[Update on Current Care Guideline: Glaucoma]. / Avokulmaglaukooma.

The up-date of the Finnish Current Care Guideline for glaucoma is based primarily on systematic reviews searched up by March 2014. The recommendations are presented in nine tables, which are based on 95 graded statements with evidence summaries. The online availability (www.kaypahoito.fi) of the English translation of guideline and evidence summaries enables the verification of the evidence and recommendations. Ten external stakeholders gave a mean value of 1.8 (range of 1 = completely agree to 4 = completely disagree) for the structured questions (e.g. definitions, goals, questions, target users) and judged the evidence and the recommendations.

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.

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.

[Treatment of eye allergies]. / Allergisten silmäoireiden hoito.

Seasonal atopic conjunctivitis is treated with antihistamines, cromoglycate and short courses of corticosteroids, in severe cases with subcutaneous or sublingual immunotherapy. Chronic conjunctivitis requires year-round treatment with mast cell stabilizers, antihistamines or topical corticosteroids. Long-term treatment of atopic blepharoconjunctivitis consists of tacrolimus or pimecrolimus cream. For atopic keratoconjunctivitis corticosteroid and, if necessary, cyclosporine eye drops are needed. First-line therapy of vernal conjunctivitis involves mast cell stabilizers and, if necessary, corticosteroid eye drops. Treatment of non-allergic eosinophilic conjunctivitis involves mast cell stabilizers, corticosteroid and, if necessary, cyclosporine eye drops.

[Non-allergic eosinophilic conjunctivitis]. / Atooppisesta allergiasta riippumaton eosinofiilinen sidekalvotulehdus.

Non-allergic eosinophilic conjunctivitis (NAEC) is a fairly common but poorly known ailment, often associated with dry eye syndrome. The majority of patients are middle-aged or elderly women. The symptoms are similar to those in allergic conjunctivitis, whereas atopic allergy cannot be found. Eosinophilic inflammation is first eased by instillation of glucocorticoid antibiotic eye drops, and the treatment is usually continued with mast cell stabilizer and moistening drops for a long time. Short courses of glucocorticoid drops and, sometimes, immunosuppressive medication of longer duration are required as additional therapies.

Cellular characteristics of non-allergic eosinophilic conjunctivitis.

PURPOSE: This study examines the histology of conjunctival biopsy samples from patients with persistent allergic eosinophilic conjunctivitis (AEC) or non-allergic eosinophilic conjunctivitis (NAEC). METHODS: Fourteen patients with conjunctivitis and eosinophilia in cytology samples were included in the study. Seven had positive skin-prick tests (the AEC group) and seven had negative skin-prick tests (the NAEC group). Eight asymptomatic subjects with negative skin-prick tests served as a control group. In conjunctival biopsies eosinophils were identified with monoclonal antibodies. Mast cells were identified by specific immunostaining and tryptase-positive granules were counted around them. The percentage of degranulated mast cells was used as a measure of cell activation. Eosinophil and goblet cell numbers were counted, epithelial thickness was measured, and the symptoms were characterized and graded. RESULTS: The numbers of eosinophils in biopsies were higher in patients with AEC than in healthy controls (p = 0.010). The proportion of activated mast cells tended to be higher in AEC patients (65%) than in NAEC patients (48%) or control subjects (40%). Patients with AEC had more goblet cells than control subjects (p = 0.049) and their epithelial layer was thicker (p = 0.054). Patients with AEC had more severe symptoms than control subjects (p = 0.0005), whereas the symptoms of NAEC patients did not differ statistically from those of controls (p = 0.065). CONCLUSIONS: Patients with NAEC were characterized by mild eosinophilic inflammation and only minor structural conjunctival changes. The condition seems to run a relatively mild but persistent clinical course.

Updates in the treatment of ocular allergies.

Allergic diseases have greatly increased in industrialized countries. About 30% of people suffer from allergic symptoms and 40%-80% of them have symptoms in the eyes. Atopic conjunctivitis can be divided into seasonal allergic conjunctivitis (SAC) and perennial allergic conjunctivitis (PAC). The treatment of SAC is simple; antihistamines, anti-inflammatory agents, or chromoglycate. In severe cases of SAC, subcutaneous or sublingual immunotherapy is helpful. PAC needs longer therapy, often year round, with mast cell stabilizers, antihistamines, and sometimes local steroids. Atopic keratoconjunctivitis is a more severe disease showing chronic blepharitis often connected with severe keratitis. It needs, in many cases, continuous treatment of the lid eczema and keratoconjunctivitis. Blepharitis is treated with tacrolimus or pimecrolimus ointment. Conjunctivitis additionally needs corticosteroids and, if needed, cyclosporine A (CsA) drops are administered for longer periods. Basic conjunctival treatment is with mast cell-stabilizing agents and in addition, antihistamines are administered. Vernal keratoconjunctivitis is another chronic and serious allergic disease that mainly affects children and young people. It is a long-lasting disease which commonly subsides in puberty. It demands intensive therapy often for many years to avoid serious complicating corneal ulcers. Treatment is mast cell-stabilizing drops and additionally antihistamines. In relapses, corticosteroids are needed. When the use of corticosteroids is continuous, CsA drops should be used, and in relapses, corticosteroids should be used additionally. Nonallergic eosinophilic conjunctivitis (NAEC) is a less known, but rather common, ocular disease. It affects mostly middle-aged and older women. The eye symptoms of NAEC are largely similar to those seen in chronic allergic conjunctivitis. Basic therapy is mast cell-stabilizing drops. Eosinophilic inflammation needs additional corticosteroids. In severe cases, CsA drops are recommended. Antihistamines should be avoided. It is important to recognize the different forms of allergic ocular diseases and to start the treatment early and intensively enough to avoid chronicity of the disease and accompanying tissue destruction.

