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Human fibroblast interferon in tears of patients with picornavirus epidemic conjunctivitis.

We report the levels of coxsackievirus type A24 (CA24) and the levels and type of interferon produced early during naturally acquired picornavirus epidemic conjunctivitis. Virus levels ranging from 10(1.8) to 10(5.8) 50% tissue culture infective doses per ml were detected in 29 of 37 acute (collected 1 to 4 days after onset of conjunctivitis) tear samples. Interferon (10(1.5) to 10(3.3) U/ml) was detected in 12 of 29 tear samples collected on day 1, in 2 of 6 tear samples collected on day 2, and in 1 tear sample collected on day 3 after onset of conjunctivitis. The interferon activity in pooled tear samples was completely neutralized by antiserum against human fibroblast interferon, stable at pH 2.0, and active against different viruses. In addition, the interferon activity in tears, like human fibroblast and leukocyte interferons produced in vitro, protected human and rabbit, but not mouse, cells. This is the first report of production and identification of the antigenic type of interferon induced by an enterovirus during natural infection. The early appearance of fibroblast interferon suggests that it may be an important host defense at the local site of implantation against this and possibly other enterovirus infections.

Animals↗

Intermediate human adenovirus type 22/H10,19,37 as a new etiological agent of conjunctivitis.

Eight strains of a new intermediate adenovirus were isolated in the course of an investigation of conjunctivitis in Hiroshima City, Japan. The strain was first isolated in July 1986. All eight strains were isolated from conjunctival swab samples from patients with conjunctivitis, mainly epidemic keratoconjunctivitis. The virus was typed as adenovirus type 22 in neutralization tests and was related closely to types 10, 19, and 37 in hemagglutination inhibition tests. The DNA cleavage patterns of the eight strains with nine restriction endonucleases were the same with one exception but different from those of the above serologically related species. We conclude that the intermediate adenovirus is a new etiological agent of conjunctivitis, mainly epidemic keratoconjunctivitis.

Adenoviruses, Human↗

Rapid identification of the coxsackievirus A24 variant by molecular serotyping in an outbreak of acute hemorrhagic conjunctivitis.

We evaluated the clinical applicability of a molecular serotyping method for determination of the cause of epidemic acute hemorrhagic conjunctivitis. Seventy conjunctival swab specimens from individuals involved in a nationwide acute hemorrhagic conjunctivitis outbreak were tested. Viral culture and a molecular biology-based assay were compared by directly using clinical specimens. On the one hand, virus culture was done to isolate the enteroviruses, and serotyping was done by a coxsackievirus A24 variant-specific PCR. On the other hand, the original clinical specimens were directly screened for enterovirus by reverse transcription (RT)-PCR with panenterovirus-specific primers. Enterovirus screening-positive specimens were subjected to RT-PCR for detection of the VP1 region of enterovirus, and the amplicons were sequenced. Molecular serotyping was done by calculating the pairwise identity scores for the sequences with the maximum identities to the sequences of known prototype enteroviruses. Thirty-two specimens (45.7%) were culture positive, whereas 37 specimens (52.8%) were screening PCR positive (P < 0.001). The VP1 regions were amplified from 21 of the 37 specimens (56.8%), and the products amplified from 9 specimens were appropriately sequenced. These nine sequences were homologous with the sequence of the coxsackievirus A24 variant. Molecular serotyping by direct use of clinical specimens without cell culture could be applied for the rapid identification of the causative agent of epidemic acute hemorrhagic conjunctivitis.

Base Sequence↗

3-day treatment with azithromycin 1.5% eye drops versus 7-day treatment with tobramycin 0.3% for purulent bacterial conjunctivitis: multicentre, randomised and controlled trial in adults and children.

