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Purpose Investigation of the efficacy and safety of 12 months of topical tacrolimus 0.03% ointment treatment against the subepithelial infiltrates (SEIs) due to adenoviral keratoconjunctivitis (AKC) resisting at least 2 years was aimed. Methods This case series included consecutive patients with SEIs secondary to AKC who were resistant to topical steroid and ciclosporin-A (CSA) treatment and treated with topical 0.03% tacrolimus (Protopic; Fujisawa Healthcare, Teva, Deerfield, Illinois, USA) for 12 months, at least 2 years after AKC. For the evaluation of treatment efficacy, best-corrected visual acuity (BCVA), Fantes score, corneal subepithelial infiltrate score (CSIS), Oxford score, Schirmer and tear breakup time results were evaluated. Intraocular pressure and complaints of the patients were followed for evaluating the safety profile of the treatment. The patients were followed after the baseline visit at the 1st, 3rd, 6th and 12th month. Results 15 eyes of 11 patients with SEIs and 16 eyes of 16 healthy controls were included in this study. 1 patient (9.1%) could not tolerate the treatment. Significant improvements in BCVA, CSIS, Fantes score and Schirmer results were observed in the study group starting from the 3rd-month visit, and the improvements persisted until the end of 12 months of treatment. Conclusion Topical 0.03% tacrolimus might show efficacy against the SEIs persisting at least 2 years despite corticosteroid and/or CSA treatment without any prominent side effect. While at least a period of 3 months was necessary for a significant improvement in the BCVA, SEIs and Schirmer results, a period of 6 months was necessary for a decrease in Oxford score.

Purpose To describe the correlation between the temporal pattern of presentation of acute epidemic keratoconjunctivitis (EKC) of presumed adenoviral etiology with meteorological parameters such as environmental temperature, rainfall, humidity, and wind speed. Methods This cross-sectional hospital-based study included 2,408,819 patients presenting between August 2010 and February 2020. Patients with a clinical diagnosis of EKC in at least one eye were included as cases. A smaller cohort of patients with acute (≤1 week) presentation hailing from the district of Hyderabad during the calendar years 2016-2019 was used to perform correlation analysis with the local environmental temperature, rainfall, humidity, and wind speed (data obtained from the Telangana State Development and Planning Society). Results Overall, 21,196 (0.87%) patients were diagnosed with EKC, of which 19,203 (90.6%) patients had acute onset; among which the cohort from the district of Hyderabad included 1,635 (8.51%) patients. The mean monthly prevalence in this cohort was 0.89% with a peak prevalence in April (1.09%). The environmental parameters of rainfall (r2 = 0.47/P = 0.0131), humidity (r2 = 0.65/P = 0.0014), and wind speed (r2 = 0.56/P = 0.0047) were significantly negatively correlated with the temporal pattern of EKC in the population. There was no visible trend or significant correlation seen with temperature (r2 = 0.08/P = 0.3793). Conclusion Contrary to popular belief, epidemic viral infections like EKC may not be affected by temperature, but rather by a complex interplay of other environmental factors such as humidity, rainfall, and wind speed. An increase in rainfall, wind speed, and humidity contributes to a lower prevalence of EKC cases during the year.

Human adenovirus (HAdV) is the most common cause of infectious conjunctivitis, accounting for up to 75% of all conjunctivitis cases and affecting people of all ages and demographics. In addition to ocular complications, it can cause systemic infections in the form of gastroenteritis, respiratory disease, and dissemination in immunocompromised individuals. HAdV causes lytic infection of the mucoepithelial cells of the conjunctiva and cornea, as well as latent infection of lymphoid and adenoid cells. Epidemic keratoconjunctivitis (EKC) is the most severe ocular manifestation of HAdV infection, in which the presence of subepithelial infiltrates (SEIs) in the cornea is a hallmark feature of corneal involvement. SEIs have the tendency to recur and may lead to long-term visual disability. HAdV persistence and dissemination are linked to sporadic outbreaks of adenoviral keratoconjunctivitis. There is no FDA-approved antiviral for treating adenoviral keratoconjunctivitis, and as such, solutions should be proffered to handle the challenges associated with viral persistence and dissemination. Several treatment modalities have been investigated, both systemically and locally, to not only mitigate symptoms but reduce the course of the infection and prevent the risk of long-term complications. These options include systemic and topical antivirals, in-office povidone-iodine irrigation (PVI), immunoglobulin-based therapy, anti-inflammatory therapy, and immunotherapy. More recently, combination PVI/dexamethasone ophthalmic formulations have shown favorable outcomes and were well tolerated in clinical trials for the treatment of EKC. Possible, future treatment considerations include sialic acid analogs, cold atmospheric plasma, N-chlorotaurine, and benzalkonium chloride. Continued investigation and evaluation of treatment are warranted to reduce the economic burden and potential long-term visual debilitation in affected patients. This review will focus on how persistence and dissemination of HAdV pose a significant challenge to the management of adenoviral keratoconjunctivitis. Furthermore, current and future trends in prophylactic and therapeutic modalities for adenoviral keratoconjunctivitis will be discussed.

Ocular microsporidiosis comprises two entirely different spectra of disease as keratoconjunctivitis and stromal keratitis. Microsporidial keratoconjunctivitis (MKC) has been increasingly reported in the past two decades, probably due to raised awareness, simpler diagnostic procedures, and a better understanding of the clinical presentation. It is characterized by the presence of raised, coarse, punctate, multifocal, round to oval, greyish-white corneal epithelial lesions which usually evolve into nummular scars before resolution. Conjunctivitis seen is non-purulent and of mild-moderate intensity, with mixed papillary-follicular reaction. The mode of transmission and pathogenesis is poorly understood. Despite lack of inflammatory response, uncommon associations reported were- endotheliitis, corneal edema, limbitis, uveitis, and sub-epithelial infiltrates. There has been no consensus on the management of MKC. It varies from the use of multiple antimicrobial agents to simple lubricants. The majority of the disease goes underdiagnosed or misdiagnosed and treated as adenoviral keratoconjunctivitis, with topical steroids or anti-virals empirically. Changing trends have been noticed in the pattern of infection, possibly with increasing evidence of Vittaforma corneae as causative organisms, previously reported to cause stromal keratitis. An elaborate review of the past and present literature on MKC is provided in this review article, along with gaps in knowledge, and future directions of research.

