Atopic Keratoconjunctivitis: Pathophysiology, Clinic, and Potential New Therapeutic Concepts. / Atopische Keratokonjunktivitis: Pathophysiologie, Klinik und potenzielle neue Therapiekonzepte.

Atopic dermatitis (AD) is a chronic recurrent inflammatory skin disease with a bipolar age distribution in childhood, adolescence and middle adulthood. Up to 50% of AD patients show ocular involvement, which can be potentially sight threatening. Clinically, the majority of cases present with atopic blepharo(kerato)conjunctivitis or atopic keratoconjunctivitis (AKC); other clinical variants from this group of inflammatory ocular surface diseases are keratoconjunctivitis vernalis in childhood and adolescence and allergic conjunctivitis. In addition to the aforementioned blepharitis, keratitis and conjunctivitis, AD is also associated with eyelid involvement with subsequent eyelid malposition, limbal insufficiency with the development of pseudopterygia, (chronic) cicatrizing conjunctivitis with symblephara formation and fornix shortening, as well as ocular surface malignancies such as conjunctival intraepithelial neoplasia (CIN) and squamous cell carcinoma. In addition, an association with AD or AKC has been described for keratoconus. Whereas the therapy of AD in dermatology has made revolutionary advances in recent years through the use of biologicals, the primary use of these biologicals in ophthalmological complications is still very hesitant. Treatment here is often provided using topical steroids and calcineurin inhibitors. The following article summarises recent developments in basic and clinical dermatological research and discusses them in the context of current concepts for ophthalmological therapy.

Increasing Comorbidities Suggest that Atopic Dermatitis Is a Systemic Disorder.

Atopic dermatitis comorbidities extend well beyond the march to allergic conditions (food allergy, asthma, allergic rhinitis, allergic conjunctivitis, and eosinophilic esophagitis), suggesting both cutaneous and systemic immune activation. In reviewing atopic dermatitis comorbidities, Councilors of the International Eczema Council found a strong pattern of immune activation in peripheral blood and the propensity to both skin and systemic infections. Associations with cardiovascular, neuropsychiatric, and malignant diseases were increasingly reported, but confirmation of their link with atopic dermatitis requires longitudinal studies. Given the possibility of atopic dermatitis-related systemic immune activation, future investigations of new interventions should concurrently examine the impact on these comorbidities.

[Eye lid hygiene in chronic allergic blepharoconjunctivitis patients before laser refractive surgery]. / Gigiena vek v podgotovke k lazernoi refraktsionnoi khirurgii.

AIM: To evaluate the effectiveness of eyelid hygiene in patients with chronic allergic blepharoconjunctivitis (ABC) as a part of their preparation for laser refractive surgery. MATERIAL AND METHODS: The study involved 32 patients (12 males and 20 females aged 25-42 years) with refractive errors, namely, compound myopic astigmatism (23 patients) and hyperopic astigmatism (9 patients) suffering from chronic ABC and secondary dry eye syndrome (DES). All the patients initially received a standard treatment for ABC and DES, that is olopatodin hydrochloride instillations - 1 mg/ml 2 times daily, preservative-free hyaluronic acid preparation - 1 mg/ml 3 times daily, and polyacrylic acid and dexpanthenol gel at night for one month. The scheme, however, appeared not effective enough. Hence, the patients were prescribed eyelid hygiene (Blepharolotion or Blepharosalfetka plus Blepharogel-1 2 times daily) to relive meibomian gland dysfunction (MGD). They also underwent a conventional ophthalmic examination, allergy tests, evaluation of ABC and DES signs and symptoms, tear film break-up time test, Schirmer's test, meibomian glands evaluation, optical coherence tomography with meniscometry, xerosis index evaluation, and lissamine green staining for lid wiper epitheliopathy. RESULTS: At the beginning of the study signs and symptoms of MGD-associated DES were predominant in all patients. Chronic ABC signs were mild. In 2-3 months, meibomian gland function and tear film break-up time improved significantly in most patients, while xerosis index decreased and lid wiper epitheliopathy resolved. Laser refractive surgery (LASIK) was performed in 81.25% of patients, all of whom were satisfied with the results. CONCLUSION: Inclusion of eyelid hygiene into preoperative management of patients with chronic ABC and DES allows to achieve optimum conditions for laser refractive surgery in most cases.

