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Biol Trace Elem Res (2009) 128:1-7 DOI 10.


Prevalence of Age-Related Cataract in High-Selenium Areas of China

Tuo Li Tao He Xiaodong Tan Shurong Yang Jiazhang Li Zuoquan Peng Hongyan Li Xiusheng Song Qingsong Wu Fanglie Yang Yiqiao Xing

Received: 17 July 2008 /Accepted: 23 September 2008 / Published online: 30 October 2008 Humana Press Inc. 2008

Abstract The objective of this study was to determine the prevalence of age-related cataract in high-selenium areas of China. This is a cross-sectional study of 1,522 persons aged 50 years and more who were selected as a representative sample from the Enshi prefecture in Hubei province. All lenses were graded and classified for opacities by slit lamp after papillary dilation, using the Lens Opacification Classification System II. The age-related cataract patients were 418 cases (33.28%). The prevalence of age-related cataract was 37.2% in women and 26.0% in men. The prevalence of nuclear cataract was 23.7%; cortical cataract was 22.4% and posterior subcapsule cataract was 5.2%. The prevalence of cataract of the 50-59 group was 13.41%; 60-69 group was 42.15%; 70 and over group was 61.9%. The prevalence of age-related cataract in high-selenium areas has not significantly increased; to some extent, the high selenium intake will not become a risk factor for the increase of cataract incidence. Keywords Selenium Age-related cataract Epidemiology Trace elements

T. Li T. He Y. Xing (El) Department of Ophthalmology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, Hubei Province 430060, China e-mail: X. Tan Department of Occupational and Environmental Health, School of Public Health, Wuhan University, Wuhan 430060, China S. Yang J. Li H. Li X. Song Q. Wu F. Yang Department of Ophthalmology, Central Hospital of Enshi Autonomous Prefecture, Enshi 445000 Hubei Province, China Z. Peng The Center for Disease Control and Prevention of Enshi Autonomous Prefecture, Enshi 445000 Hubei Province, China

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Introduction Cataracts are the leading cause of blindness worldwide, and age-related cataract is the most common cataract type. Surgical cataract repair is therapeutically effective, but the prevention and delay of cataract onset and progression is still very important. Therefore, epidemiologic studies examining cataract risk and protective factors are essential in the reduction of cataract prevalence. Selenium (Se) is an essential trace element that catalyzes all known selenoenzymes [1], Many studies have identified an association between selenium level and cataract incidence. However, the association is not clear as some studies have suggested that lack of selenium may result in cataract formation [2], while others have revealed positive correlations between elevated selenium levels and cataract incidence [3], Animal experiments have suggested that excessive selenium intake resulted in cataract formation in rabbits, guinea pigs, mice, and other rodents. However, the mechanism of this association was not identified. Animal models of selenite cataract have been widely used in the evaluation of cataract mechanisms and for the screening of new drugs and therapeutic modalities [4], Such experiments and results were derived from clinical and laboratory-based studies. To our knowledge, no population-based studies have evaluated the age-specific prevalence of lens opacities in geographic areas with high and low environmental selenium exposure. The Enshi Prefecture in the Hubei province is a typical Chinese high-selenium region with a history of human and animal selenium poisoning. Selenium levels in soil, drinking water, and food were far higher in the Huabei village in the Shadi town than in other regions, and selenium levels in the blood, hair, and urine of residents were several times higher than those from individuals in low-selenium areas [5-9]. We evaluated individuals in the Huabei village in order to survey the incidence of age-related cataracts in a typical high-selenium region. Methods Study Location Individuals were recruited from the Huabei Village in the Shadi Town of the Enshi Prefecture in the Hubei Province. The Enshi Prefecture is located in the southwestern Hubei Province and borders the Chongqing and Hunan Provinces. There was a large number of individuals with unexplained hair and nail loss in the Shadi Town from 1963 to 1979, with incidences as high as 82.16% in certain villages. Yang et al. [5-9] confirmed that these clinical signs were likely associated with human selenium poisoning. The selenium was primarily isolated from stone coal in this region, and the selenium content in Enshi soil, water, and crops were significantly greater than content in fitness and low-selenium areas. Selenium levels in the blood and hair of individuals living in the Enshi area were 30 to 160 times greater than in moderate- and low-selenium areas. Previous studies in the Shadi Town from 1986 to 1994 identified minimum selenium requirements for the human body, physical requirements for selenium, and the limits of selenium poisoning. These data have been adopted by the recommended dietary allowance in China. Reductions in human selenium poisoning in the Shadi town were identified after 1993, and this was largely due to improvements in farming methods, increased environmental protection, and changes in eating habits. However, there are still elevated selenium levels (816 g/day) in the daily food intake in the Enshi Shadi and the content of selenium in hair is still at toxic levels (>20.80 g/g). This is an optimal region to initiate a study between selenium levels and O Humana Press