AIM: To compare the efficacy and safety of Azyter, azithromycin 1.5% eye drops, for 3 days with tobramycin 0.3% for 7 days to treat purulent bacterial conjunctivitis. METHODS: This was a multicentre, randomised, investigator-masked study including 1043 children and adults with purulent bacterial conjunctivitis. Patients received either azithromycin 1.5% twice-daily for 3 days or tobramycin 0.3%, 1 drop every two hours for 2 days, then four times daily for 5 days. Clinical signs were evaluated and cultures obtained at D0, D3 and D9 (where D refers to "day"). Primary variable was the clinical cure at the Test-of-Cure (TOC)-visit (D9+/-1), for patients with D0-positive cultures. The cure was defined as: bulbar conjunctival injection and discharge scores of 0. RESULTS: Among 471 patients with D0-positivity in the per protocol set, 87.8% of the azithromycin 1.5% group and 89.4% of the tobramycin group were clinically cured at the TOC-visit. Azithromycin was non-inferior to tobramycin for clinical and bacteriological cure. Clinical cure was significantly higher with azithromycin 1.5% at D3. The safety profile of azithromycin was satisfactory with a good patient and investigator's acceptability. CONCLUSIONS: Azithromycin 1.5% for 3 days was as effective and as safe as tobramycin for 7 days. Furthermore, more azithromycin than tobramycin patients presented an early clinical cure at Day 3. Due to its twice daily dosing regimen for 3 days, azithromycin represents a step forward in the management of purulent bacterial conjunctivitis, especially in children.

Adolescent↗

A recent epidemic of Coxsackie virus type A24 acute haemorrhagic conjunctivitis in Singapore.

A recent epidemic of acute conjunctivitis in Singapore showed again the importance of Coxsackie virus type A24 variant as a causative agent of acute haemorrhagic conjunctivitis (AHC). Although the ocular manifestations appeared similar to those described for the 1970 and 1975 outbreaks, a markedly higher rate of respiratory involvements was noted. Not observed in previous epidemics were herpes-like vesicles in the conjunctiva and eyelids of one patient and vesicles in the buccal mucosa and lips of another from whom Coxsackie virus A24 was isolated. The most interesting finding in this study was the isolation of five wild (non-Sabin) poliovirus type 1 strains. Three strains were obtained from conjunctival and two from throat swabs of patients with mild to severe conjunctivitis. It is conceivable that the rare reports of polio-like paralysis or radiculomyelitis accompanying or following AHC in a few Asian countries could be attributed to concurrent infections with a poliovirus and either enterovirus type 70 or Coxsackie virus type A24.

Adolescent↗

Eosinophil cationic protein in tears in allergic conjunctivitis.

AIMS/BACKGROUND--Eosinophil cationic protein (ECP) is a quantifiable product secreted by activated eosinophils. The aim of this study was to assess the degree of eosinophil activity in different clinical stages of various forms of allergic conjunctivitis. METHODS--Tears were collected in glass capillary tubes from 14 subjects with seasonal allergic conjunctivitis (SAC), 23 subjects with vernal keratoconjunctivitis (VKC), 16 subjects with atopic keratoconjunctivitis (AKC), 10 subjects with giant papillary conjunctivitis (GPC), and 16 healthy control subjects. The samples were analysed in duplicate with a radio-immunoassay for ECP. RESULTS--Statistically significant differences were evident between healthy controls and allergic subjects (p < 0.001). Subjects with AKC and VKC had significantly higher tear ECP values than subjects with GPC and SAC. In addition, there was a significant correlation between ECP values and disease severity in all disorders. CONCLUSION--The data suggest a particular pathogenic role of the eosinophil in VKC and AKC, and a less pronounced but still important eosinophil involvement in the disease processes of GPC and SAC.

Adolescent↗

Predicting bacterial cause in infectious conjunctivitis: cohort study on informativeness of combinations of signs and symptoms.

