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BACKGROUND: Nonreversible hearing loss (HL) is the main sequelae of Susac syndrome (SuS). We aimed to identify risk factors for HL in SuS. METHODS: The CARESS study is a prospective national cohort study that started in December 2011, including all consecutive patients with SuS referred to the French reference center. The CARESS study was designed with a follow-up including fundoscopy, audiometry, and brain magnetic resonance imaging at 1, 3, 6, and 12 months after diagnosis and then annually for 5 years. The primary outcome was the occurrence at last follow-up of severe HL defined as the loss of 70 dB in at least one ear on audiometry or the need for hearing aids. RESULTS: Thirty-six patients (female 66.7%, median age 37.5 [range 24.5-42.5] years) included in the clinical study were analyzed for the primary outcome. Thirty-three patients (91.7%) had cochleovestibular involvement at SuS diagnosis including HL >20 dB in at least one ear in 25 cases. At diagnosis, 32 (88.9%), 11 (30.6%), and 7 (19.4%) patients had received steroids, intravenous immunoglobulin, and/or immunosuppressive (IS) drugs, respectively. After a median follow-up of 51.8 [range 29.2-77.6] months, 19 patients (52.8%) experienced severe HL that occurred a median of 13 [range 1.5-29.5] months after diagnosis. Multivariable analysis showed that the odds of severe HL were lower in patients who received IS drugs at diagnosis (OR 0.15, 95% CI 0.01-1.07, p = 0.058). CONCLUSIONS: Severe HL in SuS is associated with the absence of IS drugs given at diagnosis. Our findings support the systematic use of IS drugs in SuS.
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Pérdida Auditiva , Síndrome de Susac , Humanos , Femenino , Adulto Joven , Adulto , Síndrome de Susac/complicaciones , Síndrome de Susac/epidemiología , Síndrome de Susac/diagnóstico , Estudios de Cohortes , Estudios Prospectivos , Pérdida Auditiva/epidemiología , Pérdida Auditiva/etiología , Inmunosupresores , Factores de RiesgoRESUMEN
BACKGROUND: Although ocular adverse events are frequent in AD patients treated with dupilumab, their characterization remains limited due to a lack of prospective studies with a systematic ophthalmological examination. OBJECTIVE: To examine the incidence, characteristics and risk factors of dupilumab-induced ocular adverse events. METHODS: A prospective, multicenter, and real-life study in adult AD patients treated with dupilumab. RESULTS: At baseline, 27 out of 181 patients (14.9%) had conjunctivitis. At week 16 (W16), 25 out of 27 had improved their conjunctivitis and 2 remained stable and 34 out of 181 patients (18.7%) had dupilumab-induced blepharoconjunctivitis: either de novo (n = 32) or worsening of underlying blepharoconjunctivitis (n = 2). Most events (27/34; 79.4%) were moderate. A multivariate analysis showed that head and neck AD (OR = 7.254; 95%CI [1.938-30.07]; p = 0.004), erythroderma (OR = 5.635; 95%CI [1.635-21.50]; p = 0.007) and the presence of dry eye syndrome at baseline (OR = 3.51; 95%CI [3.158-13.90]; p = 0.031) were independent factors associated with dupilumab-induced blepharoconjunctivitis. LIMITATIONS: Our follow-up period was 16 weeks and some late-onset time effects may still occur. CONCLUSION: This study showed that most dupilumab-induced blepharoconjunctivitis cases are de novo. AD severity and conjunctivitis at baseline were not found to be associated risk factors in this study.