The allergen Mus m 1.0102: Dissecting the relationship between molecular conformation and allergenic potency.

BACKGROUND: The species Mus musculus experiences an obligate proteinuria: predominant are the Major Urinary Proteins (MUPs), that, collectively known as the major mouse allergen Mus m 1, are among the most important aeroallergens for mouse allergic patients. The production of a soluble and stable hypoallergenic form of Mus m 1 is essential for the development of immunotherapeutic protocols to treat allergic symptoms. METHODS: We introduced the substitution C138S in recombinant Mus m 1.0102, an allergenic isoform of Mus m 1. Solubility, conformation, stability and ability to refold after chemical denaturation were investigated with dynamic light scattering, circular dichroism, fluorescence and NMR spectroscopy. An in vitro degranulation assay was used to evaluate the protein allergenic potential, and compare it with Mus m 1.0102 and with an hypoallergenic variant bearing the substitution Y120A. RESULTS: Mus m 1.0102-C138S retains a native-like fold revealing, however, local conformational alterations that influence some of its physical and allergenic properties: it is monodispersed, thermostable up to 56°C, able to reversibly unfold and it exhibits an enhanced allergenicity. CONCLUSIONS: The unique free thiol group affects the solution structural stability of the native protein. Because the mutant C138S does not aggregate over time it is a good lead protein to develop diagnostic and therapeutic applications. GENERAL SIGNIFICANCE: We elucidated the relationship between unfolding reversibility and sulphydryl reactivity. We ascribed the enhanced allergenicity of the mutant C138S to an increased accessibility of its allergenic determinants, an enticing feature to further investigate the structural elements of the allergen-IgE interface.

Efficacy of 2 months of allergen-specific immunotherapy with Bet v 1-derived contiguous overlapping peptides in patients with allergic rhinoconjunctivitis: Results of a phase IIb study.

BACKGROUND: An immunotherapy formulation consisting of 3 contiguous overlapping peptides (COPs) derived from Bet v 1, the major birch pollen allergen, showed good clinical tolerability in a previous phase I/IIa clinical trial. OBJECTIVES: We sought to evaluate the efficacy and safety of allergen-specific immunotherapy using 2 dose regimens of Bet v 1 COPs versus placebo in subjects with birch pollen-induced allergic rhinoconjunctivitis. METHODS: A randomized, double-blind, placebo-controlled phase IIb clinical trial was performed to assess the efficacy of Bet v 1 COP immunotherapy during the 2013 birch pollen season. Before the season, Bet v 1 COPs (50 and 100 µg in aluminum hydroxide) or placebo (saline and aluminum hydroxide) were administered as 5 subcutaneous injections to 239 adults with allergic rhinoconjunctivitis to birch pollen. Bet v 1 COPs at 25 or 50 µg were administered on day 1, and 50 or 100 µg was administered on days 8, 15, 29, and 57, respectively. Patients were monitored for adverse events during the treatment period and assessed for combined rhinoconjunctivitis symptom and medication scores, as well as quality of life. RESULTS: Rhinoconjunctivitis symptom and medication scores improved in both Bet v 1 COP-treated groups, reaching statistical significance over placebo in the 50-µg group (least squares mean, -0.23; 26% improvement; P = .015). Both active groups showed significant improvement in quality of life and nighttime nasal symptom scores, supporting the primary end point findings. Bet v 1 COP injections were well tolerated, with a higher frequency of systemic adverse events in the 100-µg group. CONCLUSION: Two months of preseasonal immunotherapy with 3 COPs derived from Bet v 1 at a 50-µg dose showed promising efficacy, small risk for systemic reactions, and immunomodulatory changes in this single-season, dose-finding, phase IIb trial in patients allergic to birch pollen.