OBJECTIVE: To find an efficient set of diagnostic indicators that are optimally informative in the diagnosis of a bacterial origin of acute infectious conjunctivitis. DESIGN: Cohort study involving consecutive patients. Results of index tests and reference standard were collected independently from each other. SETTING: 25 Dutch health centres. PARTICIPANTS: 184 adults presenting with a red eye and either (muco)purulent discharge or glued eyelid(s), not wearing contact lenses. MAIN OUTCOME MEASURES: Probability of a positive bacterial culture, given different combinations of index test results; area under receiver operating characteristics curve. RESULTS: Logistic regression analysis showed optimal diagnostic discrimination for the combination of early morning glued eye(s), itch, and a history of conjunctivitis. The first of these indicators increased the likelihood of a bacterial cause, whereas the other two decreased it. The area under the receiver operating characteristics curve for this combination of symptoms was 0.74 (95% confidence interval 0.63 to 0.80). The overall prevalence of bacterial involvement of 32% could be lowered to 4% or raised to 77%, depending on the pattern of index test results. CONCLUSION: A bacterial origin of complaints indicative of acute infectious conjunctivitis can be made much more likely or unlikely by the answers to three simple questions posed during clinical history taking (possibly by telephone). These results may have consequences for more targeted prescription of ocular antibiotics.

Adult↗

A randomised controlled trial of management strategies for acute infective conjunctivitis in general practice.

OBJECTIVE: To assess different management strategies for acute infective conjunctivitis. DESIGN: Open, factorial, randomised controlled trial. SETTING: 30 general practices in southern England. PARTICIPANTS: 307 adults and children with acute infective conjunctivitis. INTERVENTION: One of three antibiotic prescribing strategies-immediate antibiotics (chloramphenicol eye drops; n = 104), no antibiotics (controls; n = 94), or delayed antibiotics (n = 109); a patient information leaflet or not; and an eye swab or not. MAIN OUTCOME MEASURES: Severity of symptoms on days 1-3 after consultation, duration of symptoms, and belief in the effectiveness of antibiotics for eye infections. RESULTS: Prescribing strategies did not affect the severity of symptoms but duration of moderate symptoms was less with antibiotics: no antibiotics (controls) 4.8 days, immediate antibiotics 3.3 days (risk ratio 0.7, 95% confidence interval 0.6 to 0.8), delayed antibiotics 3.9 days (0.8, 0.7 to 0.9). Compared with no initial offer of antibiotics, antibiotic use was higher in the immediate antibiotic group: controls 30%, immediate antibiotics 99% (odds ratio 185.4, 23.9 to 1439.2), delayed antibiotics 53% (2.9, 1.4 to 5.7), as was belief in the effectiveness of antibiotics: controls 47%, immediate antibiotics 67% (odds ratio 2.4, 1.1 to 5.0), delayed antibiotics 55% (1.4, 0.7 to 3.0), and intention to reattend for eye infections: controls 40%, immediate antibiotics 68% (3.2, 1.6 to 6.4), delayed antibiotics 41% (1.0, 0.5 to 2.0). A patient information leaflet or eye swab had no effect on the main outcomes. Reattendance within two weeks was less in the delayed compared with immediate antibiotic group: 0.3 (0.1 to 1.0) v 0.7 (0.3 to 1.6). CONCLUSIONS: Delayed prescribing of antibiotics is probably the most appropriate strategy for managing acute conjunctivitis in primary care. It reduces antibiotic use, shows no evidence of medicalisation, provides similar duration and severity of symptoms to immediate prescribing, and reduces reattendance for eye infections. TRIAL REGISTRATION: Current Controlled Trials ISRCTN32956955 [controlled-trials.com].

Acute Disease↗

Maternal genital chlamydial infection as a cause of neonatal conjunctivitis.

Infections of the cervix with Chlamydia trachomatis are common, at least in those groups of sexually active women of child-bearing age who are seen in STD (sexually-transmitted diseases) clinics. Persistent untreated infection presents a hazard to the women themselves during pregnancy and to their infants who may develop chlamydial conjunctivitis. The clinical and laboratory findings in 1009 women and in 103 infants with conjunctivitis are presented. Practical problems of diagnosis and control of neonatal chlaymdial conjunctivitis are described. A possible association between prematurity and chlamydial infection is discussed.

