Real-Life Experience of Tralokinumab for the Treatment of Adult Patients with Severe Atopic Dermatitis: A Multicentric Prospective Study.

BACKGROUND: Tralokinumab, the first fully human monoclonal antibody that binds specifically to interleukin-13, was safe and effective for treating atopic dermatitis (AD) in clinical trials, but real-life experience is still limited. OBJECTIVES: The objective of this study was to evaluate the effectiveness and safety of tralokinumab in severe AD in a real-life multicenter prospective cohort. METHODS: Adult patients with severe AD were enrolled between January 2022 and July 2022 and received tralokinumab subcutaneously for 16 weeks. Objective and subjective scores were collected at baseline, weeks 6 and 16. Adverse events were reported throughout the study. RESULTS: Twenty-one patients were included. An improvement of at least 75% on the Eczema Area and Severity Index (EASI 75) was achieved in 66.7% of patients at week 16. The median objective and subjective scores at week 16 were significantly (p < 0.001) lower than those at baseline. Combination with cyclosporine was sometimes necessary at the beginning of treatment, and addition of upadacitinib was required for some patients with very severe disease during the treatment. The most frequent adverse events were flares of eczema (23.8%) and reactions at injection site (19.0%). No cases of conjunctivitis were reported. Four patients (19.0%) discontinued treatment. CONCLUSIONS: Tralokinumab is an effective first-line biotherapy for severe AD. However, therapeutic response may be progressive. Safety data were reassuring. Atopic dermatitis flares or reactions at the injection site may lead to discontinuation of treatment. A history of conjunctivitis on dupilumab is not a contraindication to the initiation of tralokinumab.

Safety and Efficacy of Black Tea Extract in the Treatment of Acute Bacterial Conjunctivitis: A Rabbit Model.

PURPOSE: To determine the safety and efficacy of black tea extract in the treatment of bacterial conjunctivitis in a rabbit model and compare it with that of gatifloxacin drops. METHODS: Black tea extract was tested in vitro on bacterial cultures of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. Forty-two rabbit eyes were cultured with either MRSA (n=21) or P. aeruginosa (n=21) and further divided into a control group (n=5), a tea group (n=8) treated with black tea extract, and a gatifloxacin group (n=8) treated with 0.3% gatifloxacin eye drops. Conjunctival swabs were collected on the third and fifth days. RESULTS: The tea extract successfully inhibited the growth of both organisms at a concentration of 400 mg/mL. Rabbits in the treatment groups showed a reduction in the clinical index on day 2 (P<0.01), unlike the control group (P=0.1), for both organisms. Resolution of conjunctivitis was achieved on days 4 and 5 in the tea and gatifloxacin groups, respectively. On days 3 and 5, while the control group still showed considerable bacterial growth, the tea and gatifloxacin groups showed its inhibition. CONCLUSION: Tea extract has antimicrobial effects similar to those of gatifloxacin in a rabbit model of conjunctivitis.

Dupilumab dose spacing after initial successful treatment or adverse events in adult patients with atopic dermatitis: A retrospective analysis.

Strategies on long-term management of patients affected by atopic dermatitis (AD) undergoing treatment with dupilumab achieving good clinical response (GCR) or experiencing dupilumab-related adverse events (AEs) are scant. Data of patients who implemented longer than scheduled dupilumab dosing interval due to GCR (at least 52 weeks of treatment and controlled AD activity [Eczema Area Severity Index ≤7 and Dermatology Life Quality Index ≤5 for at least 6 months]) or AEs (dupilumab-related and treatment-resistant conjunctivitis) were retrospectively collected. Dupilumab was tapered to Q3W or Q4W based on physician-patient shared decision. At baseline (T0) and each follow-up (week 16 [T1] and week 32 [T2]) disease severity was assessed. A total of 59 patients implemented longer than scheduled dosing interval (44 GCR, 15 AEs). Among these, 50 (35 GCR and 15 conjunctivitis) patients switched to 300 mg Q3W, while nine GCR subjects to Q4W. In the GCR group Q3W, 34 and 31 patients maintained clinical response at T1 and T2, whereas eight and seven Q4W subjects maintained clinical response at the same timepoints, respectively. No significant differences in AD severity were observed between T1 and T2 in both groups. Contrariwise, one Q3W and one Q4W patients at T1, and three Q3W and one Q4W subjects at T2, returned to dupilumab labeled dosage due to AD worsening. In conjunctivitis group, dupilumab Q3W was maintained in eight and four patients at T1 and T2, respectively. Three patients at T1 and three at T2 subjects returned to the labeled interval due to conjunctivitis remission. Four patients at T1 and four subjects at T2 interrupted dupilumab due to the persistence of conjunctivitis. A longer dupilumab dosing interval may be a valuable option in patients with a GCR and may be a useful strategy to reduce treatment-related conjunctivitis, also with pharmacoeconomic benefit.