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Conjuntivitis , Dermatitis Atópica , Adulto , Humanos , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/diagnóstico , Estudios Prospectivos , Anticuerpos Monoclonales Humanizados/efectos adversos , Conjuntivitis/inducido químicamente , Conjuntivitis/epidemiología , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
Allergic asthma (AA) is a common asthma phenotype, and its diagnosis requires both the demonstration of IgE-sensitization to aeroallergens and the causative role of this sensitization as a major driver of asthma symptoms. Therefore, a bronchial allergen challenge (BAC) would be occasionally required to identify AA patients among atopic asthmatics. Nevertheless, BAC is usually considered a research tool only, with existing protocols being tailored to mild asthmatics and research needs (eg long washout period for inhaled corticosteroids). Consequently, existing BAC protocols are not designed to be performed in moderate-to-severe asthmatics or in clinical practice. The correct diagnosis of AA might help select patients for immunomodulatory therapies. Allergen sublingual immunotherapy is now registered and recommended for controlled or partially controlled patients with house dust mite-driven AA and with FEV1 ≥ 70%. Allergen avoidance is costly and difficult to implement for the management of AA, so the proper selection of patients is also beneficial. In this position paper, the EAACI Task Force proposes a methodology for clinical BAC that would need to be validated in future studies. The clinical implementation of BAC could ultimately translate into a better phenotyping of asthmatics in real life, and into a more accurate selection of patients for long-term and costly management pathways.
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Antígenos Dermatofagoides , Asma , Alérgenos/efectos adversos , Animales , Asma/inducido químicamente , Asma/diagnóstico , Asma/terapia , Pruebas de Provocación Bronquial/métodos , Humanos , InvestigaciónRESUMEN
BACKGROUND: Susac syndrome (SuS) is a rare occlusive microvessel disease of the brain, retina and inner ear. We aimed to determine whether brain lesion load at the acute phase predicts poor outcomes in SuS. METHODS: A prospective national cohort study was conducted from December 2012 to December 2019 in 20 centres in France. Patients included at the principal investigator's center with available brain magnetic resonance imaging (MRI) at diagnosis were analyzed. MRI was reviewed by an experienced neuroradiologist blinded to clinical status. The size, topography and number of hyperintense lesions on diffusion-weighted imaging (DWI-HL) were analyzed at diagnosis and during follow-up. Outcomes involved descriptive characteristics of patients at onset and last follow-up. RESULTS: Twenty-three patients (38.1 [18.8-56.5] years, 16 females) were prospectively studied. The triad (i.e., brain, eye and ear involvement) was complete at onset in 17 patients. Brain MRI was performed 1.1 (0.1-3.4) months after the first symptom. All patients had DWI-HL at the acute phase. Patients were separated into two groups according to the number of DWI-HL on first MRI: a first group of patients (n=15) displaying low brain lesion load (<50 DWI-HL per patient) and a second group of patients (n=8) displaying high brain lesion load (≥100 DWI-HL). The median follow-up was 57.9 (9.7-98) months. Clinical features, treatment, relapse rate, time to disappearance of DWI-HL, disabilities and professional outcome did not differ according to brain lesion load. CONCLUSION: Brain lesion load assessed by DWI at the acute phase is not associated with risks of disability in SuS.
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Síndrome de Susac , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Estudios de Cohortes , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Estudios Prospectivos , Síndrome de Susac/diagnóstico por imagen , Síndrome de Susac/patologíaRESUMEN
PURPOSE: Vernal keratoconjunctivitis (VKC) is a chronic, allergic, and potentially severe ocular disease affecting children and adolescents that can lead to impaired quality of life (QoL) and loss of vision. This study evaluated the efficacy and safety of an investigational therapy for severe VKC, cyclosporine A (CsA) cationic emulsion (CE), an oil-in-water emulsion with increased bioavailability versus conventional CsA formulations. DESIGN: The VErnal KeratoconjunctiviTIs Study (VEKTIS) is a phase 3, multicenter, double-masked, vehicle-controlled trial. PARTICIPANTS: Pediatric patients (4 to younger than 18 years) with active severe VKC (grade of 3 or 4 on the Bonini severity scale) and severe keratitis (corneal fluorescein staining [CFS] score of 4 or 5 on the modified Oxford scale). METHODS: One hundred sixty-nine patients were randomized to CsA CE 0.1% (1 mg/ml) eye drops 4 times daily (high dose), CsA CE twice daily (low dose) plus vehicle twice daily, or vehicle 4 times daily for 4 months. MAIN OUTCOME MEASURES: The primary end point was a mean composite score that reflected CFS, rescue medication use (dexamethasone 0.1% 4 times daily), and corneal ulceration over the 4 months. RESULTS: Differences in least-squares means versus vehicle for the primary end point were statistically significant for both the high-dose (0.76; P = 0.007) and the low-dose (0.67; P = 0.010) groups, with treatment effect mainly driven by CFS score. Significant differences were found between both active treatment groups and vehicle for use of rescue medication. Vernal keratoconjunctivitis symptoms and patient QoL (assessed by visual analog scale and the Quality of Life in Children with Vernal Keratoconjunctivitis questionnaire) improved in all 3 groups, with significant improvements for high-dose CsA CE versus vehicle. CONCLUSIONS: The efficacy of high-dose CsA CE in improving keratitis, symptoms, and QoL for those with severe VKC was demonstrated in these study patients. In addition, in this study cohort, CsA CE was well tolerated.
