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Background/aim: Trachomatous trichiasis frequently returns following surgery. Several factors may promote recurrence: preoperative disease severity, surgeon ability, surgical procedure, healing responses, and infection. This study investigates whether enhanced control of infection, both of Chlamydia trachomatis and other bacteria, with azithromycin can improve surgical outcome in a trachoma control programme. Methods: Individuals with trachomatous trichiasis were examined and operated. After surgery patients were randomised to the azithromycin or control group. The azithromycin group and children in their household were given a dose of azithromycin. Antibiotic treatment was repeated at 6 months. All patients were reassessed at 6 months and 12 months. Samples were collected for C trachomatis polymerase chain reaction and general microbiology at each examination. Results: 451 patients were enrolled. 426 (94%) were reassessed at 1 year, of whom 176 (41.3%) had one or more lashes touching the eye and 84 (19.7%) had five or more lashes. There was no difference in trichiasis recurrence between the azithromycin and control group. Recurrent trichiasis was significantly associated with more severe preoperative trichiasis, bacterial infection, and severe conjunctival inflammation at 12 months. Significant variability in outcome was found between surgeons. Visual acuity and symptoms significantly improved following surgery. Conclusion: In this setting, with a low prevalence of active trachoma, azithromycin did not improve the outcome of trichiasis surgery conducted by a trachoma control programme. Audit of trichiasis surgery should be routine.

Changes in immune and coagulation systems and possible viral spread through the blood–brain barrier have been described in SARS-CoV-2 infection. In this study, we evaluated the possible retinal involvement and ocular findings in severe COVID-19 pneumonia patients. A cross-sectional study was conducted on 46 patients affected by severe COVID-19 who were hospitalized in one intensive care unit (ICU) and in two infectious disease wards, including bedside eye screening, corneal sensitivity assessment and retinography. A total of 43 SARS-CoV-2-positive pneumonia patients affected with COVID-19 pneumonia were included, including 25 males and 18 females, with a median age of 70 years [IQR 59–78]. Except for one patient with unilateral posterior chorioretinitis of opportunistic origin, of whom aqueous tap was negative for SARS-CoV-2, no further retinal manifestation related to COVID-19 infection was found in our cohort. We found 3 patients (7%) with bilateral conjunctivitis in whom PCR analysis on conjunctival swabs provided negative results for SARS-CoV-2. No alterations in corneal sensitivity were found. We demonstrated the absence of retinal involvement in SARS-CoV-2 pneumonia patients. Ophthalmologic evaluation in COVID-19, particularly in patients hospitalized in an ICU setting, may be useful to reveal systemic co-infections by opportunistic pathogens.

Allergic rhinoconjunctivitis is a risk factor for asthma development. Treating the underlying allergy may represent an attractive method of asthma prevention. No regulatory guidance exists in this area, and, to our knowledge, no clinical investigations meeting modern regulatory standards have been published. The objective of this publication is to describe the rationale behind the design of and report on the recruitment for the ongoing pediatric Grazax Asthma Prevention (GAP) trial. The trial was designed for assessment of the preventive effect of an SQ-standardized grass allergy immunotherapy tablet (AIT) on asthma development, both during treatment and after the end of treatment. (The standardized quality [SQ] procedure is a standardization procedure comprising 3 components: total potency, major allergen content, and assessment of extract complexity.) The trial design was discussed with several European Competent Authorities. The GAP trial is a multinational, parallel-group, double-blind, placebo-controlled randomized trial. Main eligibility criteria were age of 5 to 12 years, grass pollen–induced allergic rhinoconjunctivitis, no asthma, and no overlapping symptomatic allergies. The children have been randomized 1:1 to receive the grass AIT or placebo once daily for 3 years, followed by a blinded observational period of 2 years. Asthma is assessed by the investigators according to specific diagnostic criteria, used at screening visits before randomization to exclude children with existing asthma, and evaluated at least half-yearly during the trial. Seven months of screening resulted in 812 randomized children at 101 centers in 11 countries. To our knowledge, the GAP trial represents the first double-blind, placebo-controlled randomized trial to assess the preventive effect of allergen-specific immunotherapy on asthma development. A total of 812 children were successfully recruited into the trial. EudraCT number: 2009-011235-12.

Proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE) is diagnosed in at least one-third of patients with suspected eosinophilic esophagitis (EoE). We aimed to evaluate the durability and factors influencing long-term efficacy of PPI therapy. Retrospective multicenter cohort study of patients with PPI-REE who had at least 12 months of follow-up. PPI therapy was tapered to the lowest dose, which maintained clinical remission. Primary outcomes were the proportion of patients with loss of histological response (<15 eos/HPF) and predictors of loss of response. CYP2C19 polymorphisms were determined from blood samples in a subset of patients. Seventy-five PPI-REE patients were included (mean follow-up 26 months (12-85)), of whom fifty-five (73%) had sustained histological remission on low-dose PPI therapy. Loss of response was significantly higher in those patients with a CYP2C19 rapid metabolizer genotype (36% vs. 6%, P = 0.01) and with rhinoconjunctivitis (40% vs. 13%, P = 0.007). On the multivariate analysis, a CYP2C19 rapid metabolizer genotype (odds ratio (OR) 12.5; 95% confidence interval (CI): 1.3-115.9) and rhinoconjunctivitis (OR 8.6; 95% CI: 1.5-48.7) were independent predictors of loss of response. Among relapsing patients, eosinophilia was limited to the distal esophagus in 14/20 (70%). Nine of ten relapsers, with distal eosinophilia, all showing a CYP2C19 rapid metabolizer genotype, regained histological remission after PPI dose intensification. Most PPI-REE patients remain in long-term remission on low-dose PPI therapy. CYP2C19 rapid metabolizer genotypes and rhinoconjunctivitis were independent predictors of loss of response to PPI, but patients frequently responded to PPI dose escalation.

Background Pathological origin of primary acquired nasolacrimal duct obstruction (PANDO) is considered as inflammation of unknown causes; however, specific predisposing factors have not been fully addressed to date. Methods In an institutional setting, background factors of 45 patients with PANDO were compared to those in 67 control subjects. The control subjects were persons with senile cataract, representing the non-pathological general population. The evaluated background factors were inflammatory medical histories (infectious conjunctivitis and allergic conjunctivitis and/or rhinitis), previously reported factors (POAG and topical timolol), and a novel factor proposed in the current study (exposure to swimming pool). Data were extracted from the patients through interview based on a standardized questionnaire as well as from their clinical records. Results After adjustment for age and gender, a history of infectious conjunctivitis was more common in the PANDO group than in the control group (55.6 % vs 32.8 %, P  = 0.0027), and regular attendance to indoor swimming pools was also more common in the PANDO group (33.3 % vs 0 %, P  < 0.0001). Furthermore, when age- and gender- matched subjects were selected, a history of conjunctivitis and swimming pool exposure were independently associated with the development of PANDO ( P  = 0.022 and P  < 0.0001 respectively). On the other hand, the frequencies of histories of POAG, topical timolol, and allergic conjunctivitis and/or rhinitis were similar between the two groups. Conclusions Histories of infectious conjunctivitis and swimming pool exposure could be associated with the development of PANDO, although the pathogenesis of this condition has been considered as inflammation of unknown causes.

Background: Nonpathogenic Escherichia coli strain Nissle 1917 (EcN) has immunomodulatory properties and can act on different cells which are important for the allergic immune response. Herein, we investigated the efficacy and tolerability of EcN in subjects with grass pollen-dependent allergic rhinoconjunctivitis. Methods: Grass pollen-allergic subjects were randomly allocated to receive EcN in a double-blind, placebo-controlled manner. The treatment was performed from 2 months before onset until the end of one grass pollen season (in total: 6 months). The clinical symptom score and the intake of symptomatic medications were assessed. A skin prick test and grass pollen-specific immunoglobulin (Ig) E and IgA were evaluated before and after treatment. Results: Our results show that coseasonal treatment with EcN in grass pollen-allergic subjects was not superior to placebo as assessed using the symptom-medication score (p = 0.257). Interestingly, an increase [median (range)] in grass pollen-specific IgA was detectable in the EcN group [20,556 LU/ml (1,812-60,800)] versus placebo [5,246 LU/ml (944-50,467)] (p = 0.048). Conclusions: The results indicate that 6 months of coseasonal nonspecific immunomodulation by EcN is not sufficient to achieve clinical efficacy in grass pollen-allergic subjects. Future approaches in which such immunomodulators are combined with an allergen-specific protocol might enhance the clinical efficacy of the allergen-specific treatment.

To establish the optimal dose of subcutaneous immunotherapy (SCIT) in patients with allergic rhinoconjunctivitis with/without asthma. One hundred and fifty-one patients were randomized to receive SCIT 0.25, 0.5, 1.0, 2.0 or 4.0 skin-prick test units ( or placebo. The primary end point was the variation in the concentration of extract needed to produce a positive nasal provocation test from baseline (V0) to final visit (FV). After 17 weeks, a dose-dependent trend was apparent in the concentration of extract needed to produce a positive nasal provocation response. Systemic adverse reactions occurred with 3.2% of administered doses. Grade III (n = 2) and IV (n = 2) events were observed only at the two highest doses. : depot SCIT showed signs of clinical and immunological efficacy by dose-dependently decreasing the allergen sensitization rate. Risk-benefit favored doses below 1.0 units for confirmatory trials.