AIM: To evaluate the clinical characteristics of adenoviral keratoconjunctivitis, the management modalities, as well as the incidence of subepithelial corneal infiltrates (SEI). METHODS: Patients with characteristic clinical symptoms and signs, who presented to our clinic within the first week of symptoms and received the diagnosis of adenoviral keratoconjunctivitis between January 2013 and April 2016, were included in the study. A total of 211 patients were included in the study. Patients were evaluated for the incidence of clinical signs, late complications, management preferences, and the effect of diluted povidone-iodine (d-PVP-I) 2%. RESULTS: Patients' mean age was 33.03±14.76y. We observed an increase in the number of cases according to the years. At presentation and/or early follow-up, the clinical signs were conjunctival hyperemia (100%), conjunctival follicules (79.1%), edema of the eyelids (39.3%), chemosis (16.1%), pseudomembrane formation (16.6%), and corneal epitheliopathy (29.9%). During late follow-up 13.3% patients developed conjunctival subepithelial fibrosis, and 39.8% developed SEI. A significant decrease in the incidence of SEI development was observed in patients who used d-PVP-I 2% (P=0.032; 33.3% vs 45.9%, respectively in patients who received d-PVP-I 2% and who did not). CONCLUSION: Adenoviral keratoconjunctivitis has a tremendous effect on patient's comfort and abilities in short-term. Additionally, almost half of the patients develop visual problems related to SEI. According to our clinical experience, using d-PVP-I 2% in the first days of adenoviral keratoconjunctivitis might be helpful in reducing the risk of SEI as a complication.

This review will provide an updated overview of the diagnosis, management, and prevention of adenoviral keratoconjunctivitis. Human adenovirus (HAdV) is undergoing nomenclature changes because of whole genome sequencing. Recombination has led to newly identified ocular pathogens like HAdV-D53, HAdV-D54, and HAdV-D56. No quick, highly sensitive and specific diagnostic test is available for ocular adenoviral infections. PCR takes a few hours but is not widely available. Results of using PCR in employees at one medical center support the view of endemic HAdV in the community. Infection control is highly important as no treatment for ocular HAdV infections exists, ocular sequelae can be significant, and HAdV is endemic. Diagnosis of HAdV ocular infections can be challenging; ophthalmologists are best positioned to diagnose the condition and provide antibiotic stewardship. Development of an accurate diagnostic test with quick turnaround would lead to major benefits in terms of less antibiotic use and fewer work furloughs. Outbreaks occur when infection control becomes lax.

We evaluated a novel silver amplification immunochromatography test for rapid detection of adenovirus (AdV) antigen equipped with an automated reader system using tears including conjunctival exudate in patients with adenoviral keratoconjunctivitis. Two kinds of immunochromatographic (IC) kits, a conventional IC kit for conjunctival scrapings (control kit) and an IC kit using tears including conjunctival exudate collected by pressing a filter paper strip on the conjunctiva (test kit), were tested on 90 patients who attended Migita Eye Clinic with suspected adenoviral conjunctivitis. The results of the test kits were automatically obtained by a specific reader, which was based on silver amplification immunochromatography system, in 15 min. The detection of AdV was confirmed by real-time polymerase chain reaction (PCR) method, and typing was performed by direct sequencing. Comparative dilution assay was carried out with the two kits, using AdV type 3 and type 54 strains. The sensitivity of the control kit and test kit was 89.8% and 98.3%, respectively. The specificity of both kits was 100%. A significant difference in the sensitivities of the two IC kits against PCR positivity was observed (P

Purpose: To compare the safety and efficacy of tacrolimus 0.03% ointment with dexamethasone 0.05% ointment for subepithelial infiltrates (SEIs) following adenoviral keratoconjunctivitis (AK). Methods: A randomized, double blind trial was done. Eligibility criteria was corrected distance visual acuity of 6/9 Snellen or worse for at least 4 weeks with corneal SEIs following AK. The grading of SEIs was done on a scale of 0 to 3; 0, no infiltrates, 1 mild infiltration, 2 moderate infiltration and 3, severe infiltration. Consecutive patients with SEIs following AK were randomized to receive either topical tacrolimus 0.03% or dexamethasone 0.05% ointment twice daily for 6 months. Treatment was successful if there was reduction of SEIs and improvement in vision. Results: A total of 45 patients each were assigned to the Tacro and Dexa groups, respectively. Baseline characteristics of patients did not differ significantly (P > 0.001). There was a significant change in symptoms, vision and SEIs in both the groups. However, the magnitude was greater in tacro group. Treatment was successful in 37 (92.5%) patients in Tacro and 34 (85%) patients in dexa group. In dexa group, after a period of 1.24 ± 0.24 months, 7 (15.6%) patients developed a significant rise in intraocular pressure (IOP). Three (7.5%) eyes in tacro and 6 (15%) eyes in dexa group had recurrence of SEIs after cessation of therapy. Conclusion: Tacrolimus 0.03% is an effective alternative to dexamethasone 0.05% with low recurrence rate, no significant rise in IOP but may cause burning and foreign body sensation in some patients.

Purpose To evaluate the ocular surface properties in epidemic keratoconjunctivitis (EKC) patients during healing process, and to detect the damage on conjunctival goblet cells. Methods Bilateral EKC patients confirmed with polymerase chain reaction (PCR) testing were included. Firstly (Group 1) and secondly (Group 2) affected eyes were compared. Ocular surface parameters were performed at the first visit and first month. Results The study included 34 eyes of 17 patients. The mean age was 44.54 +/- 16.80 (21-70) years (FM/M 20/14). The ocular findings in Groups 1 and 2 were not significant. For Groups 1 and 2, OSDI was 53.53 +/- 23.01 and 35.90 +/- 22.19 (p 0.03), tear osmolarity was 309.12 +/- 19.38 and 297.47 +/- 8.27 mOsm/mu L (p 0.029), OSSS was 1.00 +/- 0.79 and 0.18 +/- 0.39 (p 0.001), T-BUT was 3.59 +/- 2.29 and 6.00 +/- 1.83 s (p 0.002), and Schirmer's 1 test was 10.94 +/- 8.42 and 16.76 +/- 9.05 mm (p 0.061), respectively. In Groups 1 and 2, the IC was Grade (G) 0 in 23.5% and 17.6%, G1 in 35.3% and 41.2%, and G2 in 41.2% and 41.2%, respectively. The ocular surface properties were worse in Group 1 than Group 2, and the difference was significant except for Schirmer's 1 test and IC. Conclusions Dry eye disorder is a complication of EKC and may cause a significant decrease in quality of life.