[A Case of Reactive Arthritis after BCG Intravesical Infusion Therapy Successfully Treated with Salazosulfapyridine].

The patient was a 70-year-old woman who underwent transurethral resection of bladder tumor in May 2020. She was diagnosed with urothelial carcinoma (high grade, pT1 by pathology). We started bacillus Calmette-Guerin (BCG) intravesical infusion (80 mg Tokyo strain) in August of the same year after a second transurethral resection. Pain during urination persisted during the administration of BCG, and it worsened after the completion of six doses. The patient was hospitalized with back and neck pain and difficulty in physical movement. At the time of admission, bilateral conjunctivitis was observed. The patient was diagnosed with reactive arthritis associated with BCG intravesical injection therapy, as three typical symptoms were observed (bilateral conjunctivitis, urethritis, polyarthritis). The patient was treated with prednisolone and non-steroidal anti-inflammatory drugs for arthritis, but the symptoms did not improve. We administered salazosulfapyridine and her reactive arthritis improved.

Evaluation of knowledge, attitude, and behaviour of ophthalmologists about adenoviral conjunctivitis transmission and treatment : An online survey for Turkish ophthalmologists.

PURPOSE: To determine the prevalence of adenoviral conjunctivitis in Turkish ophthalmologists, to provide an overview of the treatment and prophylaxis of adenoviral conjunctivitis, and to analyze the data in the context of evidence-based treatment recommendations. METHODS: An online questionnaire consisting of 20 multiple-choice questions about the characteristics of the respondents, the individual adenoviral conjunctivitis history of the ophthalmologists, their practice's approaches, and prescription preferences were emailed to Turkish ophthalmologists. RESULTS: The survey was emailed to 500 ophthalmologists; 45% of them returned the questionnaire. According to the responses, the history of adenoviral conjunctivitis infections was positive in 46.7% (n: 120), recurrent attack prevalence was 16.2% in ophthalmologists. Lubricants (67.6%) are the most preferred first-line treatment options for adenoviral conjunctivitis, followed by povidone-iodine (59.6%), topical antibiotics (51.1%), topical antivirals (29.3%), topical corticosteroids (26.7%), and topical nonsteroidal anti-inflammatory agents (19.6%). A total of 98.2% preferred to dismiss infected patients. The preferred prophylaxis options were frequent hand washing/use of gloves (97.8%), disinfection of medical devices (95.1%), isolation of infected patients (79.1%), hand hygiene with gemicides (58.7%). The percentage of single-dose eye drop selection was 46.2. CONCLUSIONS: The findings of this survey showed that most Turkish ophthalmologists generally follow international guidelines for the treatment of adenoviral conjunctivitis. The treatment algorithm is still controversial, so ophthalmologists should be aware of treatment guideline updates in line with evidence-based recommendations. Having sufficient knowledge of the basic characteristics of viruses is important to control the spread of the disease.

Mulberry Leaf Extract Alleviates Staphylococcus aureus-Induced Conjunctivitis in Rabbits via Downregulation of NLRP3 Inflammasome and Upregulation of the Nrf2 System and Suppression of Pro-Inflammatory Cytokines.