Hereditary thrombophilia (HT) is a genetic predisposition to thrombosis. Asian mutation spectrum of HT is different from Western ones. We investigated the incidence and clinical characteristics of HT in Korean patients with unprovoked venous thromboembolism (VTE). Among 369 consecutive patients with thromboembolic event who underwent thrombophilia tests, we enrolled 222 patients diagnosed with unprovoked VTE. The presence of HT was confirmed by DNA sequencing of the genes that cause deficits in natural anticoagulants (NAs). Median follow-up duration was 40±38 months. Among the 222 patients with unprovoked VTE, 66 (29.7%) demonstrated decreased NA level, and 33 (14.9%) were finally confirmed to have HT in a genetic molecular test. Antithrombin III deficiency (6.3%) was most frequently detected, followed by protein C deficiency (5.4%), protein S deficiency (1.8%), and dysplasminogenemia (1.4%). The HT group was significantly younger (37 [32-50] vs. 52 [43-65] years; P < 0.001) and had a higher proportion of male (69.7% vs. 47%; P = 0.013), more previous VTE events (57.6% vs. 31.7%; P = 0.004), and a greater family history of VTE (43.8% vs. 1.9%; P < 0.001) than the non-HT group. Age <45 years and a family history of VTE were independent predictors for unprovoked VTE with HT (odds ratio, 9.435 [2.45-36.35]; P = 0.001 and 92.667 [14.95-574.29]; P < 0.001). About 15% of patients with unprovoked VTE had HT. A positive family history of VTE and age <45 years were independent predictors for unprovoked VTE caused by HT.

Background and Objectives: Atopic dermatitis (AD), also known as eczema, is a common chronic inflammatory skin condition affecting 16.5 million adults in the United States. AD is characterized by an impaired epidermal barrier that can predispose individuals to infection. End-stage renal disease (ESRD) is also commonly complicated by infections due to chronic vascular access and immune-system dysfunction, possibly related to uremia. Multiple studies have reported that renal disease is a common comorbidity in adults with atopic dermatitis. The aim of this study was to determine whether AD is a risk factor for certain infections in patients with ESRD. Materials and Methods: Using the United States Renal Data System, a retrospective cohort analysis was conducted on adult ESRD patients initiating dialysis between 2004 and 2019 to investigate associations between infections and AD in this population. Results: Of 1,526,266 patients, 2290 were identified with AD (0.2%). Infectious outcomes of interest were bacteremia, septicemia, cellulitis, herpes zoster, and conjunctivitis. In all infectious outcomes except for conjunctivitis, patients with the infectious outcomes were more likely to carry a diagnosis of AD. After controlling for demographic and clinical covariates, AD was associated with an increased risk of cellulitis (adjusted relative risk (aRR) = 1.39, 95% confidence interval (CI) = 1.31–1.47) and herpes zoster (aRR = 1.67, CI = 1.44–1.94), but not with bacteremia (aRR = 0.96, CI = 0.89–1.05), septicemia (aRR = 1.02, CI = 0.98–1.08), or conjunctivitis (aRR = 0.97, CI = 0.740–1.34). Conclusions: Overall, after controlling for demographic and clinical covariates and adjusting for person-years-at-risk, AD was associated with an increased risk for some, but not all, infections within the population of patients with ESRD.

Background Since the outbreak of Coronavirus Disease 2019 (COVID-19) in December 2019, many studies have reported the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the conjunctival sac of patients infected with this virus, with several patients displaying symptoms of viral conjunctivitis. However, to our best knowledge, there is no in-depth report on the course of patients with COVID-19 complicated by relapsing viral conjunctivitis or keratoconjunctivitis. Case presentation A 53-year-old man confirmed with COVID-19 developed symptoms of viral conjunctivitis in the left eye approximately 10 days after the onset of COVID-19. The results of a nucleic acid test were positive for SARS-CoV-2 in the conjunctival sac of the left eye. The symptoms were relieved 6 days after treatment. However, the patient was subsequently diagnosed with viral keratoconjunctivitis in both eyes 5 days after the symptoms in the left eye were satisfactorily relieved. The disease progressed rapidly, with spot staining observed at the periphery of the corneal epithelium. Although SARS-CoV-2 could not be detected in conjunctival secretions, the levels of inflammatory factors, such as interleukin-6, were increased in both eyes. Both eyes were treated with glucocorticoids, and symptoms were controlled within 5 days. There was no recurrence. Conclusions In this case report, the pathogenesis, clinical manifestations, treatment, and outcome of a case with COVID-19 complicated by relapsing viral keratoconjunctivitis is described, and the involvement of topical cytokine surge in the pathogenesis of COVID-19 as it relates to viral keratoconjunctivitis is reported.