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Conjuntiva/efectos de los fármacos , Conjuntivitis Alérgica/tratamiento farmacológico , Ciclosporina/administración & dosificación , Calidad de Vida , Adolescente , Niño , Preescolar , Conjuntiva/patología , Conjuntivitis Alérgica/diagnóstico , Dexametasona/administración & dosificación , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Emulsiones/administración & dosificación , Femenino , Estudios de Seguimiento , Glucocorticoides/administración & dosificación , Humanos , Inmunosupresores/administración & dosificación , Masculino , Soluciones Oftálmicas , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
In P63-related ectodermal dysplasias (ED), the clinical characteristics focus on extra-cutaneous manifestations. The dermatological phenotype remains incompletely characterized. We report the dermatological features of 22 patients carrying a TP63 mutation. Erosions, erythroderma and pigmentary anomalies are characteristics of P63-related ED. Our data suggest that patients might be classified into two major P63-related disorders: AEC and EEC. RHS and ADULT represent mild AEC and EEC forms, respectively.
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Displasia Ectodérmica/genética , Factores de Transcripción/deficiencia , Proteínas Supresoras de Tumor/deficiencia , Adolescente , Adulto , Niño , Preescolar , Labio Leporino/genética , Fisura del Paladar/genética , Dermatitis Exfoliativa/genética , Dermatoglifia , Displasia Ectodérmica/diagnóstico , Anomalías del Ojo/genética , Enfermedades de los Párpados/congénito , Enfermedades de los Párpados/genética , Femenino , Cabello/anomalías , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Lactante , Masculino , Pezones/anomalías , Trastornos de la Pigmentación/genética , Policondritis Recurrente/genética , Evaluación de Síntomas , Anomalías Dentarias/genética , Factores de Transcripción/genética , Proteínas Supresoras de Tumor/genética , Anomalías Urogenitales/genética , Adulto JovenRESUMEN
The treatment and management of ocular allergy (OA) remain a major concern for different specialties, including allergists, ophthalmologists, primary care physicians, rhinologists, pediatricians, dermatologists, clinical immunologists, and pharmacists. We performed a systematic review of all relevant publications in MEDLINE, Scopus, and Web Science including systematic reviews and meta-analysis. Publications were considered relevant if they addressed treatments, or management strategies of OA. A further wider systematic literature search was performed if no evidence or good quality evidence was found. There are effective drugs for the treatment of OA; however, there is a lack an optimal treatment for the perennial and severe forms. Topical antihistamines, mast cell stabilizers, or double-action drugs are the first choice of treatment. All of them are effective in reducing signs and symptoms of OA. The safety and optimal dosing regimen of the most effective topical anti-inflammatory drugs, corticosteroids, are still a major concern. Topical calcineurin inhibitors may be used in steroid-dependent/resistant cases of severe allergic keratoconjunctivitis. Allergen-specific immunotherapy may be considered in cases of failure of first-line treatments or to modify the natural course of OA disease. Based on the current wealth of publications and on the collective experience, recommendations on management of OA have been proposed.