Perspectivas no tratamento da alergia ocular: revisão das principais estratégias terapêuticas / Ocular allergy therapy perspectives: Review on the main therapeutic targets

As alergias oculares englobam uma série de doenças inflamatórias da superfície ocular, causadas por diferentes mecanismos de hipersensibilidade. Acometem aproximadamente 20% da população e podem ser classificadas em formas mediadas por hipersensibilidade tipo I (CAS, CAP), tipo I e IV (CCV, CCA) e tipo IV (BCC, CPG). As formas mais prevalentes são CAS e CAP. As formas crônicas (CCV, CCA) estão mais frequentemente relacionadas a complicações e comprometimento da função visual decorrentes do processo inflamatório e consequente remodelação da superfície ocular. Comorbidades como olho seco e ceratocone podem estar presentes. O tratamento envolve diagnóstico e afastamento dos fatores etiológicos envolvidos, uso de drogas anti-inflamatórias que atuem na ação de linfócitos Th2, eosinófilos, mastócitos e células dendríticas Avanços no conhecimento da ativação e tráfego de células do sistema imune têm sido promissores na perspectiva de novas abordagens terapêuticas.

Ocular allergies encompass a number of inflammatory diseases in the ocular surface which have different hypersensitivity mechanisms and occur in 20% of population. They can be classified as being type I hypersensitivity mediated (PAC, SAC), type I and IV (VKC, AKC) and type IV (BKC, GPC). The most prevalent forms are PAC and SAC. The chronic presentations are mostly related to visual impairment due to remodeling in the ocular surface caused by chronic inflammation. Dry eye disease and keratoconus are comorbidities observed in severe cases. The management is based on accurate diagnosis, avoidance of etiological factors and the rational use of drugs that control the inflammatory events caused by Th2 driven. The advances in knowledge on activation and traffic of immune cells are providing new drugs and many perspectives on different approaches.

Cockroach sensitization mitigates allergic rhinoconjunctivitis symptom severity in patients allergic to house dust mites and pollen.

BACKGROUND: Modifiers of symptom severity in patients with allergic rhinoconjunctivitis (AR) are imprecisely characterized. The hygiene hypothesis implicates childhood microbial exposure as a protective factor. Cockroach sensitization (C+) might be a proxy for microbial exposure. OBJECTIVE: We sought to determine whether C+ assayed by means of skin prick tests influenced AR symptom severity in controlled and natural settings. METHODS: Total symptom scores (TSSs) were recorded by 21 participants with house dust mite allergy (M+) in the natural setting and during repeated exposures of 3 hours per day to house dust mite allergen in an allergen challenge chamber (ACC). In M+ participants the peripheral blood and nasal cells were assayed for T-cell activation and transcriptomic profiles (by using RNA sequencing), respectively. Participants allergic to mountain cedar (n = 21), oak (n = 34), and ragweed (n = 23) recorded TSSs during separate out-of-season exposures to these pollens (any pollen sensitization [P+]) in the ACC; a subset recorded TSSs in the pollination seasons. RESULTS: The hierarchy of TSSs (highest to lowest) among M+ participants tracked the following skin prick test sensitization statuses: M+P+C- > M+P+C+ > M+P-C- > M+P-C+. In nasal cells and peripheral blood the immune/inflammatory responses were rapidly resolved in M+P+C+ compared with M+P+C- participants. Among those allergic to pollen, C+ was associated with a lower TSS during pollen challenges and the pollination season. After aggregated analysis of all 4 ACC studies, C+ status was associated with a 2.8-fold greater likelihood of a lower TSS compared with C- status (odds ratio, 2.78; 95% CI, 1.18-6.67; P = .02). CONCLUSIONS: C+ status is associated with mitigation of AR symptom severity in adults with AR.

