A 52 weeks dupilumab treatment for moderate to severe atopic dermatitis in Korea: long-term efficacy and safety in real world.

Previously, we have reported short term effectiveness and safety of dupilumab in Korea. In this study, we are trying to report the long-term effectiveness and safety of dupilumab in Korea. Ninety-nine patients with moderate to severe AD were analyzed. They were evaluated using Eczema Area and Severity Index (EASI), Numerical Rating Scale (NRS), Patient Oriented Eczema Measure (POEM), and Dermatology Quality of Life Index (DLQI) at baseline, week 16, 32 and 52. Efficacy outcomes showed higher improvement at 52 weeks compared with 16 weeks; high percentual reductions in EASI (88.1%), peak pruritus NRS (65.6%), POEM (67.2%), and DLQI (69.0%) compared to baseline. Proportion of patients achieving EASI 75 and 90 were 90.2% and 53.7%. POEM and DLQI had high correlation with clinical measured outcomes. In the analysis for the factors affecting achievement of EASI 90, female gender (OR 2.5), eosinophilia (OR 0.2) and elevated LDH (OR 0.07) were significantly associated. Most frequent adverse events included facial erythema (19.2%) and conjunctivitis (17.2%), which were mild/moderate and resolved during treatment. In conclusion, dupilumab treatment for 52 weeks in Korean patients with moderate-to-severe AD confirmed long term effectiveness and safety.

Type 1 Plasminogen Deficiency With Pulmonary Involvement: Novel Treatment and Novel Mutation.

Type 1 plasminogen deficiency is a rare genetic disorder. Type 1 plasminogen deficiency is characterized by fibrin-rich pseudomembrane formation on mucosal surfaces, particularly the conjunctiva. Tracheobronchial tree involvement is a less common reported manifestation of type 1 plasminogen deficiency. Pseudomembranes in the tracheobronchial tree may result in respiratory compromise and ultimately fail if not recognized and treated. Currently, there is no specific replacement therapy approved for the treatment of congenital plasminogen deficiency. In the present paper, we report that type 1 plasminogen deficiency with novel frameshift mutation and pulmonary involvement was treated initially with systemic fresh frozen plasma followed by pulmonary lavage with fresh frozen plasma and tissue plasminogen activator.

Treatment of ligneous conjunctivitis with heterologous serum.

Ligneous conjunctivitis is a rare form of chronic and recurrent bilateral conjunctivitis, in which thick membranes develop on the tarsal conjunctiva and on other mucosae. We report the case of a 55-year old female patient with bilateral ligneous conjunctivitis who was successfully treated with 50% heterologous serum. There was no recurrence or side effects after one-year follow-up. We suggest the use of 50% heterologous serum should be further studied to better determine its efficacy as a treatment option for ligneous conjunctivitis.

Treatment of ligneous conjunctivitis with heterologous serum / Tratamento de conjuntivite lenhosa com soro heterólogo

ABSTRACT Ligneous conjunctivitis is a rare form of chronic and recurrent bilateral conjunctivitis, in which thick membranes develop on the tarsal conjunctiva and on other mucosae. We report the case of a 55-year old female patient with bilateral ligneous conjunctivitis who was successfully treated with 50% heterologous serum. There was no recurrence or side effects after one-year follow-up. We suggest the use of 50% heterologous serum should be further studied to better determine its efficacy as a treatment option for ligneous conjunctivitis.

RESUMO A conjuntivite lenhosa é uma forma rara de conjuntivite bilateral crônica e recorrente, na qual há formação de membranas espessas na conjuntiva tarsal e em outras mucosas. Relatamos o caso de uma paciente de 55 anos com conjuntivite lenhosa bilateral, que obteve sucesso no tratamento com soro heterólogo em concentração de 50%. Não houve recorrência após um ano de seguimento e nem efeitos colaterais ao tratamento. Dessa forma, o uso de soro heterólogo a 50% poderia ser mais estudado para melhor avaliação de sua eficácia como opção de tratamento para a conjuntivite lenhosa.