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Oftalmopatías/diagnóstico , Oftalmopatías/terapia , Hipersensibilidad/diagnóstico , Hipersensibilidad/terapia , Antiasmáticos/farmacología , Antiasmáticos/uso terapéutico , Terapia Combinada/efectos adversos , Terapia Combinada/métodos , Manejo de la Enfermedad , Susceptibilidad a Enfermedades/inmunología , Oftalmopatías/etiología , Humanos , Hipersensibilidad/etiología , Factores de Riesgo , Resultado del TratamientoAsunto(s)
Conjuntivitis Alérgica , Interleucina-5 , Humanos , Conjuntivitis Alérgica/tratamiento farmacológico , Conjuntivitis Alérgica/diagnóstico , Niño , Masculino , Femenino , Interleucina-5/antagonistas & inhibidores , Resultado del Tratamiento , Anticuerpos Monoclonales Humanizados/uso terapéutico , AdolescenteAsunto(s)
Corticoesteroides/uso terapéutico , Alergólogos , Inhibidores de la Calcineurina/uso terapéutico , Conjuntivitis Alérgica/tratamiento farmacológico , Infecciones por Coronavirus/epidemiología , Antagonistas de los Receptores Histamínicos/uso terapéutico , Oftalmólogos , Neumonía Viral/epidemiología , Pautas de la Práctica en Medicina , Administración Oftálmica , Administración Oral , Antialérgicos/uso terapéutico , Betacoronavirus , COVID-19 , Manejo de la Enfermedad , Humanos , Pandemias , Guías de Práctica Clínica como Asunto , Medición de Riesgo , SARS-CoV-2 , Estaciones del AñoRESUMEN
Mucous membrane pemphigoid encompasses a group of autoimmune bullous diseases with a similar phenotype characterized by subepithelial blisters, erosions, and scarring of mucous membranes, skin, or both. Although knowledge about autoimmune bullous disease is increasing, there is often a lack of clear definitions of disease, outcome measures, and therapeutic end points. With clearer definitions and outcome measures, it is possible to directly compare the results and data from various studies using meta-analyses. This consensus statement provides accurate and reproducible definitions for disease extent, activity, outcome measures, end points, and therapeutic response for mucous membrane pemphigoid and proposes a disease extent score, the Mucous Membrane Pemphigoid Disease Area Index.
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Penfigoide Benigno de la Membrana Mucosa/diagnóstico , Penfigoide Benigno de la Membrana Mucosa/terapia , Humanos , Guías de Práctica Clínica como Asunto , Registros , Resultado del TratamientoRESUMEN
PURPOSE: The aim of this study was to assess the immediate and delayed effects of tear punctal occlusion with punctal plugs on tear meniscus height (TMH) in severe aqueous-deficient dry eye (ADDE) disease. METHODS: Consecutive patients with severe ADDE related to Sjögren syndrome or ocular graft-versus-host disease underwent inferior and superior occlusion with punctal plugs. TMH was measured using the LacryDiag ocular surface analyzer platform before, 10 minutes, and at least 1 month after punctal occlusion. The corneal fluorescein staining (CFS) score was graded with the Oxford scale (from 0 to 5). Ocular symptoms were graded with a visual analog scale (from 1 to 10). RESULTS: We included 24 eyes of 24 patients (mean age 61 ± 9 years; mean follow-up 7 ± 5 months). The mean TMH was 0.19 ± 0.06 mm at baseline and increased significantly to 0.41 ± 0.13 mm (P < 0.001) and 0.46 ± 0.17 mm (P < 0.001) at 10 minutes after punctal plug insertion and at the end of follow-up, respectively. The median CFS score decreased from 3 ± 1 before plug insertion to 1 ± 2 at the end of follow-up (P < 0.001). Many patients (67%; n = 16) reported subjective improvement of symptoms. TMH was negatively correlated with the CFS score and visual analog scale score assessing symptoms. CONCLUSIONS: Upper and lower punctal occlusion increased TMH in patients with severe ADDE as soon as 10 minutes after plug insertion. TMH remained stable over time, which led to the relief of symptoms and reduced corneal staining.
