T describe the distribution of different. Incidence and prevalence of different uveitis entities in Finland. Material and Methods.

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- ACTA OPHTHALMOLOGICA SCANDINAVICA 1997 Incidence and prevalence of different uveitis entities in Finland Taina Paivonsalo-Hietanen', Juhani Tuominen2, Hanna Vaahtoranta-Lehtonen' and K. Matti Saari' Departments of Ophthalmology' and Biostatistics', University of Turku, Turku, Finland ABSTRACT. 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 1000 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 1000 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). Key words: endogenous uveitis - epidemiology - incidencc - prevalence - uveitis entities. Acta Ophthalmol. Scand. 1997: 75: 76-81 here are several uveitis surveys that T describe the distribution of different uveitis entities in materials collected at the hospitals of different geographic areas (Imai ct al. 1971; Saari et al. 1975; Ayanru 1977; Perkins & Folk 1984; Henderly et al. 1987; Piiivonsalo-Hietanen et al. 1994). However, the percentage distribution of different uveitis entities of all uveitis cases can provide only gross indication of true incidence and prevalence rates. There are few epidemiological studies on uveitis where the incidence rates per population have been presented (Darrell et al. 1962; Miettinen 1977; vddot ct al. 1984; Saari et al. 1995). The incidence and prevalence rates of different uveitis entities have been briefly described in only one study, but without information on age, gender, and yearly variation (Vadot et al. 1984). In this paper we present the incidence and prevalence rates of different uveitis entities in different age groups and genders based on a material collected over several years in south-western Finland. Material and Methods The study protocol was approved by the Ethics Committee of the University of Turku and the Turku University Central Hospital. The case records of 1122 patients with endogenous uveitis treated at the University Eye Clinic in Turku, Finland during the years 1980-1982 and 1988 were evaluated. The years 1980-1982 and 1988 were selected, because in the 1980's practically all uveitis patients in this hospital district were treated at the University Eye Clinic in Turku and the hospital record analysis alone provided a nearly complete collection of symptomatic uvcitis cases in this area. This made it possible to study the epidemiology of endogenous uveitis in south-western Finland. More recently, due to changes in the hospital economy and referral pattern, many patients with uveitis have been treated in the clinics of private ophthalmologists. The material included all patients with endogenous uveitis of both the out-pa- tient and in-patient clinics. The cases of exogenous uveitis, e.g. postoperative endophthalmitis and corneal foreign bodies with secondary uveitis, were excluded. Patients whose residence was outside the hospital district were also excluded from the material. Information included the patient's age, gender, and residence, the location and pattern of uveitis with the years of the first and index episodes, and the diagnosis. Standard diagnostic criteria were employed for all syndromes and entities of uveitis. Of the total material of 11 22 cases with endogenous uveitis 418 were new ones. The incidence rates of different uveitis entities per 1000 population per year were calculated using corrected population statistics of the hospital district of Turku University Hospital for the years 1980-1982 and 1988 (Central Statistical Office of Finland 1980, 1981, 1982 and 1990).Duringtheyears I980 to I988 the population in the hospital district rose from 457842 to 472540 with a small majority of women. The