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Epidemiology of Uveitis among the Chinese Population in Taiwan
Epidemiology of Uveitis among the Chinese Population in Taiwan A Population-Based Study De-Kuang Hwang, MD,1,2 Yiing-Jeng Chou, MD, PhD,2 Cheng-Yun Pu, PhD,2 Pesus Chou, DrPH2,3 Purpose: This study aimed to investigate the incidence and prevalence of uveitis in Taiwan, and then analyzed the risk factors related to uveitis using multivariate regression. Design: Population-based cohort study using medical claims data. Participants: We randomly selected 1 000 000 residents from the Taiwan National Health Insurance Research Database. All participants with correct registry data (96%) were included in the study. The study period was from 2000 to 2008. Methods: All types of uveitis were identified using the International Classification of Diseases, 9th revision, Clinical Modification diagnostic codes. The annual incidence and cumulative prevalence of uveitis were calculated. A univariate and a multivariate Poisson regression were used to determine the risk factors associated with uveitis. Main Outcome Measures: The first diagnosis of uveitis noted during the study period. Results: The annual cumulative incidence rate of uveitis ranged from 102.2 to 122.0 cases per 100 000 persons over the study period, and the average incidence density was 111.3 cases per 100 000 person-years (95% confidence interval, 108.4 –114.1). The cumulative prevalence was found to have increased from 318.8 cases per 100 000 persons in 2003 to 622.7 cases per 100 000 persons in 2008. Anterior uveitis was the most common location and accounted for 77.7% of all incident cases, which was followed by panuveitis, posterior uveitis, and intermediate uveitis. Multivariate regression analysis showed that males, the elderly, and individuals who lived in an urban area had higher incidence rates for uveitis. Conclusions: The epidemiology of uveitis in Taiwan differs from most previous studies in other countries. The incidence of uveitis in Taiwan has increased significantly recently. The elderly and individuals living in urban areas are the populations that are most commonly affected by uveitis. These findings are consistent with suggestions found in several recent studies. Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. Ophthalmology 2012;119:2371–2376 © 2012 by the American Academy of Ophthalmology.
Uveitis is defined as a group of disease entities with intraocular inflammation. It can be classified as anterior, intermediate, posterior, or panuveitis based on the primary site(s) of inflammation.1 The inflammation may be owing to an infection or be associated with a systemic immunemediated disease, or it may be the result of medication, trauma, operative procedure, or even an unknown etiology.2 The course of the disease can be classified as acute, recurrent, or chronic based on the onset and duration of the inflammation. Prolonged inflammation and recurrent episodes may lead to various ocular complications, including corneal decompensation, cataract, secondary glaucoma, macular edema, retinal detachment or optic nerve atrophy, all of which can lead to a decrease in vision.3 Previous studies have shown that 4% to 35% of uveitis patients eventually suffered from visual impairment in 1 or both eyes.4,5 Based on Durrani’s review,6 uveitis may be responsible for 5% to 20% of all cases of blindness in developed countries. Thus, uveitis has not only a profound influence on © 2012 by the American Academy of Ophthalmology Published by Elsevier Inc.
the patient’s quality of life because of the aggravating pain and discomfort as well as a reduced visual function, it also has the potential to have a substantial socioeconomic impact on the entire country.6,7 Population-based studies exploring the epidemiology of uveitis are relatively scarce. Previous studies found that the incidence rate of uveitis ranged from 17 to 52 cases per 100 000 person-years in the United States and from 11 to 23 cases per 100 000 person-years in Europe, and was about 27 cases per 100 000 person-years in Africa.8 –15 With different study designs and follow-up periods, the prevalence of uveitis has been reported as being 40.4 cases per 100 000 persons in Japan, 310 to 730 cases per 100 000 persons in Southern India, and 152 cases per 100 000 persons in China.16 –19 Several risk factors have been identified as being associated with the incidence of uveitis, namely gender, age and socioeconomic status.14,20 –22 The differences in the epidemiology of uveitis tend to be mainly owing to the different etiologies related to uveitis in ISSN 0161-6420/12/$–see front matter http://dx.doi.org/10.1016/j.ophtha.2012.05.026
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Ophthalmology Volume 119, Number 11, November 2012 different populations. It is worth noting that it was found recently that uveitis has a higher incidence among the elderly.9,23 Although uveitis is an important, sight-threatening ocular disease, knowledge of its epidemiology, and especially its incidence and prevalence, in Asian countries and among Chinese populations is very limited. Taiwan implemented a National Health Insurance program in 1995, which provides a comprehensively singlepayer medical care system to all citizens in Taiwan. It covers ⬎98% of all residents, and ⬎99% of all hospitals and clinics are participate in the program. The National Health Insurance Research Database (NHIRD) collects all registration files and claim data from all ambulatory and in-hospital patients. A large number of studies have been conducted that analyzed the incidence of various diseases using this database, and the high representativeness of the population in Taiwan has been confirmed.24 –27 In the present study, we used the NHIRD to explore the epidemiology of uveitis and analyze the risk factors in Taiwan.
Materials and Methods Study Design The present population-based study was designed as a retrospective cohort study. It uses a longitudinal health insurance database to follow and analyze the incidence and the cumulative prevalence of uveitis in a fixed cohort randomly selected from the total population of Taiwan since 2000.
Study Sample The NHIRD is maintained by the National Health Research Institutes (NHRI). In 2000, for the purpose of scientific research, the NHRI randomly selected 1 million subjects from the registry data of the NHIRD, representing about 4% of all beneficiaries at the time. The database consists of all claim data, including diagnostic codes represented by the International Classification of Disease, 9th revision, Clinical Modification (ICD-9-CM), medical prescriptions, operative procedures, and insurance registry data, of all the sampled subjects from 1996 to 2008. After comparison, no differences were found in the age and gender distribution between these subjects and the total population of Taiwan. To ensure the privacy of all participants and their care providers, the NHRI scrambled all data that could possibly be used to identify patients or providers before releasing it.
Inclusion and Exclusion Criteria All subjects in the longitudinal database were enrolled in this study. Because A-codes were used as diagnostic codes in the claim data from 1996 to 1999, and because uveitis could not be clearly classified using A-codes, we used all ambulatory claim data in the database starting from 2000. Each claim made by an ophthalmologist containing ⱖ1 qualifying ICD-9-CM code relevant to uveitis was identified (Table 1, available at http://aaojournal.org). All cases were classified as anterior uveitis, intermediate uveitis, posterior uveitis, or panuveitis according to the ICD-9-CM codes. Uveitis classes were defined based on the first diagnostic code found in the database. If a diagnostic code of a different class appeared during the follow-up period, the uveitis class was then categorized as panuveitis for the remainder of the study period. Subjects with abnormal registry claim data, such as unknown gender, inconsistent birth date, or incomplete insurance data were
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excluded from the study (about 4.4%). To exclude postoperative inflammation from our study, we ignored claim data for uveitis that occurred within 90 days after any intraocular surgical procedure when identifying the incidence and prevalence of cases. Because we could not clearly distinguish endogenous from exogenous endophthalmitis from people who had ever received a surgical procedure in our database, we excluded all cases who had been diagnosed with acute purulent endophthalmitis after any intraocular surgical procedure.