Sibling number and prevalence of allergic disorders in pregnant Japanese women: baseline data from the Kyushu Okinawa Maternal and Child Health Study.

BACKGROUND: Although an inverse relationship between number of siblings and likelihood of allergic disorders has been shown in many epidemiological studies, the biological mechanism underlying this phenomenon has not yet been identified. There is no epidemiological research regarding the sibling effect on allergic disorders in Japanese adults. The current cross-sectional study examined the relationship between number of siblings and prevalence of allergic disorders among adult women in Japan. METHODS: Subjects were 1745 pregnant women. This study was based on questionnaire data. The definitions of wheeze and asthma were based on criteria from the European Community Respiratory Health Survey whereas those of eczema and rhinoconjunctivitis were based on criteria from the International Study of Asthma and Allergies in Childhood. Adjustment was made for age, region of residence, pack-years of smoking, secondhand smoke exposure at home and at work, family history of asthma, atopic eczema, and allergic rhinitis, household income, and education. RESULTS: The prevalence values of wheeze, asthma, eczema, and rhinoconjunctivitis in the past 12 months were 10.4%, 5.5%, 13.0%, and 25.9%, respectively. A significant inverse exposure-response relationship was observed between the number of older siblings and rhinoconjunctivitis, but not wheeze, asthma, or eczema (P for trend=0.03); however, the adjusted odds ratio (OR) for having 2 or more older siblings was not significant although the adjusted OR for having 1 older sibling was statistically significant (adjusted OR=0.71 [95% CI: 0.56-0.91]). Number of total siblings and number of younger siblings were not related to wheeze, asthma, eczema, or rhinoconjunctivitis. CONCLUSIONS: This study found a significant inverse relationship between the number of older siblings and the prevalence of rhinoconjunctivitis among pregnant Japanese women. Our findings are likely to support the intrauterine programming hypothesis; however, we could not rule out the hygiene hypothesis.

Allergic rhinoconjunctivitis doubles the risk for incident asthma--results from a population study in Helsinki, Finland.

OBJECTIVE: To examine the incidence of allergic rhinoconjunctivitis and asthma, and to assess allergic rhinoconjunctivitis as a risk factor for incident asthma, we performed a 11-year follow-up postal survey. METHODS: The original study population was a random population sample of 8000 inhabitants of Helsinki aged 20-69 years in 1996. Participants in the first postal questionnaire survey, 6062 subjects, were invited to this follow-up study, and provided 4302 (78%) answers out of 5484 traced subjects in 2007. RESULTS: Cumulative incidence of asthma from 1996 to 2007 was 4.0% corresponding to an annual incidence rate of 3.7/1000/year. After exclusion of those with asthma medication or physician-diagnosed chronic bronchitis or COPD at baseline in 1996, the cumulative incidence decreased to 3.5% (incidence rate 3.2/1000/year), and further to 2.7% (2.5/1000/year) when also those reporting recurrent wheeze or shortness of breath during the last year in 1996 were omitted from the population at risk. Remission of asthma occurred in 43 subjects and was 16.9% over 11 years. Cumulative 11-year incidence of allergic rhinoconjunctivitis was 16.9% corresponding to 16.8/1000/year, and cumulative remission was 18.1%. Incidence of allergic rhinoconjunctivitis was significantly lower among those who had lived in the countryside or on a farm during the first 5 years of life, but this was not true for asthma. In multivariate analysis, farm living during the first 5 years of life was protective for the development of allergic rhinoconjunctivitis, OR 0.75 (95%CI 0.57-0.99). Allergic rhinoconjunctivitis was a significant independent risk factor for incident asthma, OR 2.15 (95%CI 1.54-3.02). In the cohort, the prevalence of rhinoconjunctivitis increased from 38.0% in 1996 to 40.9% in 2007, physician-diagnosed asthma from 6.8% to 9.4%, while current smoking decreased from 31.3% to 23.3%. CONCLUSION: Incidence of allergic rhinoconjunctivitis was higher than in earlier studies, while asthma incidence remained on similar level, both being significantly higher in women. Allergic rhinoconjunctivitis doubled the risk for incident asthma.

