Adenoviral Epidemic Keratoconjunctivitis Research Articles

Keratopathy in Patients with Adenoviral Keratoconjunctivitis: Evaluation of the Effectiveness of Modern Interferon Preparations

It is considered, that one of the main directions of treatment of adenovirus conjunctivitis is the appointment of interferon alpha-2b in combination with diphenhydramine, which until recently was provided by the only original drug. In 2020, the first generic drug, Interferon-Oftalmo, would be registered in Russia.The purpose: to evaluate and compare the efficacy, safety and tolerability of treatment of patients with keratopathy against the background of adenovirus keratoconjunctivitis with Interferon-Oftalmo and Oftalmoferon.Material and methods. The comparative analysis included completed cases of treatment of 51 patients (102 eyes) aged 18–75 years with clinical signs of keratopathy against the background of epidemic adenoviral keratoconjunctivitis. Patients of the first group (n = 27, 54 eyes) on the background of tear replacement therapy received eight instillations of the drug Interferon-Ophthalmo, the second (n = 24, 48 eyes) received Oftalmoferon. The observation period was 15 days. Treatment efficacy was assessed based on a quantitative analysis of the dynamics of clinical symptoms of inflammation and the state of the cornea, the severity of subjective manifestations of ocular surface xerosis using the ocular surface damage index (OSDI), as well as the stability of the tear film. Safety and tolerability were also evaluated.Results. Against the background of complex therapy, which included the instillation of Interferon-Ophthalmo or Oftalmoferon, all patients showed comparable dynamics in the relief of the inflammatory process and keratopathy. This was expressed in a statistically significant decrease in the severity of foreign body sensation, lacrimation, itching, eyelid edema, conjunctival edema and hyperemia, follicular reaction, conjunctival hemorrhages, punctate keratopathy, subepithelial infiltrates in the cornea. In both groups, there was a steady downward trend in OSDI against the background of an increase in the stability of the tear film and an increase in maximally corrected visual acuity. The safety and tolerability profile of the drugs was assessed as comparably favorable.Conclusion. The inclusion of the drug Interferon-Oftalmo in the complex therapy of adenoviral epidemic keratoconjunctivitis allows us to expect a comparable effect on the course of the disease compared to the original drug Oftalmoferon.

Topography-Guided Transepithelial Photorefractive Keratectomy for the Treatment of Persistent and Visually-Significant Adenoviral Corneal Infiltrates.

To evaluate visual and refractive outcomes of customized photorefractive keratectomy (PRK) in subjects with persistent subepithelial corneal opacities secondary to adenoviral epidemic keratoconjunctivitis (EKC). Prospective study, which recruited patients with persistent and visually-significant post-EKC corneal opacities unresponsive to prolonged topical therapy (6 months or more). Outcome measures: uncorrected and best-corrected distance visual acuity, subjective refractive astigmatism, keratometric astigmatism, spherical equivalent, minimum corneal thickness, and corneal morphological irregularity index. Subjects were followed for 12 months post-treatment. Eighteen eyes of 18 patients aged between 32 and 75 years treated with topography-guided transepithelial PRK with iRes excimer laser (iVIS Technologies, Taranto, Italy) from June 2020 to July 2021. After 12 months, the mean UDVA improved from 1.0±0.00LogMAR pre-op to 0.15±0.154LogMAR, and the mean CDVA improved from 0.4±0.41LogMAR pre-op to 0.0±0.00LogMAR. With respect to UDVA, all treated eyes (100%) showed an improvement of 6 ETDRS lines or more and with respect to CDVA, 9 out of 18 eyes (50%) showed an improvement of 6 ETDRS lines or more. The mean ablation depth was 54.7±5.9μm. A statistically significant improvement was observed in all topographic indices. No infiltrate recurrence, post-treatment corneal haze, ocular hypertension or other side effects were observed throughout the follow-up period. Topography-guided PRK could be considered an effective and safe treatment option to improve visual acuity in patients affected by persistent and visually-significant subepithelial corneal infiltrates caused by EKC.