Incidence and Prevalence of Uveitis The first time a patient sought medical help for a disease with a uveitis diagnostic code in the database was defined as the incident time and the patient was then counted as an incident case in that year. The annual cumulative incidence rates were calculated as persons who developed uveitis divided by the total population at risk on January 1 of that year. Incidence rates were calculated stratified by age groups (ⱕ16, 17– 64, or ⬎64), gender, and degree of urbanization. Because some incident cases in the first few years could actually have been recurrent cases, the data from the first 3 years were ignored and only the incident cases diagnosed after January 1, 2003, were included when analyzing risk factors. The period incidence was calculated as the incidence density. For those participants who were not an incident case, a person-year was counted from January 1, 2003, to the last day that each individual was covered by the system, based on their individual registry data. For those incident cases, person-years were counted until the incident time. All subjects who had any diagnostic code for uveitis were counted as a prevalent case in that year. For those patients who had ⱖ2 claims containing diagnostic codes for uveitis, we defined them as recurrent cases and they were counted as the prevalence in every year from the second uveitis diagnosis to the last day that they were covered. Cumulative prevalence was calculated for each year as the number of the prevalence cases that year divided by the total study population in the database in the middle of that year.
Covariates The individual’s age, gender, degree of urbanization, and amount of insurance payment were obtained from the registry files. The age of the subjects was classified into 7 groups (ⱕ15, 16 –25, 26 –35, 36 – 45, 46 –55, 56 – 65, and ⱖ66 years old) when analyzing risk factors. The degree of urbanization was classified into 3 categories (urban, suburban, and rural) based on population density, medical resources, age, and education of the people in these areas. Based on these criteria, 70 regions were defined as urban, 144 regions were defined as suburban, and 96 regions as rural area in Taiwan.28 In Taiwan, insurance premiums vary based on income. We defined the economic status according to the subject’s insurance payment amount in the registry files. Subjects were defined as “low income” when their insurance amount was ⬍NT$20 000 (US$625), “middle income” when their insurance amount was between NT$20 000 and NT$40 000 (US$625–1250), “high income” when the insurance amount was ⬎NT$40 000 (US$1250), and “fixed premium” if the individual belonged to a class for which the premium was fixed regardless of family income (farmer, fisherman, etc). The degree of urbanization and the insurance amount of each participant first indicated in the record were used for the annual analysis.
Data Analysis To determine the relationship between incidence and demographic factors, univariate and multivariate analyses were performed using
Hwang et al 䡠 Uveitis among Chinese in Taiwan
Figure 1. Age-stratified incidence and crude cumulative incidence of uveitis across the study periods showed that incidence among elders was significantly higher than that among adults and children (P⬍0.001).
Poisson regression to calculate the rate ratio and the adjusted rate ratio (aRR). All incident cases from 2003 to 2008 were analyzed simultaneously. For the sensitivity analysis, we excluded those patients who were listed in our database as having been diagnosed in the past with acute purulent endophthalmitis or with an intraocular tumor. The SAS statistical package version 9.0 (SAS Inc, Cary, NC) was used for all estimations. The 95% confidence intervals of the incidence density and rate ratio were calculated, and the 2-sided significance level was set at 0.05.
Results In 2000, there were initially 956 147 participants with correct registry data enrolled in the study. A total of 9217 persons were
found to having claim data with a diagnostic code for uveitis. From that number, 5866 cases were first diagnosed with uveitis after January 1, 2003. The annual cumulative incidence rate of uveitis ranged from 102.2 cases per 100 000 persons to 122.0 cases per 100 000 persons between 2003 and 2008. The average incidence was 111.3 cases per 100 000 person-years from 2003 to 2008, with the 95% confidence interval ranging between 108.4 cases and 114.1 cases per 100 000 person-years (Table 2, available at http:// aaojournal.org). The cumulative incidence rates in each year were consistently higher among the elderly (ranging from 160.7 cases per 100 000 persons to 216.8 cases per 100 000 persons) compared with the adult group (from 103.5 cases per 100 000 persons to 131.1 cases per 100 000 persons) and the children group (from 28.5 cases per 100 000 persons to 46.1 cases per 100 000 persons; Fig 1). The cumulative incidence for males (ranging from 115.0 cases per 100 000 persons to 132.9 cases per 100 000 persons) was consistently higher than that for the females (from 89.3 cases per 100 000 persons to 110.7 cases per 100 000 persons). Anterior uveitis was the most common type of uveitis in each year, with the inflammation restricted to the anterior chamber in 77.7% of the incident cases. In contrast, 15.2% of the incident cases were panuveitis, 6.7% of the incident cases were posterior uveitis, and 0.4% of the incident cases were intermediate uveitis. The prevalence rate of uveitis ranged from 318.8 cases per 100 000 persons in 2003 to 622.7 cases per 100 000 persons in 2008. Similar results as for the incidence rate were found for the prevalence rate, with the elderly having a higher prevalence rate than adults or children and males having a higher prevalence rate than females; anterior uveitis was the most common type of uveitis. Using univariate analysis, the differences in the incidence rates among the age groups, gender, urbanization, and insurance income groups were statistically significant (Table 3). After adjusting for the other variables, it was found that the incidence of uveitis increased with age (P⬍0.001) and that males had a higher incidence rate than females (aRR, 1.24; P⬍0.001). Compared with
Table 3. Univariate Poisson Regression for Incident Cases After 2003 Cases Incident Cases Age group (yrs) ⱕ15 16–25 26–35 36–45 46–55 56–65 ⱖ66 P for linear trend Gender Female Male Insurance area† Rural Suburban Urban Insurance amounts (based on wages earned) Wage ⱕ20 000 (NT$) Wage ⬎20 000 and ⱕ40 000 (NT$) Wage ⱖ40 000 (NT$) Fixed premium‡
%
5866
Person-Years
ID
5271575
111.3
RR
95% CI 108.4–114.1
399 710 946 1158 1115 688 850
6.8 12.1 16.1 19.7 19.0 11.7 14.5
1005288 890962 899091 919540 734523 385607 436564
39.7 79.7 105.2 125.9 151.8 178.4 194.7
1 2.01* 2.65* 3.17* 3.83* 4.50* 4.91*
2609 3257
44.5 55.5
2620195 2651381
99.6 122.8
1 1.23*
1.17–1.30
441 1748 3677
7.5 29.8 62.7
468769 1645618 3157188
94.1 106.2 116.5
1 1.13* 1.24*
1.02–1.25 1.12–1.37
979 2103 1529 1255
16.7 35.9 26.1 21.4
1080132 1905713 1174441 1111289
90.6 110.4 130.2 112.9
1 1.22* 1.44* 1.25*
1.13–1.31 1.33–1.56 1.15–1.36
1.78–2.27 2.36–2.98 2.83–3.56 3.41–4.29 3.97–5.09 4.36–5.53 ⬍0.001
CI ⫽ confidence interval; ID ⫽ incidence density (1/100 000 year); RR ⫽ risk ratio. *P⬍0.001. † Urbanization of insurance areas was categorized based on population density, medical resource, age, and education of the areas. ‡ Fixed premium is defined as when the participants’ insurance types was farmer, fisherman, veteran, or monk.
