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Prevalence and risk factors for angle-closure disease in a rural Northeast China population: a population-based survey in Bin County, Harbin

2011; Wiley; Volume: 89; Issue: 6 Linguagem: Inglês

10.1111/j.1755-3768.2011.02146.x

1755-3768

Wei Qu, Yuanyuan Li, Wulian Song, Xinrong Zhou, Kang Yang, Yan Li-ping, Hong Sui, Huiping Yuan,

Retinal Diseases and Treatments

Purpose: To estimate the prevalence of primary angle-closure glaucoma (PACG), primary angle closure (PAC) and primary angle-closure suspect (PACS) and associated risk factors for PACG in a rural population in Northeast China. Methods: A population-based survey was conducted in Bin County, Harbin, Northeast China. Glaucoma was diagnosed using the International Society of Geographical and Epidemiological Ophthalmology (ISGEO) criteria. All subjects underwent a complete ophthalmic examination. Results: A total of 4956 (86.01%) of 5762 subjects aged 40 years or older were examined. The mean intraocular pressure (IOP) of the right eyes was 14.0 mmHg. The mean vertical cup-to-disc ratio of the right and the left eyes was 0.31 and 0.31, respectively. The prevalence of PACG, PAC and PACS was 1.57% [95% confidence interval (CI), 1.469–1.671], 1.33% (95% CI, 1.236–1.424), and 4.68% (95% CI, 4.541–4.819), respectively. Among all PACG subjects, 42 (53.84%) had elevated IOP >21 mmHg in either eye and 37 (47.44%) had been treated by laser, surgical iridectomy or trabeculectomy. Sixty-four subjects (82.05%) had vision impairment of varying degrees. Multivariate analysis revealed that old age, family history of PACG, constipation and IOP were significant independent risk factors. Conclusions: Primary angle-closure glaucoma was a disease of high prevalence in rural Northeast China. Old age, family history of PACG, constipation and IOP were significant independent risk factors for PACG. Glaucoma is the second leading cause of blindness after cataract globally (Resnikoff et al. 2004). Over 6.7 million people worldwide are blind owing to glaucoma, and half of these cases are caused by primary angle-closure glaucoma (PACG) (Thylefors et al. 1995; Quigley & Broman 2006). The prevalence of PACG varies between different races and different regions. Primary angle-closure glaucoma is the main type of glaucoma in certain Asian populations, and it is more prevalent in these Asian populations than in European or African populations (Bonomi et al. 1998; Buhrmann et al. 2000; Quigley et al. 2001; Rotchford & Johnson 2002). Data on the prevalence of PACG also vary between different regions of China. Primary angle-closure glaucoma is more prevalent in North China (Hu et al. 1989) than in South China (Yu et al. 1995). The highest prevalence of PACG in China was reported in Jilin Province (2.5%), Northeast China, by Yuan et al. (2007); however, the authors did not select random sampling process, and the response rate was low (74.5%). Besides these, in most studies conducted in China, including the study of Jilin Province, the diagnostic criteria and methods have not been clearly described and appear to deviate from the current international standards. Furthermore, even though it is very important to understand the risk factors for PACG for its prevention and treatment, data on these risk factors remain limited. Hence, this study emphasized on the diagnosis of angle-closure disease based on International Society of Geographical and Epidemiological Ophthalmology (ISGEO) criteria (Foster et al. 2002) and on the assessment of risk factors for PACG in Northeast China. The purpose of this study was to obtain results that were not only comparable but also complementary to those of previous glaucoma studies. Data collection was started in May 2007 and completed in October 2007. Here, we present the results of a population-based study on the prevalence of angle-closure disease and associated risk factors. The study was conducted in Changan town, Bin County, Harbin, Northeast China. The township encompasses an area of 156.8 km2 and comprises 18 contiguous villages of approximately equal size. Each village was divided into 8–14 second-order villages. Thus, the town comprised a total of 183 second-order villages. The total population of these villages was about 32 800, according to the report of the 2000 National Census of China. Of the total residents, 48.88% were women. Participants were selected using a random, stratified, cluster sampling process. All persons aged 40 years or older who had been residing in the selected village for at least 6 months were