Impact of ocular symptoms on quality of life (QoL), work productivity and resource utilisation in allergic rhinitis patients--an observational, cross sectional study in four countries in Europe.

OBJECTIVE: It is hypothesised that the presence of ocular, in addition to nasal, symptoms among patients with allergic rhinitis (AR) results in poorer quality of life, reduced work productivity and increased resource utilisation. This study investigated the impact on quality of life, burden of illness and healthcare resources among 1640 AR patients. METHODS: Data were drawn from an observational cross-sectional study of consulting patients undertaken in May/June 2008 in four European countries. Doctors provided records for the next four to five patients presenting with AR who filled out a self-completion survey which included the Work Productivity and Activity Impairment Allergic Specific Questionnaire (WPAI:AS), the Mini Rhinoconjunctivitis Quality of Life Questionnaire (RQOLQ) and the Pittsburgh Sleep Quality Index (PSQI). Propensity scoring allied to regression-type analysis was used to assess the extra burden associated with ocular symptoms utilising two comparison groups (patients with nasal-only symptoms versus those with nasal and ocular symptoms). The analysis controlled for differences between the groups on confounding variables age, gender, smoking status and co-morbidities. The analysis was conducted twice, once controlling for differences between the groups in nasal severity and once without, recognising that it is not clear whether or not increased nasal severity symptoms are naturally associated with ocular symptoms. The severity of ocular symptoms as opposed to their presence alone was also assessed on outcome measures using regression type methods. RESULTS: A total of 1009 patient records met the inclusion criteria, of whom 69% presented with both ocular and nasal symptoms. The results show that the presence of ocular symptoms reduces quality of life, reduces work productivity and increases resource utilisation irrespective of whether differences in severity of nasal symptoms are accounted for between the comparison groups. Patients with nasal and ocular symptoms require more healthcare consultations. All work-related domains were statistically different, with the presence of ocular symptoms associated with greater impact on work hours missed and impairment while working. For each of the above this was the case regardless of whether or not adjustment was made for nasal severity (both p < 0.05). Patients with nasal and ocular symptoms also record an additional half a day more time off work in the last 3 months as a result of AR (nasal severity unadjusted or adjusted, both p < 0.05). Clinically meaningful differences were found in overall quality of life score as represented by RQLQ, with a mean score increase of 0.6 (nasal severity unadjusted) and 0.5 (nasal severity adjusted) associated with the presence of ocular symptoms (both p < 0.05). With regard to sleep quality, the presence of ocular symptoms was associated with a mean increase in PSQI of 1 when no adjustment was made for nasal severity (p < 0.05). When nasal severity was adjusted for, no significant difference was observed. Similarly, for the number of prescribed medications, when no adjustment was made for nasal severity, patients with ocular symptoms were observed to receive a significantly higher number of AR drugs (+0.19, p < 0.05) whereas with nasal severity adjusted for the difference was +0.17 which was not significant. In addition, with the exception of the number of AR drugs prescribed, for all outcome variables, the severity of ocular symptoms, and not just their presence, had a detrimental impact on the outcome. LIMITATIONS: Since patients were recruited via the physician, the study aim was to represent the consulting population. In addition, it cannot be fully excluded that the likelihood for an individual patient to complete a questionnaire is influenced by differences in patient typology compared with those patients who chose not to complete. Given the geographical dispersion of the sample patients, it may be reasonable to assume possible differences in the intensity of the AR season based on latitude. CONCLUSION: The added presence of ocular symptoms in AR patients suffering with nasal symptoms deteriorates patients' quality of life, leads to greater lost productivity and places higher burden on resource utilisation. Studies are therefore needed to test whether treatment options that address ocular in addition to nasal symptoms will improve quality of life and reduce both direct and indirect resource use associated with AR.