Chlamydia Infections↗

Genetic relationship between two enteroviruses causing the acute hemorrhagic conjunctivitis syndrome.

The genetic relationship between two enteroviruses causing the acute hemorrhagic conjunctivitis (AHC) syndrome was examined by the RNA-RNA hybridization technique. Nucleotide sequence homology between the J670/71 strain of enterovirus type 70 (EV70) and the EH 24/70 strain of Singapore epidemic conjunctivitis (SEC) virus was found to be only 2% or less of the total RNA genome, while more than 90% homology was detected between the prototype (J670/71) and other isolates of EV70. The results indicate that the SEC virus, an agent of conjunctivitis epidemics in limited areas of southeast Asia and India since 1970, was distinguished serologically and genetically from EV70, which caused pandemics of AHC over the African and Eurasian continents from 1969 to 1972.

Acute Disease↗

Lodoxamide treatment of allergic conjunctivitis.

Lodoxamide is an antiallergic compound. The present study evaluated the efficacy on clinical and cytological parameters and safety of topical lodoxamide compared to placebo in the treatment of allergic conjunctivitis. The trial, designed as double-blind, randomized, placebo-controlled and parallel group treatment, was carried out in 30 patients, suffering from seasonal allergic conjunctivitis due to grass pollen, during the pollen season. Patients received lodoxamide tromethamine 0.1% eye drops or placebo eye drops, one drop in each eye t.i.d. for 4 weeks. The clinical and cytological evidence was investigated by clinicians on admission and after 4 weeks' treatment. At the end of the trial, only the lodoxamide-treated group showed a significant clinical improvement, associated with a reduction of inflammatory cells. No serious side effects were observed. The results show the clinical efficacy of lodoxamide in the treatment of pollen-induced allergic conjunctivitis. In addition, lodoxamide exerts its antiallergic activity by reducing inflammatory infiltrate (mainly eosinophils).

Adult↗

Quantitative evaluation of inflammatory cells in seasonal allergic conjunctivitis.

This study aimed to investigate the inflammatory changes occurring in the allergic conjunctiva due to different allergens. Ninety-two allergic conjunctivitis patients were divided into two groups: group I showed cedar pollen sensitivity only; group II showed sensitivities to cedar pollen and household dust or mites. Using brush cytology procedures, quantitative evaluation of inflammatory cells in the conjunctiva was made. The mean proportion of the neutrophils and lymphocytes in group II was significantly higher than the percentage of neutrophils in group I. The counts of eosinophils showed no significant difference between groups I and II. Our results suggest that the eosinophil numbers are not different between the allergic conjunctivitis groups. The neutrophilic and lymphocytic increase in allergic conjunctivitis may be due to two distinct groups of antigens.

Adolescent↗

A comparison of ciprofloxacin and tobramycin in bacterial conjunctivitis in children.

A study was conducted to determine the safety and efficacy of topically applied ciprofloxacin ophthalmic solution in a pediatric population experiencing acute bacterial conjunctivitis. Topically applied ciprofloxacin (3 mg/mL) is known to be a safe and effective treatment for adults suffering from bacterial conjunctivitis; however, the safety and effectiveness of this broad-spectrum fluoroquinolone in pediatric patients is not well established. Ciprofloxacin was evaluated in a double-blind, randomized, controlled study of 257 patients ranging from 0 (i.e., less than 1 year) to 12 years of age from 33 geographically diverse medical centers. The children received either 0.3% ciprofloxacin ophthalmic solution (Ciloxan, Alcon Laboratories, Fort Worth, TX) or tobramycin ophthalmic solution (Tobrex, Alcon Laboratories, Fort Worth, TX). Both test medications were administered topically every 2 hours on days 1 and 2 followed by every 4 hours on days 3 through 7. Eyes were cultured prior to enrollment and again on day 7. Treatment efficacy as determined by microbiological culture data and physicians' judgment of overall resolution was similar for the ciprofloxacin and tobramycin groups. Microbiological eradication was observed in 90.1% of the ciprofloxacin group and 84.3% of the tobramycin group (P = 0.29). Physicians judged 87.0% of the ciprofloxacin patients and 89.9% of the tobramycin patients clinically cured on day 7 (P > 0.5). There were no serious adverse medical events attributable to either treatment. This study showed that topically applied ciprofloxacin ophthalmic solution is safe and effective in a pediatric population experiencing acute bacterial conjunctivitis.