Purpose The purpose of this study was to assess the medical history of adenoviral keratoconjunctivitis (AK) and subepithelial infiltrates (SEIs) among French ophthalmologists and orthoptists and the frequency of unreported occupational diseases. We also described short-term and long-term consequences of AK and evaluated associated factors. Methods The REDCap questionnaire was diffused online several times over 7 consecutive months, from October 2019 to May 2020, through mailing lists (French Society of Ophthalmology, residents, and hospital departments), social networks, and by word of mouth. Results Seven hundred ten participants were included with a response rate of 6.2% for ophthalmologists, 3.8% for orthoptists, and 28.3% for ophthalmology residents. The medical history of AK was found in 24.1% (95% confidence interval 21%-27.2%) of respondents and SEI in 43.9% (36.5%-51.3%) of the AK population. In total, 87.1% (82.1%-92.1%) of AK occupational diseases were not declared. In total, 57.7% of respondents took 9.4 ± 6.2 days of sick leave, mostly unofficial, and 95.7% stopped surgeries for 13.0 ± 6.6 days. Among the AK population, 39.8% had current sequelae, with 17.5% having persistent SEIs, 19.9% using current therapy, and 16.4% experiencing continuing discomfort. SEIs were associated with wearing contact lenses (odds ratio 3.31, 95% confidence interval 1.19-9.21) and smoking (4.07, 1.30-12.8). Corticosteroid therapy was associated with a greater number of sequelae (3.84, 1.51-9.75). Conclusions AK and SEI affect a large proportion of ophthalmologists and orthoptists, possibly for years, with high morbidity leading to occupational discomfort. Few practitioners asked for either to be recognized as an occupational disease. Associated factors would require a dedicated study.

To examine the effects of treatments performed on children with adenoviral conjunctivitis. 50 children with Adenoviral keratoconjunctivitis (AK) were evaluated. Patients were divided into four grou...

The aim of this study was to compare the efficacy of the topical regimens of iodine/steroids vs. antibiotics/steroids in acute to subacute adenoviral keratoconjunctivitis. A prospective open-label study. Nineteen patients diagnosed with unilateral or bilateral adenoviral conjunctivitis at less than 1 week from onset were enrolled in this study. Patients were divided randomly into two groups; group 1 was treated with 1.5% levofloxacin with 0.1% fluorometholone administered four times a day and group 2 was treated with a sixfold dilution of polyvinyl alcohol iodine (PAI) solution with 0.1% fluorometholone four times a day. Conjunctival samples from all affected eyes were obtained for real-time PCR. The total scores of acute signs (i.e., eyelid edema, conjunctival injecton, conjunctival discharge, follicules, pseudomembranes, subconjunctival hemorrhage) and symptoms, HAdV DNA copy number, and the presence of multiple subepithelial corneal infiltrates (MSI) were evaluated every 5 visits up to Day 30 after diagnosis. Comparing the total scores of acute signs and symptoms and viral load, we observed no significant differences between the two groups. At day 15 after diagnosis the proportion of patients with MSI in group 2 (35.7%) was significantly lower than in group 1 (0%). The impact of topical iodine/steroid therapy on acute signs and symptoms associated with adenoviral conjunctivitis is limited and not substantially different in the responses to antibiotics/steroids. However, this regimen results in a significant decrease in the incidence of MSI during the subacute phase of infection.

OBJECTIVES: To analyze the effect of the employment of polyvinylpyrrolidone-iodine (PVP-I) 0.6% eye drop on the clinical course of patients affected by Adenoviral Keratoconjunctivitis (AKC). METHODS: Consecutive patients with clinical signs of AKC and positive results of AdenoPlus test were enrolled from four Italian Centres. Patients were randomized to receive: PVP-I 0.6% eye drops four times/daily for 20 days (Group A) or hyaluronate-based tear substitutes four times/daily for 20 days (Group B). Best-corrected visual acuity (BCVA), optical coherence tomography (OCT) Optovue iVue pachymetry map; corneal haze; conjunctival injection and chemosis; subepithelial corneal infiltrates (SEIs); corneal and conjunctival staining and corneal densitometry were recorded at diagnosis and at every follow-up visit. The primary outcome was the resolution time of AKC. RESULTS: Overall, 59 AKC patients (34 for Group A and 25 for Group B) completed the study. Patients of Group A showed a significantly shorter resolution time and lower incidence of SEIs compared to patients of Group B. In particular, SEIs were present at the last visit in 3/34 (8.82%) patients of the Group A vs 11/25 (44%) of the Group B (p = 0.005). Patients of Group A showed a significantly lower incidence of corneal haze compared to patients of Group B (0/34 vs 3/25; p = 0.038). No side effects were reported for both groups. CONCLUSIONS: Although further clinical evaluations are needed, according to our data the use of PVP-I 0.6% eye drop in the setting of AKC reduces the risk of SEIs as well as the resolution time of the disease.

Purpose To determine host and pathogen factors predictive of outcomes in a large clinical cohort with keratoconjunctivitis. Design Retrospective analyses of the clinical and molecular data from a randomized, controlled, masked trial for auricloscene for keratoconjunctivitis (NVC-422 phase IIB, NovaBay; clinicaltrials.gov identifier, NCT01877694). Participants Five hundred participants from United States, India, Brazil, and Sri Lanka with clinical diagnosis of keratoconjunctivitis and positive rapid test results for adenovirus. Methods Clinical signs and symptoms and bilateral conjunctival swabs were obtained on days 1, 3, 6, 11, and 18. Polymerase chain reaction (PCR) analysis was performed to detect and quantify adenovirus in all samples. Regression models were used to evaluate the association of various variables with keratoconjunctivitis outcomes. Time to resolution of each symptom or sign was assessed by adenoviral species with Cox regression. Main Outcome Measures The difference in composite scores of clinical signs between days 1 and 18, mean visual acuity change between days 1 and 18, and time to resolution of each symptom or sign. Results Of 500 participants, 390 (78%) showed evidence of adenovirus by PCR. Among adenovirus-positive participants, adenovirus D species was most common (63% of total cases), but a total of 4 species and 21 different types of adenovirus were detected. Adenovirus D was associated with more severe signs and symptoms, a higher rate of subepithelial infiltrate development, and a slower decline in viral load compared with all other adenovirus species. The clinical courses of all patients with non–adenovirus D species infection and adenovirus-negative keratoconjunctivitis were similar. Mean change in visual acuity between days 1 and 18 was a gain of 1.9 letters; worse visual outcome was associated with older age. Conclusions A substantial proportion of keratoconjunctivitis is not associated with a detectable adenovirus. The clinical course of those with adenovirus D keratoconjunctivitis is significantly more severe than those with non–adenovirus D species infections or adenovirus-negative keratoconjunctivitis; high viral load at presentation and non-United States origin of participants is associated with poorer clinical outcome.