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Ophthalmology Volume 119, Number 11, November 2012 Table 4. Multivariate Poisson Regression for Incident Cases After 2003 aRR Age group (yrs) ⱕ15 1 16–25 2.00 26–35 2.60 36–45 3.11 46–55 3.76 56–65 4.51 ⱖ66 5.03 Gender Female 1 Male 1.24 Insurance area* Rural 1 Suburban 1.18 Urban 1.29 Insurance amount (based on wages earned) Wage ⱖ40 000 (NT$) 1 Wage ⬎20 000 and ⱕ40 000 (NT$) 0.94 Wage ⱕ 20 000 (NT$) 0.94 Fixed premium† 0.93
95% CI
P Value
1.77–2.27 2.30–2.93 2.77–3.50 3.34–4.23 3.98–5.10 4.45–5.67
⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001
1.18–1.31
⬍0.001
1.06–1.32 1.16–1.43
0.002 ⬍0.001
0.88–1.01 0.87–1.02 0.85–1.01
0.090 0.160 0.086
aRR ⫽ adjusted risk ratio; CI ⫽ confidence interval. *Urbanization of insurance areas was categorized based on population density, medical resource, age, and education of the areas. † Fixed premium is defined as when the participants’ insurance types was farmer, fisherman, veteran, or monk.
individuals from rural areas, participants from suburban and urban regions showed to have a higher incidence rate (aRR, 1.18 and 1.29, respectively; P ⫽ 0.002 and P⬍0.001, respectively). When the insurance income group was considered, although the incidence rate among the low-income group was lower than among the high-income group (aRR, 0.94), the difference was not significant (Table 4). Within the database, there were a total of 179 participants who were diagnosed with ocular tumors and 491 cases that had been diagnosed with acute purulent endophthalmitis. After excluding these cases, the average incidence rate of uveitis was 111.1 persons and 109.2 persons per 100 000 person-years, respectively. Furthermore, the results of the risk factor estimations did not differ much, whether these cases were excluded or included.
Discussion In our study, we found that the average incidence density of uveitis in Taiwan was 111.3 persons per 100 000 personyears. There are no reports on Chinese populations with which the present study can be compared. However, Reeves et al23 studied the incidence of uveitis among the elderly using Medicare using a similar study design as the present study. They showed that the average incidence rate of the elderly population in the United States was 340.9 cases per 100 000 person-years, which was higher than our results of 194.7 cases per 100 000 person-years.23 The results of Reeves’ and our studies are relatively higher than those obtained in previous studies. One reason might be the method of data collection. Most of the previous studies
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ascertained cases based on chart review, something which is not possible in our research, and hence some overestimation might happen. Although the validity of diagnostic coding within other disease was as high as 97.9% in the NHIRD,27 we still could not obtain the evidential nonconfirmation rate of uveitis in our study. One possible reference would be the study of Gritz and Wong,9 which was conducted in northern California and ascertained uveitis cases based on diagnostic codes confirmed by chart review. After reviewing the cases, about 44.8% of them were eventually categorized as “not uveitis.”9 If the nonconfirmation rate is similar in our study, then the incidence rate in Taiwan would be 61.4 cases per 100 000 person-years, which is still higher than in previous studies in other countries. Despite the fact that our research has a study period of 9 years, some of the incident cases might actually still be recurrent cases with long latent periods, which may lead to some overestimation. However, incidences with a longer observational period may be closer to the real situation. Our results showed that the annual incidence rate since 2003 was steady and that the number of incidences in 2008 did not change much from those in 2003. The relatively lower incidence rate in previous studies might also be owing to their hospital-based design, which only includes cases that seek medical help at specific hospitals in a region. In such cases, underestimation would happen if participants seek medical help at other hospitals and it would lower the results in relation to the population-based data. Another reason might be the association with the national health system in Taiwan, which has made access to health care much easier and more available compared with many other countries. The cumulative annual prevalence found in our study ranges from 319 to 623 cases per 100 000 persons. These findings are higher than previous population-based reports for southern China, Japan, and India.17–19 Most previous studies define the prevalent cases as “active uveitis,” which theoretically cannot be addressed without reviewing the medical charts. Because systemic evaluation is suggested clinically and awareness of recurrence made clear at the time the second uveitis occurs or when the disease course is prolonged, we counted the patient as a prevalent case in the incident year and in every year after the second time the uveitis code occurred. The prevalence of uveitis among the elderly in the study by Reeve et al, which used a similar definition of prevalent cases, ranged from 511 cases per 100 000 persons to 1231 cases per 100 000 persons, was comparable with our finding (537.5 cases per 100 000 persons in 2002 to 1274.7 cases per 100 000 persons in 2008).23 We might have overestimated the actual prevalence because some cases may never have been active during the year based on this definition of prevalence. However, if we defined the prevalent cases as having ⱖ1 code reported during each calendar year, the average 1-year period prevalence would be 193.9 cases per 100 000 persons. Across all types of uveitis, anterior uveitis was the most common type in our results. Overall, 77.7% of all new cases were diagnosed as anterior uveitis, and this proportion is higher than the previous 2 studies carried out in Taiwan, one
Hwang et al 䡠 Uveitis among Chinese in Taiwan of which revealed that panuveitis represented 40% of all cases in a medical center.29,30 One reason for this is that anterior uveitis is relatively mild and easy to treat compared with other types of uveitis, and previous studies in Taiwan have only analyzed uveitis cases from a single medical center. The NHIRD contains not only medical centers, but also local hospitals. Local hospitals tend to deal with a greater number of milder cases and this would lead to an underestimation in the previous studies. Comparing with the results in the study by Reeves et al, the proportion of anterior uveitis among all incident cases was similar, but the proportion of panuveitis was higher in our database than in Medicare.23 The results might owing to the higher incidence of uveitis with some specific etiology such as Behçet’s disease and Vogt-Koyanagi-Harada disease in the Chinese population. Multivariate regression showed that males in our database were at a slightly higher risk of uveitis than females, and this finding was consistent for every year of the study period. This finding is similar to previous studies in Asia and Taiwan.17,19,29 –31 The relationship between aging and the incidence of uveitis was also significant. The incidence and prevalence of uveitis among the elderly was consistently higher than among adults or children. Multivariate analysis showed that getting older resulted in a higher incidence of uveitis and that this trend effect was significant. This finding is quite different from previous reports.31 It does, however, agree with recent findings of Gritz and Wong’s study9 in the United States and the study by Rathinam et al19 in India. Although the reason for the increasing incidence rate among the elderly is not clear, an explanation might be changes in the epidemiology of some specific types of uveitis, such as virus-induced uveitis or rheumatic arthritis–related uveitis. Our results nevertheless suggest that the disease burden of uveitis among the elderly and its increasing impact should not be ignored, especially as the population continues to age. Few studies have explored the relationship between socioeconomic status and the incidence of uveitis. Research in Finland has shown that the incidence of uveitis is higher among individuals with a lower socioeconomic status, and a study in Iran found that ⬎80% of uveitis cases occurred in the upper socioeconomic ranks.21,22 We analyzed socioeconomic status by linking it with the resident’s insurance area and their insurance amount. The former usually indicates where the individual lives and/or works, and the latter reflects to a degree the individual’s income. Our result showed that the incidence of uveitis was significantly higher among individuals who lived in an urban environment. However, although individuals with higher insurance amounts run a slightly higher risk, after adjustment this difference was not significant. The increased medical utilization among people living in urban areas may have increased their likelihood of being captured as a case given the methodology of the present study. Another possible explanation is that sicker people may move to a more urbanized area. We have tried to eliminate cases that moved to an area with higher urbanization after the first diagnosis of uveitis by measuring each individual’s level of urbanization based on their area of insurance during their first visit
to a physician. The possibility, however, remains that ophthalmologists in the urban area are more aware of the disease and are thus more likely to code for uveitis. The findings in our study could also be explained by the hardscrabble hypothesis that theorizes that the human’s immune system has developed a defense for the exposure to some damage-related antigens. Reduction in chronic tissue injury may be followed by underpresentation of the self-antigens and influence the maturity of the human adaptive immune system, which in turn leads to an increase in autoimmune disease among people with higher socioeconomic status.32 Although making a clinical diagnosis of uveitis is easier than for other systemic diseases, which may need to be supported by laboratory tests, misdiagnosis still occurs. To eliminate misdiagnosis caused by the uveitis masquerade syndrome, we excluded all cases that were ever diagnosed as having an ocular malignancy. To exclude exogenous endophthalmitis related to surgery or trauma from our report, we excluded all cases with a diagnosis of acute purulent endophthalmitis after intraocular operative procedures. However, we might overcount those cases that underwent surgery years earlier and do not appear during our study period. Hence, we tried to exclude all cases that were diagnosed with acute endophthalmitis for the sensitivity analysis. The incidence and the results for the modified risk factors estimations without these 2 specific diagnoses remained similar. Another limitation of our study is that the etiology and severity of each case could not be clarified without the individual’s medical record, and thus the variation between different types of uveitis may have affected the epidemiological findings for all types of uveitis. Although we could have tried to presume the etiology by using the patient’s specific diagnostic codes or by finding the comorbidity with other associated diagnoses, uncertainties and misclassifications would be unavoidable. As a result of this limitation, further population-based studies designed to use medical records are needed. In summary, we attempted to explore the epidemiology of uveitis in a Chinese population and made several findings. Firstly, the incidence of uveitis in Taiwan is relatively higher than in other countries. Secondly, our results indicate that males have a higher incidence rate than females. Thirdly, increased age is a risk factor and the elderly are more commonly affected by uveitis. Fourthly, urbanites show a higher incidence of uveitis. More studies exploring the epidemiology of uveitis are required as the incidence of this sight-threatening disease is on the rise.