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Vernal keratoconjunctivitis (VKC) is a chronic severe ocular allergic inflammation mostly observed in children and young adults. The ocular manifestations are the expression of multifactorial immune mechanisms that generally have a good prognosis, however long-term inflammation may remarkably reduce the visual function due to complications and poor therapeutic responses. Lack of responsiveness to a drug or treatment is relatively common in VKC and it is not only due to corneal involvement, which is considered the main sign of severity. The concept of refractory may be relative to multiple factors including the clinical condition, systemic co-morbidities, previous or concomitant drugs or regiments, compliance, patient's psychological condition or expectations, type of exposome and environmental conditions, doctor's experience and expectations, or timing of clinical evaluation. In this narrative review, the authors propose a definition of refractory VKC based on revised literature and clinical experience and consider potential new treatments for refractory patients and surgical management in case of complications.
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Background: Lichen planus pemphigoides (LPP), an association between lichen planus and bullous pemphigoid lesions, is a rare subepithelial autoimmune bullous disease. Mucous membrane involvement has been reported previously; however, it has never been specifically studied. Methods: We report on 12 cases of LPP with predominant or exclusive mucous membrane involvement. The diagnosis of LPP was based on the presence of lichenoid infiltrates in histology and immune deposits in the basement membrane zone in direct immunofluorescence and/or immunoelectron microscopy. Our systematic review of the literature, performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, highlights the clinical and immunological characteristics of LPP, with or without mucous membrane involvement. Results: Corticosteroids are the most frequently used treatment, with better outcomes in LPP with skin involvement alone than in that with mucous membrane involvement. Our results suggest that immunomodulators represent an alternative first-line treatment for patients with predominant mucous membrane involvement.
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Liquen Plano , Membrana Mucosa , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Corticoesteroides/uso terapéutico , Liquen Plano/tratamiento farmacológico , Liquen Plano/patología , Liquen Plano/inmunología , Liquen Plano/diagnóstico , Membrana Mucosa/patología , Membrana Mucosa/inmunología , Penfigoide Ampolloso/inmunología , Penfigoide Ampolloso/tratamiento farmacológico , Penfigoide Ampolloso/patología , Penfigoide Ampolloso/diagnósticoRESUMEN
Importance: Pediatric blepharokeratoconjunctivitis (PBKC) is a chronic, sight-threatening inflammatory ocular surface disease. Due to the lack of unified terminology and diagnostic criteria, nonspecific symptoms and signs, and the challenge of differentiation from similar ocular surface disorders, PBKC may be frequently unrecognized or diagnosed late. Objective: To establish a consensus on the nomenclature, definition, and diagnostic criteria of PBKC. Design, Setting, and Participants: This quality improvement study used expert panel and agreement applying the non-RAND modified Delphi method and open discussions to identify unified nomenclature, definition, and definitive diagnostic criteria for PBKC. The study was conducted between September 1, 2021, and August 14, 2022. Consensus activities were carried out through electronic surveys via email and online virtual meetings. Results: Of 16 expert international panelists (pediatric ophthalmologists or cornea and external diseases specialists) chosen by specific inclusion criteria, including their contribution to scientific leadership and research in PBKC, 14 (87.5%) participated in the consensus. The name proposed was "pediatric blepharokeratoconjunctivitis," and the agreed-on definition was "Pediatric blepharokeratoconjunctivitis is a frequently underdiagnosed, sight-threatening, chronic, and recurrent inflammatory eyelid margin disease associated with ocular surface involvement affecting children and adolescents. Its clinical spectrum includes chronic blepharitis, meibomitis, conjunctivitis, and corneal involvement ranging from superficial punctate keratitis to corneal infiltrates with vascularization and scarring." The diagnostic criteria included 1 or more suggestive symptoms accompanied by clinical signs from 3 anatomical regions: the eyelid margin, conjunctiva, and cornea. For PBKC suspect, the same criteria were included except for corneal involvement. Conclusions and Relevance: The agreements on the name, definition, and proposed diagnostic criteria of PBKC may help ophthalmologists avoid diagnostic confusion and recognize the disease early to establish adequate therapy and avoid sight-threatening complications. The diagnostic criteria rely on published evidence, analysis of simulated clinical cases, and the expert panel's clinical experience, requiring further validation with real patient data analysis.