Human adenovirus (HAdV) is a ubiquitous virus that infects the mucosa of the eye. It is the most common cause of infectious conjunctivitis worldwide, affecting people of all ages and demographics. Pharyngoconjunctival fever outbreak is due to HAdV types 3, 4, and 7, whereas outbreaks of epidemic keratoconjunctivitis are usually caused by HAdV types 8, 19, 37, and 54. Primary cellular receptors, such as CAR, CD46, and sialic acid interact with fiber-knob protein to mediate adenoviral attachment to the host cell, whereas adenoviral penton base–integrin interaction mediates internalization of adenovirus. Type 1 immunoresponse to adenoviral ocular infection involves both innate immunity mediated by natural killer cells and type 1 interferon, as well as adaptive immunity mediated mainly by CD8 T cells. The resulting ocular manifestations are widely variable, with pharyngoconjunctival fever being the most common, manifesting clinically with fever, pharyngitis, and follicular conjunctivitis. Epidemic keratoconjunctivitis, however, is the severest form, with additional involvement of the cornea leading to development of subepithelial infiltrates. Because there is currently no US Food and Drug Administration-approved treatment for adenoviral ocular infection, current management is palliative. The presence of sight-threatening complications following ocular adenoviral infection warrants the necessity for developing antiadenoviral therapy with enhanced therapeutic index. Future trends that focus on adenoviral pathogenesis, including adenoviral protein, which utilize host receptors to promote infection, could be potential therapeutic targets, yielding shorter active disease duration and reduced disease burden.

Introduction: Highly contagious adenoviral conjunctivitis represents 15-70% of all conjunctivitis worldwide. Human adenovirus (hAdV) serotypes 3,4,7,8,19 and 37 contributes to 89% of all adenoviral conjunctivitis. Accurate and rapid diagnosis of adenoviral infections at serotype level could prevent misdiagnosis, spread of disease, unnecessary antibiotic use and increased treatment costs. Methodology: Sixty-two suspected viral conjunctivitis cases were recruited from November2013-January2015. Swabs collected from inferior palpebral conjunctiva and processed for viral culture (Hep2 cell line), immunofluorescence assay (IFA) and polymerase chain reaction (PCR) (targeting hexon gene). Serotype 3,4,7,8,19 and 37 identification was carried out with an optimized multiplex-PCR (based on hypervariable region of hexon gene) and confirmed by sequence analysis. Bayesian Latent Class Model (LCM) analysis was used to compare sensitivity and specificity of three tests. Results: Adenovirus was detected in 54.8% (34/62) of cases by combination of all three methods. Culture was positive in 23/34 cases (67.6%). PCR and IFA detected adenovirus in 24 (70.5%) and 21 (61.7%) cases respectively. LCM analysis revealed, sensitivity and specificity of PCR, Culture and IFA was 77.8% and 92.4%; 72.2% and 90.8%; 67.6% and 92.9% respectively. Serotyping by multiplex-PCR showed, two cases each were hAdV3 and hAdV4, 18 hAdV8 and two remained unidentified. Results of Multiplex-PCR and sequence analysis showed 100% concordance Conclusion: LCM analysis revealed, PCR is the most appropriate method for identification. Multiplex-PCR is a simple and rapid method (serotypes identification within two days); owing its short turnaround time and accuracy, it can be used as a diagnostic tool for surveillance of adenoviral keratoconjunctivitis.

The features of the clinic and treatment of patients with adenoviral keratoconjunctivitis were studied on the example of 112 patients aged 19- 57 years

The common approach of the diagnosis of Alzheimer’s Disease (AD) is made with an analysis of the cerebrospinal fluid or the study of retinal fundus and the plaques formation through optical corneal tomography (OCT), or more simply with a fundus camera. Tears analysis is widely discussed in literature as an essential method to describe molecular and biochemical alterations in different diseases. The aim of our study was the identification with immunocytochemistry of Amyloid Beta-42 in tears from patients with or without familiarity for Alzheimer Disease, in order to make the diagnosis earlier and more accessible compared to other invasive methods. Our study was performed on tears from three phenotypically healthy subjects: two of them were Caucasian with Alzheimer familiarity (48 and 55 years old) and the other one was Asian without Alzheimer familiarity (45 years old) and affected by an adenoviral keratoconjunctivitis at the moment of withdrawal. Tear samples were collected from eye fornix and were examinated by immunocytochemistry (ICC) assay using anti-Amyloid Beta X-42 antibody. Two out of three tears samples showed positive Amyloid Beta-42. Considering that our patients were phenotypically healthy, the identification of Amyloid Beta-42 by ICC could be a candidable method to make the diagnosis of the disease earlier and more accessible and available then other current and invasive methods and it could be a candidate for a screening method too.

The dry eye syndrome ranges among widespread and persisting ophthalmic diseases. It is also called a disease of civilization. Among the causes particularly often leading to the dry eye syndrome adenoviral infection has to be listed. Over the last years, in Saint Petersburg, an increasing incidence rate of the epidemic adenoviral keratoconjunctivitis is noted, which is proceeding in severe membranous and infiltrative forms, involving the cornea. Occurring therewith secondary dry eye syndrome demands using effective medications. In the article, the experience in Cationorm (Santen, Japan) clinical use for secondary dry eye syndrome treatment is disclosed.

Purpose The objective of this study was to determine the efficacy and safety of topical tacrolimus compounded in the Pharmacy Service for the treatment of subepithelial corneal infiltrates (SEIs) secondary to adenoviral keratoconjunctivitis. Methods This retrospective study included patients who had been dispensed topical tacrolimus for the treatment of SEIs during the previous year. Patients were treated with tacrolimus 0.03% eye drops twice daily or tacrolimus 0.02% ointment once daily. The following data were recorded: length of treatment, visual acuity before and after treatment, intraocular pressure before, during, and at the end of treatment, previous treatments, and the presence of SEIs after treatment. The subjective symptoms of the patients were also assessed. Results Fifty-five patients (85 eyes) were included, 54.5% with bilateral involvement. A total of 31 (36.5%) eyes were treated with tacrolimus ointment and 54 eyes (63.5%) with tacrolimus eye drops. The median length of treatment was 185 days (p25-75: 93.5-426), and the mean follow-up duration was 363 days (p25-75: 148-540). In 62.35% of the eyes, the SEIs were reduced in number and size, and in 31.76%, they were eliminated. The patients had better visual acuity after treatment with highly statistically significant differences. Tolerance was good overall, being better in the eye drops group. Conclusions Topical tacrolimus, compounded in the pharmacy, seems to be an effective and safe alternative for the treatment of SEIs secondary to adenovirus keratoconjunctivitis.