Prevalence of Age-Related Cataract in High-Selenium Areas of China

cataract incidence because of the insular nature of the community due to the rural location, inconvenient traffic patterns, and the backward economy. Study Population There are 13 natural villages in the main Huabei Village with a total population of 4,986 individuals. This includes 1,522 individuals aged 50 years or older. These individuals represented our target population in this study. The study was conducted from June 2006 to December 2006. Cluster sampling methods were adopted. All individuals aged 50 years and older were recorded, and suitable locations were selected and deemed "eye checkpoints." The study was conducted in accordance with the guidelines of the Declaration of Helsinki and was approved by the local Ethics Committee. Procedures All study participants completed a questionnaire survey. The questionnaire included basic information (including level of education and marriage status) and other demographic information (Table ). It also included information describing time of residence in the region, outdoor sun exposure, diet, presence of comorbidities and systemic diseases, ocular medical history, and family medical history. The international standard visual acuity chart was used for far visual inspection. The corrected vision was evaluated if the naked visual acuity was <0.3. The degree of lens opacity was graded after mydriasis with slit lamp instrumentation. A detailed eye examination was performed if the corrected visual acuity was <0.3 in order to deteimine the reasons for visual impairment. The detailed examination included evaluation by instrumentation including slit lamp microscopy, gonioscopy, and fundic and intraocular pressure examinations. Lens Opacity Classification The lens opacity was classified by an experienced oculist after pupillary dilation with 1% tropicamide. Cataract lens opacities were divided into cortical, nuclear, and posterior subcapsular opacities according to the Lens Opacities Classification System II (LOCS II) [10]. Subjects who had undergone surgical repair of cataracts were stratified into a specific surgical group (Table 2 Lens opacity classification in this study included cortical opacities, nuclear opacities, posterior subcapsular opacities, cataracts of any type, and individuals who received cataract surgery. The LOCS II system uses multiple cortical, nuclear, and subcapsular standards to grade cataracts. Table 1 Demographic Characteristics of Surveyed Population Characteristics
Male Female Age groups (year) 50-59 60-69 >70

Enumerated (=1,552)

Examined (=1,263)

Lens grading (= 1,244)


442 821

433 811

412 276

406 266

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cataract Table 2 Number (%) of of specific cataract Numbercataract Cortical cataract Posterior subcapsule Nuclear (%) Specific Cataract

cataract survey

51 112 118 70 211

Age 50-59 60-69 >70 Gender Male Female

9 22 34 21 44

75 169 162 109 297

2 3 7 5

119 142 76

Cataract Definitions The parameters graded in the LOCS II classification system include cortical cataracts (C), nuclear opalescence (N), nuclear color (NC), and posterior subcapsular (P) cataracts. An Nl cataract indicates an early degree of nuclear opacification; a CI cataract indicates more extensive opacification; and a PI cataract fills approximately 3% of the posterior capsule. Cataracts were classified as follows: (1) cortical cataract, significant cortical opacities in at least one eye with a score of >C1 according to LOCS II; (2) nuclear cataract, significant nuclear opacities of >N1 or colors of >NC1 in at least one eye according to LOCS II; (3) posterior subcapsular cataract, significant posterior subcapsular opacities of >P1 in at least 1 eye according to LOCS II; (4) any cataract, defined by two or more types of significant nuclear, cortical, or posterior subcapsular cataracts in at least one eye; and (5) any cataract surgery, defined by surgical repair of cataracts in one or both eyes. The LOCS II grading reproducibility between two examiners was evaluated throughout the study. Reproducibility was measured by a proportionally weighted K statistics model for agreement. Results revealed a moderate to good intergrader agreement, with a weighted confidence interval of 0.69 (range, 0.49-0.85). Statistical Analysis The SPSS 13.0 software was used for data processing. The overall cataract incidence, different lens opacity incidence, and the associations between age, gender, and cataract incidence were analyzed. Statistical analyses were performed using the SPSS 13.0 software package.

Results There were 1,522 individuals initially selected for inclusion into the study. A few individuals died (n=4) or moved outside the study district prior to the study period (n=95). Therefore, a total of 1,423 individuals were initially included for study entry, and 1,263 of these subjects

underwent examination with an overall response rate of 88.76% (1,263 of 1,423). All study participants were derived from the local farming population with a mean [SD] age of 60.62 [7.65] years (range, 50-82 years). Both men (=442) and women (n=

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Prevalence of Age-Related Cataract in High-Selenium Areas of China