Conjutivite alérgica / Allergic conjunctivitis

Neste artigo, os autores fazem uma revisão bibliográfica sobre a conjuntivite alérgica e seus subtipos, abordando suas manifestações clinicas, fisiopatologia, diagnóstico e manejo específicos.

Evaluation of lipid oxidative stress status and inflammation in atopic ocular surface disease.

BACKGROUND: Although the oxidative stress status in atopic skin disease has been reported to be elevated, there are still no studies related to the status of oxidative stress in atopic ocular surface disease. The purpose of this study was to evaluate the ocular surface lipid oxidative stress status and inflammation in atopic keratoconjunctivitis (AKC) patients and normal subjects. METHODS: Twenty eight eyes of 14 patients (9 males, 5 females) with AKC and 18 eyes of 9 age and sex matched (4 males and 5 females) normal healthy controls were examined in this prospective study. The severity of atopic dermatitis (AD) was scored by the SCORing Atopic Dermatitis (SCORAD) index. All subjects underwent Schirmer test, tear film break up time (BUT), fluorescein/Rose Bengal stainings, tear collection, and brush cytology from the upper palpebral conjunctiva. The brush cytology samples were stained with Diff-Quik for differentiation of inflammatory cells and immunohistochemistry (IHC) staining with HEL (hexanoyl-lysine) and 4-HNE (4-hydroxy-2-nonenal) to study lipid oxidation. HEL and cytokine (interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ)) levels were measured by enzyme-linked immunosorbent assay (ELISA) from tear samples of AKC patients and control subjects. Toluidine Blue and IHC staining with HEL, 4-HNE and cluster of differentiation 45 (CD45) were performed on papillary samples of AKC patients. This study was conducted in compliance with the "Declaration of Helsinki." RESULTS: The tear stability and vital staining scores were significantly worse in eyes of AKC patients (p<0.05) compared to the controls. Inflammatory cells and positively stained conjunctival epithelial cells for HEL and 4-HNE showed a significant elevation in brush cytology samples of AKC patients. Significantly higher levels of HEL and cytokines were detected in tears of AKC patients compared to controls. Papillary specimens also revealed many CD45 inflammatory cells as well as many cells positively stained with HEL and 4-HNE in IHC. A strong significant linear positive correlation between conjunctival inflammation and epithelial lipid oxidative stress status was observed. Conjunctival lipid oxidative stress also correlated strongly with tear HEL levels and epithelial damage scores. CONCLUSIONS: The ocular surface disease in AKC was characterized by marked tear instability, ocular surface epithelial damage, increase in inflammatory infiltrates and presence of increased lipid oxidation.

Alergia ocular / Ocular allergy

En el presente artículo revisaremos los aspectos más relevantes de la alergia ocular: su epidemiología, fisiopatología, cuadros clínicos y su terapéutica. Se encontrará una descripción más detallada de la fisiopatología ya que es, sin duda, la base del éxito terapéutico

In the present article we will review the most important aspectsof ocular allergy: its epidemiology, physiopathology, clinicalcharacteristics and treatment. A more detailed description ofthe physiopathology is addressed because is the basis for asuccessful treatment.

Risk factors for development of asthma in Thai adults in Phitsanulok: a university-based study.