To evaluate the results of intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment for retinopathy of prematurity (ROP) in infants with active adenoviral keratoconjunctivitis (AKC).A retrospective analysis was performed using the medical records of all infants treated with intravitreal injections of anti-VEGF agents during an AKC outbreak previously reported in the literature at a tertiary center for treatment of ROP. The infants were divided into two groups. Group 1 included nine infants (18 eyes) with AKC, while Group 2 included 13 infants (26 eyes) without AKC.During the AKC outbreak, 22 infants were treated with anti-VEGF agents for treatment-requiring ROP. In all patients in both groups, the ROP and plus disease displayed a significant regression within 2 days after the intravitreal injections. Moreover, no serious complications such as endophthalmitis, retinal detachment, cataract or intravitreal hemorrhage were observed after the treatment and there were no statistically significant differences between the groups in terms of postoperative complications.Immediate and appropriate intervention is very important in cases of treatment-requiring ROP otherwise it can result in blindness. However, laser treatment for ROP is technically difficult in infants with active AKC. The results of this study showed that favorable outcomes without serious ocular complications could be obtained via intravitreal injections of anti-VEGF agents in infants with active AKC.

Epidemic viral conjunctivitis caused by adenovirus is the most common infectious conjunctivitis. The exact incidence of adenoviral conjunctivitis is still poorly known, but there are two well-defined adenoviral keratoconjunctivitis clinical syndromes: epidemic keratoconjunctivitis (EKC) and pharyngoconjunctival fever (PCF). Epidemic keratoconjunctivitis is also the most severe form and presents with watery discharge, hyperemia, chemosis and ipsilateral lymphadenopathy. Diagnosis is mainly clinical, but its etiology can be confirmed using cell cultures, antigen detection, polymerase chain reaction or immune-chromatography. Multiple treatments have been tried for this disease, but none of them seem to be completely effective. Viruses are resistant to desiccation and certain common surface disinfectants. Prevention is the most reliable and recommended strategy to control this epidemic infection. Global epidemic surveillance system definitely needs to be established to monitor and analyze the epidemic conjunctivitis in the future. There is clearly a need for the national and the military public health institutions to work together on guidelines to handle future challenges.

Background and Objectives: Adenoviral keratoconjunctivitis is an extremely frequent ophthalmological disease caused by various serological subtypes of human adenovirus (HAdV) worldwide. Adenoviruses serotypes 8, 11, 19, 37 frequently cause epidemic keratoconjunctivitis (EKC). This study was conducted to evaluate the frequency of adenovirus serotypes in patients with EKC in Ahvaz , Iran. Materials and Methods: Eighty- eight ocular swabs were collected from patients with EKC. The specimens were analyzed for detection of adenovirus by standard PCR. The PCR products were further sequenced and analyzed to determine the serotypes. Results: The study population consisted of 49/88 (55.7%) males and 39/88 (44.3%) females. Among them 25 (51.02%) males and 22 (56.41%) females were positive for HAdV serotype 8 (p= 0.488). Overall forty-seven (53.4%) samples were positive for AdV serotype 8 while forty- one patients (46.59%) were negative for the adenovirus serotypes. Conclusion: The results of this study revealed predominanance of HAdV 8 with high prevalence of 53.4% among patients with Keratoconjunctivitis. Forty- one patients (46.59%) were negative for adenovirus. Still, the role for other related viruses such as enteroviruses need to be investigated in patients with EKC.

WOS: 000459824600002, PubMed: 30829017, Objectives: To investigate the relationship between pseudoexfoliation syndrome (PES) and the use of antidepressant medications. Materials and Methods: This population-based, cross-sectional study included 2,017 of 2,356 invited subjects who were randomly selected from the Turkish Statistical Institute database (www.turksat.gov.tr/) as part of an epidemiologic study which specifically aimed to detect the prevalence of PES in the province of Eskisehir. During the examination, a detailed questionnaire was administered to determine physician-diagnosed systemic disease and drug use. Results: Eight of the 2,017 participants in the study were excluded for various reasons (2 with posterior synechiae, 2 with corneal opacity, 1 uncooperative patient, 1 eviscerated patient, 1 with active adenoviral keratoconjunctivitis, and 1 with a history of angle closure). PES was detected in 100 (5%) of the 2,009 patients whose data were analyzed. The percentage of subjects with concurrent antidepressant drug use in the PES and non-PES non-glaucoma groups were 4.1% (n=3) and 1.1% (n=21), respectively. The difference between the two groups was statistically significant (p=0.024). In addition, the use of medications for hypertension (p

To evaluate the safety and efficacy of the use of the bandage contact lenses (BCLs) in adenoviral keratoconjunctivitis-related ocular surface problems.Fifteen eyes of 15 consecutive patients presenting at the Ankara University Medical Center, Cornea and Contact Lens Service, and requiring BCL use for adenoviral keratoconjunctivitis-related ocular surface problems were enrolled. Visual acuity, slitlamp examination findings, indication and duration of the BCL use, the total follow-up, and any adjuvant medication were recorded. All patients were followed regarding the success of treatment and adverse effects associated with BCL use.The average age at the time of presentation was 26.8±15.5 years. The major reasons for BCL use included epithelial defect (7 eyes), filamentous keratopathy (5 eyes), epithelial edema (1 eyes), and filamentous keratopathy together with epithelial defect (2 eyes). After the first appearance of conjunctivitis symptoms, the mean time to BCL application was 9.0±3.9 days. The mean duration of contact lens wear was 9.9±6.5 days, and the mean follow-up was 26.4±15.8 days. Preservative-free artificial tears and topical antibiotics were used in all cases. Besides, topical ganciclovir 0.15% gel (8 eyes), topical 0.4% povidone-iodine solution (9 eyes), and topical steroids (11 eyes) were used in various combinations. At the end of the follow-up period, the mean visual acuity improved from 0.23±0.32 logMAR units (∼0.6 Snellen line) to 0.0l±0.04 logMAR units (∼1.0 Snellen line) (P=0.042). No sight-threatening complication related to contact lens wear was encountered.Adjuvant use of BCLs seems to be safe and effective in the treatment of adenoviral keratoconjunctivitis-related ocular surface problems. Close follow-up and prophylactic use of topical antibiotics are rationalistic for prevention of secondary infections.

Subepithelial infiltrates secondary to adenoviral keratoconjunctivitis may persist for years and cause blurred vision, halos, glare, and photophobia. These infiltrates arise from immune reaction against the virus, and few studies have reported topical cyclosporine A to be effective in the treatment of subepithelial infiltrates. Herein, we describe a patient with adenoviral keratoconjunctivitis-related subepithelial infiltrates who did not respond to treatment with a new topical cyclosporine A emulsion prepared with castor oil (Depores 0.05%; Deva İlaç, Kocaeli, Turkey), while the FDA-approved nanoemulsion formulation provided improvement in symptoms and reduced the inflammatory reaction (Restasis 0.05%; Allergan, Irvine, Calif., USA).