age distribution of the population in 10-year intervals was counted from the population statistics to calculate the incidence rates in the different age groups. The prevalence rates per 1000 population per year were calculated for the years 1981, I982 and 1988. The statistical computations were done by using SAS System (SAS Institute Inc., Gary, NC, USA). The dependence of incidence rates on various demographic factors (e.g. calendar year and age) was separately tested by Pearson's chi-square test. A p-value less than 0.05 was,&nsidered statistically significant. Results During the years 1980-1982 and 1988 the mean annual incidence of uveitis was 22.6 per 100000 population in southwestern Finland. Idiopathic acute ante- - 76

~~~ ACTA OPHTHALMOLOGICA SCANDINAVICA 1997 - nor uveitis was the most common uveitis entity with a mean annual incidence of 17.1 per 100000 population (Table 1). The incidence rates of other anterior uveitis entities, which were more than 30 times rarer than idiopathic acute anterior uveitis, are shown in Table 1. Ankylosing spondylitis was the most frequently diagnosed associated disease in patients with idiopathic acute anterior uveitis, the mean annual incidence being 2.0 per 100000 population, and it was diagnosed significantly more often in men than in women (3.5 vs 0.6 per 100000; p < 0.001) (Table 2). The other associated diseases occurred rather equally in both sexes (Table 2). The mean annual incidence of all cases with anterior uveitis was 21.3 per 1000 population (Table 1). The incidence rates of various anterior uveitis entities in different years did not show marked differences (Table 3). Table 1. Mean annual incidence of different anterior uveitis entities per 1000 population. Male Female Total Diagnosis No. Incidence No. Incidence No. Incidence Idiopathic acute anterior uveitis 154 17.4 162 16.7 316 17.1 Sarcoid uveitis 3 0.3 7 0.7 1.5 Posner-Schlossman syndrome 5 0.6 2 0.2 I 0.4 Varicella iridocyclitis 1 0.1 3 0.3 4 0.2 Herpes zoster uveitis 3 0.3 5 0.5 8 0.4 Herpes simplex keratouveitis 3 0.3 3 0.3 6 0.3 Idiopathic chronic anterior uveitis 1 0.1 5 0.5 6 0.3 Fuchs' heterochromic iridocyclitis 1 0.1 2 0.2 3 0.2 Juvenile rheumatoid arthritis 4 0.4 4 0.2 Tuberculous iridocyclitis 2 0.2 2 0.1 Anterior uveitis associated with other systemic diseases 16 1.8 13 1.3 29 1.6 Total 189 21.4 206 21.3 395 21.3 Table 2. Mean annual incidence of diseases associated with idiopathic acute anterior uveitis (MU) per 1000 population. Diseases associated with Male Female Total idiopathic AAU No. Incidence No. Incidence No. Incidence Ankylosing spond ylitis 31 3.5" 6 0.6 37 2.0 Reiter's disease 2 0.2 I 0.1 3 0.2 Psoriatic arthritis 1 0.1 1 0.1 Ulcerative colitis 3 0.3 2 0.2 5 0.3 No associated disease 119 13.5 152 15.7 271 14.6 * p < 0.001 male vs female New cases of tuberculous iridocyclitis did not appear after the year 1981. The mean annual incidence of intermediate uveitis (pars planitis) was 0.3 per 1000 population. Toxoplasmic retinochoroiditis was the most frequently diagnosed posterior uveitis entity with a mean annual incidence of 0.3 per 100000 population. There were only single cases of tuberculous posterior uveitis, geographic choroiditis, juvenile hemorrhagic maculopathy and candida endophthalmitis, each accounting for an incidence of 0.1 per 1000 population. New cases of tuberculous posterior uveitis did not appear after the year 1980. The mean annual incidence of all cases with posterior uveitis was 0.8 per 100000 population (Table 4). The mean annual incidence of panuveitis was 0.2 per I00000 population. There was not a single new case of Beh- Get's disease in this material. The prevalence of idiopathic acute anterior uveitis ranged from 47.9 to 48.9 (mean 48.5) per 1000 population in