 or worse. Epithelial keratitis and stromal keratitis were independent risk factors for visual loss after resolution of HZO (P = 0.003 and P = 0.004, respectively). The corresponding odds ratio was 6.59 [95% confidence interval (CI): 1.87-23.19] and 7.55 (95% CI: 1.88-30.30), respectively. The number of ocular manifestations was also associated with an increased risk of visual loss with an odds ratio of 1.49 (95% CI: 1.01-2.20; P = 0.043). CONCLUSIONS: A substantial proportion of patients with HZO were <60 years old in this study. The absence of zoster vaccination across the study cohort was noteworthy. Keratitis was the main reason for poor visual outcome in these patients.

Altered hyaluronic acid content in tear fluid of patients with adenoviral conjunctivitis.

The adenoviral conjunctivitis is one of the biggest causes of conjunctival infection in the world. Conjunctivitis causes relatively nonspecific symptoms, as hyperaemia and chemosis. Even after biomicroscopy, complex laboratory tests, such as viral culture, are necessary to identify the pathogen or its etiology. To contribute to the better understanding of the pathobiology of the adenoviral conjunctivitis, the tear fluids of patients with unilateral acute adenovirus conjunctivitis (UAAC), normal donors (control) and patients with allergic conjunctivitis were analyzed. Tear samples were collected with Schirmer strips from control, allergic conjunctivitis and UAAC patients, diagnosed by clinical signs. UAAC tears were tested positive in viral cultures. After the elution, HA was quantified using an ELISA-like fluorometric assay and the protein profile was determined by SDS-PAGE. A profound increase in the HA tear content in UAAC patients was found when compared to control and ALC. This HA increase in UAAC tears remarkably was not observed in tears from contralateral eyes without clinical signs, nor in allergic conjunctivitis. In addition a distinct profile of UAAC tear proteins was observed in patients with UAAC. The quantification of HA in the tear fluid is a rapid, sensitive and specific test. This molecule might be a biomarker candidate for acute conjunctivitis.

Photorefractive keratectomy with mitomycin-C for the combined treatment of myopia and subepithelial infiltrates after epidemic keratoconjunctivitis.

PURPOSE: To report the use of photorefractive keratectomy (PRK) with mitomycin-C (MMC) to treat concomitant myopia and visually significant infiltrates associated with epidemic keratoconjunctivitis (EKC). SETTING: Ophthalmic Consultants of Long Island, Nassau University, Long Island, New York, USA. DESIGN: Interventional case series. METHODS: Consecutive patients with myopia and recalcitrant subepithelial infiltrates after EKC were treated with custom wavefront PRK (Visx S4 IR) and MMC with a target of emmetropia in all cases. RESULTS: The study evaluated 6 eyes of 3 patients. One year after treatment, all eyes attained an uncorrected distance visual acuity of 20/20 or better. There was no recurrence of infiltrates within the ablation zone in any eye. CONCLUSION: The use of topical MMC in conjunction with PRK to treat subepithelial infiltrates due to EKC provided good visual and refractive results.

Phototherapeutic keratectomy for the treatment of corneal opacities after epidemic keratoconjunctivitis.

PURPOSE: To assess visual results and compare methods of measuring central corneal thickness (CCT) and corneal opacity thickness (COT) in patients with corneal opacities induced by epidemic keratoconjunctivitis (EKC) and treated with phototherapeutic keratectomy (PTK) using low-dose mitomycin C (MMC). DESIGN: Prospective consecutive case series. METHODS: Patients with chronic adenoviral corneal opacity underwent transepithelial PTK with MMC 0.002% for 1 minute. The presence of photophobia, the best spectacle-corrected visual acuity (BSCVA), and the contrast sensitivity were evaluated. CCT measurements were obtained with ultrasound pachymeter (US), ultrasound biomicroscopy (UBM), Scheimpflug tomography (Pentacam Oculus), and optical coherence tomography (OCT Visante). COT measurements were obtained with UBM, Pentacam, and OCT. RESULTS: Thirty-one eyes of 23 patients, comprising 15 women (65.2%) and 8 men (34.8%), mean age 41.8 years, were enrolled in the study. Duration of visual disturbance was 19.1 ± 14 months. The number of patients with photophobia was reduced from 100% to 29% after surgery. BSCVA improved 2 or more lines in 78% of the patients at 12 months. A hyperopic shift of 1.52 ± 0.91 diopters was achieved. Contrast sensitivity improved in both photopic and mesopic conditions. For each of the instruments, the CCT postoperative mean was significantly smaller than the preoperative measurement (P < .0001) and COT values were significantly reduced in comparison to the preoperative values (P < .001). CONCLUSION: Improvements in photophobia, BSCVA, and contrast sensitivity were observed in patients treated using excimer laser PTK with low-dose MMC for subepithelial infiltrates.