[Dry eye--an increasing ailment]. / Kuivasilmäisyys--lisääntyvä vaiva.

The dry eye syndrome is probably the most common eye symptom. Its severity varies form mild to the incapacitating and difficult Sjögren's syndrome. Factors increasing the symptom are our northern environment, mechanical ventilation, ageing population, medicaments causing eye dryness, and various diseases. Refractive surgery of the eye may cause or exacerbate the dry eye syndrome. The majority of patients are women over 40 years. The disease is often accompanied by mild eosinophilic conjunctivitis without allergy, which must be taken into account in the treatment.

Tear fluid concentration of mmp-8 is elevated in non-allergic eosinophilic conjunctivitis and correlates with conjunctival inflammatory cell infiltration.

BACKGROUND: To investigate tear fluid concentration of matrix metalloproteinase 8 (MMP-8) and its relation to conjunctival inflammatory cell infiltration in persistent non-allergic eosinophilic conjunctivitis (NAEC). METHODS: Two groups were included: 26 consecutive adult patients with NAEC (conjunctival eosinophils at least 1+ [1-10 eosinophils/slide], skin prick test [SPT] to common allergens negative), and 26 asymptomatic adult persons (no conjunctival eosinophils, SPT negative). MMP-8 tear fluid concentrations were determined by immunofluorometric assay, and conjunctival brush cytology samples from NAEC patients were used for MMP-8 immunocytochemistry. Gelatin zymography was used to illustrate proteolytic activity within the tear fluid samples. RESULTS: The mean MMP-8 concentration was significantly higher among NAEC patients (214.3 +/- 327.7 microg/l) than among healthy persons (50.4 +/- 62.3 microg/l, P < 0.0001). In the NAEC patients, tear fluid MMP-8 correlated with the numbers of conjunctival neutrophils (r = 0.66, P = 0.0002) as well as with goblet cells and columnar epithelial cells (r = 0.54 for both, P = 0.045), but not with the lymphocyte numbers (r = -0.36, P = 0.0741). By immunocytology, MMP-8 protein could also be detected in vivo in the inflammatory cell population within the conjunctiva. Zymography revealed that proteolysis was significantly higher in the NAEC group, and activated enzymes were practically found only in the NAEC group. CONCLUSIONS: The results showed that NAEC is an inflammatory condition characterized by increased tear fluid MMP-8 levels, probably derived from both inflammatory and structural conjunctival cells. The increased proteolytic activity in NAEC patients may indicate risk of conjunctival structural changes (remodeling).

Elevated expression and activation of matrix metalloproteinase 8 in tear fluid in atopic blepharoconjunctivitis.

PURPOSE: Matrix metalloproteinase 8 (MMP-8) is an effective collagenolytic enzyme that is associated with many ocular inflammatory diseases, such as uveitis, keratitis, and ocular rosacea. We studied the tear fluid concentration and activation of MMP-8 in atopic blepharoconjunctivitis (ABC) and the presence of the enzyme in conjunctival inflammatory cells in vivo. METHODS: Tear fluid samples were collected from 26 patients with ABC and 26 healthy controls. MMP-8 concentrations were determined by immunofluorometric assay, and its molecular forms and degrees of activation were studied by Western blotting. Conjunctival brush cytology samples from patients with ABC were used for MMP-8 immunocytochemistry. RESULTS: : The mean MMP-8 concentration was statistically significantly higher among the patients with ABC (545.6 +/- 879.3 microg/L) than among the healthy controls (50.4 +/- 62.3 microg/L, P = 0.0001). There was a statistically significant correlation between neutrophils detected in brush cytology and tear fluid MMP-8 (P = 0.032, r = 0.47). Both the control and ABC tear fluid samples contained predominantly the larger (60-80 kDa), highly glycosylated polymorphonuclear leukocyte-type MMP-8 isoform, as identified by Western blotting, but neither was found to contain the mesenchymal-type isoform. The active enzyme was in practice present only in the ABC samples. Immunostainings show the MMP-8 protein to be present in all the main inflammatory cell types within the conjunctiva. CONCLUSIONS: : A higher mean concentration and activation of MMP-8 is present in tear fluid in ABC. This finding probably reflects persistent inflammatory and collagenolytic activity associated with the disease.

Effect of 0.03% tacrolimus ointment on conjunctival cytology in patients with severe atopic blepharoconjunctivitis: a retrospective study.