the years 1981,1982 and 1988 (Table 5). Ankylosing spondylitis was the most frequently diagnosed associated disease in the patients with idiopathic acute anterior uveitis showing the mean prevalence of 10.3 per 1000 population (Table 6). The mean prevalence of idiopathic chronic anterior uveitis was 7.3 per 1000. The mean prevalence of sarcoid uveitis, Posner-Schlossman syndrome and of juvenile rheumatoid arthritis ranged from 1.5 to 2.4 per 1000 population. The mean prevalence of varicella iridocyclitis, herpes zoster uveitis, herpes simplex keratouveitis, Fuchs' heterochromic iridocyclitis and of tuberculous iridocyclitis ranged from 0.1 to 0.9 per Table 3. Annual incidence of different anterior uveitis entities per 100000 population in years 1980-1982 and 1988. 1980 1981 1982 1988 Diagnosis No. Incidence No. Incidence No. Incidence No. Incidence Idiopathic acute anterior uveitis 67 14.6 73 15.9 77 16.7 99 21.0 Sarcoid uveitis 2 0.4 4 0.9 3 0.6 Posner-Schlossman syndrome 2 0.4 3 0.6 Varicella iridocyclitis 2 0.4 2 0.4 Herpes zoster uveitis 5 1.1 2 0.4 Herpes simplex keratouveitis I 0.2 3 0.7 I 0.2 Idiopathic chronic anterior uveitis 2 0.4 3 0.7 I 0.2 Fuchs' heterochromic iridocyclitis 2 0.4 Juvenile rheumatoid arthritis 2 0.4 I 0.2 Tuberculous iridocyclitis 2 0.4 Anterior uveitis associated with other systemic diseases 2 0.4 6 1.3 13 2.8 8 1.7 Total 82 17.9* 89 19.4" 105 22.7" 119 25.2* * p = 0.07 between years. 77 -

- ACTA OPHTHALMOLOGICA SCANDINAVICA 1997 Table 4. Mean annual incidence of different posterior uveitis entities per 1000 population. Diagnosis Male Female Total No. Incidence No. Incidence No. Incidence Toxoplasmic retinochoroiditis 1 0.1 5 0.5 6 0.3 Tuberculous uveitis I 0.1 1 0.1 Geographic choroiditis 1 0.1 1 0.1 Juvenile hemorrhagic maculopathy 1 0.1 I 0.1 Candida endophthalmitis 1 0.1 1 0.1 Other forms of posterior uveitis 2 0.2 3 0.3 5 0.3 Total 3 0.3 12 1.2 15 0.8 100000 population. The prevalence of all cases with anterior uveitis ranged from 61.6 to 76.6 (mean 68.7) per 100000 population (Table 5). The prevalence of intermediate uveitis (pars planitis) ranged from 0.63 to 2.2 (mean 1.4) per 100000 population. Toxoplasmic retinochoroiditis was the most common posterior uveitis entity with a mean prevalence of 2.4 per 100000 population. The other posterior uveitis entities had a mean prevalence of only 1.1 per 100000 population or less. The pre- Table 5. Annual prevalence of different anterior uveitis entities per 1000 population in years 1981,1982 and 1988. 1981 1982 1988 Total Diagnosis Idiopathic acute anterior uveitis Sarcoid uveitis Posner-Schlossman syndrome Varicella iridocyclitis Herpes zoster uveitis Herpes simplex keratouveitis Idiopathic chronic anterior uveitis Fuchs heterochromic iridocyclitis Juvenile rheumatoid arthritis Tuberculous iridocyclitis Anterior uveitis associated with other systemic diseases Total No. Prevalence No. Prevalence No. Prevalence No. Prevalence 224 48.8 221 47.9 7 1.5 6 1.3 11 2.4 7 1.5 6 1.3 2 0.4 4 0.9 61 13.3 27 5.9 2 0.4 3 0.6 15 3.3 12 2.6 7 1.5 4 0.9 18 3.9 28 6.1 231 48.9 676 48.5 8 1.7 21 1.5 8 1.7 26 1.9 2 0.4 2 0.1 2 0.4 1.7 2 0.4 7 0.5 13 2.8 101 7.3 2 0.4 7 0.5 6 1.3 33 2.4 12 0.9 16 3.4 62 4.5 ~ ~ 352 76.6 314 68.0 291 61.6 957 68.7 Table 6. Annual prevalence of diseases associated with idiopathic acute anterior uveitis (AAU) per 1000 population in years 1981,1982 and 1988. Diseases associated with 1981 1982 1988 Total idiopathic AAU No. Prevalence No. Prevalence No. Prevalence No. Prevalence Ankylosing spondylitis 46 10.0 50 10.8 48 10.2 144 10.3 Reiter s syndrome 3 0.7 7 1.5 6 1.3 16 1.2 Psoriatic arthritis 2 0.1 Crohn s disease 2 0.4 3 0.2 Ulcerative colitis 2 0.4 5 1.1 3 0.6 1.7 No associated disease 175 38.1 160 34.7 175 37.0 510 36.6 Table 7. Annual prevalence of different posterior uveitis entities per 1000 population in years 1981,1982 and 1988. 