included in the study. The 18 villages were numbered clockwise. Twelve of 18 villages comprising 109 second-order villages (a total population of 7543 individuals) were randomly selected by computer. Subsequently, 84 second-order villages within these 12 villages were randomly selected by computer, thereby providing a total sample population of 5762 individuals. A single survey team conducted the entire study. Each team member was assigned specific tasks and received additional training of the study procedures. A standard questionnaire was administered by a trained health worker to collect details of demographic information, lifestyle, general medical history and ophthalmic history. All the responding subjects underwent detailed ophthalmic examinations after their blood pressure and blood glucose levels were measured. Visual acuity was recorded at 4 m by using Early Treatment Diabetic Retinopathy Study (ETDRS) logarithm of minimum angle of resolution (logMAR) E chart (Precision Vision, Villa Park, IL, USA). An optometrist assessed the best-corrected vision using the readings of a handheld autorefractor with necessary subjective refinement in those individuals with visual acuity of <6/12. Slit-lamp examination was carried out by an experienced ophthalmologist, and any abnormalities in the anterior segment of the eye, such as evidence of ischaemic sequelae of angle closure and lens opacity, were noted. Peripheral anterior chamber depth was graded using van Herick’s technique (Van Herick et al. 1969). Static gonioscopy was performed on all subjects with a Goldmann-type one-mirror lens (Haag Streit, Bern, Switzerland) in dim ambient illumination with a shortened slit that did not fall on the pupil by two glaucoma specialists. Dynamic examination with increased illumination and slit height was performed after static gonioscopy of all four quadrants was completed. In cases in which iridotrabecular contact could not be satisfactorily reversed, a four-mirror lens was used and gentle pressure was placed on the cornea. The angle was graded using the Scheie system, and the peripheral iris contour, degree of trabecular meshwork pigmentation, peripheral anterior synechiae and other angle abnormalities were recorded. Intraocular pressure (IOP) was recorded with a Goldmann applanation tonometer (HA-2; Kowa, Xinghe, Japan) under topical anaesthesia using 0.5% proparacaine, along with fluorescein staining of the tear film. This measurement was first taken in the right eye, and one reliable measurement was recorded for each eye. The instrument was daily calibrated before use. Stereoscopic evaluation of the optic nerve head was performed using a+ 78-dioptre (D) lens (Ocular, Bellevue, WA, USA) and reference to standard disc images. The vertical and horizontal cup-to-disc ratios (CDRs) were measured and recorded. The presence of any optic disc rim notching, splinter haemorrhages and peripapillary atrophy was documented. A subject with one or more suspected glaucomatous damage (IOP of 21 mmHg or greater in either eye, vertical cup-to-disc ratio (VCDR) of 0.7 or greater in either eye, CDR asymmetry of 0.2 or greater) was diagnosed to have suspected glaucoma. All these subjects were advised to undergo a visual field test (THG-10-BA210-013; Octopus, Bern-koniz, Switzerland). Glaucoma cases were defined using the ISGEO criteria (Foster et al. 2002). Glaucoma was classified in accordance with three levels of evidence. Category 1 requires optic disc and visual field abnormalities (VCDR or asymmetry ≥97.5th percentile with a definite visual field defect consistent with glaucoma). In category 2, if a visual field test could not be performed satisfactorily, a severely damaged optic disc (VCDR or asymmetry ≥99.5th percentile for the normal population) was sufficient to make the diagnosis. In category 3, if the optic disc could not be examined because of media opacity, the condition of an IOP exceeding the 99.5th percentile or evidence of previous glaucoma filtering surgery was diagnosed as glaucoma. Visual fields were judged acceptable for analysis if fixation losses were <20%; false positives, <33%; and false negatives, <33%. After excluding the superior four points and the four points immediately adjacent to the blind spot, an abnormal visual field was defined if it was ≥18° × 12° in size and ≥10 dB in depth (Bourne et al. 2003). Primary angle-closure suspect (PACS) was diagnosed when the trabecular meshwork was not visible over 270° or more on gonioscopy. Primary angle closure (PAC) was defined as PACS with the evidence of peripheral anterior synechiae and/or an