Anti-Bacterial Agents↗

Acute cerebellar syndrome, conjunctivitis, and hearing loss associated with low-dose cytarabine administration.

An unusual reaction associated with chronic low-dose cytarabine is described. A 77-year-old man complained of three to four weeks of hearing loss and progressive inability to walk without assistance. He had received two courses of cytarabine 100 mg sc/wk for the management of myelofibrosis myeloid metaplasia over 21 months. He received a total of 3 g over seven months during his first course followed ten months later with a 1.2 g over four months. Conjunctivitis was also identified on physical examination at the time of his admission. He was admitted to the neurology service where a complete neurological work-up with consultations from the ophthalmology, audiology, hematology, and ear, nose, and throat services failed to identify a cause of his symptoms. Cytarabine was discontinued on the suspicion that his symptoms were drug induced. The conjunctivitis resolved completely with ophthalmic antibiotics and corticosteroids. His hearing slowly improved over three to four weeks, and he was able to ambulate with a walker. He continued to improve at home although some hearing loss remained three months after his initial presentation. Although conjunctivitis and neurotoxicity are well-known complications of high-dose cytarabine, there are no prior reports of these reactions after low-dose therapy. Hearing loss, which has not been previously reported with cytarabine alone, appears to be a new complication of cytarabine administration.

Aged↗

Difficulties in the mutation analysis of plasminogen gene: a study in two patients with ligneous conjunctivitis.

The absence or very low levels of plasminogen cause a rare disabling disease called ligneous conjunctivitis, characterized by the growth of fibrin-rich pseudomembranes in the conjunctiva and on other mucosal surfaces. Several mutations have been detected in the plasminogen gene of patients affected with ligneous conjunctivitis. The human plasminogen gene, located on chromosome 6, has a marked homology with the genes belonging to the plasminogen-apo(a) family, and with a number of pseudogenes and plasminogen-like genes located on chromosome 2. This work describes a series of nucleotide variations related to genes other than the plasminogen one, found during the genetic characterization of plasminogen defect in two unrelated patients with ligneous conjunctivitis. The results of automated sequences of each exon and intron-exon boundaries were compared with those of the human plasminogen gene from the NCBI gene bank. In particular, a co-amplified gene on chromosome 2 mimicking a 14 bp deletion in exon 5 of the plasminogen gene was identified by sequencing two different bands obtained from a long run of the PCR exon 5 product in NuSieve agarose gel, and by PstI restriction enzyme analysis of the same amplicons. Moreover, 21 single nucleotide exchanges due to plasminogen-like genes co-amplification were observed, namely one in exon 1, two in exon 4, three in exons 3, 5 and 16, four in exon 13, and five in exon 17. In conclusion, these data confirm the difficulty of plasminogen genetic analysis and may help researchers to better identify the true plasminogen gene mutations causing molecular defects.

Conjunctivitis↗

Tumor necrosis factor-alpha (TNF-alpha) in seasonal allergic conjunctivitis and vernal keratoconjunctivitis.