1981 1982 1988 Total Diagnosis No. Prevalence No. Prevalence No. Prevalence No. Prevalence Toxoplasmic retinochoroiditis Tuberculous uveitis Sarcoid uveitis Acute posterior multifocal placoid pigmentepitheliopathy Geographic choroiditis Juvenile hemorrhagic maculopathy Acute retinal necrosis Candida endophthalmitis Idiopathic posterior uveitis 12 2.6 7 1.5 18 3.9 3 0.6 I 1.5 4 0.9 I 0.2 34 2.4 5 0.4 1 0.1 I 0.1 2 0.1 1 0.1 3 0.2 2 0.1 15 1.1 Total 24 5.2 31 6.7 9 1.9 64 4.6-78

ACTA OPHTHALMOLOGICA SCANDINAVICA 1997 - Table 8. Mean annual incidence of different anterior uveitis entities in different age groups. Age group (years) Diagnosis Idiopathic acute anterior uveitis Sarcoid uveitis Posner-Schlossman syndrome Varicella iridocyclitis Herpes zoster uveitis Herpes simplex keratouveitis Idiopathic chronic anterior uveitis Fuchs heterochromic iridocyclitis Juvenile rheumatoid arthritis Tuberculous iridocyclitis Anterior uveitis associated with other systemic diseases 0-9 10-19 20-29 30-39 40-49 50-59 60-69 70orover 0.9 4.1 16.9* 27.2* 27.1* 21.5* 23.5* 14.4* 0.4 0.7 1.8 1.4.4 1.1 0.3 0.4.6 0 0.4 0.8 0.4 0 0.4 0.5 1.7 1.7.4 0.7 0.3 0.4.6 0 0.4 0.7.5 0.6 0.6 0.7 0.6 0.9 0.8.5 0.6 0 0.4 0.8 2.2 I.0 1.3 1.4 2.8 3.3 Total 2.6 7.3 22.6 30.1 31.5 25.6 30.3 20.5 *p<o.001 vs agegroup 0-19. Table 9. Mean annual incidence of diseases associated with idiopathic acute anterior uveitis (MU) per 1000 population in different age groups. Age group (years) Diseases associated with idiopathic AAU 0-9 10-19 20-29 30-39 40-49 50-59 60-69 70orover Ankylosing spondylitis Reiters disease Psoriatic arthritis Ulcerative colitis No associated disease.4 0.7 4.6 4.4 3.3 1.1 0.6 0.4 0.3 0.4 0 0.4 0.4.3 0.9 0.5 0.9 3.7 15.4 21.9 21.3 17.7 22.4 13.9 Total 0.9 4.5 16.9 27.2 27.1 21.5 23.5 14.4 Table 10. Mean annual incidence of posterior uveitis entities in different age groups. Age group (years) Diagnosis 0-9 10-19 20-29 30-39 40-49 50-59 60-69 70orover Toxoplasmic retinochoroiditis 1.8 0.3 Tuberculous uveitis.5 Geographic choroiditis.3 Juvenile hemorrhagic maculopathy 0.4 0 Candida endophthalmitis.5 Other forms of posterior uveitis.8 0.4 0.7 Total ~ ~ ~.8 2.5 1. 0.9 valence of all cases with posterior uveitis ranged from 1.9 to 6.7 (mean 4.6) per 1000 population (Table 7). The prevalence of panuveitis ranged from 0.7 to 0.9 (mean 0.8) per 1000 population. The incidence of uveitis varied according to the patient s age. 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), and it was highest in the age group 30-49 years (Table 8). Juvenile rheumatoid arthritis and varicella iridocyclitis appeared only in children and young adults under 30 years. Herpes zoster uveitis and tuberculous iri- docyclitis appeared only after the age of 40 years. The incidence of other anterior uveitis entities in different age groups is shown in Table 8. Of the diseases associated with idiopathic acute anterior uveitis, ankylosing spondylitis appeared after the age of 10-19 years and the incidence increased to a maximum of 4.6 per 1000 population in the age group 30-39 years and after that decreased gradually to the oldest age group (Table 9). Reiter s disease appeared only in the age group 20-49 years and ulcerative colitis in the age group 10-59 years (Table 9). Toxoplasmic retinochoroiditis, juve- nile hemorrhagic maculopathy and geographic choroiditis were diseases of young adults and appeared in the age group 20-39 years (Table 10). Tuberculous posterior uveitis and candida endophthalmitis appeared in the age group 50-59 years. Discussion The most common uveitis entity in this study was idiopathic acute anterior uveitis with a mean annual incidence of 17.1 per 1000 population, which was as high as the incidence of all uveitis cases 79 -