Ligneous conjunctivitis due to plasminogen deficit: Diagnostic and therapeutic approach. With literature review.

Ligneous conjunctivitis is a rare and poorly understood pathology. Infections and repeated microtraumas are often involved in acute disease flare-ups. This masquerade may lead to misdiagnosis and delayed treatment. We report two cases of ligneous conjunctivitis, describing various presentations of its natural history and focusing on the treatment of this rare disease.

Evaluating the novel application of cyclosporine 0.1% in ocular surface disease.

INTRODUCTION: Ocular surface disease (OSD) is a highly prevalent symptomatic condition caused by dry eye disease (DED), intrinsic, environmental, or iatrogenic causes. It affects patient's visual function and quality of life. Its pathophysiology is centered on tear hyperosmolarity, inflammation, and epithelial damage. Current management is suboptimal and includes artificial tear supplementation and short-term use of topical steroids in severe cases. The recent approval of cyclosporine 0.1% has transformed management strategies of severe DED and moderate-to-severe OSD. Areas covered: This review summarizes existing information on the efficacy, safety, and tolerability of the new cyclosporine 0.1% formulation. Expert opinion: Topical cyclosporine A 0.1% represents a promising, novel medication for the management of DED, Meibomian gland dysfunction, and inflammatory OSD. It is primarily beneficial for those patients requiring topical immunomodulatory therapy. This topical formulation also has the potential to meaningfully improve the management of moderate-to-severe glaucoma therapy-related OSD. Currently there is limited published clinical data concerning the efficacy of topical cyclosporine. There are, however, theoretical advantages when comparing this cyclosporine formulation with other established commercial preparations. Future research is needed to delineate the precise role and value of this medication.

Seasonal Local Allergic Rhinitis in Areas With High Concentrations of Grass Pollen.

BACKGROUND: Local allergic rhinitis (LAR) is a phenotype of allergic rhinitis characterized by the presence of a localized immune response in the nasal mucosa of patients with negative skin prick test (SPT) results and undetectable serum specific IgE (sIgE). It unknown whether LAR is limited to areas with low or moderate aeroallergen exposure. OBJECTIVE: To explore the presence of LAR and the clinical and immunological characteristics of this entity in geographic areas with high grass pollen loads. METHODS: A cross-sectional observational study was carried out in 2 hospitals in central Spain (Madrid and Ciudad Real). Sixty-one patients with seasonal rhinitis and negative SPT results and undetectable serum sIgE were evaluated using a clinical questionnaire, determination of serum total IgE, and a nasal allergen provocation test (NAPT) with Phleum species. The response to NAPT was monitored using assessment of nasal symptoms, acoustic rhinometry, and determination of sIgE, tryptase, and eosinophil cationic protein in the nasal cavity. RESULTS: Seasonal LAR was detected in 37 patients (61%) using the techniques described above. Eleven percent of patients with LAR were adolescents or children, and 14% reported onset of rhinitis in childhood. Most patients reported persistent-moderate seasonal nasal symptoms, and 41% reported worsening of the disease during the last 2 years. Conjunctivitis was the most common comorbidity, affecting 95% of cases. CONCLUSIONS: LAR to grass pollen is relevant in patients with seasonal symptoms indicative of allergic rhinitis but with a negative skin test result who live in areas with high allergenic pollen loads. This entity should be included the differential diagnosis of rhinitis.

Beyond hemostasis: the challenge of treating plasminogen deficiency. A report of three cases.

