Long-term results after treatment of basal cell carcinoma of the eyelid in South-Western Finland.

PURPOSE: Basal cell carcinoma (BCC) is the most common skin cancer of the eyelid, showing an increasing incidence in the white population. The authors studied the clinical characteristics and the treatment results of BCC of the eyelid in southwestern Finland during 1977-1997. METHODS: The authors reviewed the case records of 191 patients with BCC of the eyelids treated at the Turku University Eye Clinic during 1977-1997. The mean follow-up period after the treatment was 8.6+/-5.2 years. RESULTS: The 191 patients had altogether 194 BCC tumors of the eyelid with the mean diameter of the tumor being smaller than 10 mm in 77.3% of cases. Of the 194 BCC tumors of the eyelid 16.0% showed recurrence, and the recurrence rate of all surgically treated tumors was 13.7%. In this study 61 patients (31.9%) developed other malignancies than the BCC of the eyelid including 28 patients (14.7 %) with carcinoma in other locations than skin. CONCLUSIONS: Incompletely removed BCCs of the eyelid showed only 18.9% recurrence rate during the follow-up time. On the other hand, BCCs of the eyelid should not be underestimated because of the rather high total recurrence rate. The frequency of 31.9% of other malignancies than BCC of the eyelid is remarkably high and requires special attention from the ophthalmologist taking care of the patient with BCC of the eyelid.

Group II phospholipase A2 content of tears in patients with senile cataract and primary open-angle glaucoma.

PURPOSE: To determine the group II phospholipase A2 (PLA2) content of tears in patients with senile cataract or primary open-angle glaucoma (POAG) and to compare it with the PLA2 content of tears in age-matched healthy controls. METHODS: The PLA2 concentration of tears was measured with time-resolved fluoroimmunoassay in 21 patients with senile cataract, 23 patients with POAG and in 40 healthy controls. RESULTS: The PLA2 content of tears was 38.3+/-30.1 microg/ml in patients with senile cataract, 32.1+/-22.3 microg/ml in patients with POAG, and 36.6+/-31.1 microg/ml in healthy controls. There were no significant differences between the patient and the control groups. CONCLUSIONS: We conclude that neither senile cataract nor POAG has any effect on the PLA2 content of tears.

Epidemiology of basal cell carcinoma of the eyelid in south-western Finland.

BACKGROUND: Basal cell carcinoma (BCC) is the most common malignant tumour of the skin in Caucasians. It often appears on the eyelids but there are no population-based studies on the incidence of BCC of the eyelid in Nordic countries. METHODS: The mean annual incidence rates of BCC of the eyelid in the region of South-Western Finland from 1977 to 1997 were calculated. RESULTS: The mean annual incidence (per 100,000 population) of BCC of the eyelid showed a statistically significant increase from 0.82 (in 1977-1979) to 2.88 (in 1995-1997). The incidence of BCC of the eyelid was 0.8 in the age group of 30-49 years and rose significantly with age (P < 0.0005) to the maximum of 17.2 in the age group of 80-89 years. There were no statistically significant differences in the incidence rates of BCC of eyelid between males and females or between urban, semi-urban and rural populations. CONCLUSION: In South-Western Finland the incidence of BCC of the eyelids more than tripled during the years from 1977 to 1997. This may be due to the increase of the elderly population, because the incidence showed a significant increase with age.

Group II PLA(2) content of tears in normal subjects.

PURPOSE: To determine the concentration of group II phospholipase (PL) A(2), an antimicrobial molecule, in tears of normal subjects in different age and sex groups. METHODS: PLA(2) content of tears was measured in 122 healthy volunteers with ages ranging from 20 to 89 years (mean, 49.5 years) by a time-resolved fluoroimmunoassay using a polyclonal rabbit antibody to recombinant human PLA(2). RESULTS: The mean concentration of PLA(2) in tears was 54.5 +/- 33.9 microg/ml. It was highest in the age group 20 to 29 years (81.6 +/- 32.0 microg/ml), and a decrease of concentration occurred with an increase of age. PLA(2) values were statistically significantly lower in the age group 60 to 69 years (P = 0.0013) and 70 years or more (P = 0.0001) than in the age group 20 to 29 years. There were no statistically significant differences in PLA(2) content of tears between the genders in any age group (P = 0.798). CONCLUSIONS: The results indicate that tears contain a high concentration of PLA(2) and that PLA(2) levels decrease with an increase of age and/or reflex tear component of the sample analyzed.

Uveitis in children: population-based study in Finland.