INTRODUCTION: Mulberry (Morus alba L.) leaves are widely used in traditional Chinese medicine for their antioxidant, anti-inflammatory, antibacterial, anti-obesity, antidiabetic, antiatherosclerotic, and anticancer properties. The current study aimed to investigate the effect of mulberry leaf extract (MLE) on Staphylococcus aureus (S. aureus)-induced conjunctivitis (5 × 109 colony-forming units, 0.5 mL/eye) in a rabbit model. METHODS: Rabbits were treated with MLE (5 mL/kg·d-1 and 10 mL/kg·d-1), 0.9% saline, pearl bright eye (PBE) drops, or erythromycin eye ointment (EEO) group for 5 days. The ocular infection symptoms, bacterial negative conversion rate, and conjunctival histopathological changes of rabbits in each group were observed. The expression of caspase-1, apoptosis-associated speck-like protein containing a caspase recruitment domain, NOD-like receptor leucine-rich pyrin domain-containing protein 3 (NLRP3), interleukin (IL)-18, IL-6, IL-1ß, TNFα, Keap1, and nuclear factor erythroid 2-related factor 2 (Nrf2) in conjunctival tissue of rabbits were detected by quantitative real-time reverse transcription PCR and/or Western blot analysis. RESULTS: The results showed that MLE treatment significantly reduced the clinical sign scores of conjunctivitis, alleviated clinical signs, and decreased bacterial load, and histological damage in a time- and dose-dependent manner was compared to that in the control group. The antibacterial and anti-inflammatory activities of MLE (10 mL/kg·d-1) were similar to those of the positive control drug PBE and EEO. In addition, MLE significantly decreased the levels of pro-inflammatory cytokines, downregulated the NLRP3 inflammasome, and upregulated the Nrf2 system. CONCLUSIONS: MLE is effective in alleviating S. aureus-induced conjunctivitis in rabbits, and this mechanism is associated with the inhibition of the NLRP3 inflammasome and activation of the Nrf2 system to regulate pro-inflammatory signaling.

Dupilumab-Associated Adverse Events During Treatment of Allergic Diseases.

Among the new biological therapies for atopic diseases, dupilumab is a fully human monoclonal antibody directed against IL-4Rα, the common chain of interleukin-4 and interleukin-13 receptors. Dupilumab showed clinical improvements in patients with atopic dermatitis, asthma, and chronic rhinosinusitis and is currently under development for other indications. While dupilumab is considered to be well tolerated, a number of recent publications have reported various adverse events. This review aims to summarize the current knowledge about these adverse events, which may help clinicians to improve the follow-up of patients on dupilumab. Injection-site reactions are the most common reported adverse event. However, dupilumab has also been shown to cause ophthalmic complications (e.g., dry eyes, conjunctivitis, blepharitis, keratitis, and ocular pruritus), head and neck dermatitis, onset of psoriatic lesions, progression of cutaneous T-cell lymphoma exacerbation, alopecia areata, hypereosinophilia, and arthritis. Most are managed during dupilumab treatment continuation, but some (e.g., severe conjunctivitis) may result in a discontinuation of treatment. Their molecular origin is unclear and requires further investigations. Among other hypothesis, it has been suggested that T helper (Th)2-mediated pathway inhibition may worsen Th1/Th17-dependent immune responses. An ophthalmological examination for the presence of potential predictive indicators of ophthalmic adverse events is recommended before initiation of dupilumab therapy.

Update on the Management of Demodex Blepharitis.

ABSTRACT: Demodex blepharitis is a common ophthalmologic disease that is often overlooked in the workup of blepharitis. Demodex infestation occurs in both symptomatic and asymptomatic individuals at similar rates; consequently, its role in the development of blepharitis has not been well elucidated. Two species have been confirmed to inhabit the human eyelid- Demodex folliculorum and Demodex brevis. These species differ in their preferred location of infestation, with D. folliculorum occupying the base of the eyelash and D. brevis inhabiting the meibomian glands, contributing to anterior and posterior Demodex blepharitis, respectively. A clinical index of suspicion must be developed from the history when blepharitis, conjunctivitis, or keratitis in adults and blepharoconjunctivitis or chalazia in children are resistant to treatment. The diagnosis can be strongly suspected by the presence of cylindrical dandruff at the base of the eyelash and confirmed by light microscopy of an epilated lash or by in vivo confocal microscopy. No cure is currently available. Management most frequently includes topical tea tree oil and its active ingredient terpinen-4-ol, both of which have produced good clinical outcomes. Topical tea tree oil is typically applied by a professional due to risk of toxicity. Several second-line treatment options have been studied, including ivermectin, metronidazole, selenium sulfide, microblepharoexfoliation, and lid hygiene. Novel, targeted therapies such as TP-03 (Tarsus Pharmaceuticals) are also currently being investigated in phase 2b/3 clinical trials. The purpose of this review purpose is to characterize Demodex blepharitis in detail, including its historical perspective and various classifications, and describe the latest diagnostic and management strategies.