PURPOSE: To quantify the presence of the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) in allergic conjunctivitis. MATERIALS AND METHODS: Tears and peripheral blood samples were collected from patients with seasonal allergic conjunctivitis (SAC, n=6), vernal keratoconjunctivitis (VKC, n=12), and normal subjects (CT, n=12). From an additional six nonactive allergic patients, tears were collected before and after specific conjunctival allergen challenge (CAC). Upper tarsal conjunctival biopsies were obtained from five CT and five VKC patients. TNF-alpha in tears was measured by enzyme-linked immunoassay and identified in tissues by immunohistochemistry. RESULTS: Tear TNF-alpha levels in VKC patients were significantly increased compared to CT (p=0.03), and were significantly correlated with the severity of the disease. No differences were found between SAC and CT tear samples. TNF-alpha serum levels were higher in VKC than CT, however, this difference was not statistically significant. After CAC, tear TNF-alpha levels were found increased in only one of six patients. In VKC tissues, TNF-alpha positive cells were significantly increased compared to CT (p=0.03). CONCLUSIONS: TNF-alpha may have a significant role in severe forms of allergic conjunctivitis.

Adolescent↗

Ciprofloxacin ophthalmic solution in the treatment of conjunctivitis and blepharitis: a comparison with fusidic acid.

The efficacy and safety of ciprofloxacin ophthalmic solution (0.3%) and fusidic acid gel (1%) were compared in the treatment of bacterial conjunctivitis and blepharitis in a randomized, open, parallel group study. Thirty-nine patients, 21 treated with ciprofloxacin solution and 18 treated with fusidic acid gel, were culture-positive on admission and were evaluable for efficacy. At the end of a 7-day treatment, the infecting organism was eradicated in 81% of those treated with ciprofloxacin and 72% of those treated with fusidic acid gel. There was clinical cure or improvement in 95% and 89% respectively. The clinical cure rate appeared to be higher with ciprofloxacin than fusidic acid (62% compared with 28%) but this was related to the higher proportion of patients with acute conjunctivitis in the ciprofloxacin group. Two patients using ciprofloxacin had mild discomfort and stinging on instillation and one given fusidic acid had moderate edema and discomfort; the latter patient stopped treatment. Topical ciprofloxacin is effective and well tolerated and is a useful treatment of bacterial conjunctivitis and blepharitis.

Adolescent↗

Comparison of topical 0.05% levocabastine and 0.1% lodoxamide in patients with allergic conjunctivitis. Study Group.

PURPOSE: The aim of the study was to assess the efficacy and safety of 0.05% levocabastine eyedrops (H1 receptor blocker given BID + vehicle BID) compared with 0.1% lodoxamide ophthalmic solution (mast-cell stabilizer instilled QID) in reducing ocular signs and symptoms of allergic conjunctivitis. METHODS: A randomized, double-masked, parallel-group study was conducted in seven centres in France, in which 93 patients suffering from seasonal or perennial allergic conjunctivitis were randomly allocated to either 0.05% levocabastine (n = 47) or 0.1% lodoxamide (n = 46) in both eyes for a 14-day period. Efficacy was evaluated by subjective (prickling, burning, photophobia, itching) and objective (redness, chemosis, eyelid edema, tearing) sign scores at visits on days 7 and 14, and from data noted daily by the patient in a self-evaluation form. Safety was assessed as tolerance upon instillation and adverse event reports. RESULTS: The ocular allergy symptom and sign scores were comparable in the two treatment groups at baseline. With time, statistically and clinically significant reductions (p < 0.001) from baseline were observed for the subjective and objective scores, with no difference between the treatment groups. After the first instillation, signs were alleviated more rapidly in levocabastine-treated patients than in the lodoxamide group (p < 0.001). Overall assessments by the patient and investigator were similar in both groups. No serious adverse events were reported. CONCLUSIONS: Levocabastine ophthalmic suspension 0.05% (BID) appears to be as effective and safe as lodoxamide 0.1% (QID) in the management of allergic conjunctivitis.

Adolescent↗