821) were included in the study. Men had a mean [SD] age of 61.22 [7.58] years and women had a mean [SD] age of 63.12 [8.78] years. A single male patient's left cornea was turbid and the lens could not be assessed. However, the other lens was transparent upon evaluation and he was placed in the normal population. A second male patient's left globe had been previously extracted due to trauma, with a cortical opacity in the other eye. This individual was included in the statistical analysis as a cataract patient. Pupillary dilation was not conducted in seven individuals due to narrow-angle or angle-closure glaucoma or refusal to allow dilation. These individuals were excluded from further study and classified into the data loss group. Age-Related Cataract Morbidity Age-related cataracts were present in 418 individuals (33.28%). The prevalence of agerelated cataracts was 37.2% in women and 26.0% in men. The prevalence of age-related cataracts was significantly higher in women than in men (X2=15.93, P<0.05). Nuclear cataracts were present in 23.7% of individuals, cortical cataracts in 22.4%, and posterior subcapsule cataracts in 5.2%. Cataract prevalence in participants aged 50 to 59 years was 13.41%; in 60 to 69 years, it was 42.15%, and in 70 years and older it was 61.9%. The difference in prevalence among the age groups was significant (X =216.92, /><0.05). Blindness and Low Vision Induced by Age-Related Cataracts Binoculus blindness was diagnosed in nine study participants, and seven (77.8%) were cataract-induced blindness cases. Diagnosis was made secondary to the World Health Organization standard of blindness and low vision. A total of 64 cases were classified as low-vision cases, and 71.9% of these (=46) were due to the presence of cataracts. Binoculus blindness from age-related cataracts was present in 0.55% of participants and binoculus low vision was present in 3.64%. Binoculus blindness (1.72%) and binoculus low vision (11.33%) were attributable to age-related cataracts in 406 cases. Discussion Selenium is an essential trace element in human physiology. It is well established that selenium plays an essential role in a variety of physiological functions. Selenium is the main component of the glutathione peroxidase (GSH-Px), and GSH-Px activity is positively correlated with selenium content. It also catalyzes the reduced glutathione into oxidized glutathione and reduces the toxic peroxidate into innoxious hydroxy compounds and peroxide. Therefore, it protects the cell membrane structure and functions from damage and oxide interference. Peroxidative damage-based injury is one of the first age-related cataract risk factors, and therefore selenium is a strongly associated trace element in cataract pathogenesis. Selenium-induced cataract animal models are similar to senile cataracts in pathogenesis and are widely used in pathogenesis exploration in cataract and anticataract drugs [4]. We therefore evaluated individuals residing in a region with uniquely high selenium levels in order to study the effects of excessive selenium intake on lens opacity. We wished to elucidate the relationship between selenium levels and lens opacities. Our study results revealed that the incidence of age-related cataracts in Huabei was 33.28%, with a higher incidence in women than in men. Nuclear and cortical opacities account for the majority of age-related cataracts. The cataract incidence rates increased with O Humana Press

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advancing age (X2=216.92, P<0.05). Cataracts are the primary reason for blindness and low vision in the elderly population in this region. Direct comparisons between our study and other reports are difficult because of differences in grading methods, definitions of lens opacities, age distributions, geography, environment, race, climate, economy, and culture. However, Xu Jing-Jing et al. [11] performed a study similar to ours, with participants of the same race, adoption of the same lens opacity classification method, and similar detection technologies to investigate cataract incidence. This study is reasonably comparable to our study. The cataract incidence rate for individuals aged 50 years or older in our high-selenium geographic region (nuclear 23.7%, cortical 22.4%, posterior subcapsule 5.2%) was lower than that from Xu Jing-Jing's report (nuclear 28.6%, cortical 30.2%, posterior subcapsule 8.7%). Our cataract incidence rate was lower than the rate reported by Foster et al. [12]. At present, there are no precise data of the incidence of age-related cataract in low- and medium-Se regions. However, Shanxi, Shenzhen, and Chongqing are not known high-selenium areas. So, the cataract incidence in these areas may represent the incidence in low- or medium-Se area. The prevalence of age-related cataract in Enshi is not higher than in those areas (Table 3). This suggested that the high intake of selenium may not significantly increase the risk of cataracts in humans. Published clinical research data on the association between selenium intake and human cataract prevalence must incorporate larger sample sizes and further define the mechanisms of pathogenesis. Few results have examined the association between selenium levels and the presence of human cataracts. The literature suggests that selenium supplementation is of great significance in cancer prevention [1,13], enhancement of immunity [14], and the improvement of endocrine function [15]. Our research suggests high selenium levels and selenium supplementation may not contribute to cataract pathogenesis and may not be a cataract risk factor. Selenium is an essential trace element in bodily functions but also functions as a toxic mineral. Excessive or insufficient selenium intake can result in clinical problems. The examination of the effects of insufficient selenium intake on the incidence of cataracts has not been examined. Large single or small repeated selenium doses can induce cataract formation in a variety of laboratory animals. Cataract animal models induced by selenium administration are widely used in cataract mechanism studies and the screening of new anticataract drugs. Our study did not identify excessive vision decline or cataract formation in the Enshi Shadi region with a history of human selenium poisoning and excessive selenium levels. Shearer et al. [4] proposed that the formation mechanisms of human cataracts differ from those of animals, particularly rodents. They additionally postulated that anticataract drugs screened by animal models may not be appropriate for human use and may require further research. Our results support this view. Table 3 The Different Prevalence of Age-Related Cataract in China Author Tuo Li et al. (our) Yangsheng Peng et al. Lu Chen et al. Yihua Xu 7^ Humana Press Location Huabei, Enshi county Shanxi Province Baoan District, Shenzhen Lianglu, Chongqing The prevalence of cataract among adults aged 50 years or older (%) 33.28 37.2 29.64 38.27

Prevalence of Age-Related Cataract in High-Selenium Areas of China

Our data suggested that age-related cataract prevalence in a high-selenium geographic region is not significantly increased. They further suggest that high selenium intake may not serve as a risk factor for the increase in cataract incidence. References
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