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Ophthalmology Volume 119, Number 11, November 2012 4. Couto C MJ. Epidemiological Study of Patients with Uveitis in Buenos Aires, Argentina. Amsterdam: Kugler; 1993. 5. Rothova A, Suttorp-van Schulten MS, Frits Treffers W, Kijlstra A. Causes and frequency of blindness in patients with intraocular inflammatory disease. Br J Ophthalmol 1996;80: 332– 6. 6. Durrani OM, Meads CA, Murray PI. Uveitis: a potentially blinding disease. Ophthalmologica 2004;218:223–36. 7. Gardiner AM, Armstrong RA, Dunne MC, Murray PI. Correlation between visual function and visual ability in patients with uveitis. Br J Ophthalmol 2002;86:993– 6. 8. Darrell RW, Wagener HP, Kurland LT. Epidemiology of uveitis. Incidence and prevalence in a small urban community. Arch Ophthalmol 1962;68:502–14. 9. Gritz DC, Wong IG. Incidence and prevalence of uveitis in Northern California; the Northern California Epidemiology of Uveitis Study. Ophthalmology 2004;111:491–500. 10. Suhler EB, Lloyd MJ, Choi D, et al. Incidence and prevalence of uveitis in Veterans Affairs Medical Centers of the Pacific Northwest. Am J Ophthalmol 2008;146:890 – 6[e8]. 11. Freedman J. Incidence of uveitis in Bantu-speaking negroes of South Africa. Br J Ophthalmol 1974;58:595–9. 12. Mercanti A, Parolini B, Bonora A, et al. Epidemiology of endogenous uveitis in north-eastern Italy. Analysis of 655 new cases. Acta Ophthalmol Scand 2001;79:64 – 8. 13. Paivonsalo-Hietanen T, Tuominen J, Vaahtoranta-Lehtonen H, Saari KM. Incidence and prevalence of different uveitis entities in Finland. Acta Ophthalmol Scand 1997;75:76 – 81. 14. Miettinen R. Incidence of uveitis in Northern Finland. Acta Ophthalmol (Copenh) 1977;55:252– 60. 15. Tran VT, Auer C, Guex-Crosier Y, et al. Epidemiological characteristics of uveitis in Switzerland. Int Ophthalmol 1994; 18:293– 8. 16. Dandona L, Dandona R, John RK, et al. Population based assessment of uveitis in an urban population in southern India. Br J Ophthalmol 2000;84:706 –9. 17. Hu SXC, Yang P, Huang X. An epidemiological survey of uveitis in Southern China. Chinese Journal of Ophthalmology 2002;2:1. 18. Nakao K, Ohba N. Epidemiology of endogenous uveitis in Kagoshima Prefecture, Southwest Japan. Nippon Ganka Gakkai Zasshi 1996;100:150 –5.
19. Rathinam SR, Krishnadas R, Ramakrishnan R, et al. Populationbased prevalence of uveitis in Southern India. Br J Ophthalmol 2011;95:463–7. 20. Paivonsalo-Hietanen T, Tuominen J, Saari KM. Seasonal variation of endogenous uveitis in south-western Finland. Acta Ophthalmol Scand 1998;76:599 – 602. 21. Soheilian M, Heidari K, Yazdani S, et al. Patterns of uveitis in a tertiary eye care center in Iran. Ocul Immunol Inflamm 2004;12:297–310. 22. Saari KM, Paivonsalo-Hietanen T, Vaahtoranta-Lehtonen H, et al. Epidemiology of endogenous uveitis in south-western Finland. Acta Ophthalmol Scand 1995;73:345–9. 23. Reeves S, Sloan F, Lee P, Jaffe G. Uveitis in the elderly: epidemiological data from the National Long-term Care Survey Medicare Cohort. Ophthalmology 2006;113:302–7[e1]. 24. Chen Y-Y, Lai C-H. Nationwide population-based epidemiologic study of Huntington’s disease in Taiwan. Neuroepidemiology 2010;35:250 – 4. 25. Chiu YM, Lai CH. Nationwide population-based epidemiologic study of systemic lupus erythematosus in Taiwan. Lupus 2010;19:1250 –5. 26. Bih S-H, Chien IC, Chou Y-J, et al. The treated prevalence and incidence of bipolar disorder among National Health Insurance enrollees in Taiwan, 1996-2003. Soc Psychiatry Psychiatr Epidemiol 2008;43:860 –5. 27. Cheng CL, Kao YHY, Lin SJ, et al. Validation of the National Health Insurance Research Database with ischemic stroke cases in Taiwan. Pharmacoepidemiol Drug Saf 2011;20:236 – 42. 28. Liu CY HYT, Chuang YL, Chen YJ, et al. Incorporating development stratification of Taiwan Township into sampling design of large scale health interview survey. Jian Kang Guan Li 2006;4:1–22. 29. Chung YM, Yeh TS, Liu JH. Endogenous uveitis in Chinese: an analysis of 240 cases in a uveitis clinic. Jpn J Ophthalmol 1988;32:64 –9. 30. Chou LC, Sheu SJ, Hong MC, et al. Endogenous uveitis: experiences in Kaohsiung Veterans General Hospital. J Chin Med Assoc 2003;66:46 –50. 31. Rathinam SR, Namperumalsamy P. Global variation and pattern changes in epidemiology of uveitis. Indian J Ophthalmol 2007;55:173– 83. 32. Naugler C, Conrad DM. The hardscrabble hypothesis: a reduction in chronic tissue damage has increased the incidence of autoimmune disease. Med Hypotheses 2010;74:366 –7.