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Blefaritis , Queratoconjuntivitis , Adolescente , Niño , Humanos , Queratoconjuntivitis/diagnóstico , Queratoconjuntivitis/complicaciones , Queratoconjuntivitis/tratamiento farmacológico , Blefaritis/diagnóstico , Blefaritis/tratamiento farmacológico , Párpados , Conjuntiva , Córnea , Enfermedad CrónicaRESUMEN
BACKGROUND/OBJECTIVES: Cyclosporine A cationic ophthalmic emulsion (CsA CE) was evaluated in paediatric and adolescent patients with vernal keratoconjunctivitis (VKC) in the NOVATIVE (NCT00328653) and VEKTIS (NCT01751126) trials. The similarity of these studies permitted pooled assessment of the effect of CsA CE on corneal damage as well as safety and tolerability. SUBJECTS/METHODS: Pooled outcomes were assessed for the first 28 days of treatment. In NOVATIVE, 118 patients were randomised to 4 times daily (QID) CsA CE 0.05%, 0.1%, or vehicle eye drops. In VEKTIS, 169 patients were randomised to CsA CE 0.1% QID or twice daily (BID) or vehicle. For these analyses, treatment groups comprised: (1) pooled CsA CE 0.1% QID arms (high-dose; n = 96); (2) pooled CsA CE 0.05% QID arm from NOVATIVE and CsA CE 0.1% BID data from VEKTIS (low-dose; n = 93); and (3) pooled vehicle QID arms (vehicle; n = 98). RESULTS: Changes from baseline to day 28 (mean ± standard deviation) in corneal fluorescein staining (CFS) scores for CsA CE high-dose, low-dose, and vehicle groups were -1.6 ± 1.47 (95% CI: -0.9, -0.1; p = 0.0124 vs vehicle), -1.7 ± 1.39 (95% CI: -1.1, -0.3; p = 0.0015 vs vehicle), and -1.0 ± 1.55, respectively. Adverse events (AEs) of any type were reported in 37.5%, 34.4%, and 37.8% of the high-dose, low-dose, and vehicle groups, respectively. Most were mild or moderate in severity. CONCLUSIONS: CsA CE significantly decreased corneal damage and was safe and well tolerated in patients with VKC. These data support CSA CE as a treatment option for the management of VKC.
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Conjuntivitis Alérgica , Lesiones de la Cornea , Síndromes de Ojo Seco , Adolescente , Humanos , Niño , Ciclosporina/uso terapéutico , Inmunosupresores/uso terapéutico , Conjuntivitis Alérgica/inducido químicamente , Conjuntivitis Alérgica/tratamiento farmacológico , Emulsiones/uso terapéutico , Resultado del Tratamiento , Síndromes de Ojo Seco/tratamiento farmacológico , Método Doble Ciego , Soluciones OftálmicasRESUMEN
PURPOSE: This study evaluates the efficacy and tolerability of cyclosporine A cationic emulsion (CsA-CE) in patients ≥4 years of age with moderate-to-severe vernal keratoconjunctivitis (VKC). METHODS: This Phase II/III, multicenter, double-masked, dose-ranging study had 2 treatment periods: a 4-week, randomized, vehicle-controlled period in which patients received 0.05% CsA-CE, 0.1% CsA-CE, or vehicle eye drops 4 times daily (period 1) and a 3-month period in which patients received 0.05% CsA-CE or 0.1% CsA-CE 2 or 4 times daily (period 2). The primary efficacy end point was rating of subjective symptoms at day 28 in period 1 per the BenEzra scale. FINDINGS: All groups showed improvement in subjective VKC symptoms at day 28, without a statistically significant difference between 0.05% or 0.1% CsA-CE vs vehicle. Both CsA-CE doses produced statistically significant improvements in corneal fluorescein staining scores vs vehicle at day 28; improvements were evident as early as week 1 and continued through month 1. Progressive reduction in subjective itching was evident after week 1 and continued through month 1. Treatment for an additional 3 months further improved subjective symptoms and objective signs of VKC in both CsA-CE groups. Improvement was most notable with 0.1% CsA-CE in patients with severe keratitis. The safety and tolerability profile is favorable. IMPLICATIONS: Although treatment with 0.05% and 0.1% CsA-CE showed clinical efficacy in alleviating keratitis and itching as early as week 1, with sustained benefit through 1 month, the primary efficacy end point was not met. These findings informed the design of the Phase III trial of 0.1% CsA-CE (Vernal Keratoconjunctivitis Study). CLINICALTRIALS: gov identifier: NCT00328653.