Design and evaluation of ocular hydrogel containing combination of ofloxacin and dexamethasone for the treatment of conjunctivitis

Abstract Conjunctivitis is an inflammation of the conjunctiva, which covers the white part of the eyeball. It can be caused by allergies, bacterial or viral infection. In situ hydrogels are three-dimensional hydrophilic cross-linked network of polymers. In situ hydrogel provided better therapeutic index when compared to conventional treatment. The present work describes the formulation and evaluation of ofloxacin and dexamethasone based on the concept of pH triggered in situ gelation. Carbopol 934p was used as the gelling agent in combination with HPMC, as a viscosity-enhancing agent, benzalkonium chloride as preservative, sodium chloride as tonicity adjusting agent. The prepared formulations were liquid at the low pH and underwent rapid transition into viscous gel at the pH of the tear fluid. Formulations were evaluated for various rheological, in vitro and in vivo release characteristics. Infrared spectroscopy studies showed that there were no interactions between the drug and polymers. Viscosity of the prepared hydrogels lies in the optimum range and drug was released up to 85 % as the end of 13 h. The prepared in situ hydrogel was sterile, non-irritant to the eye. The present study indicated that it is possible to develop safe and physiologically effective in situ hydrogel which is patient compliant.

[Pharmaceutical supply of human plasminogen replacement therapy for the treatment of ligneous conjunctivitis: Logistics for a university hospital]. / Approvisionnement hospitalier en plasminogène humain substitutif pour le traitement de la conjonctivite ligneuse : comment faire en pratique ?

In order to treat a pediatric patient with ligneous conjunctivitis secondary to congenital plasminogen deficiency, a supply of topically administered replacement human plasminogen has been required. In the absence of market approval, this blood-derived drug is managed by a temporary authorisation for nominative use, allowing monthly hospital dispensations. To ensure regulatory compliance and proper use of the drug, it took two years of interactions between various hospital departments and the laboratory to define the pharmaceutical supply chain in our hospital and allow the patient to receive treatment. The main difficulties lie in respecting the cold chain of this drug stored frozen in the bottles not ready for use. Transportation from the laboratory to the patient's home via the hospital pharmacy is carried out in calibrated conditions, ensuring a temperature below -20°C for 72h. Reception and dispensing steps were combined into a single pharmaceutical service in order to optimise transport time while ensuring the safety and traceability of the drug lots. Each month, a date is scheduled between the hospital pharmacy, the laboratory and the family to ensure that delivery and dispensing take place on the same day. Appropriate use and handling are explained to the family. However, two issues remain to be addressed by the manufacturer to facilitate future use of human plasminogen: the thermostability problem, which does not allow stays away from home longer than three days, and self-administration by the child, which is unlikely to be feasible due to handling difficulties.

Povidone iodine for the treatment of adenoviral conjunctivitis.

Adenoviral conjunctivitis is the most common cause of ocular viral infection in the world, but currently has no approved therapeutic treatments. The antiseptic povidone-iodine (PVP-I) has been used as an off-label treatment for the condition, but high-quality evidence for its use is limited. This paper aims to review the literature surrounding the use of PVP-I in the management of adenoviral conjunctivitis. Unfortunately, treatment regimens, inclusion criteria, outcome measures, and review periods vary widely between studies, making direct comparisons between outcomes difficult. The majority of studies investigate daily instillation of 0.4 to 2.0% PVP-I rather than one-time instillation of PVP-I as has been used anecdotally in practice. In addition, only one treatment arm investigates daily PVP-I alone, with no significant difference in the duration of disease or clinical outcome compared to placebo. All other treatment arms investigate PVP-I in combination with dexamethasone which generally improve outcomes. Tolerability of PVP-I is generally good for low concentrations <1.0%, but efficacy of treatment is generally reported to be concentration dependent. Future research should investigate the optimal concentration, dosing regimen and role of each agent in combination treatment and aim to use laboratory techniques to improve diagnosis and provide quantifiable outcomes.