Allergy and infections: long-term improvement of vernal keratoconjunctivitis following viral conjunctivitis.

PURPOSE: Vernal keratoconjunctivitis (VKC) is a severe, chronic allergic inflammatory disease of the ocular surface poorly responsive to antiallergic treatments and possibly leading to permanent visual impairment. VKC, because of mast cell, eosinophil, and Th2-type inflammation, polyclonal IgE activation, and tissue remodeling, is considered to be a typical Th2- driven disease. Viral infection stimulates a Th1 type immune response, potentially attenuating allergen-induced inflammation. The purpose of this report is to describe the effect of viral keratoconjunctivitis in a patient with VKC. METHODS: The authors report on a patient with a severe form of VKC, poorly responsive to antiallergic treatments, who developed a viral keratoconjunctivitis. Signs, symptoms, and cytologic findings were recorded during the 5-year follow-up period. RESULTS: The authors observed a prompt and permanent improvement of signs and symptoms of the allergic condition after the viral infection. Conjunctival scraping confirms that the inhibition of the eosinophilic inflammation lasts at least for 5 years. CONCLUSIONS: In this case, the viral infection seemed to induce a clinical recovery of allergic disease, suggesting that an immune deviation induced by Th1-polarizing agents may revert an ongoing Th2 inflammation.

Mousepox conjunctivitis: the role of Fas/FasL-mediated apoptosis of epithelial cells in virus dissemination.

BALB/c mice infected with the Moscow strain of Ectromelia virus (ECTV-MOS) show a large number of apoptotic cells, and an influx of lymphoid cells in the epithelium and substantia propria of conjunctivae, respectively. The presence of ECTV-MOS antigens in the epithelium of conjunctivae significantly upregulates Fas in the epithelial layer and FasL in the suprabasal layer of conjunctiva. Inhibition of FasL with blocking antibodies in cultures of conjunctival cells isolated from ECTV-MOS-infected BALB/c mice showed that the Fas/FasL pathway is important in apoptosis of ECTV-MOS-infected cells. The results also showed that the presence of cytokines, in particular interferon (IFN)-gamma, upregulated expression of Fas. Interleukin (IL) 2, 4, 10 and IFN-gamma were produced at the peak of conjunctivitis (at day 15 of infection) with a predominance of IFN-gamma and a small, but significant, production of IL4 and IL10 compared with non-infected animals. These results suggest that not only is Fas/FasL expression in conjunctiva involved in elimination of migrating Fas+ cells but also plays an important role in the turnover of conjunctival epithelium and thus may be crucial for ECTV spreading to the surrounding environment.

The change of etiological agents and clinical signs of epidemic viral conjunctivitis over an 18-year period in southern Taiwan.

BACKGROUND: Epidemic viral conjunctivitis is a highly contagious eye disease that occurs worldwide and is caused mainly by adenoviruses and enteroviruses. An 18-year analysis of the changes of pathogens and clinical signs in a subtropical and densely populated island presents certain special features. METHODS: We retrospectively analyzed the clinical information and laboratory records of the conjunctivitis patients with positive conjunctival swabs from 1980 to 1997. RESULTS: The positive rate of laboratory diagnosis of epidemic conjunctivitis was 50.0% (1,233/2,467). From 1980 to 1994, the predominant causative agent of adenoviral keratoconjunctivitis was adenovirus type 8 (Ad8), with six genotypes being evolved. Three of the new Ad8 genotypes each caused a new epidemic. After 1995 the predominant adenoviral pathogens shifted to Ad37 and Ad19, and no more Ad8 was isolated. Enterovirus type 70 (EV70) was isolated from four outbreaks of acute hemorrhagic conjunctivitis (AHC) from 1980 to 1984, but rarely in later years. Coxsackievirus A type 24 variant (CA24v), which first appeared in 1985, appeared later as the causes of four major epidemics of AHC from 1985 to 1994. The overall clinical symptoms of viral conjunctivitis were more severe in the 1990s than in the 1980s. CONCLUSION: In southern Taiwan, outbreaks of adenoviral keratoconjunctivitis caused by new genomic variants could be associated with the long-term endemic co-circulation of Ad8, Ad19, and Ad37, while epidemics of CA24v AHC were caused mainly by introduction of new viral strains from neighboring countries. The aggravation of host symptoms in the 1990s needs further investigation and close follow-up.

