K. Matti Saari

Ocular Inflammation Associated with Yersinia Infection

We studied characteristics of ocular inflammation associated with Yersinia infection in 23 patients. After an acute onset with fever, diarrhea, and abdominal pain, 22 patients developed arthritis, 11 patients developed myalgia, 11 patients developed Reiters syndrome, 17 patients developed acute anterior uveitis, and nine patients developed conjunctivitis. Sacroiliitis was found in 12 patients. The patients had high erythrocyte sedimentation rates, leukocytosis, and lack of antinuclear antibodies and rheumatoid factor. All 17 patients tested had HLA-B27 antigen. The patients with acute anterior uveitis showed aqueous flare, cells, fine keratic precipitates, and often exudates, posterior synechiae, vitritis, and macular edema. Acute anterior uveitis was mostly unilateral and resolved during corticosteroids on the average during the first six weeks; recurrences were seen in about half of the cases. Conjunctivitis was generally mild with no chemosis, follicles, or keratitis; and it resolved in one week without treatment. Our results indicate that in HLA-B27 positive patients infective agents can trigger acute anterior uveitis or conjunctivitis, which often occur together with rheumatic diseases.

Plasma and aqueous humour concentrations and systemic effects of topical betaxolol and timolol in man.

Abstract Plasma and aqueous humour concentrations and systemic effects of timolol and betaxolol were studied after ocular administration in 45 patients scheduled for extracapsular cataract extraction and intraocular lens implantation. The patients were divided randomly into three groups and received 40 μl of either 0.5% betaxolol, 0.25% timolol or placebo into the lower cul‐de‐sacs of both eyes. Blood samples were collected over a period of 4 h and blood pressure and heart rate were monitored during the study. Aqueous humour samples were aspirated at the beginning of the operation. Plasma and aqueous humour concentrations of timolol and betaxolol were analyzed using a sensitive radioreceptor assay. The mean plasma concentrations of betaxolol were lower than those of timolol. The concentration of betaxolol in the aqueous humour was twice as high as the concentration of timolol. Both drugs produced a significant decrease in heart rate. In the timolol group a decrease in heart rate was found 15 min after drug administration, and in the betaxolol group after one hour.

Acute Glaucoma in Hemorrhagic Fever with Renal Syndrome (Nephropathia Epidemica)

Bilateral eyelid edema, chemosis, conjunctival injection and hemorrhages, shallowing of the anterior chamber with transitory myopia, and acute glaucoma were observed in three patients with hemorrhagic fever with renal syndrome (nephropathia epidemica). One patient had anterior uveitis with posterior synechiae. Two patients had congestion of retinal venules and retinal edema, and one patient had small retinal hemorrhages. Fluorescein angiography revealed early leakage of the conjunctival capillaries and delayed filling of the lower retinal arterioles with retinal edema. The acute glaucoma subsided rapidly. The myopia disappeared slowly with a gradual deepening of the anterior chamber after onset of the diuretic phase of the illness. In nephropathia epidemica, the transitory shallowing of the anterior chamber, myopia, and acute glaucoma are due to lesions in the small blood vessels of the ciliary body, resulting in its swelling, with relaxation of the zonules and forward movement of the lens.

Genetic Background of Acute Anterior Uveitis

To determine the hereditary pattern of acute anterior uveitis, we examined seven families-one family with four cases, one family with three cases, and four families with two cases of acute anterior uveitis. A total of 16 patients with uveitis and 28 relatives underwent ocular examinations and serologic determination of HLA antigens, protease inhibitor alpha 1-antitrypsin typing, and X-ray examination of sacroiliac joints. Sacroiliitis was found in 11 of 16 patients (68.8%) and incomplete Reiters disease in seven of 16 (43.8%). HLA-B27 antigen was found in all patients with uveitis and in six of 21 (28.6%) relatives. HLA-Cw1 antigen was found in nine of 14 (64.3%) patients with uveitis, often in the same haplotype with HLA-B27 antigen. HLA-DR4 antigen was found in seven of 11 (63.6%) patients with uveitis. There was no significant association of the alpha 1-antitrypsin variant MZ with uveitis. We believe that a pleiotropic gene associated with HLA-B27 antigen with autosomal dominant inheritance, incomplete penetrance, and variable expressivity may determine susceptibility to acute anterior uveitis in linkage disequilibrium with HLA-Cwl antigen.

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.

Comparison of topical 0.7% dexamethasone–cyclodextrin with 0.1% dexamethasone sodium phosphate for postcataract inflammation

BackgroundTo compare 0.7% dexamethasone–cyclodextrin aqueous eye drop solution applied once daily with 0.1% dexamethasone sodium phosphate eye drops applied three times a day for the control of postoperative inflammation after cataract surgery.MethodsTwenty cataract patients who underwent phacoemulsification and intraocular lens implantation were randomly divided into two postoperative treatment groups. Postoperative medication in group I included 0.1% dexamethasone sodium phosphate eye drops three times daily and in group II 0.7% dexamethasone–cyclodextrin eye drop solution once daily. Testing of visual acuity, biomicroscopic examination, applanation tonometry and laser flare cell meter (LFCM) examination were carried out before operation and days 1, 3, 7 and 21 after surgery.ResultsPreoperative and postoperative visual acuity, aqueous flare and cells in biomicroscopic examination, and the mean intraocular pressure did not show any statistically significant differences between the treatment groups. LFCM examination showed that the mean postoperative photon count values (P=0.032) and the median cell count values on the 1st (P=0.014), 3rd (P=0.031), 7th (P=0.034), and 21st (P=0.0097) postoperative days in group I were more elevated than in group II.Conclusions0.7% dexamethasone–cyclodextrin eye drops applied once daily is a more effective postoperative anti-inflammatory medication than 0.1% dexamethasone sodium phosphate applied three times a day. In both groups, 3 weeks after the operation the mean visual acuity was normal and intraocular pressure significantly lower than before operation. The use of 0.7% dexamethasone–cyclodextrin eye drops may be useful especially in elderly people who cannot apply themselves the eye drops onto the eye.