Footnotes and Financial Disclosures Originally received: November 3, 2011. Final revision: May 14, 2012. Accepted: May 14, 2012. Available online: July 17, 2012. 1
The National Health Research Institutes supplied data for this study.
Manuscript no. 2011-1596.
Department of Ophthalmology, Taoyuan Veterans Hospital, Taoyuan, Taiwan.
2
Department of Public Health and Institute of Public Health, National Yang-Ming University, Taipei, Taiwan.
3
Community Medicine Research Center, National Yang-Ming University, Taipei, Taiwan.
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Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. Correspondence: Cheng-Yun Pu, PhD, Institute of Public Health, School of Medicine, National Yang-Ming University. No.155, Section 2, Linong Street, Taipei, 11221 Taiwan (ROC). E-mail: [email protected]
Uveitis is defined as a group of disease entities with intraocular inflammation. It can be classified as anterior, intermediate, posterior, or panuveitis based on the primary site(s) of inflammation.1 The inflammation may be owing to an infection or be associated with a systemic immunemediated disease, or it may be the result of medication, trauma, operative procedure, or even an unknown etiology.2 The course of the disease can be classified as acute, recurrent, or chronic based on the onset and duration of the inflammation. Prolonged inflammation and recurrent episodes may lead to various ocular complications, including corneal decompensation, cataract, secondary glaucoma, macular edema, retinal detachment or optic nerve atrophy, all of which can lead to a decrease in vision.3 Previous studies have shown that 4% to 35% of uveitis patients eventually suffered from visual impairment in 1 or both eyes.4,5 Based on Durrani’s review,6 uveitis may be responsible for 5% to 20% of all cases of blindness in developed countries. Thus, uveitis has not only a profound influence on © 2012 by the American Academy of Ophthalmology Published by Elsevier Inc.
the patient’s quality of life because of the aggravating pain and discomfort as well as a reduced visual function, it also has the potential to have a substantial socioeconomic impact on the entire country.6,7 Population-based studies exploring the epidemiology of uveitis are relatively scarce. Previous studies found that the incidence rate of uveitis ranged from 17 to 52 cases per 100 000 person-years in the United States and from 11 to 23 cases per 100 000 person-years in Europe, and was about 27 cases per 100 000 person-years in Africa.8 –15 With different study designs and follow-up periods, the prevalence of uveitis has been reported as being 40.4 cases per 100 000 persons in Japan, 310 to 730 cases per 100 000 persons in Southern India, and 152 cases per 100 000 persons in China.16 –19 Several risk factors have been identified as being associated with the incidence of uveitis, namely gender, age and socioeconomic status.14,20 –22 The differences in the epidemiology of uveitis tend to be mainly owing to the different etiologies related to uveitis in ISSN 0161-6420/12/$–see front matter http://dx.doi.org/10.1016/j.ophtha.2012.05.026
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Ophthalmology Volume 119, Number 11, November 2012 different populations. It is worth noting that it was found recently that uveitis has a higher incidence among the elderly.9,23 Although uveitis is an important, sight-threatening ocular disease, knowledge of its epidemiology, and especially its incidence and prevalence, in Asian countries and among Chinese populations is very limited. Taiwan implemented a National Health Insurance program in 1995, which provides a comprehensively singlepayer medical care system to all citizens in Taiwan. It covers ⬎98% of all residents, and ⬎99% of all hospitals and clinics are participate in the program. The National Health Insurance Research Database (NHIRD) collects all registration files and claim data from all ambulatory and in-hospital patients. A large number of studies have been conducted that analyzed the incidence of various diseases using this database, and the high representativeness of the population in Taiwan has been confirmed.24 –27 In the present study, we used the NHIRD to explore the epidemiology of uveitis and analyze the risk factors in Taiwan.
Materials and Methods Study Design The present population-based study was designed as a retrospective cohort study. It uses a longitudinal health insurance database to follow and analyze the incidence and the cumulative prevalence of uveitis in a fixed cohort randomly selected from the total population of Taiwan since 2000.
Study Sample The NHIRD is maintained by the National Health Research Institutes (NHRI). In 2000, for the purpose of scientific research, the NHRI randomly selected 1 million subjects from the registry data of the NHIRD, representing about 4% of all beneficiaries at the time. The database consists of all claim data, including diagnostic codes represented by the International Classification of Disease, 9th revision, Clinical Modification (ICD-9-CM), medical prescriptions, operative procedures, and insurance registry data, of all the sampled subjects from 1996 to 2008. After comparison, no differences were found in the age and gender distribution between these subjects and the total population of Taiwan. To ensure the privacy of all participants and their care providers, the NHRI scrambled all data that could possibly be used to identify patients or providers before releasing it.
Inclusion and Exclusion Criteria All subjects in the longitudinal database were enrolled in this study. Because A-codes were used as diagnostic codes in the claim data from 1996 to 1999, and because uveitis could not be clearly classified using A-codes, we used all ambulatory claim data in the database starting from 2000. Each claim made by an ophthalmologist containing ⱖ1 qualifying ICD-9-CM code relevant to uveitis was identified (Table 1, available at http://aaojournal.org). All cases were classified as anterior uveitis, intermediate uveitis, posterior uveitis, or panuveitis according to the ICD-9-CM codes. Uveitis classes were defined based on the first diagnostic code found in the database. If a diagnostic code of a different class appeared during the follow-up period, the uveitis class was then categorized as panuveitis for the remainder of the study period. Subjects with abnormal registry claim data, such as unknown gender, inconsistent birth date, or incomplete insurance data were
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excluded from the study (about 4.4%). To exclude postoperative inflammation from our study, we ignored claim data for uveitis that occurred within 90 days after any intraocular surgical procedure when identifying the incidence and prevalence of cases. Because we could not clearly distinguish endogenous from exogenous endophthalmitis from people who had ever received a surgical procedure in our database, we excluded all cases who had been diagnosed with acute purulent endophthalmitis after any intraocular surgical procedure.
Incidence and Prevalence of Uveitis The first time a patient sought medical help for a disease with a uveitis diagnostic code in the database was defined as the incident time and the patient was then counted as an incident case in that year. The annual cumulative incidence rates were calculated as persons who developed uveitis divided by the total population at risk on January 1 of that year. Incidence rates were calculated stratified by age groups (ⱕ16, 17– 64, or ⬎64), gender, and degree of urbanization. Because some incident cases in the first few years could actually have been recurrent cases, the data from the first 3 years were ignored and only the incident cases diagnosed after January 1, 2003, were included when analyzing risk factors. The period incidence was calculated as the incidence density. For those participants who were not an incident case, a person-year was counted from January 1, 2003, to the last day that each individual was covered by the system, based on their individual registry data. For those incident cases, person-years were counted until the incident time. All subjects who had any diagnostic code for uveitis were counted as a prevalent case in that year. For those patients who had ⱖ2 claims containing diagnostic codes for uveitis, we defined them as recurrent cases and they were counted as the prevalence in every year from the second uveitis diagnosis to the last day that they were covered. Cumulative prevalence was calculated for each year as the number of the prevalence cases that year divided by the total study population in the database in the middle of that year.