This chapter covers conditions which are painful and require early treatment for the sake of comfort, and may have a more gradual onset of symptoms, or a less profound impact on the patient. Various inflammatory conditions including ulcers due to bacterial, viral, amoebic and fungal infection as well as non infective causes are described. Acute uveitis is discussed and for completion chronic presentations of uveitis are included. Acute onset neurological problems leading to diplopia also fall into the same day management category. Other conditions included are allergic eye disease, blepharokeratitis and scleritis. The techniques for creating a Gunderson flap and for inducing ptosis using botulinus toxin are described. An overview of immunosuppressive agents is tabulated.

Purpose To investigate how corneal aberrations change after phototherapeutic keratectomy (PTK) for subepithelial infiltrates after adenoviral keratoconjunctivitis. Methods The records of patients who underwent transepithelial PTK for subepithelial infiltrates were retrospectively reviewed. Preoperative best-corrected visual acuity (VA) and the results of slit-lamp biomicroscopy examinations were recorded. The PTK procedure was performed under topical anesthesia with an Amaris excimer laser. Patients' manifest refraction values, topographical examination results, and corneal aberrations before and after surgery were analyzed. Results Twenty-four eyes of 16 women (84.3%) and 3 men (15.7%) were treated. The mean follow-up time was 6.0 ± 2.5 (range: 3-12) months, and the mean ablation depth was 82.3 ± 1.0 (range: 80-88) μm. Postoperative median best-corrected VA increased from 0.6 (range: 0.4-1.0) logarithm of the minimum angle of resolution to 0.2 (range: 0.1-0.5) logarithm of the minimum angle of resolution (P = 0.048), coma decreased from 0.56 (range: 0.29-0.37) to 0.44 (range: 0.07-0.74), secondary astigmatism decreased from 0.45 (range: 0.12-1.9) to 0.17 (range: 0.03-0.49), and total higher-order aberrations decreased from 1.24 (range: 0.61-6.74) to 0.9 (range: 0.33-1.64) (P = 0.008, 0.0032, and 0.018, respectively). Conclusions PTK is an effective method for treating corneal opacity after epidemic keratoconjunctivitis, which yields significant improvements in both VA and visual quality.

Background Epidemic keratoconjunctivitis is a highly contagious infection that mainly involves the surface of the eye. Keratitis may appear approximately 10 days after the onset of follicular conjunctivitis, with the formation of subepithelial corneal infiltrates (SEIs), usually bilaterally and asymmetric. SEIs have the potential to cause significant ocular morbidity, with reduced vision, photophobia, glare, halos and foreign body sensation, and can persist for months or years after the initial infection. Tacrolimus has demonstrated effectiveness in this ocular pathology in some studies. Purpose Our aim was to determine the efficacy of compounding topical tacrolimus treatments for SEIs after adenovirus keratoconjunctivitis. Material and methods This retrospective study included patients who were treated with tacrolimus 0.03% eye drops twice daily or tacrolimus 0.2% ointment once daily for SEIs. The parameters measured were visual acuity before and after treatment, measured by LogMAR, intraocular pressure before, during and at the end of treatment, measured by Perkin’s tonometer, and other treatments before tacrolimus and the result of SEIs after treatment. The data were analysed using IBM Microsoft SPSS Statistics V.22.0. Results We analysed 63 patients (99 eyes); 57.1% were affected bilaterally. Mean age was 46.85 years (SD 14.93). 26 patients (41.3%) were treated with tacrolimus 0.02% ointment and 37 patients (58.7%) with tacrolimus 0.03% eye drops. Mean duration of treatment was 105 days (range 55–199) and mean follow-up was 112.5 days (57.25–426.75). In 56.56% of eyes there was a decrease in SEIs, and in 19.19% they disappeared. We had data for visual acuity (VA) for 32 eyes. We observed an increase in VA in 17 eyes (53.1%), with a mean value of 0.331 (range 0.1–0.7). In 3 eyes (9.37%), VA decreased (0.1); there was no differences for 12 eyes (37.5%). Mean intraocular pressure was reduced in the right eyes based on media data. Conclusion Topical tacrolimus eye drops and ointment, which?are compounded in the pharmacy service, seems to be an effective treatment for SEIs after adenovirus keratoconjunctivitis. References and/or acknowledgements Ghanem RC, Vargas JF, Ghanem VC. Tacrolimus for the treatment of subepithelial infiltrates resistant to topical steroids after adenoviral keratoconjunctivitis. Cornea2014;33:1210–13. No conflict of interest

Purpose To compare the clinical outcome with different treatment regimens in Acute Adenoviral Keratoconjunctivitis (AAK). Methods The records of 110 patients diagnosed as AAK in two tertiary eye care centers were evaluated retrospectively. The treatment regimen, follow-up duration, time until improvement of the symptoms, visual acuity, clinical findings, Schirmer's test and the Ocular Surface Disease Index (OSDI) score at the first day, first week and third week were recorded. The Kruskal-Wallis Test and Chi-square test were used for comparison of quantitative and categorical variables, respectively. Results Forty six patients were receiving topical corticosteroids (Group 1), 32 topical 2% Cyclosporin A (CsA) (Group 2) and 32 only artificial tears (Group 3). Mean time until resolution of the symptoms was lowest in Group 1 (9.5 +/- 4.9 days) and highest in Group 3 (13.3 +/- 4.2 days)(p: 0.001). OSDI scores at the first and third weeks were highest in Group 3 (52.4 +/- 16.4 and 32.3 +/- 13.0) and lowest in Group 1 (41.0 +/- 21.3 and 23.9 +/- 13.2)(p: 0.01 and p: 0.009). At day 21, percentage of the patients with subepthelial infiltrates was the highest in Group 3 (63.4%) and lowest in Group 1 (42.5%). Conclusions The symptoms were less severe and had a shorter duration with topical corticosteroids and CsA when compared with palliative therapy. Topical 2% CsA may inhibit development of corneal subepithelial infiltrates when used in the acute phase of infection, similar to corticosteroids.

To describe the use of topical 0.03% tacrolimus in patients with symptomatic corneal subepithelial infiltrates (SEIs) secondary to adenoviral keratoconjunctivitis (AK) that were resistant to tapering of corticosteroid eye drops.This was a prospective, nonrandomized, noncomparative interventional case series that included consecutive patients treated with tacrolimus for resistant SEIs after AK. The patients had active SEIs and corrected distance visual acuity (CDVA) of 20/25 or worse when treatment was initiated. The recorded data included age, sex, CDVA, intraocular pressure, duration and intensity of symptoms, biomicroscopy findings, and duration of therapy. The treatment was considered successful if there was a reduction in SEIs, as well as CDVA stabilization or improvement. The treatment was considered unsuccessful if the patient could not tolerate tacrolimus or if there was an increase in SEIs.Seven patients were included (10 eyes). The mean age was 36.7 ± 12.3 years. The mean duration of tacrolimus therapy was 8.8 ± 2.4 months, and the mean duration of follow-up was 13.6 ± 10.7 months. Treatment was successful in 8 eyes of 6 patients. One patient could not tolerate the medication. Statistically significant improvement in the CDVA was observed (from a mean of 0.29 to 0.07) (P = 0.001). No statistically significant changes in the intraocular pressure were observed (P = 0.574). SEI scores showed a significant reduction from 2.20 ± 0.92 to 0.25 ± 0.46 (P = 0.011). All patients who completed treatment had improvement in ocular symptoms.Topical 0.03% tacrolimus seemed to be an effective corticosteroid-sparing agent for the treatment of SEIs after AK.