Endophthalmitis following cataract surgery in southwest Finland from 1987 to 2000.

PurposeTo investigate the incidence, causes, prevention, treatment and outcome of postoperative endophthalmitis (POE) following cataract surgery in south-west Finland from 1987 to 2000.MethodsWe reviewed the medical records of all patients with POE following cataract surgery treated in the hospital district of Southwest Finland from 1 January 1987 to 31 December 2000. Population-based annual incidence rates of cataract extractions and POE were calculated using the corrected population statistics of the hospital district.ResultsThere were 29,350 cataract procedures during the 14-year period. POE developed in 47 patients. The annual incidence of cataract operations increased more than fivefold from 1987 (155 per 100,000 population) to the maximum in 1999 (930 per 100,000 population), whereas the annual incidence of postcataract endophthalmitis decreased from the maximum of 11.1 per 1,000 cataract extractions (1.91 per 100,000 population) in 1988 to the minimum of 0–0.6 per 1,000 cataract extractions in 1999 and 2000. POE occurred statistically significantly more frequently after extracapsular cataract extraction (ECCE) than after phacoemulsification (Phaco) (P=0.0006). Gram-positive bacteria were the most frequent cause of acute POE and Propionibacterium acnes was the most frequent reason for delayed-onset POE. The complications of POE after cataract surgery included visual loss to below 0.05 (25.5% of affected eyes), opacification of the cornea (21.3%), secondary cataract (40.4%), increase in intraocular pressure (29.8%), vitreous clouding (63.8%), and retinal detachment (6.4%). Nearly one half of the eyes achieved final visual acuity of 0.5 or better.ConclusionsDuring the 14-year study period there was a shift from ECCE to Phaco, a fivefold increase in cataract extractions, and a decrease in the annual incidence of POE from 5.5–11.1 to 0–0.6 per 1,000 operations. Phaco was associated with a lower risk of POE than ECCE.

ß1‐ and ß2‐antagonist activity of topically applied betaxolol and timolol in the systemic circulation

Abstract. The ß1‐ and ß2‐antagonist activity of betaxolol and timolol in the systemic circulation was studied ex‐vivo after their ocular administration in thirty patients during cataract surgery. The patients received 40 μl of 0.5% betaxolol or 0.25% timolol into the lower cul‐de‐sacs of both eyes. Blood samples were collected up to four h after instillation of the doses. Plasma concentrations of betaxolol and timolol were analyzed using a radioreceptor assay. The ex‐vivo‐ß1‐and ß2‐receptor occupancies corresponding drug plasma levels were calculated using radioligand binding techniques. The extent of ß1‐receptor occupancy of betaxolol in the systemic circulation was less than 20% and its ß2‐receptor occupancy was negligible. The extent of ß1‐receptor occupancy of timolol was about 65% and its ß2‐receptor occupancy about 80%. Because receptor occupancy is the basis of antagonist activity of ß‐blocking agents, this study shows that the ß1‐antagonist activity of betaxolol in the systemic circulation is much less than that of timolol, and that its ß2‐antagonist activity is negligible. The study suggests that the reported side effects of betaxolol in patients with obstructive pulmonary diseases are not mediated via its ß2‐receptor blocking properties.

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.

Absorption of ocular timolol: drug concentrations and ß‐receptor binding activity in the aqueous humour of the treated and contralateral eye

Abstract. We studied the ocular and systemic absorption of 40 μl of topical 0.5% timolol in 57 patients using radioligand binding techniques. The mean concentration of timolol in aqueous humour of the treated eye was 1.9 ± 0.8 μg/ml 74 minutes after instillation of the drug. About 18 h after drug instillation the aqueous humour concentration of timolol was 105.5 ± 60.9 ng/ml. Timolol was found in 15 (42%) contralateral eyes. Concentration of timolol in the contralateral eye increased from 0.04 ± 0.08 ng/ml at 50 min to 0.3 ± 0.2 ng/ml at 134 min and was 0.2 ± 0.4 ng/ml at 18 h after instillation. Timolol concentrations in the aqueous humour of the treated eye appeared to be high enough to occupy ß1‐ and ß2‐receptors completely (100%) at 74 min and at 18 h after drug instillation. Timolol concentrations in the contralateral eye were high enough to occupy up to 33.0 ± 24.7% of the ß2‐receptors and up to 51.7 ± 35.1% of ß2‐receptors. High drug concentrations and complete ß‐receptor occupancy in the aqueous humour of the treated eye after topical timolol are in agreement with the long‐lasting ocular hypotensive effects. The low drug concentrations and partial receptor occupancy in the contralateral eye may also be of some clinical significance.