Surto de conjuntivite aguda no período de 2017-2018 em Recife, Brasil / Outbreak of acute conjunctivitis in the period 2017-2018 in Recife, Brazil

RESUMO Objetivo: Avaliar o perfil clínico, epidemiológico e o impacto econômico do surto de conjuntivite no período 2017-2018 no município de Recife-PE. Métodos: Estudo transversal com base na análise de prontuários de pacientes com diagnóstico de conjuntivite, atendidos na emergência da Fundação Altino Ventura entre dezembro/2017 e março/2018. Os dados coletados incluíram manifestações oculares no exame, complicações subsequentes, manejo e dias de licença médica. Resultados: Dos 12.712 pacientes atendidos na FAV entre dezembro de 2017 e março de 2018, 6.359 (50,0%) foram diagnosticados com conjuntivite, dos quais 3.543 pacientes (55,7%) foram atendimentos únicos. A média de idade dos pacientes ao atendimento foi de 29,5 ± 14,1 anos (variação, 1-85 anos), com distribuição semelhante entre os sexos (2.288 casos [50,1%] masculino; 2.282 casos [49,9%] feminino). O diagnóstico mais comum foi conjuntivite sem pseudomembrana (5.645 casos [88,8%]). Hiperemia conjuntival (6.278 casos [98,7%]) e reação folicular (6.255 casos [98,4%]) foram os achados mais frequentes ao exame. A complicação mais frequente foi pseudomembrana (1.062 casos [16,7%]). Os colírios lubrificantes (4.308 [67,7%]) e os colírios de associação antibiótico com corticoide (2.033 [32%]) foram os mais prescritos no tratamento. A média de dias de atestado médico foi de 4,8 ± 2,9 dias (variação, 1- 47 dias) e a perda de produtividade estimada em R$1.159.329,14. Conclusão: O surto de conjuntivite em Pernambuco foi responsável por metade das consultas em um pronto-socorro oftalmológico. Surtos de conjuntivite podem causar um impacto econômico, uma vez que afeta principalmente adultos jovens em idade produtiva. As características clínicas observadas sugerem um surto de conjuntivite de etiologia viral.

Abstract Purpose: To evaluate the epidemiological and clinical profile and economic impact of the acute conjunctivitis outbreak in the period of 2017-2018 in Recife-PE. Methods: Cross-sectional study based on the analysis of medical records of patients diagnosed with conjunctivitis at the emergency room of the Altino Ventura Foundation (FAV) between December 2017 and March 2018. The collected data included ocular manifestations at examination, subsequent complications, management, and days of sick leave. Results: Out of 12,712 patients assisted at FAV from December 2017 to March 2018, 6,359 (50.0%) were diagnosed with conjunctivitis. The mean age of patients was 29.5 ± 14.1 years (range, 01-85 years), with similar distribution between sex (2,288 50.1% male; 2,282 49.9% female). The most common diagnosis was non-pseudomembranous conjunctivitis (5,645 cases 88.8%). Conjunctival hyperemia (6,278 cases 98.7%) and follicular reaction (6,255 cases 98.4%) were the most frequent ocular findings. The most common complication was pseudomembrane in 1,062 cases (16.7%). Lubricants (4,308 67.7%) and antibiotic associated to corticosteroid eyedrops (2,033 32.0%) were the most prescribed medications. The average days of sick leave per patient was 4.8 ± 2.9 days (range, 1- 47 days) and the productivity loss estimated in R$1.159.329,14. Conclusion: The conjunctivitis outbreak in Pernambuco, Brazil was responsible for half of the consultations in an ophthalmic emergency room. Conjunctivitis outbreaks may cause an economic impact as it mostly affects young adults in their productive ages and take in average a 5-day sick leave. The clinical characteristics observed suggest an outbreak of conjunctivitis of viral etiology.

Preparation and Characterization of Tacrolimus-Loaded SLNs in situ Gel for Ocular Drug Delivery for the Treatment of Immune Conjunctivitis.