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.

A literature review of nosocomial cases of adenoviral keratoconjunctivitis was undertaken to identify the preventative measures that could assist ophthalmic teams in minimising the risks associated with management of the infectious patient. In addition to the published actions, the use of surveillance to continually monitor and action changes in trend is advocated as an important preventative measure.

The objective of this review is to describe the clinical and epidemiological characteristics of adenoviral conjunctivitis, as well as to present a practical update on its diagnosis, treatment and prophylaxis. There are two well-defined adenoviral keratoconjunctivitis clinical syndromes: epidemic keratoconjunctivitis and pharyngoconjunctival fever, which are caused by different adenovirus serotypes. The exact incidence of adenoviral conjunctivitis is unknown. However, cases are more frequent during warmer months. Contagion is possible through direct contact or fomites and the virus is extremely resistant to different physical and chemical agents. The symptomatology of conjunctival infection is 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, 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 way to control this contagious infection.

Aim To study the demographic profile, clinical features, treatment outcome and ocular morbidity of smear-positive microsporidial keratoconjunctivitis. Methods Retrospective case series of all patients with clinical features of microsporidial keratoconjunctivitis and who were smear positive for the same on Gram stain from January 2013 to December 2015. Demographic data, predisposing factors, microbiological investigations, clinical course and visual outcome were analysed. Results Of the 10 655 patients with conjunctivitis, 550 (5.2%) patients were positive for microsporidia on Gram stain during this time period. The disease was prevalent throughout the year with an increased incidence from July to December. Bilateral involvement was seen in 27 (4.9%) patients. There was no predisposing risk factor in 428 (77.8%) patients. 384 (69.1%) patients had received prior treatment before presentation to us with the most common drug being antibiotic in 285 (49.4%) patients. All the patients underwent diagnostic corneal debridement and received topical 0.3% fluconazole eye drops four times a day. Of the 296 patients who followed-up, 187 (63.1%) patients had complete resolution without sequelae. 68 (22.9%) had persistent superficial punctate keratopathy, 30 (10.1%) developed subepithelial nummular keratitis. No significant change in visual acuity was seen in 255 (80.7%) eyes, two or more line improvement was seen in 48 (15.2%) eyes, while two or more line worsening was seen in 13 (4.1%) eyes. Conclusions Microsporidial keratoconjunctivitis is prevalent in South India throughout the year. The characteristic clinical signs and simple microbiological investigation help us to differentiate it from adenoviral keratoconjunctivitis. The visual prognosis is good.

Purpose To determine the efficacy of combination povidone-iodine (PVP-I) 1.0% eyedrops and dexamethasone 0.1% eyedrops in the treatment of adenoviral keratoconjunctivitis. Materials and methods In a prospective, randomized, controlled, double-blinded clinical trial patients with recent adenoviral keratoconjunctivitis (diagnosed clinically and confirmed by PCR), we randomly divided into three treatment groups: study group – received PVP-I 1.0% and dexamethasone 0.1%, control 1 group – received dexamethasone 0.1% and control 2 group – received lubricating eyedrops (hypromellose 0.3%). The treatment was administered four times a day in each group. All patients were examined and filled a questionnaire before treatment and on the 3rd, 5th and 7th days of treatment. Results We included in the study 78 eyes (26 in each group). Adenovirus type 8 was the most common pathogen (83% of cases). The fastest improvement in patients red eyes, discharge, superficial punctate keratitis and pseudomembranes was observed in the study group (p

A 44-year-old woman with recurrent attacks of bilateral adenoviral keratoconjunctivitis infections presented with excessive tearing of 5 months' duration. Slit-lamp examination showed bilateral punctal stenosis. Tearing improved for 2 months after insertion of perforated silicone punctal plugs, after which she had a bilateral foreign-body sensation due to pyogenic granuloma pushing through the lumen of the silicone plugs. The foreign-body sensation improved after removing the plugs and a short course of topical steroid-antibiotic eye drops.

PURPOSE Adenoviral keratoconjunctivitis is recognized as one of the major pathogens of ophthalmological nosocomial infection worldwide. N-Chlorotaurine (Cl-HN-CH(2)-CH(2)-SO(3)H, NCT) is the N-chloro derivative of the amino acid taurine, which is an oxidant produced by human granulocytes and monocytes during inflammatory reactions. Using conventional viral plaque assay, it was previously shown that NCT causes inactivation of several human adenovirus (HAdV) serotypes. In this study, we evaluated the antiadenoviral effect of NCT by quantitative polymerase chain reaction (PCR) methods. METHODS A549 cells were used for viral cell culture, and HAdV serotypes 3, 4, 8, 19, and 37 were used. After calculating 50% cytotoxic concentration (CC(50)) of NCT by MTS (3-(4,5- dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) method, HAdV was cultured with NCT for 7 days, and extracted adenoviral DNA was quantitatively measured by real-time PCR. RESULTS A statistically significant (P < 0.05) dose-dependent inhibition was indicated for all serotypes except HAdV type 4 (HAdV4), which was maximally inhibited by only ~50%. Among the serotypes, NCT was particularly effective against HAdV8, HAdV19a, and HAdV37. The 50% effective concentration (EC(50)) obtained by real-time PCR of NCT ranged between 49 and 256 μM. EC(50) of NCT against HAdV3 was slightly higher than that against serotypes of species D. The selective index (CC(50)/EC(50)) ranged between 41 and 60 except for HAdV4 (11.5). CONCLUSIONS These results show that NCT has an antiviral effect against most serotypes of human HAdV inducing keratoconjunctivitis, indicating its possible therapeutic use.

Ganciclovir (GCV) is a potent broad-spectrum antiviral with proven efficacy against herpes viruses. As it inhibits viral but not cellular DNA, it is expected to avoid the toxicity associated with trifluridine – the only currently approved treatment for herpes simplex keratitis in the USA. Preclinical studies have demonstrated GCV to be as effective as trifluridine against experimental herpes simplex keratitis. Clinical studies conducted in Europe, Asia, and Africa that compared the efficacy and tolerability of GCV ophthalmic gel with acyclovir (ACV) ophthalmic ointment in patients with herpetic keratitis showed that GCV-treated patients had higher overall healing rates and lower relapse rates than ACV-treated patients. The ganciclovir gel formulation was also much better tolerated than the ACV ointment base. Finally, a controlled, masked, randomized series of 18 patients with adenoviral keratoconjunctivitis compared GCV gel with preservative-free artificial tears. Ganciclovir-treated patients experienced ...