elevated IOP without glaucomatous damage of the optic disc. Primary angle-closure glaucoma was defined as PAC with evidence of glaucoma as described above. Blindness was defined as the best-corrected visual acuity of <2/40 and/or visual field constriction of 200 mg/dl), systemic hypertension (determined based on current use of systemic antihypertensive medications or a measured systolic blood pressure of 140 mmHg or greater and/or a diastolic blood pressure of 90 mmHg or greater), heavy smoker (more than 20 cigarettes per day), excessive alcohol (more than 210 g alcohol per week), blood group, constipation [defined as less than two bowel movements per week or presence of two or more of the following complaints when laxatives and/or enemas were not used: <3 bowel movements per week, straining during defecation or hard stools (Bracci et al. 2007)] and IOP. Statistical analysis was conducted by the Department of public health, Harbin Medical University. The database was established with Epidata 3.0 (EpiData Association, Odense, Denmark). Statistical analysis was performed with spss 17.0 (SPSS Inc., Chicago, IL, USA) programs. Data are presented as prevalence and odds ratios with corresponding 95% confidence intervals (CIs). Age- and sex-specific prevalence of PACG, PAC and PACS and their 95% CIs were calculated. Univariate and multivariate logistic regression models were used to identify the risk factors of PACG. The probable risk factors for PACG were selected by the univariate logistic regression analysis. All risk factors associated with PACG in the univariate analysis were modelled using the multivariate logistic regression analysis. To find the best model, a forward elimination stepwise procedure was carried out such that the factor would be incorporated into the analysis if the corresponding p value < 0.2. A value of p < 0.05 was defined as statistically significant. The study was approved by the Ethics Committee of the Second Affiliated Hospital, Harbin Medical University. Consent for participation was obtained from the head of each village before commencement of the survey, and written informed consent was obtained from all willing participants. The study was conducted in accordance with the Declaration of Helsinki. A total of 5762 participants were considered eligible for this study, and 4956 were examined in the clinic (2228 men, 2728 women); therefore, the response rate was 86.01%. Distribution of the age and sex of subjects who underwent clinical examination is shown in Table 1. Tables 2 and 3 show details of the IOP in the right eyes and CDR parameters for the population except for those who were patients with glaucoma and those who did not measure the IOP and examine the optic discs. Subjects in whom the IOP was not measured or the optic discs were not examined were in the minority. These data could not be obtained because of media opacities, trauma and inflammation, or refusal of the subject to be examined. The IOP declined with age in normal subjects. Table 4 summarizes the prevalence, age and sex distribution of angle-closure disease (PACG, PAC and PACS). The census data from the year 2000 in Heilongjiang is used as the standard population. The prevalence of PACG in any category in at least one eye was 1.57% (95% CI, 1.469–1.671). Based on categories 1, 2 and 3, glaucoma was diagnosed in 19 (24.36%), 44 (56.41%) and 15 (19.23%) subjects, respectively. Forty-two (53.84%) subjects had elevated IOP >21 mmHg in either eye. Forty-eight (61.54%) subjects had been diagnosed PACG previously. Of them, 37 (47.44%) subjects had been treated by laser, surgical iridectomy or trabeculectomy. Sixty-four subjects (82.05%) had vision impairment of varying degrees. The prevalence of bilateral and unilateral blindness was 14.10% (11/78) and 37.18% (29/78), respectively. We examined 10 selected risk factors for PACG. To assess the importance of these risk factors, we used univariate and multivariate logistic regression analyses. Univariate logistic regression analysis of risk factors for PACG is shown in Table 5. Ten factors were analysed using univariate logistic regression. Of these factors, gender, old age, family history of PACG, diabetes mellitus, blood group A, constipation and IOP were regarded as significant independent risk factors. Multivariate logistic regression analysis of risk factors for PACG is shown in Table 6. In multivariate analysis, old age, family history of PACG, constipation and IOP were regarded as significant independent risk factors. To our knowledge, this study is the first population-based study conducted