PURPOSE: To investigate the incidence and prevalence rates of different types of uveitis in children, and to compare them with the rates in adults. SUBJECTS AND METHODS: For this population-based retrospective study the medical records of all residents of the district of Turku University Hospital with a diagnosis of uveitis seen at the Eye Clinic of Turku University Hospital during the years 1980-1982 and 1988 were reviewed. RESULTS: A total of 1122 uveitis cases were identified, and 55 (4.9%) of them were children under 16 years. The incidence per 100 000 population per year for all uveitis cases in children was 4.3 (95% confidence interval [CI], 2.2 to 6.4), and the prevalence was 27.9 (95% CI, 17.1 to 38.6), which was significantly lower compared with the rates in adults (p=0.001 for incidence and prevalence). The vast majority of children, 50 (90.9%), had anterior uveitis (AU), and the incidence and prevalence rates of AU were significantly lower than in adults (p=0.001 for incidence and prevalence). Three (5.5%) children had posterior uveitis (PU), but there was no significant difference in the incidence and only marginally significant difference in the prevalence rate of PU in children compared with the rates in adults (p=0.33 for incidence, and p=0.07 for prevalence). Only one case (1.8%) was found with intermediate and one with panuveitis, but no new cases. The commonest diagnostic groups in children were AU associated with juvenile rheumatoid arthritis, idiopathic acute anterior uveitis, and idiopathic chronic anterior uveitis. Toxoplasmic retinochoroiditis was found in all of the PU cases with the incidence 0.3, and the prevalence 1.1, which did not differ significantly from the rates in adults (p=1.0 for incidence, and p= 0.48 for prevalence). CONCLUSION: Uveitis is rarer in children than in adults. However, in contrast to studies from tertiary referral centers, the distribution of different forms of uveitis in children in this population-based study seems to resemble the distribution in adults.

Systemic bioavailability of ocularly applied 1% atropine eyedrops.

PURPOSE: To investigate the pharmacological basis of systemic effects of atropine eyedrops, we estimated the bioavailability of ophthalmic 1% atropine solution in healthy volunteers. METHODS: In a randomized crossover study we administered 0.3 mg atropine either intravenously or ocularly to six healthy volunteers. The plasma concentrations of the biologically active atropine enantiomer, 1-hyoscyamine, were determined using a muscarinic cholinoceptor binding assay. RESULTS: The mean area under the curve from zero to infinitum (AUC0-infinity) for 1-hyoscyamine was 1.862+/-0.580 microg/L x hr after intravenous, and 1.092+/-0.381 microl/L x hr after ocular administration (mean+/-sd, n=6), respectively. The mean bioavailability was 63.5+/-28.6% (mean+/-SD, n=6; min 19%, max 95%). Large interindividual differences characterized the absorption and elimination phases of 1-hyoscyamine kinetics. The terminal half-life (t1/2beta) of 1-hyoscyamine in plasma was not affected by the route of drug administration. CONCLUSION: The systemic bioavailability of 1-hyoscyamine was considerable and may explain the systemic anticholinergic side effects reported in association with the clinical use of atropine eyedrops.

Seasonal variation of endogenous uveitis in south-western Finland.

PURPOSE: To evaluate if there is a seasonal pattern to the incidence of endogenous uveitis in south-western Finland with special reference to acute anterior uveitis. METHODS: The incidence rates per month of the 414 new uveitis cases from years 1980-82 and 1988 in the district of Turku University Hospital were calculated. The months of the year were grouped into warm (June to September), transitional (April, May, October, November), and cold (December to March) seasons based on the mean air temperature of the months in Turku. RESULTS: We observed a statistically significant increase in the incidence of all uveitis cases in the warm and transitional seasons compared with the cold season (p=0.030 and p=0.008 respectively). A similar seasonal trend was found among anterior uveitis cases, but not among the intermediate, posterior or panuveitis cases. The incidence of acute anterior uveitis cases was higher in the transitional than in the cold season (p=0.025). No seasonal variation of the incidence was found in the subgroup of acute anterior uveitis where ankylosing spondylitis had been confirmed (p=0.70). CONCLUSION: The present data suggests that there is seasonal variation of the incidence of uveitis in south-western Finland.

Quantitative determination of aqueous flare and cells in healthy eyes.