ACTA OPHTHALMOLOGICA SCANDINAVICA 1997 in France (Vadot et al. 1984) and in the United States (Darrell el al. 1962). The high incidence of acute anterior uveitis in Finland may be due to genetic factors, e.g. the high frequencies of HLA-B27 in general population and of HLA-B27 associated acute anterior uveitis in Finland. In general populations the frequency of HLA-B27 is 14% in Finland (Saari el al. 1981a), 8.2% in England (Mapstone & Woodrow 1975), 1 o/u in Japan (Sasaki et al. 1979) and there is a practical absence of HLA-B27 and rheumatic acute anterior uveitis among black people in West Africa (Ayanru 1977). The frequency of HLA-B27 in patients with acute anterior uveitis is 83.8% in Finland (Saari el al. 1981a), 55.7% in England (Mapstone & Woodrow 1975), and 18.8% in Japan (Sasaki et al. 1979). Infections caused by infective agents including Yersinia (Saari et al. 1980a), Salmonella (Saari el al. 1980b), Campylobacter (Saari & Kauranen 1980), Shigella and Chlamydia (Saari et al. 1981b) may trigger acute anterior uveitis in HLA-B27 positive patients. However, the frequency of these environmental factors cannot explain the differences in the incidence rates of acute anterior uveitis e.g. between Finland, France and West Africa. In this study the low incidence rates of other anterior uveitis entities than idiopathic acute anterior uveitis were comparable to those reported in France (Vadot et al. 1984). The incidence of herpes zostcr uveitis was 0.4 per 1000 in this study and 0.48 per 100000 in France, of Posner-Schlossman syndrome 0.4 per 1000 in this study and 0.24 per 100000 in France, and of Fuchs heterochromic iridocyclitis 0.2 per 1000 in this study and 0.24 per 100000 in France. The incidence of idiopathic chronic anterior uveitis was only 0.3 per 1000 in this study whereas it was 1.7 per 1000 in France (vddot ct al. 1984). The incidence of intermediate uveitis (pars planitis) was 0.3 per 1000 population in this study while it was over three times higher in France (Vadot et al. 1984), suggesting that the genetic and/or triggering factors of intermediate uveitis may be more common in France than in Finland. Toxoplasmic retinochoroiditis was the leading cause of posterior uveitis, accounting for 20-54% of these cases both in Europe (Saari et al. 1975; Perkins & Folk 1984; Vadot et al. 1984; Paivonsalo-Hietanen et al. 1994) and in the United States (Perkins & Folk 1984; Henderly et al. 1987; Holland & Engstrom 1988) and it was the leading cause of all uveitis cases in Nigeria (Ayanru 1977) and in Brazil (Belfort 1988). The incidence of toxoplasmic retinochoroiditis was 0.3 per 1000 population in this study and 2.16 per 1000 population in France (Vadot et al. 1984). Toxoplasma cysts and tachyzoites cannot survive freezing under natural conditions (Saari & Raisanen 1976), which may explain the more rare occurrence of toxoplasmosis in northern countries. Antibodies against Toxoplasma gondii were present in 25% of the adult population in southern Finland (Turunen et al. 1985) and in 84% in France (Desmonts & Couvreur 1974). However, the incidence rate of congenital toxoplasmosis was 2 per 1000 births in Finland (Turunen et al. 1985) and 3 per 1000 births in France (Desmonts & Couvreur 1974). In France there is a smaller proportion of non-immunized fertile women than in Finland, which may explain the more equal maternal infection and congenital toxoplasmosis in these countries with different epidemiological conditions. In northern Finland 94% of cases with acute lesions of toxoplasmic retinochoroiditis showed recurrent active toxoplasmic retinochoroiditis of congenital origin and 6% showed acquired toxoplasmic retinochoroiditis (Saari 1977). Acquired ocular toxoplasmosis is a well-documented disease also in the United States (Holland & Engstrom 1988), and it may be more frequent in heavily contaminated areas (Belfort 1988). This may partly explain why the incidence rates of toxoplasmic retinochoroiditis and of congenital toxoplasmosis in Finland and in France are not directly comparable. In this study different anterior, intermediate and posterior uveitis entities did not show any significant variation of the incidencc rates in the years 1980-1982 and 1988. However, new cases of tuberculous uveitis did not appear after the year 1981, which reflects the decrease of the incidence of systemic tuberculosis during past decades. In this study there was not a single case of syph Similar disappearance of tuberculosis and syphilis as conspicuous causes of uveitis could be seen both in Finland (Miettinen 1958; Saari et al. 1975; Paivonsalo-Hietanen et al. 1994) and in the United States (Woods 1960; Perkins & Folk 1984; Henderly et al. 1987). The acquired immunodeficiency syndrome led to a marked increase in the number of cytomegalovirus retinitis in Los Angeles during the 1980 s (Henderly et al. 1987). In this material not a single case of acquired immunodeficiency syn- drome was seen. Neither was there any case of Lyme disease, but some cases were seen after the completion of this study, suggesting that this disease may show an increasing frequency in southwestern Finland during the 1990 s. Toxocariasis accounted for 2.6-3.0% of uveitis cases in the United States (Perkins &Folk 1984; Henderly et al. 1987), 1.5% in England (Perkins & Folk 1984), and 0.8% in France (Vadot et al. 1984). Toxocariasis has not been reported earlier in Finland and there was not a single case of toxocariasis in this study. BehGet s disease and Vogt-Koyanagi- Harada disease were the leading causes of uveitis in Japan (Imai et al. 1971). Our material included only one case of Behget s disease (prevalence 0.05 per 1000 population), but not a single new case was observed. The incidence of Beh- Get s disease was 0.24 per 100000 and the prevalence 0.6 per 1000 in France (Vadot et al. 1984). This study did not reveal any case of Vogt-Koyanagi-Harada disease and only one such case has been reported earlier in Finland (Saari 1974). Vogt-Koyanagi-Harada disease was reported neither in uveitis surveys in France (Vadot et al. 1984) nor in England (Perkins & Folk 1984), but it occurred in 3.3% of all cases in Los Angeles (Henderly et al. 1987). The prevalence of uveitis was 75.4 per 1000 population in our study, which was clearly higher than the prevalence of 38 per 100000 reported from France (Vadot et al. 1984). The difference is due to the high number of anterior uveitis (prevalence 68.7 per 1000) and especially of idiopathic acute anterior uveitis cases (prevalence 48.5 per 100000) in south-western Finland. The prevalences of Posner-Schlossman syndrome, Fuchs heterochromic iridocyclitis and of herpes zoster iriodcyclitis were comparable to the prevalence rates reported in France (Vadot et al. 1984). The prevalence rate of intermediate uveitis was lower in our material than in France (Vadot et, al. 1984). Also, the prevalence rates gf POST terior and panuveitis can be deducea to be lower in Finland than in France, although definitive prevalence rates.,were lacking in the French study (Vadh et al. 1984). This is the first study to present incidence rates per population of different uveitis entities in different age groups. Our results support the concept that many uveitis entities tend to affect mostly adolescents and adults, but some of them may occur in all age groups (Godfrey 1988). Such entities are idiopathic acute 80

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