Congenital plasminogen deficiency is a rare autosomal recessive disorder, characterized by chronic mucosal membranous lesions. Although the most common clinical manifestation is eye involvement as ligneous conjunctivitis, extra-ocular lesions affecting other mucosal surfaces indicates a systemic disease. In this report we describe two cases with atypical extra-ocular involvement that includes pericarditis and recurrent hematocolpos, and one with paradoxical correlation between ocular lesions and plasminogen levels. In ligneous conjunctivitis, although different treatment strategies have been tried with mild success, the only effective therapy is topical or systemic plasminogen concentrates that are not commercially available. Unfortunately there is not either effective management for cases with multisystemic disease. Hence, treatment for plasminogen deficiency is still a challenge and the variability of the clinical spectrum in this pathology makes necessary a multidisciplinary approach.

Successful treatment of ligneous conjunctivitis with topical fresh frozen plasma in an infant.

A 6-month-old female infant presented to our clinic with bilateral eyelid swelling, yellowish-white membranes under both lids, and mucoid ocular discharge. Her aunt had similar ocular problems that were undiagnosed. The conjunctival membranes were excised and histopathological investigation of these membranes showed ligneous conjunctivitis. Further, laboratory examination revealed plasminogen deficiency. A good response was observed to topical fresh frozen plasma (FFP) treatment without systemic therapy, and the membranes did not recur during the treatment. Topical FFP treatment may facilitate rapid rehabilitation and prevent recurrence in patients with ligneous conjunctivitis.

Successful treatment of ligneous conjunctivitis with topical fresh frozen plasma in an infant / Sucesso do tratamento da conjuntivite lenhosa com uso tópico de plasma fresco congelado em uma criança

ABSTRACTA 6-month-old female infant presented to our clinic with bilateral eyelid swelling, yellowish-white membranes under both lids, and mucoid ocular discharge. Her aunt had similar ocular problems that were undiagnosed. The conjunctival membranes were excised and histopathological investigation of these membranes showed ligneous conjunctivitis. Further, laboratory examination revealed plasminogen deficiency. A good response was observed to topical fresh frozen plasma (FFP) treatment without systemic therapy, and the membranes did not recur during the treatment. Topical FFP treatment may facilitate rapid rehabilitation and prevent recurrence in patients with ligneous conjunctivitis.

RESUMOUma criança feminina com seis meses de idade se apresentou à nossa clínica com edema palpebral bilateral, membranas brancas amareladas sob as pálpebras de ambos os olhos e descarga mucosa. Sua tia já havia apresentado problemas oculares semelhantes que não foram diagnosticados. As membranas conjuntivais foram excisadas e a investigação histopatológica das membranas demonstraram conjuntivite lenhosa. O diagnóstico de deficiência de plasminogênio foi obtido a partir de um exame laboratorial. Tratamento tópico com plasma fresco congelado (FFP) sem qualquer terapia sistêmica mostrou boa resposta. Não foram observadas recorrências das membranas. O tratamento tópico com FFP pode ajudar a reabilitação rápida e prevenir a recorrência em pacientes com conjuntivite lenhosa.

Prednisolone-loaded nanocapsules as ocular drug delivery system: development, in vitro drug release and eye toxicity.

OBJECTIVE: To develop non-toxic aqueous ocular drug delivery systems containing prednisolone by means of its nanoencapsulation. MATERIALS AND METHODS: Nanocapsules were prepared by interfacial deposition of preformed polymer [poly(ε-caprolactone) or Eudragit® RS100]. Particle size distribution was determined by laser diffractometry, photon correlation spectroscopy and nanoparticle tracking analysis. Ocular irritation and cytotoxicity were evaluated in vitro on the chorioallantoic membrane (CAM) and rabbit corneal epithelial cell line, respectively. RESULTS AND DISCUSSION: Nanocapsules showed mean particle sizes between 100 and 300 nm and prednisolone encapsulation efficiency of around 50%. Controlled release of prednisolone occurred for 5 h for both formulations according to the biexponential model. Both formulations were found to be non-irritant in the CAM test and non-cytotoxic toward rabbit corneal epithelial cells. CONCLUSIONS: Encapsulation of prednisolone in nanocapsules was reported for the first time, being suitable for producing eye drops for the treatment of ocular inflammatory and no eye toxicity was indicated.