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Conjuntivitis Alérgica , Ciclosporina , Queratitis , Humanos , Conjuntivitis Alérgica/tratamiento farmacológico , Ciclosporina/uso terapéutico , Método Doble Ciego , Emulsiones/uso terapéutico , Queratitis/tratamiento farmacológico , Soluciones Oftálmicas/uso terapéutico , Prurito , Resultado del TratamientoRESUMEN
Vernal keratoconjunctivitis (VKC) is a severe ocular allergic disease characterized by chronic inflammation of the cornea and conjunctiva that may lead to loss of visual acuity and blindness. The disease occurs primarily in children and is more common in geographical regions characterized by warm temperatures and high humidity. The clinical manifestations of VKC, when inadequately treated, may lead to severe complications and corneal damage. The prevalence of allergen sensitization, specific serum immunoglobulin E (IgE), and specific tear IgE was reported in approximately 55%-60% of patients with VKC, confirming the involvement of IgE-mediated and non-IgE-mediated mechanisms in the pathophysiology of the condition. This article explores current knowledge on the immunological pathways of VKC and the role of the monoclonal anti-IgE antibody, omalizumab, in its management. The review evaluated the effects of omalizumab beyond the direct IgE-mediated reactions and discusses its potential as a therapeutic target for VKC. Multiple retrospective analyses, case series, and case reports have reported the effectiveness of omalizumab in the management of VKC. A summary of the clinical data from these studies revealed that in children with VKC omalizumab treatment was well tolerated with improvement or resolution of ocular symptoms, reduction in steroid use, and enhancement of quality of life. Omalizumab may serve as a promising treatment option for VKC due to its ability to target both IgE-mediated and non-IgE-mediated pathophysiological pathways. Larger, controlled clinical trials are needed to support these findings.
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Dry eye is a common disease that develops as a result of alteration of tear fluid, leading to osmotic stress and a perturbed epithelial barrier. Matrix metalloproteinase-9 (MMP-9) may be important in dry eye disease, as its genetic knockout conferred resistance to the epithelial disruption. We show that extracellular matrix metalloproteinase inducer (EMMPRIN; also termed CD147), an inducer of MMP expression, participates in the pathogenesis of dry eye through MMP-mediated cleavage of occludin, an important component of tight junctions. EMMPRIN expression was increased on the ocular surface of dry eye patients and correlated with those of MMP-9. High osmolarity in cell culture, mimicking dry eye conditions, increased both EMMPRIN and MMP-9 and resulted in the disruption of epithelial junctions through the cleavage of occludin. Exogenously added recombinant EMMPRIN had similar effects that were abrogated in the presence of the MMP inhibitor marimastat. Membrane occludin immunostaining was markedly increased in the apical corneal epithelium of both EMMPRIN and MMP-9 knock-out mice. Furthermore, an inverse correlation between EMMPRIN and occludin membrane staining was consistently observed both in vitro and in vivo as a function of corneal epithelial cells differentiation. These data suggest a possible role of EMMPRIN in regulating the amount of occludin at the cell surface in homeostasis beyond pathological situations such as dry eye disease, and EMMPRIN may be essential for the formation and maintenance of organized epithelial structure.
