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Summary: Background: Dupilumab blocks the shared receptor component for interleukin (IL)‐4 and IL‐13. It is approved in the U.S.A. for patients aged ≥ 12 years with moderate‐to‐severe atopic dermatitis (AD) uncontrolled by topical prescription medicines or who cannot use topical medicines, for patients in Japan whose AD is uncontrolled with existing therapies, for patients with moderate‐to‐severe AD in Europe who are candidates for systemic therapy and for patients aged ≥ 12 years for maintenance treatment of moderate‐to‐severe asthma uncontrolled with their current medicines. AD trials have reported increased incidence of conjunctivitis for dupilumab vs. placebo. Objectives: To characterize further the occurrence and risk factors of conjunctivitis in dupilumab clinical trials. Methods: We evaluated randomized placebo‐controlled trials of dupilumab in AD (n = 2629), asthma (n = 2876), chronic rhinosinusitis with nasal polyps (CRSwNP) (n = 60) and eosinophilic oesophagitis (EoE) (n = 47). Results: In most AD trials, dupilumab‐treated patients had higher conjunctivitis incidence than placebo controls. Higher baseline AD severity and previous history of conjunctivitis were associated with increased conjunctivitis incidence. Conjunctivitis was mostly mild to moderate. Most cases recovered or resolved during the treatment period; two patients permanently discontinued dupilumab due to conjunctivitis or keratitis. Common treatments included ophthalmic corticosteroids, antibiotics, and antihistamines or mast cell stabilizers. Most cases were diagnosed by the investigators. In asthma and CRSwNP trials, the incidence of conjunctivitis was lower for both dupilumab and placebo than in AD trials; dupilumab did not increase the incidence compared with placebo. In the EoE trial, no patients had conjunctivitis. Conclusions: Conjunctivitis was more frequent with dupilumab treatment in most AD trials. In dupilumab trials in other type 2 diseases, incidence of conjunctivitis was overall very low, and was similar for dupilumab and placebo. In AD, the incidence of conjunctivitis was associated with AD severity and prior history of conjunctivitis. The aetiology and treatment of conjunctivitis in dupilumab‐treated patients require further study. What's already known about this topic? Ocular disorders, including allergic conjunctivitis, are common in patients with atopic dermatitis (AD).In most dupilumab AD trials, dupilumab‐treated patients had higher conjunctivitis incidence than those receiving placebo.Most cases were mild to moderate and recovered or were recovering during study treatment; study treatment discontinuation due to conjunctivitis was rare.Conjunctivitis incidence was very low and similar for dupilumab and placebo in clinical trials in asthma, chronic rhinosinusitis with nasal polyps and eosinophilic oesophagitis. What does this study add? This analysis confirms and extends the results of the individual clinical trials.Baseline disease‐related factors, including AD severity, prior conjunctivitis history and certain biomarkers (thymus and activation‐regulated chemokine, IgE, eosinophils), were associated with increased incidence of conjunctivitis.Patients who responded well to dupilumab had reduced incidence of conjunctivitis.Further study is needed to elucidate the aetiology and treatment of conjunctivitis in dupilumab‐treated patients with AD. Linked Editorial: Chia‐Yu Chu. Br J Dermatol 2019; 181:436–437. Plain language summary available online Respond to this article [ABSTRACT FROM AUTHOR]

AIMS: Possible risk factors were evaluated for herpes simplex virus (HSV) epithelial keratitis in patients with stromal keratouveitis. METHODS: The study population included 260 patients who had active stromal keratitis and/or iridocyclitis without epithelial disease and who were enrolled in one of three clinical trials of the Herpetic Eye Disease Study. Study treatment involved a 10 week course of topical placebo, topical prednisolone phosphate, or topical prednisolone phosphate with oral acyclovir. All groups received topical trifluridine four times daily for 3 weeks then twice daily for another 7 weeks. Patients were examined for HSV epithelial keratitis for 16 weeks. RESULTS: Dendritic or geographic epithelial keratitis occurred in 12 (4.6%) study patients. Adverse effects attributable to trifluridine prophylaxis were acute allergic blepharoconjunctivitis in 10 (3.8%) study patients and corneal epithelial erosions in 11 (4.2%) study patients. No significant difference in the occurrence of HSV epithelial keratitis was found among the study treatment groups: one (2.0%) of 49 topical placebo treated patients, nine (6.5%) of 138 patients treated with topical corticosteroids without acyclovir, and two (2.7%) of 73 patients treated with topical corticosteroids and oral acyclovir. Univariate exponential models suggested that patients with a history of previous HSV epithelial keratitis and non-white patients were more likely to develop HSV epithelial keratitis during treatment of stromal keratouveitis. CONCLUSION: Individuals with prior HSV epithelial keratitis and certain ethnic groups may have a higher rate of recurrent epithelial keratitis during the acute treatment of HSV stromal keratouveitis. [ABSTRACT FROM PUBLISHER]