Conjunctival inflammation in patients under topical glaucoma treatment with indication to surgery.

PURPOSE: To compare the frequency of conjunctival HLA-DR expression (a surrogate marker for inflammation) in eyes treated with topical prostaglandin analogues versus eyes treated with other topical antiglaucomatous drugs. METHODS: Patients diagnosed with primary open-angle glaucoma presenting indication for trabeculectomy were divided in groups according to the use or not of prostaglandin analogues. All subjects were treated with the maximum tolerated dose of antiglaucomatous drugs until the date of the surgery. At the beginning of the surgical procedure, a 5 x 5 mm biopsy of the bulbar conjunctiva was collected, incubated with monoclonal anti-HLA-DR antibody and processed for histological analysis. RESULTS: Of the 31 eyes included (31 patients), 25 were under topical prostaglandin analogues (Group 1) and six under other topical pharmacological agents (Group 2). Fourteen eyes of Group 1 (56%) and three of Group 2 (50 %) were positive for the inflammatory marker HLA-DR (P=1.0). The percentage of stained cells ranged from 15.49 to 48.09% (median: 27.61) in Group 1, and from 18.35 to 28 (median: 20.71) in Group 2, with no differences statistically significant (p=0.33). CONCLUSION: The use of prostaglandin analogues did not increase conjunctival expression of HLA-DR compared to other topical antiglaucomatous agents.

Conjunctival inflammation in patients under topical glaucoma treatment with indication to surgery / Inflamação conjuntival em pacientes em tratamento tópico para glaucoma com indicação de cirurgia

PURPOSE: To compare the frequency of conjunctival HLA-DR expression (a surrogate marker for inflammation) in eyes treated with topical prostaglandin analogues versus eyes treated with other topical antiglaucomatous drugs. METHODS: Patients diagnosed with primary open-angle glaucoma presenting indication for trabeculectomy were divided in groups according to the use or not of prostaglandin analogues. All subjects were treated with the maximum tolerated dose of antiglaucomatous drugs until the date of the surgery. At the beginning of the surgical procedure, a 5 x 5 mm biopsy of the bulbar conjunctiva was collected, incubated with monoclonal anti-HLA-DR antibody and processed for histological analysis. RESULTS: Of the 31 eyes included (31 patients), 25 were under topical prostaglandin analogues (Group 1) and six under other topical pharmacological agents (Group 2). Fourteen eyes of Group 1 (56%) and three of Group 2 (50 %) were positive for the inflammatory marker HLA-DR (P=1.0). The percentage of stained cells ranged from 15.49 to 48.09% (median: 27.61) in Group 1, and from 18.35 to 28 (median: 20.71) in Group 2, with no differences statistically significant (p=0.33). CONCLUSION: The use of prostaglandin analogues did not increase conjunctival expression of HLA-DR compared to other topical antiglaucomatous agents.

OBJETIVO: Comparar a frequência da expressão conjuntival de HLA-DR (marcador inflamatório) em olhos tratados com análogos de prostaglandinas de uso tópico com a frequência em olhos tratados com outros medicamentos. MÉTODOS: Pacientes com glaucoma primário de ângulo aberto apresentando indicação de trabeculectomia foram agrupados segundo o uso ou não de análogos de prostaglandinas. Todos os participantes foram tratados com medicação máxima tolerada até o momento da cirurgia. Ao início do procedimento cirúrgico, uma biópsia de 5 x 5 mm da conjuntiva bulbar foi coletada, incubada com anticorpo monoclonal anti-HLA-DR e processada para análise histológica RESULTADOS: Dentre os 31 olhos incluídos (31 pacientes), 25 estavam em uso de análogos de prostaglandinas (Grupo 1) e seis em uso de outros agentes antiglaucomatosos (Grupo 2). Quatorze olhos do Grupo 1 (56%) e três do Grupo 2 (50%) apresentaram positividade para o marcador HLA-DR (p=1,0). A porcentagem de células coradas variou de 15,49 a 48,09% (mediana: 27,61%) no Grupo 1 e de 18,35 a 28% (mediana: 20,71%) no Grupo 2, com diferenças não estatisticamente significativas (p=0,33). CONCLUSÃO: O uso de análogos de prostaglandinas não aumenta a expressão conjuntival de HLA-DR comparado com outros medicamentos tópicos para o tratamento de glaucoma.