We studied 263 eyes of 141 normal subjects, 33 men and 108 women, including 129 Finns and 12 Ibero-Americans, with the age ranging between 12 and 89 (mean 43.0 +/- 20.4) years using the Kowa FC-1000 laser flare cell meter. The mean photon count/ms was 4.5, it was 3.1 in the age groups of 10-19 years and 11.5 in the age group of 80 years or over; the increase with age was statistically significant (p = 0.0001). There were no significant differences in the photon count/ms between right and left eyes (p = 0.75), between sexes (p = 0.61), or between Ibero-Americans and age-matched Finns (p = 0.62). The mean cell count was 1.1 and there were no significant changes between the right and left eyes (p = 0.56) or between different age (p = 0.38), sex (p = 0.32) and race (p = 0.64) groups. There were no significant differences in the mean photon count/ms (p = 0.97) and cell counts (p = 0.35) between the first and second measurements 5 min later. There was no subject-within variability after 24 h and 7 days in the flare (p = 0.95) and cell counts (p = 0.89).

Measurement of protein concentration of aqueous humour in vivo: correlation between laser flare measurements and chemical protein determination.

We studied the correlation between laser flare cell meter photon count/ms and actual protein concentration both in vitro and in vivo. Laser flare cell meter measurement of human albumin concentrations of 0 to 10 g/l showed photon counts/ms from 0.3 +/- 0.3 to 78.9 +/- 3.9. There was a statistically highly significant linear correlation between photon count/ms and human albumin concentration (r = 0.98, p = 0.0001). Laser flare cell meter measurements were done on 39 cataract patients with the mean age of 77.9 +/- 6.7 years. Aqueous humour obtained by peroperative paracentesis was analysed for total protein. The mean photon count/ms before pupillary dilatation was 11.93 +/- 6.03. There was a significant linear correlation (r = 0.4, p = 0.019) between the photon count/ms after pupillary dilatation (mean 14.73 +/- 12.9, range 2.6-62.4) and anterior chamber protein concentration (mean 0.62 +/- 0.27, range 0.23-1.3 g/l) with the linear regression formula being y = 0.231 x -1.105 where y = log protein concentration (g/l) and x = log of photon count/ms. Laser flare cell meter photon counts/ms may be converted into an equivalent anterior chamber total protein concentration using this formula.

Incidence and prevalence of different uveitis entities in Finland.

We studied the case records of 1122 patients with endogenous uveitis including 418 new cases treated at the University Eye Clinic in Turku during the years 1980-1982 and 1988. The mean annual incidence and prevalence rates (per 100,000 population) of idiopathic acute anterior uveitis were 17.1 and 48.5, respectively, sarcoid anterior uveitis 0.5 and 1.5, Posner-Schlossman syndrome 0.4 and 1.9, herpes zoster uveitis 0.4 and 0.7, idiopathic chronic anterior uveitis 0.3 and 7.3, herpes simplex keratouveitis 0.3 and 0.5, juvenile rheumatoid arthritis 0.2 and 2.4, Fuchs' heterochromic iridocyclitis 0.2 and 0.5, intermediate uveitis 0.3 and 1.4, and of toxoplasmic retinochoroiditis 0.3 and 2.4. The incidence and prevalence rates of acute anterior uveitis associated with ankylosing spondylitis were 2.0 and 10.3 per 100,000 population, respectively, and this disease association occurred more often in men than in women (p < 0.001). The mean annual incidence of idiopathic acute anterior uveitis was significantly lower in the age group 0-19 years than in the other age groups (p < 0.001).

Bacteriology of lacrimal duct obstruction in adults.

AIMS: To determine the current bacteriology of lacrimal duct obstruction (LDO) and to relate the bacteriological findings to the type of symptoms. METHODS: 127 samples were obtained from the lacrimal sac in 118 consecutive adult patients with LDO, including nine bilateral cases. RESULTS: Altogether, 156 isolates were recovered from the 127 samples cultured. Cultures were positive from 84% of the samples. Gram positive bacteria were isolated in 79 (62%) samples. The most frequently cultured bacterial species was Staphylococcus epidermidis, representing 27% of the isolates. Gram negative bacteria were recovered from 26 (20%) samples, and these bacteria were statistically significantly more common in cases with copious discharge than in cases with minor discharge (p = 0.000). Cases with simple stenosis of the lacrimal duct (SSLD) showed significantly less Streptococcus sp (p = 0.004) and Gram negative organisms (p = 0.004) than those with chronic dacryocystitis. CONCLUSION: The bacteriology of SSLD resembles that of normal conjunctival flora. Chronic dacryocystitis in adults is associated with an increased proportion of Gram negative bacteria which may be a reservoir for postoperative intraocular infection. They should also be taken into account in selecting antimicrobial prophylaxis in lacrimal drainage surgery.

Synthesis of group II phospholipase A2 and lysozyme in lacrimal glands.