Studies have shown that asthma in children is caused by environmental and genetic factors. In adult asthma, risk factors were less well recognized. Likewise, in Thailand, data in adult asthma is limited. This study aimed to evaluate risk factors, determine skin reactivities to allergens, and assess concomitant allergy among adult asthma in Phitsanulok, a major city in the lower northern Thailand. Five hundred and thirteen Naresuan University staff members and students completed 2 sets of questionnaires and underwent allergy skin prick tests. The first set of questionnaires was standardized Thai version of ISAAC questionnaire for identifying asthma, allergic rhinitis, and atopic eczema. The second set was modified from ISAAC phase II questionnaire to identify asthma risk factors. Fifty-eight subjects (11.6%) were identified as having physician's diagnosed asthma and 89 subjects (17.7%) wheezed in the past 12 months. Among 89 subjects, 14.4% wheezed more than once a month, 45.6% had wheezes interfering with sleep. Concomitant allergic rhinitis, rhinoconjunctivitis and atopic eczema among these asthma subjects were 82.5%, 67.9%, and 14.9%, respectively. Eighty seven point nine percent of asthmatic subjects had positive skin reactivities to at least one allergen. Two of the most common allergens were house dust mites and cockroaches. Maternal smoking during pregnancy, smoking among family members, and family history of allergy were statistically significant risks for developing asthma, while having a rice field around the residence represented a significant protective factor. In conclusion, high prevalence of asthma presented in Phitsanulok and many asthmatic subjects were partly controlled or uncontrolled. The environment such as a rice field could protect against asthma, however atopy and smoking exposure were significant risks for asthma development

Cytokine responses by conjunctival epithelial cells: an in vitro model of ocular inflammation.

OBJECTIVES: We examined the differential secretion of cytokines by a conjunctival epithelial cell line in response to proinflammatory cytokines to identify the potential contributions during ocular surface inflammation. METHODS: A conjunctival epithelial cell line was exposed to IFN-gamma, TNF-alpha, IL-4, or IL-13, and cytokine production was determined in supernatants at different times after exposure. Cell apoptosis was measured by flow cytometry. RESULTS: TNF-alpha induced the greatest effect on cytokine secretion, which was time-dependent. TNF-alpha-stimulated secretion of IL-12p40 was significantly increased by 30 min; GM-CSF, MCP-1, IL-6, IL-7, IL-8, and RANTES were significantly increased by 2 h, and IFN-gamma and IL-1alpha by 24 h. After 48 h, TNF-alpha also induced a significant increase in IL-1beta, IL-3, and IP-10 secretion. IFN-gamma significantly enhanced IP-10 and RANTES secretion after 48 h of exposure. Following IL-4 treatment there was a significant increase in eotaxin-1 after 24h, and IL-12p40 and IL-3 after 48 h. IL-13 significantly increased the secretion of eotaxin-1 after 24 h, and IL-8 after 48 h. CONCLUSION: Our results suggest that conjunctival epithelial cells are an important source of cytokines and chemokines that are regulated by proinflammatory cytokines and may play an important role in ocular surface inflammation.

Pathergy-like reaction following intravitreal triamcinolone acetonide injection in a patient with Behçet disease.

PURPOSE: To describe a patient with Behcet disease who developed a pathergy-like reaction following intravitreal triamcinolone acetonide injection. METHODS: Case report. RESULTS: A 30-year-old man with a history of Behçet disease received an intravitreal injection of triamcinolone acetonide for the treatment of cystoid macular edema. The following day, he was noted to have erythematous swelling around the injection site. The lesion disappeared spontaneously within 2 weeks. CONCLUSION: Pathergy-like reaction to minor trauma may develop not only on the skin but also in the mucous membranes such as conjunctiva in patients with Behçet disease.

CD27 and CD70 do not play a critical role in the development of experimental allergic conjunctivitis in mice.

CD27, which belongs to the TNF receptor family, is a costimulatory molecule that participates in T-cell activation. Unlike costimulatory molecules such as OX40 and 4-1BB, little is known about the role CD27 plays a role in the development of experimental diseases. We asked whether CD27 and its ligand CD70 participate in the development of experimental allergic conjunctivitis (EC) in BALB/c mice, which is generated by immunization with ragweed (RW) in alum and challenged 10 days later with RW in eye drops. The roles of CD27 and CD70 were tested by intraperitoneally injecting the mice with anti-CD27, anti-CD70 or a control Ab during the induction or effector phase. Twenty-four hours after challenge, the conjunctivas, blood and spleens were harvested for histological analysis, measuring Ig levels and cytokine analysis, respectively. Regardless of when the mice were treated, anti-CD27 or anti-CD70 Ab treatment did not significantly affect the severity of EC as evaluated by conjunctival eosinophil numbers. However, anti-CD27 or anti-CD70 Ab treatment during the induction phase did significantly modulate systemic humoral and cellular immune responses. In vitro treatment of RW-primed splenocytes with anti-CD27 or anti-CD70 Ab did not affect the EC-inducing capability of the splenocytes. Taken together, CD27 and CD70 do not play a critical role in the development of EC.