[Intratarsal triamcinolone acetonide injection for treatment of refractory chronic tropical endemic limboconjunctivitis (TELC): experience at Aristide-Le-Dantec university hospital in Dakar]. / Injection intratarsale de triamcinolone acétonide dans le traitement des formes graves de la limboconjonctivite chronique endémique des tropiques (LCET) : expérience du CHU Aristide-Le-Dantec de Dakar.

PURPOSE: To evaluate the efficacy of intratarsal triamcinolone acetonide (TA) injection versus dexamethasone ointment in the treatment of refractory chronic tropical endemic limboconjunctivitis (TELC). PATIENTS AND METHODS: This one-year prospective study enrolled 20 patients with refractory TELC. One millilitre containing 40 mg TA was injected intratarsally on the most affected eye and dexamethasone ointment applied in the fellow eye. Efficacy was judged by clinical criteria according to a specially designed scale for the study. Statistical analysis was carried out using Fisher's chi(2) test and Student's t test with comparisons of the means of paired samples. RESULTS: In both cases, symptoms improved in all patients, as early as the following day or week, and clinical signs improved from the second week through the first month after injection, with an effective dose of 1 mL TA and three weeks of dexamethasone, with no recurrence at three months. Efficacy of the ointment alone was less (33.3-75%) than that with injection (90.9-100%) and could only be maintained after the first month by repeated application. CONCLUSION: Intratarsal TA injection, relatively easy and well-tolerated by patients, may be a better alternative to dexamethasone ointment in the treatment of refractory TELC.

Lichen planus and cicatricial conjunctivitis: disease course and response to therapy of 11 patients.

BACKGROUND: Lichen planus is an autoimmune, inflammatory dermatosis of unknown cause that affects the skin and mucous membranes. OBJECTIVE: The aim of this study was to report the clinical features and response to therapy in a series of patients with ocular lichen planus. METHODS: A retrospective chart review was performed to identify patients with ocular lichen planus. Information about clinical presentation, treatment, and therapeutic response was extracted from the medical records. RESULTS: Eleven patients with ocular lichen planus were identified. The diagnosis was confirmed histologically for 10 patients. Nine patients were women. The average time from onset of ocular symptoms to diagnosis was 4.1 years. Eight patients had mucous membrane involvement at other sites. Disease was well controlled in eight patients. CONCLUSION: Lichen planus should be considered in the differential diagnosis of cicatricial conjunctivitis, especially when severe lichen planus is noted at other sites.

Experimental infection of goats with an unusual strain of Mycoplasma mycoides subsp. capri isolated in Jordan.

Goats were infected experimentally with a mycoplasma (the "Irbid" strain) isolated previously from a goat with contagious agalactia in northern Jordan. The strain was unusual in that, although it had been identified by molecular methods as Mycoplasma mycoides subsp. mycoides LC/Mycoplasma mycoides subsp. capri, it showed no inhibition of growth by any of the hyperimmune rabbit antisera conventionally used to speciate members of the Mycoplasma mycoides cluster. Animals were infected either intratracheally or by aerosol and placed "in-contact" with other goats. After 2 weeks, those infected intratracheally became febrile, showing a nasal discharge and slight conjunctivitis, followed a week later by respiratory distress and polyarthritis; lesions seen at necropsy included coagulative necrotic pneumonia, fibrinous pleurisy with pleural exudate, and inflammatory exudates, necrosis and fibrosis in the joints. Animals infected by aerosol showed much milder clinical signs, including nasal discharge and occasional swollen joints. In the "in-contact" goats, seroconversion was first seen after 7 weeks, accompanied by coughing and laboured respiration; lesions in this group consisted of fibrinous pneumonia with focal areas of necrosis and abundant pleural exudate.