Наиболее значимые постнатальные факторы, влияющие на течение различных форм ретинопатии недоношенных

Purpose.To evaluate the most significant factors affecting the course of ROP. Material and methods. From 2009 to 2018, we examined 4120 children with ROP. The examination of children was carried out as part of a neonatal screening to detect ROP using standard diagnostic methods. Results. Against the background of prolonged oxygen therapy in children with broncho-pulmonary dysplasia (BPD), severe forms of ROP developed in 9.7% of cases, which is significantly lower than similar indicators in the pathology departments of premature and newborns. Among children with severe apnea, the onset of different-sized hemorrhages, mainly preretinal located in various parts of the fundus, mostly at the ends of the vascular arcades is observed in 70.4% of cases. In 25.9% of children with severe ROP, partial hemophthalmus appears. During blood transfusions in children with severe forms of ROP, the transition of the disease to a more severe stage was reduced in 64.0%, caliber and tortuosity of the retinal vessels increased in 79.8%, retinal edema and exudative manifestations intensified in 39,3%, hemorrhagic changes rose in 49,4%, extraretinal proliferation increased in 50.6%. Against the background of adenoviral epidemic keratoconjunctivitis (AEK) in children with severe forms of ROP, the exudation in the vitreous body sharply increased in 34.7%, retinal detachment developed in 4.1% of cases, even though the children had already undergone laser coagulation of the retina at the time of infection, fresh hemorrhages mainly at the ends of the vascular arcades appeared in 57.1%. Conclusions. Prolonged oxygen therapy under BPD reduces the severity of the ROP. The impact of blood transfusions is observed only in severe forms of ROP. Frequent episodes of apnea contribute to the development of intraocular hemorrhages during ROP. The course of adenoviral AEK exacerbates the course of severe forms of ROP. Key words: retinopathy of prematurity, blood transfusion, apnea, broncho-pulmonary dysplasia, adenoviral epidemic keratoconjunctivitis, risk factors of retinopathy of prematurity

A complicated course of the membranous form of epidemic keratoconjunctivitis. A case report

A case report is presented of a film y form o f adenoviral epidemic keratoconjunctivitis (EKC) in an adult patient. The case is interesting in that the onset of EKC did not predict a complicated, hyperergic course of the condition, which ultimately led to cicatricial changes in the conjunctiva in the form of a partial external symblepharon. The ophthalmologists need to be on the alert for this form of EKC, which requires differential diagnosis, first of all, with true toxic diphtheria lesion of the conjunctiva. Adequate combined antiviral treatment of EKC using corticosteroids, immunomodulatory and symptomatic therapy helps to stop the process.

Клинический случай пленчатой формы аденовирусного кератоконъюнктивита

This article describes a clinical case of a filmy form of adenoviral epidemic keratoconjunctivitis (EKC) in an adult patient. The given case is interesting in that the onset of EKC did not foreshadow a complicated, hyperergic course of the filmy form in an adult patient. That ultimately led to cicatricial changes in the conjunctiva in the form of a partial external symblepharon. Alertness of ophthalmologists in relation to this form of EKC, which requires differential diagnosis, first of all, with true toxic diphtheria lesion of the conjunctiva, is necessary. Adequate complex antiviral treatment of EKC with the use of corticosteroids, immunomodulatory and symptomatic therapy helps to stop the process. Key words: adenovirus conjunctivitis, epidemic keratoconjunctivitis, membranous form, complicated course, partial simblefaron, dry eye syndrome.

Visual rehabilitation by using corneal wavefront-guided transepithelial photorefractive keratectomy for corneal opacities after epidemic keratoconjunctivitis.

To evaluate long-term visual and refractive outcomes of corneal wavefront-guided transepithelial photorefractive keratectomy (t-PRK) with mitomycin C for the treatment of corneal opacities secondary to adenoviral epidemic keratoconjunctivitis. Records of patients who underwent corneal wavefront-guided t-PRK with excimer laser from January 2012 to December 2018 were retrospectively reviewed. Preoperative and postoperative uncorrected visual acuity, best-spectacle corrected visual acuity, slit-lamp biomicroscopic examination findings, manifest refraction, and corneal aberrations and fundus examination findings were evaluated. Twenty-two eyes of 22 patients comprising 12 male (55%) and 10 female (45%) were treated. The mean age was 34.5 ± 10.8years (range 19-55). The mean follow-up time was 34.4 ± 17.50months (range 13-61months). There was a statistically significant improvement in UCVA and BSCVA (p < 0.001 and p = 0.02), and there was a significant decrease in total higher-order aberrations, spherical, coma and trefoil aberration at postoperative first year (p < 0.001 in each). In two eyes of two patients, minimal haze formation was observed after the procedure, and both eyes were treated with topical steroid. No recurrence was observed in subepithelial infiltrates in any patient during long-term follow-up. In long-term clinical follow-up, corneal wavefront-guided t-PRK treatment is an effective and reliable treatment method for rehabilitation of visual impairment due to corneal scars following adenoviral infections, in properly selected patients.