Covariates The individual’s age, gender, degree of urbanization, and amount of insurance payment were obtained from the registry files. The age of the subjects was classified into 7 groups (ⱕ15, 16 –25, 26 –35, 36 – 45, 46 –55, 56 – 65, and ⱖ66 years old) when analyzing risk factors. The degree of urbanization was classified into 3 categories (urban, suburban, and rural) based on population density, medical resources, age, and education of the people in these areas. Based on these criteria, 70 regions were defined as urban, 144 regions were defined as suburban, and 96 regions as rural area in Taiwan.28 In Taiwan, insurance premiums vary based on income. We defined the economic status according to the subject’s insurance payment amount in the registry files. Subjects were defined as “low income” when their insurance amount was ⬍NT$20 000 (US$625), “middle income” when their insurance amount was between NT$20 000 and NT$40 000 (US$625–1250), “high income” when the insurance amount was ⬎NT$40 000 (US$1250), and “fixed premium” if the individual belonged to a class for which the premium was fixed regardless of family income (farmer, fisherman, etc). The degree of urbanization and the insurance amount of each participant first indicated in the record were used for the annual analysis.
Data Analysis To determine the relationship between incidence and demographic factors, univariate and multivariate analyses were performed using
Hwang et al 䡠 Uveitis among Chinese in Taiwan
Figure 1. Age-stratified incidence and crude cumulative incidence of uveitis across the study periods showed that incidence among elders was significantly higher than that among adults and children (P⬍0.001).
Poisson regression to calculate the rate ratio and the adjusted rate ratio (aRR). All incident cases from 2003 to 2008 were analyzed simultaneously. For the sensitivity analysis, we excluded those patients who were listed in our database as having been diagnosed in the past with acute purulent endophthalmitis or with an intraocular tumor. The SAS statistical package version 9.0 (SAS Inc, Cary, NC) was used for all estimations. The 95% confidence intervals of the incidence density and rate ratio were calculated, and the 2-sided significance level was set at 0.05.
Results In 2000, there were initially 956 147 participants with correct registry data enrolled in the study. A total of 9217 persons were
found to having claim data with a diagnostic code for uveitis. From that number, 5866 cases were first diagnosed with uveitis after January 1, 2003. The annual cumulative incidence rate of uveitis ranged from 102.2 cases per 100 000 persons to 122.0 cases per 100 000 persons between 2003 and 2008. The average incidence was 111.3 cases per 100 000 person-years from 2003 to 2008, with the 95% confidence interval ranging between 108.4 cases and 114.1 cases per 100 000 person-years (Table 2, available at http:// aaojournal.org). The cumulative incidence rates in each year were consistently higher among the elderly (ranging from 160.7 cases per 100 000 persons to 216.8 cases per 100 000 persons) compared with the adult group (from 103.5 cases per 100 000 persons to 131.1 cases per 100 000 persons) and the children group (from 28.5 cases per 100 000 persons to 46.1 cases per 100 000 persons; Fig 1). The cumulative incidence for males (ranging from 115.0 cases per 100 000 persons to 132.9 cases per 100 000 persons) was consistently higher than that for the females (from 89.3 cases per 100 000 persons to 110.7 cases per 100 000 persons). Anterior uveitis was the most common type of uveitis in each year, with the inflammation restricted to the anterior chamber in 77.7% of the incident cases. In contrast, 15.2% of the incident cases were panuveitis, 6.7% of the incident cases were posterior uveitis, and 0.4% of the incident cases were intermediate uveitis. The prevalence rate of uveitis ranged from 318.8 cases per 100 000 persons in 2003 to 622.7 cases per 100 000 persons in 2008. Similar results as for the incidence rate were found for the prevalence rate, with the elderly having a higher prevalence rate than adults or children and males having a higher prevalence rate than females; anterior uveitis was the most common type of uveitis. Using univariate analysis, the differences in the incidence rates among the age groups, gender, urbanization, and insurance income groups were statistically significant (Table 3). After adjusting for the other variables, it was found that the incidence of uveitis increased with age (P⬍0.001) and that males had a higher incidence rate than females (aRR, 1.24; P⬍0.001). Compared with
Table 3. Univariate Poisson Regression for Incident Cases After 2003 Cases Incident Cases Age group (yrs) ⱕ15 16–25 26–35 36–45 46–55 56–65 ⱖ66 P for linear trend Gender Female Male Insurance area† Rural Suburban Urban Insurance amounts (based on wages earned) Wage ⱕ20 000 (NT$) Wage ⬎20 000 and ⱕ40 000 (NT$) Wage ⱖ40 000 (NT$) Fixed premium‡
%
5866
Person-Years
ID
5271575
111.3
RR
95% CI 108.4–114.1
399 710 946 1158 1115 688 850
6.8 12.1 16.1 19.7 19.0 11.7 14.5
1005288 890962 899091 919540 734523 385607 436564
39.7 79.7 105.2 125.9 151.8 178.4 194.7
1 2.01* 2.65* 3.17* 3.83* 4.50* 4.91*
2609 3257
44.5 55.5
2620195 2651381
99.6 122.8
1 1.23*
1.17–1.30
441 1748 3677
7.5 29.8 62.7
468769 1645618 3157188
94.1 106.2 116.5
1 1.13* 1.24*
1.02–1.25 1.12–1.37
979 2103 1529 1255
16.7 35.9 26.1 21.4
1080132 1905713 1174441 1111289
90.6 110.4 130.2 112.9
1 1.22* 1.44* 1.25*
1.13–1.31 1.33–1.56 1.15–1.36
1.78–2.27 2.36–2.98 2.83–3.56 3.41–4.29 3.97–5.09 4.36–5.53 ⬍0.001
CI ⫽ confidence interval; ID ⫽ incidence density (1/100 000 year); RR ⫽ risk ratio. *P⬍0.001. † Urbanization of insurance areas was categorized based on population density, medical resource, age, and education of the areas. ‡ Fixed premium is defined as when the participants’ insurance types was farmer, fisherman, veteran, or monk.
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Ophthalmology Volume 119, Number 11, November 2012 Table 4. Multivariate Poisson Regression for Incident Cases After 2003 aRR Age group (yrs) ⱕ15 1 16–25 2.00 26–35 2.60 36–45 3.11 46–55 3.76 56–65 4.51 ⱖ66 5.03 Gender Female 1 Male 1.24 Insurance area* Rural 1 Suburban 1.18 Urban 1.29 Insurance amount (based on wages earned) Wage ⱖ40 000 (NT$) 1 Wage ⬎20 000 and ⱕ40 000 (NT$) 0.94 Wage ⱕ 20 000 (NT$) 0.94 Fixed premium† 0.93
95% CI
P Value
1.77–2.27 2.30–2.93 2.77–3.50 3.34–4.23 3.98–5.10 4.45–5.67
⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001
1.18–1.31
⬍0.001
1.06–1.32 1.16–1.43
0.002 ⬍0.001
0.88–1.01 0.87–1.02 0.85–1.01
0.090 0.160 0.086
aRR ⫽ adjusted risk ratio; CI ⫽ confidence interval. *Urbanization of insurance areas was categorized based on population density, medical resource, age, and education of the areas. † Fixed premium is defined as when the participants’ insurance types was farmer, fisherman, veteran, or monk.
individuals from rural areas, participants from suburban and urban regions showed to have a higher incidence rate (aRR, 1.18 and 1.29, respectively; P ⫽ 0.002 and P⬍0.001, respectively). When the insurance income group was considered, although the incidence rate among the low-income group was lower than among the high-income group (aRR, 0.94), the difference was not significant (Table 4). Within the database, there were a total of 179 participants who were diagnosed with ocular tumors and 491 cases that had been diagnosed with acute purulent endophthalmitis. After excluding these cases, the average incidence rate of uveitis was 111.1 persons and 109.2 persons per 100 000 person-years, respectively. Furthermore, the results of the risk factor estimations did not differ much, whether these cases were excluded or included.