The differences of tear function and ocular surface findings in patients with atopic keratoconjunctivitis and vernal keratoconjunctivitis.

BACKGROUND: The pathogenesis of the ocular surface disease in atopic keratoconjunctivitis (AKC) and vernal keratoconjunctivitis (VKC) has not been fully understood. We tried to clarify the differences in the ocular surface status in patients with AKC, VKC, and healthy control subjects. METHODS: Twenty-four eyes of 12 AKC patients, 12 eyes of six VKC patients, and 20 eyes of 10 normal control subjects were studied. The subjects underwent corneal sensitivity measurements, Schirmer test, tear film break-up time (BUT), vital staining of the ocular surface, conjunctival impression and brush cytology. Impression cytology samples underwent periodic acid Schiff staining for goblet cell density, squamous metaplasia grading, and immunohistochemical staining for MUC1, 2, 4, and 5AC. Brush cytology specimens underwent staining for inflammatory cell counting and Real Time PCR for MUC1, 2, 4, and 5AC mRNA expression. RESULTS: The mean BUT, corneal sensitivity, and conjunctival goblet cell density values in AKC patients were significantly lower compared with VKC patients and control subjects. The squamous metaplasia grades in eyes with AKC were significantly higher compared to eyes with VKC and controls. The inflammatory cell response in brush cytology specimens was different between patients with AKC and VKC. Eyes with AKC showed significantly higher MUC1, 2 and 4 and lower MUC5AC mRNA expression compared to eyes with VKC. CONCLUSIONS: Differences of the infiltrates, higher level of tear instability, lower corneal sensitivity, up-regulation of MUC1, 2, and 4, and down regulation of MUC5AC were important differential features of the ocular surface disease in AKC compared with VKC.

Nerve growth factor has a modulatory role on human primary fibroblast cultures derived from vernal keratoconjunctivitis-affected conjunctiva.

PURPOSE: To evaluate the role of nerve growth factor (NGF) in remodeling processes of vernal keratoconjunctivitis (VKC). VKC is a chronic inflammatory disorder of the conjunctiva and is characterized by marked tissue remodeling. NGF, a pleiotrophic factor with documented profibrogenic activities, is produced by inflammatory and structural cells populating the VKC conjunctiva and is increased in the serum and tears of VKC patients. METHODS: Primary cultures of VKC-derived fibroblasts (VKC-FBs) were exposed to increasing NGF concentrations (1-500 ng/ml) to evaluate and compare the expression of alpha-smooth muscle actin (alphaSMA, a defining myofibroblast marker), collagens (types I and IV), and metalloproteinases and tissue inhibitors (MMP9/TIMP1, MMP2/TIMP2) at the biochemical as well as molecular levels. RESULTS: Endogenous NGF was increased in the VKC-FB supernatant, as compared to healthy-FB supernatant. VKC-FBs expressed alphaSMA and increased types I and IV collagens. VKC-FBs, and in particular all alphaSMA positive cells, expressed both trkA(NGFR) and p75(NTR), while healthy-FBs only expressed trkA(NGFR). Exogenous NGF did not change alphaSMA expression, while alphaSMA expression was enhanced by specific neutralization of p75(NTR). NGF (10 ng/ml) exposure significantly decreased type I collagen expression, without affecting type IV collagen, and increased MMP9mRNA and protein. CONCLUSIONS: The autocrine modulation of differentiation and response of VKC-FBs to NGF exposure with downregulation of type I collagen and upregulation of MMP9 expression supports a relevant role for NGF in tissue remodeling of VKC.