Transepithelial Surface Ablation With Mitomycin C for the Treatment of Chronic Central Corneal Scars Following Adenoviral Keratoconjunctivitis

To assess visual and refractive outcomes and recurrence rates of subepithelial infiltrates after corneal surface ablation with mitomycin C (MMC) 0.02% for the treatment of chronic corneal scars following epidemic keratoconjunctivitis and to compare these results with a control group receiving only medical treatment. This was a retrospective case series enrolling patients with central corneal scars following epidemic keratoconjunctivitis. Patients were divided into two groups: (1) control with clinical follow-up and refractive correction with glasses or rigid gas-permeable contact lenses when necessary and (2) transepithelial phototherapeutic keratectomy (PTK) with MMC 0.02%, combined with photorefractive keratectomy (PRK) in selected cases (treatment group). Signs and symptoms, corrected distance visual acuity (CDVA) in logMAR units, manifest and cycloplegic refraction, and depth of the corneal opacities were assessed. Thirty-five eyes of 27 patients (11 men [40.7%] and 16 women [59.3%]) were enrolled, with a mean follow-up of 54.4 ± 19.7 and 27.5 ± 22.8 months in the control and treatment groups, respectively. Mean improvement in CDVA was 0.13 ± 0.17 logMAR (P = .007) in the control group and 0.29 ± 0.24 logMAR (P = .001) in the treatment group. Intergroup comparison showed a greater improvement in the treatment group (P = .041). Mean hyperopic shift induced in the treatment group was +0.46 ± 1.20 diopters. The recurrence rate of subepithelial infiltrates was 77.7% in the control group and 11.7% in the treatment group throughout the follow-up (54.4 ± 19.7 and 27.5 ± 22.8 months, respectively). Corneal surface ablation with MMC 0.02% was efficient in treating corneal scars following adenoviral epidemic keratoconjunctivitis, with greater visual improvement in comparison to clinical treatment and a decreased rate of infiltrate recurrence. [J Refract Surg. 2020;36(1):55-61.].

A treatment protocol for minimizing duration and complications of adenoviral epidemic keratoconjunctivitis.

PURPOSE:The purpose of the study was to assess the treatment protocol of topical 2.5% Povidone-Iodine (PovI) and 0.1% fluorometholone (FluM) for Adenoviral Epidemic keratoconjunctivitis (EKC) in reducing the duration and severity of the disease as compared to conventional treatment. This was a retrospective case–control study.MATERIALS AND METHODS:Cases were defined as patients with EKC receiving the treatment protocol and conjunctival swab taken for polymerase chain reaction. Controls were defined as similar patients receiving conventional treatment protocol. Forty-one cases and 35 controls were identified for analysis. Cases were treated with a protocol using 2.5% povidone-iodine eye drops and 0.1% FluM eye drops. Controls received conventional treatment until resolution of signs and symptoms. Both the groups were followed up for 1 month. Data collected were analyzed for effect of the two treatment protocols on the duration of EKC, rate of recovery, and incidence of complications.RESULTS:The treatment protocol was significantly better than conventional treatment protocol in achieving cure (P = 0.002) with large effect size. The proportion of cases achieving cure was significantly higher with treatment protocol (64% vs. 11% at 5 days, P < 0.001) by 5 days. There was a significant reduction of the subepithelial infiltrates (SEI) incidence group (10% vs. 57%, P < 0.001). There were no SEI at 1 month in the treatment group (0% vs. 31%).CONCLUSION:Treatment protocol used in our study can significantly reduce the severity and duration of EKC. It can prevent chronic keratitis in majority of cases. Since povidone-iodine is nonspecific and virucidal for adenovirus, this therapy can be used for other types of adenoviral conjunctivitis.

Assessment of clinical signs associated with adenoviral epidemic keratoconjunctivitis cases in southern Japan between 2011 and 2014

Adenoviral epidemic keratoconjunctivitis (EKC) is a major cause of ocular morbidity worldwide and specific antiviral therapies are not available. EKC is primarily caused by Human adenovirus D (HAdV-D) types 8, 37, 53, 54, 56 and 64. Considering the genomic variation in HAdV-D, we hypothesized that clinical signs could be differentiated by virus type. The hypothesis was retrospectively tested with clinical signs recorded from 250 patients with ocular infections visiting an ophthalmological clinic in southern Japan between 2011 and 2014. The results showed that conjunctival opacity, corneal epithelial disorders and pre-auricular lymphadenopathy, were more frequently associated with EKC than other ocular infections. Furthermore, HAdV types 8, 37 and 54, caused corneal complications and longer infections significantly more frequently than infections by types 53 and 56 (P < 0.05). Our descriptive results supported that symptoms severity vary with the infecting type, however, further research is needed to improve diagnosis of EKC.