Discussion In our study, we found that the average incidence density of uveitis in Taiwan was 111.3 persons per 100 000 personyears. There are no reports on Chinese populations with which the present study can be compared. However, Reeves et al23 studied the incidence of uveitis among the elderly using Medicare using a similar study design as the present study. They showed that the average incidence rate of the elderly population in the United States was 340.9 cases per 100 000 person-years, which was higher than our results of 194.7 cases per 100 000 person-years.23 The results of Reeves’ and our studies are relatively higher than those obtained in previous studies. One reason might be the method of data collection. Most of the previous studies
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ascertained cases based on chart review, something which is not possible in our research, and hence some overestimation might happen. Although the validity of diagnostic coding within other disease was as high as 97.9% in the NHIRD,27 we still could not obtain the evidential nonconfirmation rate of uveitis in our study. One possible reference would be the study of Gritz and Wong,9 which was conducted in northern California and ascertained uveitis cases based on diagnostic codes confirmed by chart review. After reviewing the cases, about 44.8% of them were eventually categorized as “not uveitis.”9 If the nonconfirmation rate is similar in our study, then the incidence rate in Taiwan would be 61.4 cases per 100 000 person-years, which is still higher than in previous studies in other countries. Despite the fact that our research has a study period of 9 years, some of the incident cases might actually still be recurrent cases with long latent periods, which may lead to some overestimation. However, incidences with a longer observational period may be closer to the real situation. Our results showed that the annual incidence rate since 2003 was steady and that the number of incidences in 2008 did not change much from those in 2003. The relatively lower incidence rate in previous studies might also be owing to their hospital-based design, which only includes cases that seek medical help at specific hospitals in a region. In such cases, underestimation would happen if participants seek medical help at other hospitals and it would lower the results in relation to the population-based data. Another reason might be the association with the national health system in Taiwan, which has made access to health care much easier and more available compared with many other countries. The cumulative annual prevalence found in our study ranges from 319 to 623 cases per 100 000 persons. These findings are higher than previous population-based reports for southern China, Japan, and India.17–19 Most previous studies define the prevalent cases as “active uveitis,” which theoretically cannot be addressed without reviewing the medical charts. Because systemic evaluation is suggested clinically and awareness of recurrence made clear at the time the second uveitis occurs or when the disease course is prolonged, we counted the patient as a prevalent case in the incident year and in every year after the second time the uveitis code occurred. The prevalence of uveitis among the elderly in the study by Reeve et al, which used a similar definition of prevalent cases, ranged from 511 cases per 100 000 persons to 1231 cases per 100 000 persons, was comparable with our finding (537.5 cases per 100 000 persons in 2002 to 1274.7 cases per 100 000 persons in 2008).23 We might have overestimated the actual prevalence because some cases may never have been active during the year based on this definition of prevalence. However, if we defined the prevalent cases as having ⱖ1 code reported during each calendar year, the average 1-year period prevalence would be 193.9 cases per 100 000 persons. Across all types of uveitis, anterior uveitis was the most common type in our results. Overall, 77.7% of all new cases were diagnosed as anterior uveitis, and this proportion is higher than the previous 2 studies carried out in Taiwan, one
Hwang et al 䡠 Uveitis among Chinese in Taiwan of which revealed that panuveitis represented 40% of all cases in a medical center.29,30 One reason for this is that anterior uveitis is relatively mild and easy to treat compared with other types of uveitis, and previous studies in Taiwan have only analyzed uveitis cases from a single medical center. The NHIRD contains not only medical centers, but also local hospitals. Local hospitals tend to deal with a greater number of milder cases and this would lead to an underestimation in the previous studies. Comparing with the results in the study by Reeves et al, the proportion of anterior uveitis among all incident cases was similar, but the proportion of panuveitis was higher in our database than in Medicare.23 The results might owing to the higher incidence of uveitis with some specific etiology such as Behçet’s disease and Vogt-Koyanagi-Harada disease in the Chinese population. Multivariate regression showed that males in our database were at a slightly higher risk of uveitis than females, and this finding was consistent for every year of the study period. This finding is similar to previous studies in Asia and Taiwan.17,19,29 –31 The relationship between aging and the incidence of uveitis was also significant. The incidence and prevalence of uveitis among the elderly was consistently higher than among adults or children. Multivariate analysis showed that getting older resulted in a higher incidence of uveitis and that this trend effect was significant. This finding is quite different from previous reports.31 It does, however, agree with recent findings of Gritz and Wong’s study9 in the United States and the study by Rathinam et al19 in India. Although the reason for the increasing incidence rate among the elderly is not clear, an explanation might be changes in the epidemiology of some specific types of uveitis, such as virus-induced uveitis or rheumatic arthritis–related uveitis. Our results nevertheless suggest that the disease burden of uveitis among the elderly and its increasing impact should not be ignored, especially as the population continues to age. Few studies have explored the relationship between socioeconomic status and the incidence of uveitis. Research in Finland has shown that the incidence of uveitis is higher among individuals with a lower socioeconomic status, and a study in Iran found that ⬎80% of uveitis cases occurred in the upper socioeconomic ranks.21,22 We analyzed socioeconomic status by linking it with the resident’s insurance area and their insurance amount. The former usually indicates where the individual lives and/or works, and the latter reflects to a degree the individual’s income. Our result showed that the incidence of uveitis was significantly higher among individuals who lived in an urban environment. However, although individuals with higher insurance amounts run a slightly higher risk, after adjustment this difference was not significant. The increased medical utilization among people living in urban areas may have increased their likelihood of being captured as a case given the methodology of the present study. Another possible explanation is that sicker people may move to a more urbanized area. We have tried to eliminate cases that moved to an area with higher urbanization after the first diagnosis of uveitis by measuring each individual’s level of urbanization based on their area of insurance during their first visit
to a physician. The possibility, however, remains that ophthalmologists in the urban area are more aware of the disease and are thus more likely to code for uveitis. The findings in our study could also be explained by the hardscrabble hypothesis that theorizes that the human’s immune system has developed a defense for the exposure to some damage-related antigens. Reduction in chronic tissue injury may be followed by underpresentation of the self-antigens and influence the maturity of the human adaptive immune system, which in turn leads to an increase in autoimmune disease among people with higher socioeconomic status.32 Although making a clinical diagnosis of uveitis is easier than for other systemic diseases, which may need to be supported by laboratory tests, misdiagnosis still occurs. To eliminate misdiagnosis caused by the uveitis masquerade syndrome, we excluded all cases that were ever diagnosed as having an ocular malignancy. To exclude exogenous endophthalmitis related to surgery or trauma from our report, we excluded all cases with a diagnosis of acute purulent endophthalmitis after intraocular operative procedures. However, we might overcount those cases that underwent surgery years earlier and do not appear during our study period. Hence, we tried to exclude all cases that were diagnosed with acute endophthalmitis for the sensitivity analysis. The incidence and the results for the modified risk factors estimations without these 2 specific diagnoses remained similar. Another limitation of our study is that the etiology and severity of each case could not be clarified without the individual’s medical record, and thus the variation between different types of uveitis may have affected the epidemiological findings for all types of uveitis. Although we could have tried to presume the etiology by using the patient’s specific diagnostic codes or by finding the comorbidity with other associated diagnoses, uncertainties and misclassifications would be unavoidable. As a result of this limitation, further population-based studies designed to use medical records are needed. In summary, we attempted to explore the epidemiology of uveitis in a Chinese population and made several findings. Firstly, the incidence of uveitis in Taiwan is relatively higher than in other countries. Secondly, our results indicate that males have a higher incidence rate than females. Thirdly, increased age is a risk factor and the elderly are more commonly affected by uveitis. Fourthly, urbanites show a higher incidence of uveitis. More studies exploring the epidemiology of uveitis are required as the incidence of this sight-threatening disease is on the rise.
