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.

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.

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.

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.

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.