In Vivo Confocal Microscopy Analysis of the Corneal Layers in Adenoviral Epidemic Keratoconjunctivitis

Objectives:To describe the clinical features and microstructural characteristics assessed by in vivo confocal microscopy (IVCM) in patients with adenoviral epidemic keratoconjunctivitis (EKC).Materials and Methods:The study included 20 eyes of 12 patients who presented to the Kocaeli University Medical Faculty, Department of Ophthalmology with complaints of watering, crusting, and stinging, were clinically diagnosed EKC, and were examined by slit-lamp biomicroscopy and IVCM during the prodromal phase and the punctate keratitis, deep epithelial keratitis, and subepithelial infiltration stages of EKC.Results:While biomicroscopic examination findings were normal during the prodromal period of EKC, IVCM showed an increase in Langerhans cell numbers in the subbasal plexus. After onset of clinical EKC, the punctate epithelial keratitis stage was characterized by findings of hyperreflective cell clusters in the basal epithelium layer, increased accumulation of Langerhans cells in Bowman’s layer, and hyperreflectivity in the anterior stromal layers. In the deep epithelial keratitis stage, the basal epithelial cells displayed peripheral hyperreflectivity and the hyperreflectivity of the anterior stromal surface increased and became more rounded. In the subepithelial keratitis stage, these findings persisted in addition to increased anterior stromal surface hyperreflectivity and focal round plaques.Conclusion:This study shows that the inflammatory process in the cornea starts in the prodromal period of EKC. Massive inflammation of the epithelium and stroma was observed in the active phase and focal changes were observed on the anterior stromal surface starting in the subepithelial infiltration period.

Investigation of the efficacy of alcohol-based solutions on adenovirus serotypes 8, 19 and 37, common causes of epidemic keratoconjunctivitis, after an adenovirus outbreak in hospital

Hand antiseptics are of great importance in the prevention of nosocomial infections. Due to the frequent occurrence of adenoviral epidemic keratoconjunctivitis outbreaks in the study hospital, it was necessary to investigate the efficiency of alcohol-based solutions on adenoviruses. To investigate the efficacy of alcohol-based solutions commonly found in hand antiseptics against adenovirus serotypes 8, 19 and 37. The efficacy of ethanol, isopropanol, chlorhexidine-digluconate, n-butanol and different combinations of these antiseptics on adenovirus serotypes that typically cause epidemic keratoconjunctivitis was investigated. The effect of antiseptic substances was investigated using a quantitative suspension test technique according to EN-14476. Antiseptics were prepared as follows: 70% ethanol, 70% isopropanol, 70% ethanol+0.5% chlorhexidine-digluconate, 70% isopropanol+0.5% chlorhexidine-digluconate, 60% ethanol+10% isopropanol, 60% ethanol+10% isopropanol+0.5% chlorhexidine-digluconate and 60% ethanol+10% isopropanol+1% n-butanol. The effect of antiseptics was evaluated at 30, 60 and 120 s. The highest reduction in virus titre was detected with 60% ethanol+10% isopropanol+1% n-butanol. This caused a reduction of 2.5log10, 3 log10 and 2.5log10 in adenovirus serotypes 8, 19 and 37, respectively. The lowest reduction in virus titre was detected with 70% ethanol+0.5% chlorhexidine-digluconate and 70% isopropanol+0.5% chlorhexidine-digluconate. These combinations caused a reduction of 1.62log10 in adenovirus serotypes 19 and 37. All antiseptics showed efficacy levels below 4log10 which is regarded as the efficiency limit by EN-14476. The alcohol-based solutions tested in this study were not found to be sufficiently effective against adenovirus serotypes. Further studies to investigate the efficiency of different alcohol-based solutions are required.

Recombinant type Human mastadenovirus D85 associated with epidemic keratoconjunctivitis since 2015 in Japan.

The aim of this study was to report the emergence of a recombinant human mastadenovirus (HAdV) type 85 (HAdV-85) and to describe its genomic and clinical characteristics. The strains were detected and identified in Japan in cases of adenoviral conjunctivitis including epidemic keratoconjunctivitis (EKC). The type was designated as HAdV-85 based on the novel combination of penton base (P = HAdV-37), hexon (H = HAdV-19), and fiber (F = HAdV-8). The whole genome sequence determined for HAdV-85 was compared against sequences of other types in the same species. The results of the phylogenetic analysis suggested a recombinant origin between HAdV-53 and HAdV-64, which have been two major causes of adenoviral EKC in Japan over the past decade. During the period between 2008 and 2016 in Kumamoto city, southwest of Japan, 311 cases diagnosed with conjunctivitis were diagnosed as being the consequence of adenoviral infections. Among them, 11 cases were determined to have been caused by HAdV-85 since 2015. Thus, HAdV-85 could be an emerging causative agent of adenoviral conjunctivitis.