References 1. Jabs DA, Nussenblatt RB, Rosenbaum JT. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthalmol 2005;140: 509 –16. 2. Forrester JV. Uveitis: pathogenesis. Lancet 1991;338:1498–501. 3. Durrani OM, Tehrani NN, Marr JE, et al. Degree, duration, and causes of visual loss in uveitis. Br J Ophthalmol 2004; 88:1159 – 62.
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Ophthalmology Volume 119, Number 11, November 2012 4. Couto C MJ. Epidemiological Study of Patients with Uveitis in Buenos Aires, Argentina. Amsterdam: Kugler; 1993. 5. Rothova A, Suttorp-van Schulten MS, Frits Treffers W, Kijlstra A. Causes and frequency of blindness in patients with intraocular inflammatory disease. Br J Ophthalmol 1996;80: 332– 6. 6. Durrani OM, Meads CA, Murray PI. Uveitis: a potentially blinding disease. Ophthalmologica 2004;218:223–36. 7. Gardiner AM, Armstrong RA, Dunne MC, Murray PI. Correlation between visual function and visual ability in patients with uveitis. Br J Ophthalmol 2002;86:993– 6. 8. Darrell RW, Wagener HP, Kurland LT. Epidemiology of uveitis. Incidence and prevalence in a small urban community. Arch Ophthalmol 1962;68:502–14. 9. Gritz DC, Wong IG. Incidence and prevalence of uveitis in Northern California; the Northern California Epidemiology of Uveitis Study. Ophthalmology 2004;111:491–500. 10. Suhler EB, Lloyd MJ, Choi D, et al. Incidence and prevalence of uveitis in Veterans Affairs Medical Centers of the Pacific Northwest. Am J Ophthalmol 2008;146:890 – 6[e8]. 11. Freedman J. Incidence of uveitis in Bantu-speaking negroes of South Africa. Br J Ophthalmol 1974;58:595–9. 12. Mercanti A, Parolini B, Bonora A, et al. Epidemiology of endogenous uveitis in north-eastern Italy. Analysis of 655 new cases. Acta Ophthalmol Scand 2001;79:64 – 8. 13. Paivonsalo-Hietanen T, Tuominen J, Vaahtoranta-Lehtonen H, Saari KM. Incidence and prevalence of different uveitis entities in Finland. Acta Ophthalmol Scand 1997;75:76 – 81. 14. Miettinen R. Incidence of uveitis in Northern Finland. Acta Ophthalmol (Copenh) 1977;55:252– 60. 15. Tran VT, Auer C, Guex-Crosier Y, et al. Epidemiological characteristics of uveitis in Switzerland. Int Ophthalmol 1994; 18:293– 8. 16. Dandona L, Dandona R, John RK, et al. Population based assessment of uveitis in an urban population in southern India. Br J Ophthalmol 2000;84:706 –9. 17. Hu SXC, Yang P, Huang X. An epidemiological survey of uveitis in Southern China. Chinese Journal of Ophthalmology 2002;2:1. 18. Nakao K, Ohba N. Epidemiology of endogenous uveitis in Kagoshima Prefecture, Southwest Japan. Nippon Ganka Gakkai Zasshi 1996;100:150 –5.
19. Rathinam SR, Krishnadas R, Ramakrishnan R, et al. Populationbased prevalence of uveitis in Southern India. Br J Ophthalmol 2011;95:463–7. 20. Paivonsalo-Hietanen T, Tuominen J, Saari KM. Seasonal variation of endogenous uveitis in south-western Finland. Acta Ophthalmol Scand 1998;76:599 – 602. 21. Soheilian M, Heidari K, Yazdani S, et al. Patterns of uveitis in a tertiary eye care center in Iran. Ocul Immunol Inflamm 2004;12:297–310. 22. Saari KM, Paivonsalo-Hietanen T, Vaahtoranta-Lehtonen H, et al. Epidemiology of endogenous uveitis in south-western Finland. Acta Ophthalmol Scand 1995;73:345–9. 23. Reeves S, Sloan F, Lee P, Jaffe G. Uveitis in the elderly: epidemiological data from the National Long-term Care Survey Medicare Cohort. Ophthalmology 2006;113:302–7[e1]. 24. Chen Y-Y, Lai C-H. Nationwide population-based epidemiologic study of Huntington’s disease in Taiwan. Neuroepidemiology 2010;35:250 – 4. 25. Chiu YM, Lai CH. Nationwide population-based epidemiologic study of systemic lupus erythematosus in Taiwan. Lupus 2010;19:1250 –5. 26. Bih S-H, Chien IC, Chou Y-J, et al. The treated prevalence and incidence of bipolar disorder among National Health Insurance enrollees in Taiwan, 1996-2003. Soc Psychiatry Psychiatr Epidemiol 2008;43:860 –5. 27. Cheng CL, Kao YHY, Lin SJ, et al. Validation of the National Health Insurance Research Database with ischemic stroke cases in Taiwan. Pharmacoepidemiol Drug Saf 2011;20:236 – 42. 28. Liu CY HYT, Chuang YL, Chen YJ, et al. Incorporating development stratification of Taiwan Township into sampling design of large scale health interview survey. Jian Kang Guan Li 2006;4:1–22. 29. Chung YM, Yeh TS, Liu JH. Endogenous uveitis in Chinese: an analysis of 240 cases in a uveitis clinic. Jpn J Ophthalmol 1988;32:64 –9. 30. Chou LC, Sheu SJ, Hong MC, et al. Endogenous uveitis: experiences in Kaohsiung Veterans General Hospital. J Chin Med Assoc 2003;66:46 –50. 31. Rathinam SR, Namperumalsamy P. Global variation and pattern changes in epidemiology of uveitis. Indian J Ophthalmol 2007;55:173– 83. 32. Naugler C, Conrad DM. The hardscrabble hypothesis: a reduction in chronic tissue damage has increased the incidence of autoimmune disease. Med Hypotheses 2010;74:366 –7.
Footnotes and Financial Disclosures Originally received: November 3, 2011. Final revision: May 14, 2012. Accepted: May 14, 2012. Available online: July 17, 2012. 1
The National Health Research Institutes supplied data for this study.
Manuscript no. 2011-1596.
Department of Ophthalmology, Taoyuan Veterans Hospital, Taoyuan, Taiwan.
2
Department of Public Health and Institute of Public Health, National Yang-Ming University, Taipei, Taiwan.
3
Community Medicine Research Center, National Yang-Ming University, Taipei, Taiwan.
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Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. Correspondence: Cheng-Yun Pu, PhD, Institute of Public Health, School of Medicine, National Yang-Ming University. No.155, Section 2, Linong Street, Taipei, 11221 Taiwan (ROC). E-mail: [email protected]