Over a period of approximately 7 months, multiple subepithelial spots were noted in one or both corneas of some patients examined 2 to 6 months after laser in situ keratomileusis (LASIK). The lesions appeared identical to adenovirus keratitis. The eyes were quiet, had good vision, and no patient had a history of adenoviral keratoconjunctivitis. In all eyes, the lesions resolved spontaneously or with topical steroid eyedrops. All investigations were negative for adenovirus. Corneal laser scanning in vivo confocal microscopy revealed Langerhans cells in the epithelium, which disappeared after the lesions resolved.

Most clinicians would agree that there is no reason to obtain a magnetic resonance (MR) scan to evaluate a patient with viral conjunctivitis. We scheduled a patient for an annual MR scan to monitor his optic nerve meningiomas. By coincidence, he had florid viral conjunctivitis the day the scan was performed. It showed severe eyelid edema, contrast enhancement of the anterior orbit, enlargement of the lacrimal gland, and obstruction of the nasolacrimal duct. Adenovirus produces deep orbital inflammation, in addition to infection of the conjunctival surface.

Purpose: To determine the effects of topical cyclosporine A (CsA), an immunomodulating T-cell inhibitor, on the formation of subepithelial immune corneal infiltrates (SEIs) and acute adenovirus replication in the NZW Rabbit Ad5 SEI and Ad5 replication models. Methods: In the Ad5 SEI model, eyes were treated topically with either 2% CsA in corn oil, 0.5% CsA in artificial tears, or their respective control vehicles 4 times daily for 14 days and then twice daily for 4 days. SEIs were graded on day 23 by masked slit-lamp examination. Using the same treatment protocol in the Ad5 replication model, rabbit eyes were cultured on days 0, 1, 3, 4, 5, 7, 9, 11, 14, 16, 18, and 21 postinoculation, and their tear film viral titers were determined on A549 cells. Results: The formation of SEIs was significantly reduced following treatment with either 2.0% or 0.5% CsA. However, 2% and 0.5% CsA significantly increased viral titers on several days, prolonged the duration of Ad5 shedding, and increased the number of Ad5-positive cultures per total during the late phase of infection (days 7–21) compared with their respective controls. The 0.5% CsA was equipotent to 2% CsA for most outcome parameters tested. Conclusions: A role for topical CsA in the treatment of adenovirus ocular infections remains to be defined in large, randomized controlled clinical trials. During acute infection, reducing SEI formation is highly desirable, but enhancing viral replication may inadvertently serve to promote local epidemics. Future trials should address the important issues of optimized formulation and dose regimen and the possibility of prolonging virus shedding.

Letter to the editor

To study: the epidemiology of an outbreak of adenoviral keratoconjunctivitis in a UK teaching hospital; disease presentation and its effect on clinical diagnostic efficiency; patterns of viral transmission between staff and patients; the effectiveness of infection control procedures in minimising outbreaks.Prospective/retrospective clinical audit and retrospective audit of virological culture results: all viral culture swabs taken during an outbreak of adenoviral keratoconjunctivitis were analysed. The case records of patients whose viral swabs were positive for adenoviral culture were traced. The time for viral cultures to become positive (culture positive time) was calculated. Analysis of the case notes was performed to elucidate (1) the source of infection and (2) the risk factors for acquisition of the infection. Retrospective clinical audit was performed to evaluate the effectiveness of infection control procedures. Adenovirus isolates underwent serotyping.During the 3-month period of study, there were 38 confirmed cases of adenoviral keratoconjunctivitis. This represented a 217% increase in the number of new cases per 3-month period. The case notes for five patients were untraceable. Of the remaining 33 patients, 21 (63%) had acquired their infection either directly or indirectly from the eye department and 22 (67%) had presented with unilateral disease. The rate of misdiagnosis was higher (9/22=42%) in patients presenting with unilateral disease than those presenting with bilateral disease (2/11=18%). Intradepartmental acquisition of infection was associated with invasive procedures, for example use of diagnostic/therapeutic contact lenses. Culture positive times ranged from 3 to 29 days. The introduction of infection control procedures was associated with a dramatic decrease in the incidence of departmentally acquired cases with no new cases after 2 weeks. Multiple serotypes of adenovirus were involved.Outbreaks of adenoviral keratoconjunctivitis are a serious public health issue concerning ophthalmic departments. This audit study illustrates several important points: (1) how hospital-acquired infection can account for a significant proportion of the cases seen, (2) how multiple types of adenovirus can be involved in a single outbreak, (3) that severe unilateral disease is associated with a higher rate of misdiagnosis; and (4) how standard viral culture techniques may not be satisfactory in confirming/disproving infection when the diagnosis is in doubt. The potential benefit of infection control procedures in minimising this outbreak could not be proven within this audit.

Objective To evaluate the efficacy of cidofovir 1% eyedrops with and without cyclosporin A 1% eyedrops as a treatment of acute adenoviral keratoconjunctivitis (AKC). Design Randomized, controlled trial. Participants Thirty-four patients with acute adenoviral keratoconjunctivitis of recent onset. Methods Patients were divided into 4 treatment groups: 1) cidofovir four times daily, 2) cidofovir 10 times daily, 3) cidofovir four times daily and cyclosporin A four times daily, and 4) sodium chloride four times daily (control). The diagnosis was confirmed by adenoviral polymerase chain reaction from conjunctival swabs. Duration of treatment was 21 days. Main outcome measures Severity of conjunctival injection, conjunctival chemosis, punctate epithelial keratitis during the course of treatment, and presence and severity of corneal subepithelial infiltrates were evaluated by a clinical score. Duration until subjective improvement of symptoms was recorded. Results The frequency of severe corneal opacities was lower with cidofovir ( P = 0.048). Cidofovir was toxic locally to the skin of the eyelids and the conjunctiva in a dose-dependent manner. Symptoms of local toxicity were clinically similar to the signs of the initial viral inflammation. They first appeared 8 to 12 days after beginning of treatment and completely subsided 7 to 28 days after discontinuation of cidofovir. The outcome measures of local inflammation did not differ between the four treatment groups. Cyclosporin A did not alter the course of the infection. Conclusions Cidofovir lowers the frequency of severe corneal opacities, but its clinical use 4 to 10 times daily at a 1% concentration is limited by local toxicity. Further clinical studies to find an efficacious yet tolerable dosage regimen of cidofovir, possibly using an improved pharmaceutical preparation, are required.