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Basigina/farmacología , Síndromes de Ojo Seco/etiología , Inhibidores de la Metaloproteinasa de la Matriz , Proteínas de la Membrana/efectos de los fármacos , Animales , Basigina/metabolismo , Diferenciación Celular , Síndromes de Ojo Seco/metabolismo , Epitelio Corneal/efectos de los fármacos , Homeostasis , Humanos , Ratones , Ratones Noqueados , Ocludina , Concentración Osmolar , Proteínas Recombinantes/farmacologíaRESUMEN
PURPOSE/AIM OF THE STUDY: To evaluate the improvement of ocular signs and symptoms in patients suffering from Demodex blepharitis using a combined treatment approach: use of eyelid wipes impregnated with 2.5% terpinen-4-ol (T4O) and 0.2% hyaluronic acid (HA) in the initial treatment period and investigation of maintenance of the treatment effect with the use of eyelid cleansing wipes. MATERIALS AND METHODS: Fifty patients with Demodex blepharitis were treated in the initial treatment period with sterile eyelid T4O impregnated wipes for 28 days. In the following four-week maintenance period, 82% patients received sterile eyelid maintenance wipes, while 16% continued treatment with T4O impregnated wipes. Global ocular discomfort, adapted TOSS, SANDE score, and individual blepharitis symptoms were assessed by patients at day 28 and day 56. Ocular signs were evaluated by the investigator at the study visits. Investigator's assessment of the overall treatment performance, patient's assessment of treatment satisfaction, and tolerability were evaluated with questionnaires. RESULTS: All global ocular discomfort symptoms and disease specific symptoms assessed by patients as well as all parameters evaluated by the investigators significantly improved in the initial treatment period with the application of eyelid wipes impregnated with 2.5% terpinen-4-ol until day 28. The therapeutic effect was maintained or even improved during the maintenance period under administration of mainly eyelid maintenance wipes until day 56. Both products were well tolerated. No adverse events and no clinically relevant changes in visual acuity were observed during both periods. CONCLUSIONS: Once daily treatment with T4O impregnated eyelid wipes in the initial treatment period significantly improved the ocular symptoms and signs and reduced the mite count in patients with Demodex blepharitis within four-weeks administration. Subsequent maintenance treatment with maintenance wipes for another 4 weeks preserved or further intensified the treatment success. The products were well tolerated and were convenient to use.
Asunto(s)
Blefaritis , Infecciones Parasitarias del Ojo , Pestañas , Infestaciones por Ácaros , Ácaros , Animales , Blefaritis/diagnóstico , Blefaritis/tratamiento farmacológico , Infecciones Parasitarias del Ojo/diagnóstico , Infecciones Parasitarias del Ojo/tratamiento farmacológico , Humanos , Infestaciones por Ácaros/diagnóstico , Infestaciones por Ácaros/tratamiento farmacológicoRESUMEN
PURPOSE: To describe clinical, meibographic, and interferometric signs in children with ocular rosacea. DESIGN: Prospective case-control study. METHODS: This single-center study at the Fondation Ophtalmologique Rothschild (Paris, France) included 42 children with ocular rosacea and 44 healthy volunteers (median ages of 10 and 11 years old, respectively) who had infrared meibography images of their lower lids and tear lipid layer thickness measurements taken with the LipiView II device (Tearscience). Clinical severity was graded on a 0 to 4 scale and compared with meiboscores (range 0-4) and tear film lipid layer thickness (range 0-100 nm). RESULTS: Seven patients presented with unilateral disease and 29 had an asymmetrical form. Twenty-four patients had associated cutaneous rosacea. Ten of 84 eyes presented with a loss of vision <20/25. The mean clinical severity grade was 2.5 ± 1.4. Meibographic abnormalities were significantly more important in children with ocular rosacea (mean meiboscore 2.1 ± 1.36) than in healthy volunteers (0.61 ± 0.78, P < .001). Clinical severity (r = 0.44, P < .001), duration of disease (r = 0.28, P = .011), and a history of chalazia (r = 0.30, P = .006) were correlated to meibographic severity. Mean lipid layer thickness was not significantly different between cases and controls (74.4 ± 18.7 nm and 76.6 ± 18 nm, respectively, P = .47). CONCLUSION: Meibomian structural alterations in children can be severe and are correlated to ocular rosacea severity. Meibography is an essential tool for diagnosis and follow-up, whereas the contribution of tear film interferometry is uncertain.