Actinic conjunctivitis in children: Clinical features, relation to sun exposure, and proposed staging and treatment.

BACKGROUND: Actinic conjunctivitis is an ocular photosensitivity reaction found mainly in children in certain populations in the Andean regions of South America, Mexico, and in the southwestern United States. Its clinical features, treatment, and possible relation to duration of sun exposure have not been fully described in the ophthalmologic literature. METHODS: A 20-member ophthalmic team traveled to an Andean region of Ecuador to provide ophthalmic care to children. All children with conjunctivitis were examined. A novel 3-stage classification of actinic conjunctivitis, devised by one of the authors, was used to stage the disease. The parents of each child with actinic conjunctivitis were asked how much time the child spent outside. Histopathological evaluations were performed on children who underwent surgery. RESULTS: A total of 206 children were examined, of whom 36 had changes consistent with actinic conjunctivitis. Stage 1 disease was diagnosed in 17 children, stage 2 in 9, and stage 3 in 10 in the most severely affected eye. The amount of time the child spent outside correlated with disease severity (r = 0.77, p < 0.001). Histopathologic samples showed an intense inflammatory response with hyperplasia of the vascular endothelium, pigmentary migration, and occasional eosinophilia. CONCLUSIONS: Actinic conjunctivitis is prevalent among children of the highlands of Ecuador. Although it has an allergic component, our data suggest that the severity of the disease is significantly associated with sun exposure. The finding that the lesions are found only in the exposed conjunctiva supports the hypothesis that UV exposure is the main cause of the disease.

Ligneous conjunctivitis secondary to a congenital plasminogen deficiency in a dog.

CASE DESCRIPTION: A 7-month-old 16.6-kg (36.5-lb) sexually intact female Golden Retriever was evaluated because of progressive severe bilateral membranous conjunctivitis, oral lesions, nasal discharge, and cough. CLINICAL FINDINGS: Histologic examination of conjunctival biopsy specimens revealed findings consistent with ligneous conjunctivitis. Circulating plasminogen activity was repeatedly low, and congenital plasminogen deficiency was identified as the underlying cause of the ocular, oral, and respiratory lesions. TREATMENT AND OUTCOME: Topical and subconjunctival administrations of fresh frozen plasma (FFP), topical administration of cyclosporine, and oral administration of azathioprine had no effect on the conjunctival membranes. Excision of the membranes followed by intensive treatment with topical applications of heparin, tissue plasminogen activator, corticosteroid, and FFP and IV administration of FFP prevented membrane regrowth. Intravenous administration of FFP increased plasma plasminogen activity to within reference limits, improved respiratory and oral lesions, and resulted in weight gain; discontinuation of this treatment resulted in weight loss, signs of depression, and worsening of lesions. After euthanasia because of disease progression, necropsy findings included mild hydrocephalus; multifocal intestinal hemorrhages; and fibrinous plaques in the oral cavity, nasopharynx, trachea, esophagus, and pericardium. Microscopically, the plaques were composed of fibrin and poorly organized granulation tissue. Fibrin thrombi were present within vessels in the lungs, oral cavity, and trachea. CLINICAL RELEVANCE: In dogs, congenital plasminogen deficiency can occur and may be the underlying cause of ligneous conjunctivitis. A combination of surgical and medical treatments may improve conjunctival membranes, and administration of FFP IV appears to be effective in treating nonocular signs of plasminogen deficiency.