PURPOSE: The aim of this study was to demonstrate the synthesis and cellular distribution of group II phospholipase A2 and lysozyme in the main and accessory lacrimal glands. METHODS: The authors studied samples of normal main lacrimal glands of seven autopsied subjects and accessory lacrimal glands of eight patients who underwent ptosis surgery. The specimens were immunostained with a rabbit antiserum against group II phospholipase A2 and a monoclonal antibody against lysozyme. Expression of group II phospholipase A2 gene was shown using Northern hybridization and in situ hybridization. RESULTS: Lysozyme was present in the secretory granules of most acini, whereas group II phospholipase A2 was seen in a minority of acinar cells, primarily in the central parts of lobules in the main and accessory lacrimal glands. Synthesis of group II phospholipase A2 in the glandular cells was confirmed by Northern hybridization and by in situ hybridization. CONCLUSIONS: There are two specialized cell types in the main and accessory lacrimal glands, one synthesizing group II phospholipase A2 and the other synthesizing lysozyme. These enzymes are important nonspecific antibacterial factors in tears.

Epidemiology of endogenous uveitis in south-western Finland.

We studied the case records of 1122 patients with endogenous uveitis including 418 new cases treated at the University Eye Clinic in Turku during the years 1980-1982 and 1988. The mean annual incidence and prevalence rates of anterior uveitis were, respectively, 21.3 and 68.7 per 100,000, of posterior uveitis 0.8 and 4.6 per 100,000, of panuveitis 0.2 and 0.8 per 100 000, and of all uveitis cases 22.6 and 75.4 per 100,000 population. The incidence of uveitis was higher in the age group 20-69 years than in the age groups 0-19 years (p < 0.001) and 70 years or over (p = 0.049). The incidence rates were not different between sexes in any age group (p = 0.2). The incidence of uveitis was higher in lower socio-economic groups than in higher socio-economic groups (p < 0.001). There were no significant differences in the incidence of uveitis between sexes in different socio-economic groups (p = 0.1).

[Foreign body reaction after lens implantation. Correlation between visual acuity and density of giant cells]. / Fremdkörperreaktion nach Linsenimplantation. Beziehung zwischen Visus und Dichte der Riesenzellen.

In the early postoperative stage giant cells often appear on IOLs. Independent of this, a foreign-body reaction may start about 3 months after surgery from posterior synechia. Foreign-body reaction occur more frequently in diabetic patients or patients with glaucoma. In a prospective trial, we examined the surface of the IOLs from 115 patients with diabetes or glaucoma using specular microscopy. We compared the maximal density of the cells to visual acuity. One week and 1 month after surgery, the maximal density of giant cells was between 0 und 20/mm2; vision (median) was independent of the giant cell density in all groups between 20/25 and 20/30. Three months after surgery, the maximal density of giant cells was between 0 und 35/mm2; vision (median) was 20/25 in patients with no giant cells or cell densities up to 15/mm2. Seven patients had cell densities between 16 and 35/mm2; visual acuity (median) was 20/125. The difference was significance was (P < or = 0.05). Six months and 1 year later after surgery, the maximal density of giant cells was between 0 and 41/mm2; the vision (median) in patients with giant cell densities up to 15/mm2 was between 20/20 and 20/25. In five examinations the cell densities were found to be in the range of 16 to 40/mm2; visual acuity (median) was 20/80 in these cases. The difference is not significant (P < or = 0.05). A foreign-body reaction with more than 15 giant cells/mm2 is a rare complication of cataract surgery with lens implantation. Three months after surgery, this complication correlates with poor vision.

Phospholipase A2 content of aqueous humour in cataract patients.

In order to determine the content of group II phospholipase A2 in the aqueous humour we studied 41 cataract patients including 8 men and 33 women with age ranging between 65 and 92 (mean +/- SD being 77.0 +/- 6.7) years. In all patients preoperative biomicroscopy showed neither aqueous flare nor cells. Eleven patients (26.8%) had pseudoexfoliation syndrome. Aqueous humour tap was done at the beginning of cataract surgery before perforating the corneoscleral wound. We used time-resolved fluoroimmunoassay for the detection of group II phospholipase A2 in the aqueous humour. The group II phospholipase A2 content in the aqueous humor varied between less than measurable (in 23 patients) and 3.3 ng/ml, with an interquartile range from less than measurable to 1.4 ng/ml. There was no significant difference in the group II phospholipase A2 content of the aqueous humour whether or not the patient had pseudoexfoliation syndrome. The results show that the aqueous humour of cataract patients contains only minute amounts of group II phospholipase A2.

Uveitis survey at the University Eye Clinic in Turku.