in Northeast China to classify angle-closure disease based on the ISGEO (Foster et al. 2002) criteria; therefore, it is comparable to other studies that used the same criteria. Of the sample population of 5762 individuals aged 40 years or older, 4956 individuals participated in the study, and the participation rate was 86.01%. This rate is reasonable for glaucoma survey, and it is similar to that of the studies conducted in Tamil Nadu, India (81.75%) (Vijaya et al. 2006); Thailand (88.7%) (Bourne et al. 2003); and Mandalay Division, Myanmar (83.7%) (Casson et al. 2007), and higher than that of study conducted in Dhaka, Bangladesh (66%) (Rahman et al. 2004). Subjects who did not undergo clinical examination probably thought that they were in good health condition and that they did not require clinical examination or they could not visit the examination place because of sickness. Regardless of this fact, the high response rate suggests that the data of this study reflect the true condition of the population accurately. Goldmann tonometry used in this study is a ‘gold standard’ for IOP measurement. This study only presents the IOP result in the right eyes. The mean IOP in normal subjects was 14.0 mmHg, which is consistent with the mean IOP reported in other studies (Foster et al.1996; Bourne et al. 2003; Casson et al. 2007) that had used the same criterion. The IOP declined with age in normal subject; a similar finding was reported by Shiose (1984), which suggests that ophthalmologists should consider the influence of age on the IOP during the diagnosis of PACG in older subjects. In this study, the mean VCDR of the right and the left eyes was 0.31 and 0.31, respectively, which is similar to that of Bangladesh (0.34) (Rahman et al. 2004) and German (0.34) (Jonas et al. 1988) but lower than that of studies conducted in India (0.56) (Jonas et al. 2003) and Holland (0.49) (Ramrattan et al. 1999). Therefore, the mean VCDR varies between different regions and different races. In addition, the VCDR in this study was assessed by ophthalmoscope rather than photographs, so the mean VCDR may be underestimated. In this study, a CDR of ≥0.7 was chosen as the cut-off for field testing; this may result in losing subjects with small discs even though they have glaucomatous visual field loss. Furthermore, some subjects who had media opacities and were not examined for disc assessment could also have had glaucoma. Therefore, the prevalence of PACG in this study may be underestimated. Marked variations were found in the prevalence of PACG between countries. The prevalence of PACG in our survey is 1.57% (95% CI, 1.47–1.67), which is similar to those reported in other studies (Hu et al. 1989; He et al. 2006); it is lower than that reported in Myanmar (2.5%) (Casson et al. 2007) but considerably higher than reported in India (0.87%) (Vijaya et al. 2006), Japan (0.34%) (Shiose et al. 1991) and Bangladesh (0.23%) (Raychaudhuri et al. 2005). This may be partly related to race difference. Furthermore, the prevalence rate may be influenced by the cold climate of the study site located in Northeast China. The prevalence of PACG in Greenland with a similar cold climate is 5.0% (Clemmesen & Alsbirk 1971), and the very shallow anterior chamber depth was described in the same population (Alsbirk 1992). Casson (2008) also reported that a shallow anterior chamber remains an undisputed risk factor for PACG and that shallow anterior chamber found in certain people of Asian extraction originated in north-east Asia 40 000–15 000 years ago as an anatomical adaptation to resist corneal freezing and that their descendants possess the trait. Therefore, the association between high prevalence of PACG and cold climate suggests that the occurrence and development of shallow anterior chamber and PACG are probably affected by cold climate. The data obtained in this study suggest a preponderance of PACG among women; similar findings have been reported in other studies (Foster et al. 2000; Bourne et al. 2003; Vijaya et al. 2006), which may be explained by the fact that women have significantly shorter eyes, shallower anterior chambers and thicker lenses (risk factors for a narrow angle) than men (Vijaya et al. 2006). Although we found a preponderance of PACG among women in this study (23 men, 55 women), this finding was not statistically significant. This result is consistent with those obtained in Thailand (Bourne et al. 2003) and Guangzhou, China (He et al. 2006). Primary open-angle glaucoma (POAG) was diagnosed if the criteria outlined above for category 1–3 were met in one or