A randomized, double-masked trial of topical ketorolac versus artificial tears for treatment of viral conjunctivitis.

OBJECTIVE: To determine if topical ketorolac 0.5% relieves the symptoms and signs of viral conjunctivitis better than artificial tears. DESIGN: Randomized, controlled trial. PARTICIPANTS: One hundred seventeen patients with a clinical diagnosis of viral conjunctivitis were randomized to the treatment group or control group. METHODS: Physicians and patients were masked to treatment. Patients in the treatment group received topical ketorolac 0.5% four times daily. Patients in the control group received artificial tears four times daily. Symptom and sign scores were recorded on the day of recruitment and at the time of a follow-up examination 3 to 4 days later. MAIN OUTCOME MEASURES: Change in six symptoms of conjunctivitis (overall discomfort, itching, foreign body sensation, tearing, redness, and lid swelling) and four signs of conjunctivitis (conjunctival injection, conjunctival chemosis, conjunctival mucus, and lid edema). Adverse effects were also studied. RESULTS: A total of 105 patients returned for their 3- to 4-day follow-up. Both the artificial tear and ketorolac groups showed improvement in all symptom scores at their 3- to 4-day follow-up visit. There was no statistically significant difference between the change in symptom scores between the treatment group and control group in any symptom category except redness. Patients in the control group were more likely to report improvement in redness than those in the treatment group, P = 0.012. There was no statistically significant difference between the change in sign scores between the treatment and control groups. Ketorolac 0.5% was more likely to produce stinging than artificial tears, 59.2% versus 18.8%, P < 0.001. CONCLUSIONS: Topical ketorolac 0.5% used four times daily is no better than artificial tears at relieving the symptoms or signs of viral conjunctivitis and produces more stinging than artificial tears.

Common ocular infections. A prescriber's guide.

While most ocular infections are benign, others can be associated with devastating visual consequences. Most patients present with either ocular discharge, visual symptoms or a red or painful eye. The primary care physician is usually the first to evaluate these patients. We have separated ocular infections into 3 groups. Infections affecting the cornea and conjunctiva often present with eye pain and a red eye; noninfectious aetiologies can have a similar presentation. Infections inside the eye (endophthalmitis) often have devastating consequences. They usually occur following penetrating ocular trauma or after intraocular surgery. Prompt referral to an ophthalmologist is crucial. Infections in the soft tissue surrounding the eye (ocular adnexa and orbit) can involve the eye indirectly and can spread from the orbit into the brain. The purpose of this article is to review ocular infections and current opinion regarding treatment. A general guideline should be that the approach to treatment be governed by the severity of symptoms and the magnitude of possible consequences. Mild external infections can be typically treated empirically. Severe conjunctivitis, and any corneal infection, require aggressive management, often including cultures and broad spectrum antibiotics; cultures are often used to guide treatment. Devastating vision loss can occur, even with aggressive management. Preseptal cellulitis in adults and older children can be managed conservatively with oral antibiotics if the orbit and optic nerve are not involved and the patient is otherwise healthy. Orbital or optic nerve involvement, on the other hand, demands orbital imaging and more aggressive intervention. Patients who have had recent surgery are at risk for developing endophthalmitis. Complaints of pain or a red eye must be taken very seriously. These patients must be considered to have an intraocular infection until it can be ruled out, and should be aggressively managed by a physician trained in eye diseases and surgery.

Viral and bacterial conjunctivitis. Prevention of disastrous results.

Conjunctivitis has many bacterial and viral causes. If the cause is bacterial, treatment with a broad-spectrum antibiotic resolves the problem in 1 to 3 days in almost all cases. If signs and symptoms persist, referral to an ophthalmologist is wise. Most cases of viral conjunctivitis are accompanied by follicular reactions in the inferior fornix, as observed with adult inclusion disease. If dendrites are seen, trifluridine (Viroptic) is preferred for treatment. Referral to an ophthalmologist is advisable because recurrence with scarring and permanent loss of vision is possible. Many topical antibiotics include a corticosteroid component that never should be used unless the conjunctivitis or keratitis is proven to be nonherpetic.