Cell Cycle-Dependent Kinase Cdk9 Is a Postexposure Drug Target against Human Adenoviruses.

Human adenoviruses (HAdVs) infect respiratory, gastrointestinal, and urinary tracts and give rise to eye infections and epidemic keratoconjunctivitis (EKC). They persist in lymphoid tissue and cause morbidity and mortality in immunocompromised people. Treatments with significant postexposure efficacy are not available. Here, we report that inhibition of the cell cycle-dependent kinase 9 (Cdk9) by RNA interference, or the compound flavopiridol, blocked infections with HAdV-C2/5, EKC-causing HAdV-D8/37, and progeny formation in human corneal epithelial and cancer cells. Flavopiridol abrogated the production of the immediate early viral transactivating protein E1A without affecting nuclear import of viral DNA. In morphometric plaque assays, the compound exhibited antiviral efficacy in both pre- and postexposure regimens with therapeutic indexes exceeding 10. The study identifies Cdk9 as a postexposure drug target against adenovirus infections in vitro and suggests that the clinically tested anticancer drug flavopiridol is a candidate for treating adenoviral EKC or adenovirus emergence upon immune suppression.

FEATURES OF THE CLINICAL COURSE, OBSERVATION AND PREVENTION OF ADENOVIRAL EPIDEMIC KERATOCONJUNCTIVITIS IN INFANT IN THE PERINATAL CENTER

In recent years, the number of adenoviral epidemic keratoconjunctivitis (EKC) cases in a neonatal intensive care unit (NICU) has increased, which is primarily due to the establishment of an ophthalmologic service in these institutions, and the increase of the number of ophthalmologic examinations and manipulations. To characterize the features of the course and to identify the most effective methods of preventing adenoviral EKC of children during the first months of life who are on care and treatment in NICU. Adenoviral EKC is diagnosed in 284 children aged from 2 days to 3 months, who are on nursing in perinatal centers of Moscow. In 165 children with EKC retinopathy of prematurity (ROP) was noted. The course of adenoviral EKC in children in the age of the first months was accompanied by eyelids edema and conjunctiva edema, the formation of membranes (49.3%), hemorrhages (69.7%), corneal edema (30.3%), and absence of folliculosis of the eyelid conjunctiva. Cornea infiltrates occurred in 1.9% of cases and always disappeared in 1—2 weeks. after appearance. The development of adenoviral EKC in premature infants against the background of ROP complicates its course. Carrying out laser coagulation in children with ROP against the background of adenoviral EKC is safe and causes the same effect as in children without conjunctivitis. Conducting cryocoagulation at the peak of the conjunctivitis course is ineffective. Adherence to measures of the prevention of adenoviral EKC reduced the duration of the outburst to 1 month. The course of adenoviral EKC of children during the first months of life is severe, but in the end, no one child had any complications (long-term corneal infiltrates, conjunctivitis adhesions).

Human adenovirus: Viral pathogen with increasing importance

The aim of this review is to describe the biology of human adenovirus (HAdV), the clinical and epidemiological characteristics of adenoviral epidemic keratoconjunctivitis and to present a practical update on its diagnosis, treatment, and prophylaxis. There are two well-defined adenoviral keratoconjunctivitis clinical syndromes: epidemic keratoconjunctivitis (EKC) and pharyngoconjunctival fever (PCF), which are caused by different HAdV serotypes. The exact incidence of adenoviral conjunctivitis is still poorly known. However, cases are more frequent during warmer months. The virus is endemic in the general population, and frequently causes severe disease in immunocompromised patients, especially the pediatric patients. Contagion is possible through direct contact or fomites, and the virus is extremely resistant to different physical and chemical agents. The clinical signs or symptoms of conjunctival infection are similar to any other conjunctivitis, with a higher incidence of pseudomembranes. In the cornea, adenoviral infection may lead to keratitis nummularis. Diagnosis is mainly clinical, but its etiology can be confirmed using cell cultures, antigen detection, polymerase chain reaction or immunochromatography. Multiple treatments have been tried for this disease, but none of them seem to be completely effective. Prevention is the most reliable and recommended strategy to control this contagious infection.