BACKGROUND: The aim of this study is to develop a novel in situ gel of tacrolimus-loaded SLNs (solid lipid nanoparticles) for ocular drug delivery. METHODS: The optimal formulation was characterized by surface morphology, particle size, zeta potential, entrapment efficiency, drug loading and in vitro release behavior. In vivo studies were also conducted to evaluate the pharmacokinetic and pharmacodynamic results. RESULTS: In this study, TAC-SLNs ISG were prepared using homogenization followed by probe sonication method. The average particle size of TAC-SLNs ISG was observed to be 122.3±4.3 nm. Compared with TAC-SLNs, in situ gel did not increase particle size, and there was no significant difference between them. The results of viscosity measurement showed that TAC SLNs-ISG were typical of pseudo plastic systems and showed a marked increase in viscosity as temperature increased and ultimately formed a rigid gel (32°C). In vitro and in vivo studies illustrated the sustained release model of the drug from TAC-SLNs ISG. Animal model showed that TAC-SLNs ISG had good pharmacodynamics when compared with eye drops and SLNs. CONCLUSION: Our results demonstrated that TAC SLNs-ISG had the potential for being an ideal ocular drug delivery system.

Dupilumab-Associated Ocular Surface Disease: Clinical Characteristics, Treatment, and Follow-Up.

PURPOSE: A consecutive case series of patients with dupilumab-associated ocular surface disease (DAOSD) that describes common ocular symptoms and signs, proposes a symptom disease severity grading system, and describes treatment strategies of DAOSD patients was evaluated. METHODS: A retrospective chart review of patients with concomitant dupilumab-treated atopic dermatitis and DAOSD with ophthalmic evaluation between January 2014 and May 2019 was conducted. RESULTS: Twenty-nine patients (mean age 46 years, M/F: 12/17) with 57 ophthalmic exams were identified. The most common ocular symptoms included irritation/pain (n = 28, 97%), redness (n = 24, 83%), pruritus (n = 18, 62%), discharge (n = 18, 62%), and light sensitivity (n = 6, 21%). The most frequent signs included conjunctival injection (n = 18, 62%), superficial punctate keratitis (n = 16, 55%), and papillary reaction (n = 8, 28%). Topical corticosteroids (TCS) (n = 23, 79%), tacrolimus (n = 6, 21%), and artificial tears (n = 7, 24%) were the most commonly used therapies. Of those with follow-up documentation (n = 21), 20 were noted to have partial or complete response with TCS based on symptoms and reduction of signs. Using our proposed symptom-based grading scale, scaled 1 to 5 based on the presence of common symptoms listed above, 66% (n = 19) requiring topical immunomodulating therapy were found in the 'severe' group (≥3 symptoms) and 17% (n = 5) were found in the 'mild' group (≤2 symptoms). CONCLUSIONS: This study provides insight into the commonly presenting ocular signs and symptoms associated with DAOSD and highlights the efficacy of TCS and other immunomodulators in improving symptoms associated with DAOSD. Based on our findings, we propose a symptom-based grading system that can guide nonophthalmic physicians regarding ophthalmology consult.

Efficacy of Topical Ivermectin for the Treatment of Cutaneous and Ocular Rosacea.

Purpose: To investigate the efficacy of once-daily topical treatment of ocular and cutaneous rosacea with ivermectin 1% cream (Soolantra®, Galderma).Methods: Ten patients with rosacea were evaluated in a retrospective monocentric pilot study. Subjective symptoms (measured with the Ocular Surface Disease Index), skin findings, and ocular changes (blepharitis with telangiectasia and meibomian gland dysfunction, conjunctival redness, tear breakup time (TBUT), and fluorescein staining of the cornea) were evaluated. The follow-up was 8 months (range: 5-12 months).Results: The OSDI score decreased in the 8th week of treatment (38.5 ± 21.7, P = .004). After 16 weeks, blepharitis (P = .004), and conjunctival redness (P = .008) had strongly improved, and grade 1 was seen in all patients until the end of follow-up. Fluorescein staining of the cornea (P = .001) and TBUT (P = .016) showed significant improvement until the last follow-up visit. No side effects were observed. Conclusion: Topical ivermectin cream 1% given daily is an effective and safe therapy against rosacea.