Osmo Kari

Tear fluid levels of MMP-8 are elevated in ocular rosacea—treatment effect of oral doxycycline

BackgroundOcular rosacea (OcR) is a chronic inflammatory disease especially affecting lid margins. Previous studies have shown that it is accompanied by increased levels and activation of tear fluid gelatinases. Matrix metalloproteinase 8 (MMP-8; collagenase 2) levels and activation are commonly elevated in many inflammatory conditions. Therefore we studied here whether MMP-8 concentration and activation in tear fluid are increased also in OcR, and if an oral doxycycline regimen could rectify the situation.MethodsTear fluid samples were collected from 22 OcR patients and 22 healthy controls. The OcR patients were then treated with an oral doxycycline regimen for 8 weeks and tear fluid samples collected again after 4 and 8 weeks. Conjunctival brush cytology and patients’ subjective symptoms were scored. MMP-8 concentrations in the tear fluid were assessed by immunofluorometric assay and the molecular forms and isoenzyme expression of MMP-8 were studied by Western immunoblotting.ResultsThe mean MMP-8 concentration was statistically significantly higher in OcR (156.8±207.4xa0μg/ml) than in the normal subjects (53.5±66.7xa0μg/ml) (P=0.036), but decreased to 79.2±141.6xa0μg/l and 53.6±75.2xa0μg/l after 4 and 8 weeks doxycycline treatment, respectively. There was a statistically significant difference between the untreated OcR and the MMP-8 results after 4 or 8 weeks of oral doxycycline (P=0.041 and 0.069, respectively) and the OcR patients experienced statistically significant relief of their subjective symptoms (P=0.0001) after the doxycycline regimen. Both the normal and OcR tear fluid contained the larger, 60-80xa0kDa highly- glycosylated polymorphonuclear leukocyte-type MMP-8 isoform in Western immunoblotting, but not the 45–55xa0kDa less glycosylated mesenchymal-type isoform. MMP-8 activation was in practice present only in the OcR samples, and was inhibited by oral doxycycline.ConclusionsMMP-8 concentration and activation degree in tear fluid are increased in OcR, probably reflecting increased inflammatory activity. Doxycycline effectively reduces these pathologically excessive levels and activation of MMP-8, and relieves patients’ subjective symptoms.

IgE-mediated allergy to fungal allergens in Finland with special reference toAlternaria alternata and Cladosporium herbarum

BACKGROUNDnAlternaria alternata and Cladosporium herbarum are common fungi in outdoor environments, but their clinical significance has not been elucidated in Finland.nnnOBJECTIVEnTo evaluate the prevalence of IgE-mediated allergy and clinical outcomes caused by sensitization to fungal allergens in patients with suspected allergy.nnnMETHODSnSkin prick tests (SPTs) were performed with C. herbarum in 6,376 patients and also with A. alternata in 1,504 of these patients. SPTs were repeated in 40 patients who showed a positive reaction to either allergen using commercial and in-house extracts. The association of SPT with allergen-specific IgE antibodies in serum was evaluated. Seven patients also underwent a conjunctival challenge test with these fungal allergens.nnnRESULTSnThe prevalence of positive SPT results to A. alternata and C. herbarum was low (2.8% and 2.7%, respectively). Among the 40 patients, atopic eczema/dermatitis syndrome was found in 58%, asthma in 44%, and rhinitis in 31%. Most of the patients displayed SPT reactions also to several other fungal allergens, and 75% to 80% showed a positive SPT reaction to allergens of pet animals or pollens. Four patients had a positive reaction to A. alternata and 6 to C. herbarum in the conjunctival challenge test.nnnCONCLUSIONnIn the Finnish population with allergic symptoms, IgE-mediated sensitization to 2 common fungal allergens was rare and of minor clinical importance. SPT reactions to fungi are mostly observed in patients with multiple sensitivity to various allergens.