AIMS--A study was conducted to estimate the frequency of contamination of topical antiglaucoma medications used by asymptomatic patients. METHODS--The drops and the bottle tips of 194 in use topical medications and the conjunctiva from 109 treated glaucoma patients were cultured. RESULTS--Bacteria were recovered from 55 (28%) medications. The bottle tip was more frequently contaminated than the drops (p = 0.008). Gram positive organisms were cultured from 50 (91%) of 55 contaminated medications. Thirteen patients (12%) had the same microorganism recovered from the conjunctiva and from the contaminated medication. The frequency of contamination of medications increased with increasing duration of use. Bacterial contamination occurred in 19% of eyedrops less than 8 weeks old in contrast with 40% of bottles used for more than 8 weeks. CONCLUSION--Our data suggest that ocular medications to treat glaucoma frequently become contaminated with bacteria and that contamination is related to duration of use. We therefore recommend that opened topical antiglaucoma eyedrops should be replaced on a regular basis. [ABSTRACT FROM PUBLISHER]

There are conflicting reports on the propensity of topical beta blockers to produce corneal anaesthesia. We measured corneal sensitivity thresholds quantitatively for 10 minutes following the administration of one drop of topical timolol maleate (0.5%), betaxolol hydrochloride (0.5%), or saline in 30 eyes of 18 normal subjects in a randomised, double-masked study. Most subjects had insignificant changes in corneal sensitivity thresholds. We identified, however, a subgroup of four subjects (five eyes) that had a marked and prolonged increase of corneal sensitivity threshold (corneal anaesthesia) after timolol (three eyes) and betaxolol (two eyes). The group mean age of these 'responders' (49.0 years) was significantly greater (p less than 0.005) than that of the non-responders (35.0). We recommend periodic measurements of corneal sensitivity in older patients receiving topical timolol or betaxolol, especially when given in higher concentrations, to identify responders, who may be at risk of developing keratitis. [ABSTRACT FROM PUBLISHER]

Sixteen patients enrolled in the PERK study were evaluated by fluorophotometry 24 hours or six months following radial keratotomy. A comparison of eyes operated and not operated upon showed that endothelial permeability was not significantly altered 24 hours and six months after surgery. Aqueous humour flow rates and anterior chamber elimination coefficients were significantly higher 24 hours after surgery in the eyes operated on than in those not operated on. Six months after surgery there was no longer a significant difference in these factors. The increase in aqueous humour flow rates 24 hours after surgery may represent a subclinical breakdown in the blood-aqueous barrier. [ABSTRACT FROM PUBLISHER]

We reviewed the charts of neonates who received a diagnosis of conjunctivitis or ophthalmia neonatorum during a 10-year period at the Mount Sinai Hospital, New York City. Ninety-five cases were discovered, four of these were born elsewhere and were not subject to our protocol, which at present consists of intramuscular penicillin and topical tetracycline ointment (1%). The 91 cases represent an incidence of 3.1 cases per 1000 live births (9.1/year), an incidence approximately equal to that reported in other published studies. The clinical characteristics examined were: age, sex, race, birth weight, gestational age, Apgar scores, presence or absence of fever or other systemic illnesses, complications, type of delivery, time of year, incubation period, presence and type of discharge, uni- or bilaterality, Gram stain, Giemsa stain, culture results, antibiotic disc sensitivities, cervical culture, antibiotic therapy, sequelae, and type of prophylaxis received. Seven aetiological diagnostic categories were established: gonococcal (3%), chlamydial (3%), staphylococcal (30%), other pathogens (25%), chemical conjunctivitis (7%), culture negative/normal flora (22%), and unobtainable (10%). This distribution differs from others published. In contrast with other studies, moreover, we found few gonococcal and no chlamydial cases in neonates subject to the Mount Sinai Hospital treatment protocol. Correlation of clinical characteristics and aetiological categories showed no statistically significant trend. So far there have been no cases of ophthalmia neonatorum, treated as on our protocol, caused by penicillin resistant gonococci or chlamydiae. [ABSTRACT FROM PUBLISHER]

The Prospective Evaluation of Radial Keratotomy Study is a nine-center clinical trial of a surgical technique to reduce simple myopia by making incisions in the cornea. There were 435 patients (one eye per patient is reported) enrolled in the study with a 91% follow-up rate at 4 years after surgery. After surgery, uncorrected visual acuity was 20/40 or better in 76% of eyes. Fifty-five percent of the eyes had a refractive error within +/- 1.00 diopter; 28% were undercorrected, and 17% were overcorrected by more than 1.00 D. The width of the prediction 90% interval for the refractive change was 4.42 D, indicating a lack of predictability. The refractive error was not stable in some eyes; between 6 months and 4 years after surgery, 23% of eyes had a continued effect of the surgery of more than 1.00 D. For 323 patients with both eyes operated on, 64% stated they wore no optical correction. There were few serious complications. Eleven eyes (3%) lost two or three lines of best corrected visual acuity. Two eyes developed delayed bacterial keratitis without significant loss in best corrected visual acuity. [ABSTRACT FROM AUTHOR]