PURPOSE: To evaluate the efficacy and effect of tacrolimus ointment on conjunctival cytology in patients with atopic blepharoconjunctivitis or keratoconjunctivitis. METHODS: Ten patients with severe atopic blepharoconjunctivitis treated with 0.03% tacrolimus ointment once daily as an intermittent treatment were analysed retrospectively. The main outcome measures were clinical response to topical tacrolimus, adverse events and changes in the inflammatory cells obtained from conjunctival brush samples. RESULTS: Marked clinical responses in blepharitis and conjunctivitis symptoms were seen after a mean follow-up time of 6 weeks. Clinical scores decreased by 67% in blepharitis and 74% in conjunctivitis symptoms. No severe adverse events or signs of immunosuppression such as herpes simplex infections occurred. No significant changes occurred in visual acuity, refraction, anterior chamber, retina or intraocular pressure. Median decreases were 85% (p =0.01) in conjunctival eosinophils, 50% (p = 0.01) in neutrophils and 58% (p = 0.02) in lymphocytes. CONCLUSIONS: Tacrolimus ointment is potentially a safe and effective treatment for atopic blepharoconjunctivitis. Regular treatment of the eyelids once daily may also lead to clinical and cytological improvement of the conjunctivitis.

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

BACKGROUND: Ocular 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. METHODS: Tear 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. RESULTS: The mean MMP-8 concentration was statistically significantly higher in OcR (156.8+/-207.4 mug/ml) than in the normal subjects (53.5+/-66.7 mug/ml) (P=0.036), but decreased to 79.2+/-141.6 mug/l and 53.6+/-75.2 mug/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, 60-80 kDa highly- glycosylated polymorphonuclear leukocyte-type MMP-8 isoform in Western immunoblotting, but not the 45-55 kDa less glycosylated mesenchymal-type isoform. MMP-8 activation was in practice present only in the OcR samples, and was inhibited by oral doxycycline. CONCLUSIONS: MMP-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.

Group IIA phospholipase A(2) concentration of tears in patients with ocular rosacea.

PURPOSE: To determine the concentration of group IIA phospholipase A(2) (GIIAPLA(2)) in tears of patients with ocular rosacea, and to compare it with GIIAPLA(2) concentration in tears of age-matched healthy controls. METHODS: The GIIAPLA(2) concentration in tears was measured with a time-resolved fluoroimmunoassay in 21 patients with ocular rosacea (mean age 55.6+/-9.2 years) and in 21 normal subjects (mean age 53.4+/-8.2 years). Conjunctival brush cytology was carried out and eosinophils, neutrophils, lymphocytes, squamous epithelial cells, columnar epithelial cells, metaplastic changes and goblet cells were calculated separately. RESULTS: The GIIAPLA (2) concentration in tears was statistically significantly lower in patients with ocular rosacea (31.0+/-18.4 microg/ml, p=0.0099) and, more specifically, in patients who had dry eye (25.8+/-15.1 microg/ml, p=0.0034), compared to that in normal controls. There was no correlation between the GIIAPLA (2) content of tears and the conjunctival cells collected by the brush cytology. CONCLUSION: The tears of patients with dry eye symptoms due to ocular rosacea have decreased GIIAPLA (2) content. The pathogenic importance of this finding is discussed.

Group IIA phospholipase A2 content of tears in patients with atopic blepharoconjunctivitis.

BACKGROUND: To determine the concentration of group IIA phospholipase A(2) (GIIAPLA(2)) in tears of patients with atopic blepharoconjunctivitis (ABC), and to compare it with the GIIAPLA(2) concentration of tears in age-matched healthy controls. METHODS: The diagnosis of ABC was confirmed with a positive skin prick test and the presence of atopic dermatitis in lids. Conjunctival brush cytology was taken, and the cells including eosinophils, neutrophils, lymphocytes, squamous epithelial cells, columnar epithelial cells, metaplastic changes and the goblet cells were calculated separately. The GIIAPLA(2) concentration of tears was measured with a time-resolved fluoroimmunoassay in 29 patients with ABC (mean age 36.3+/-12.7 years) and 29 normal subjects (mean age 37.0+/-12.0 years). RESULTS: The GIIAPLA(2) concentration of tears in patients with ABC was 43.8+/-33.0 microg/ml, and in normal subjects it was 67.1+/-23.3 microg/ml. The difference was statistically significant (p=0.0018). The concentration of GIIAPLA(2) of tears was lowest in the subgroup of patients with ABC and dry eye (25.8()+/-23.6 microg/ml), whereas it was only slightly decreased in patients with ABC and normal tear secretion (56.6+/-33.3 microg/ml). The difference between these two subgroups was statistically significant (p=0.011). There was no statistically significant correlation between the GIIAPLA(2) concentration of tears and the quantity of different conjunctival cells gathered by the brush cytology. However, an almost significant correlation was found between the GIIAPLA(2) concentration in tears and conjunctival eosinophils. CONCLUSIONS: The results indicate that in patients with ABC the GIIAPLA(2) content of tears was decreased, without any dependence on the quantity of different conjunctival cells.