Diagnostics and New Developments in the Treatment of Ocular Allergies

About 30% of people suffer from allergic symptoms, and 40% to 80% of them have eye symptoms. Atopic conjunctivitis is divided into seasonal allergic conjunctivitis and perennial allergic conjunctivitis. The treatment of seasonal allergic conjunctivitis is simple: antihistamines, anti-inflammatory agents, or cromoglycate. Perennial allergic conjunctivitis needs longer therapy with mast cell stabilizers and sometimes local steroids. Atopic keratoconjunctivitis requires long-term treatment of the lid eczema and keratoconjunctivitis. Vernal keratoconjunctivitis mainly affects children and young people. It commonly calms down after puberty. It demands intensive therapy, often for many years, to avoid serious complicating corneal ulcers. Giant papillary conjunctivitis is a foreign body reaction in contact lens users or patients with sutures following ocular surgery. Nonallergic eosinophilic conjunctivitis affects mostly middle-aged and older women with eosinophilic conjunctivitis and dry eye. Contact allergic blepharoconjunctivitis is often caused by cosmetics and eye medication. Work-related ocular allergies should be considered as a cause of resistant ocular symptoms in workplaces.

Conjunctival eosinophilia in atopic and non-atopic external eye symptoms.

Abstract. We studied the occurrence in an ophthalmological office practice of conjunctival eosinophilia in 333 normal subjects (mean age 26 years) and in 152 atopic and 484 non‐atopic patients (mean age 40 years) with various external eye symptoms. Eosinophils were present in 131/636 patients (21%) and in 22/333 asymptomatic normal subjects (7%). In those patients with conjunctival eosinophilia, a history of some kind of atopic condition was obtained only in 53/131 (40%). When the patients were characterized according to the presence of both eosinophilia and atopy, eosinophilia without signs of atopy was observed in 7–15% in different diagnostic groups. Patients with conjunctivitis or blepharoconjunctivitis had a fourfold risk for eosinophilia compared to normal subjects (odds ratios 4.52 and 4.09, confidence intervals 2.02, 10.12 and 2.40, 6.99), when atopy, sex, age, time of the examination and presence of bacteria were included as potential confounders in the regression model. We conclude that a considerable portion of patients with external eye symptoms, and especially with various forms of conjunctivitis, show eosinophilic inflammation without any evidence of atopic background. They can be labelled as having ‘intrinsic’ eosinophilic conjunctivitis analogously to the classification used in patients with intrinsic rhinitis and asthma. The etiology of this common non‐atopic syndrom remains to be established.

Cellular characteristics of non-allergic eosinophilic conjunctivitis

Purpose:u2002 This study examines the histology of conjunctival biopsy samples from patients with persistent allergic eosinophilic conjunctivitis (AEC) or non‐allergic eosinophilic conjunctivitis (NAEC).

Complement Activation in Tear Fluid During Occupational Mold Challenge

Introduction: Indoor air quality is important in occupational healthcare when evaluating the health risks of a work environment. Components of the classical and alternative complement pathways are present in ocular tissues and fluids. The authors determined the levels of complement components C1INH, C3, and C4 in sera and C3a in tear fluids of normal persons and of those who were exposed to molds. Methods: Nine patients environmentally exposed to molds and 6 controls were selected from the Indoor Air Clinic of the Skin and Allergy Hospital. Tear fluid samples were collected from patients during the exposure to molds and after 2 weeks without mold exposure. At the same time, conjunctival cytology samples were obtained from each patient. Tear fluid was taken from 6 control subjects. All had negative skin prick tests to common environmental allergens. Results: In 4 patients subjective eye symptoms and tear fluid C3a levels decreased during 2 weeks of sick leave as did conjunctival eosinophils but other inflammatory cells were unchanged. Conclusion: Elevated complement C3a levels in tear fluids may be influenced by environmental exposure to molds. According to the authors clinical experience, eosinophilia is not a consistent finding in patients exposed to molds. However, molds may cause eosinophilic inflammation in the eye.

Clinical Measurement of Eosinophil Numbers in Eosinophilic Conjunctivitis

Cytological examination of conjunctival scrapings is a valuable technique in differentiating various types of conjunctivitis. Brush conjunctival cytology is easy to use, and it may show a rich cell sample also from the deeper conjunctival layers. It is atraumatic and suitable for tarsal conjunctival cytology. The Papanicolaou staining can be used for examination of epithelial cells and inflammatory cells. The semiquantitative counting method is rapid to use and gives some information about the severity and nature of the inflammation. Our modified method identifies the presence of eosinophils which are the hallmark both in allergic conjunctivitis and in non-allergic eosinophilic conjunctivitis (NAEC). NAEC is quite common affecting in most cases middle-aged or older people with the majority being women. NAEC is often connected with dry eye which in many cases can be seen in conjunctival cytology.