We conducted a retrospective analysis of 1122 patients with endogenous uveitis treated at the University Eye Clinic in Turku during the years 1980-1982 and 1988. Of the 1122 patients 568 were men and 554 women; 1034 (92.2%) had anterior uveitis, 15 (1.3%) intermediate uveitis, 64 (5.7%) posterior uveitis and 9(0.8%) panuveitis; 867 (77.3%) were unilateral and 255 bilateral; 789 of 1067 cases (73.9%) were of sudden onset and 278 of insidious onset; 808 of 1102 cases (73.3%) were of short duration and 294 of long duration; and 519 (46.3%) single and 603 repeated. In this study uveitis occurred significantly more often (44.2%) in the age group 20-39 years than in other age groups (p < 0.00001). Anterior and posterior uveitis were more often unilateral than bilateral (p < 0.0005) and of sudden onset than of insidious onset (p < 0.00008). Acute anterior uveitis was the most common uveitic entity and accounted for 745 cases (66.4%). Acute anterior uveitis associated with ankylosing spondylitis was the single most frequently seen diagnostic group including 144 cases (12.8%) with a statistically significant male predominance (p < 0.00001).

Systemic absorption and anticholinergic activity of topically applied tropicamide.

We studied the plasma levels and systemic anticholinergic activity of tropicamide after ocular administration in eight women. Two 40 microliters drops of 0.5% tropicamide were instilled into the lower cul-de-sac of one eye of the subjects and concentrations and respective muscarinic receptor occupancy of tropicamide in plasma were monitored using radioligand binding techniques. Tropicamide was rapidly absorbed systemically with the mean peak concentration in plasma being 2.8 +/- 1.7 ng/ml (mean +/- SD) at five minutes after instillation. Tropicamide disappeared rapidly from the systemic circulation: drug concentration in plasma was 0.46 +/- 0.51 ng/ml (mean +/- SD) at 60 minutes and below 240 pg/ml at 120 minutes after instillation. Tropicamide bound to muscarinic receptors of rat brain with an apparent equilibrium binding constant (Ki-value in plasma) 220 +/- 25 nM (mean +/- SD, n = 3). Tropicamide occupied maximally 8% of muscarinic receptors in plasma after ocular application. The low affinity of tropicamide for muscarinic receptors and its negligible receptor occupancy in plasma can explain the low incidence of systemic side-effects of tropicamide eyedrops.

Absorption of ocular timolol: drug concentrations and beta-receptor binding activity in the aqueous humour of the treated and contralateral eye.

We studied the ocular and systemic absorption of 40 microliters 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 micrograms/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 beta 1- and beta 2-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 beta 2-receptors and up to 51.7 +/- 35.1% of beta 2-receptors. High drug concentrations and complete beta-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.

Concentrations and antagonist activity of topically applied betaxolol in aqueous humour.

Aqueous humour concentrations and antagonist activity of betaxolol were studied after ocular administration in forty-five patients scheduled for cataract surgery. The patients were randomly divided into five groups and received 40 microliters of 0.5% betaxolol into the lower cul-de-sac of one eye. In groups I, II, III and IV the drug was instilled 5-6, 12, 24 and 48 h, respectively, before surgery, into the eye to be operated, and in group V 4 h before surgery into the contralateral eye. Aqueous humour samples were aspirated at the beginning of the operation. Aqueous humour concentrations of betaxolol were analyzed using a radioreceptor assay, and the ex-vivo-beta 1- and beta 2-receptor occupancies of betaxolol were calculated. The highest concentration of betaxolol in aqueous humour was found 5-6 hours after instillation of the drug. Topical betaxolol was found to stay in aqueous humour for 48 h, a much longer time than the recommended interval of dosage. Betaxolol beta 1-receptor occupancy was 99-95% during the study, but also beta 2-receptor occupancy was significant (52%) 24 h after instillation of the drug. Because receptor occupancy is the basis of antagonist activity, the role of beta 2-receptor blocking effect of betaxolol in lowering intraocular pressure cannot be excluded.

Beta 1- and beta 2-antagonist activity of topically applied betaxolol and timolol in the systemic circulation.

The beta 1- and beta 2-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 microliters 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-beta 1-and beta 2-receptor occupancies corresponding drug plasma levels were calculated using radioligand binding techniques. The extent of beta 1-receptor occupancy of betaxolol in the systemic circulation was less than 20% and its beta 2-receptor occupancy was negligible. The extent of beta 1-receptor occupancy of timolol was about 65% and its beta 2-receptor occupancy about 80%. Because receptor occupancy is the basis of antagonist activity of beta-blocking agents, this study shows that the beta 1-antagonist activity of betaxolol in the systemic circulation is much less than that of timolol, and that its beta 2-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 beta 2-receptor blocking properties.