BACKGROUND--The Surecell herpes (HSV) test kit is a test for detecting the presence of herpes simplex viral antigen by means of a monoclonal antibody based immunoassay. The test has proved to be highly sensitive and specific in diagnosing genital, oral, and dermatological herpes infections. METHODS--In this study, samples from patients with ocular keratitis were evaluated by tissue cultures and the Surecell test. The eyes of New Zealand rabbits were then inoculated with HSV type 1 acute keratitis, acute Staphylococcus keratitis, and HSV type 1 postkeratitis (healed corneas). Tear film samples collected from each eye with a cotton swab were evaluated by routine culture (A-549 monolayers) and by the Surecell test with and without prior placement of the swab in Hank's medium. RESULTS--The Surecell system had a 70% sensitivity and a 100% specificity in the detection of HSV antigen in ocular infections, and was shown to be a quick, efficient, and accurate method of testing for HSV antigen in humans. CONCLUSION--These results from humans and rabbits indicate that the Surecell test, which requires no special equipment, can be a useful in office adjunct in the clinical diagnosis of ocular herpes simplex. [ABSTRACT FROM PUBLISHER]

Summary: 结膜炎是一种导致眼睛变红、瘙痒和渗出的常见疾病。它在特应性皮炎(也称为湿疹)和其他过敏性疾病(包括哮喘)的患者中常见。除了过敏,感染、化学品、刺激物和其他疾病也可引起结膜炎。Dupilumab 是一种处方药,在美国批准用于不能通过局部外用(外用到皮肤)处方药控制或不能局部外用药物的≥ 12 岁中重度 AD 患者,在其他国家批准用于通过现有治疗无法控制的 AD 成人,和用于通过当前用药无法控制的≥12 岁中重度哮喘患者的维持治疗。Dupilumab 可阻滞导致这些过敏性疾病的特定物质的活性。在大部分 AD 研究中,接受dupilumab治疗患者中的结膜炎发生率多于安慰剂(模拟药物)组。为了研究这一作用,作者们评估了在 AD、哮喘、慢性鼻窦炎伴鼻息肉(CRSwNP) 和嗜酸性粒细胞性食管炎(EoE) 中开展的 11 项 dupilumab 研究中的结膜炎的发生率、风险因素、严重程度和结局。在 6 项 AD 研究的 5 项中,dupilumab治疗患者较安慰剂治疗患者更容易发生结膜炎。没有确认因感染导致的结膜炎,其性质似乎也不是过敏性的。进入这些研究时 AD 较严重患者或之前曾患过结膜炎的患者更容易患结膜炎。在哮喘和 CRSwNP 研究中,dupilumab 和安慰剂组的结膜炎发生率均低于 AD 研究,且dupilumab 和安慰剂组相似。在 EoE 研究中,没有人患有结膜炎。在所有研究中,结膜炎大部分为轻中度;大部分病例在治疗期间恢复。需要进一步研究 dupilumab治疗患者中的结膜炎原因。 Linked Article: Akinlade et al. Br J Dermatol 2019; 181:459–473 [ABSTRACT FROM AUTHOR]

Summary: Conjunctivitis is a common condition that causes the eye to become red, itchy and oozing. It is common in patients with atopic dermatitis (also called eczema), and in other allergic diseases, including asthma. Apart from allergies, conjunctivitis can also be caused by infections, chemicals, irritants, and other diseases. Dupilumab is a prescription medicine approved in the USA for people 12 years and older with moderate‐to‐severe AD uncontrolled by topical (applied to the skin) prescription medicines or who cannot use topical medicines, for adults in other countries whose AD is uncontrolled with existing therapies, and for people 12 years and older for maintenance treatment of moderate‐to‐severe asthma uncontrolled with their current medicines. Dupilumab blocks activity of specific substances that cause these allergic diseases. In most AD studies, more dupilumab‐treated patients had conjunctivitis than patients on placebo (dummy drug). To investigate this effect, the authors assessed rates, risk factors, severity, and outcomes of conjunctivitis in 11 dupilumab studies in AD, asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), and eosinophilic esophagitis (EoE). In 5 of 6 AD studies, dupilumab‐treated patients were more likely to get conjunctivitis than placebo‐treated patients. No conjunctivitis was confirmed to be caused by infection, and it does not seem to be allergic in nature. Patients who entered these studies with more severe AD or who previously had conjunctivitis were more likely to get conjunctivitis. In asthma and CRSwNP studies, conjunctivitis rates were less frequent for both dupilumab and placebo than in AD studies, and were similar for dupilumab and placebo. In the EoE study, nobody had conjunctivitis. In all studies, conjunctivitis was mostly mild to moderate; most cases recovered during the treatment period. Causes of conjunctivitis in dupilumab‐treated patients require further study. Linked Article: Akinlade et al. Br J Dermatol 2019; 181:459–473 [ABSTRACT FROM AUTHOR]