both eyes, ≥180° of posterior (usually pigmented) trabecular meshwork was visible on static gonioscopy and no secondary cause for glaucoma was present. Mingguang He et al. (2006) reported that 57.1% of PACG cases had been previously diagnosed by a hospital or clinic (compared to 6.9% of POAG cases), and more PACG subjects (42.9%) were blind in one or both eyes than POAG subjects (17%); therefore, these authors surmised that PACG is more likely to be symptomatic than POAG, resulting in the subject seeking medical advice, and that reduced vision is the main symptom of PACG. The treatment rate was 47.44% in the present study. However, more PACG subjects (82.05%) had vision impairment of varying degrees than those reported in Thailand (Bourne et al. 2003). This was related to poor awareness of medical treatment and poor level of medical treatment in rural counties; this resulted in delay in receiving treatment or in incomplete cure owing to no further consultation with the doctor after treatment. Hence, early diagnosis and early treatment are crucial for the prevention and treatment of PACG. We think to spread earlier education among the patients is very important. The high prevalence of PACG and severe vision impairment has attracted researchers’ interests in identifying the risk factors for this disease. In our survey, univariate and multivariate logistic regression analyses revealed that old age, family history of PACG, constipation and IOP were significant independent risk factors for PACG. Old age has often been shown to be associated with an increased risk of PACG (Foster et al. 2000; Bourne et al. 2003; Vijaya et al. 2006), which is consistent with the findings of our study. Anterior chambers tend to be more shallow in hypermetropia than in emmetropia, and many patients with shallow anterior chamber glaucoma were found to be hypermetropic (Lowe 1970). Therefore, the increased risk of old age is probably associated with hyperopia (Lowe 1970) and shallowing of the peripheral anterior chamber (Bourne et al. 2001) in ageing people. In this study, family history was found to be a strong risk factor for the development of PACG, and the importance of family history has also been highlighted in other studies (Congdon et al. 1992; Yuan et al. 2007); therefore, it is essential to study and reveal the pathogenesis of PACG by ophthalmic molecular genetics. Our study confirmed constipation as a risk factor in patients with PACG. Constipation can cause one to use the Valsalva manoeuvre, which may lead to elevation of IOP (Brody et al. 1999) and significant narrowing of the angle recess (Dada et al. 2006). Sihota et al. (2008) also reported that the occurrence of a Valsalva manoeuvre or similar physiological changes during activities of daily living may be responsible for intermittent angle closure in predisposed eyes as well as large, acute elevations of IOP which could be detrimental for a glaucomatous optic neuropathy and may play a role in progression of the disease even after a laser iridotomy. Hence, we think that PACG patient with a history of constipation should be advised to avoid Valsalva manoeuvre and receive clinical therapy if possible. In this study, IOP was another risk factor for PACG; among all PACG subjects, 42 (53.84%) had elevated IOP >21 mmHg in either eye. This finding is in agreement with the result of Zhong et al. (2004), who reported that in patients with PACG with severe visual field loss in one eye, the visual field defect score positively correlated with the mean IOP. Klein et al. (2006) also reported that people who are at least 75 years old were at greater risk of developing optic disc cupping, which is associated with greater IOP. In conclusion, PACG was a disease of high prevalence in rural Northeast China. Old age, family history of PACG, constipation and IOP were significant independent risk factors for PACG in this region. Furthermore, based on the study results, we could not identify an association between PACG and gender, diabetes mellitus, systemic hypertension, smoking habits, alcohol intake and blood group. The authors are grateful to all volunteers for their participation and the government of Bin County for support, organization and help in this investigation. This study was supported by Natural Science Foundation of Heilongjiang province (ZD201015), Overseas Scholar Project of Education Department of Heilongjiang Province (1152hq35) and Science Foundation of Public Health Department of Harbin (2009-158). This project was funded by Scholars Abroad Program of Heilongjiang province Educational Committee.