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Abstract
Purpose To describe the prevalence of age-related macular degeneration (AMD) among older adults in rural southern mainland China.
Methods Eligible persons aged 50 years or over were identified by geographically defined cluster sampling from Yangxi County, Guangdong Province, China. Participants underwent a standardised interview and comprehensive eye examinations from August to November in 2014. Digital retinal photographs were graded for AMD lesions using the Clinical Classification of Age-Related Macular Degeneration developed by the Beckman Initiative for Macular Research Classification Committee. Age-standardised prevalence of AMD and AMD lesions was calculated using the 2010 world population data and compared with those of other populations.
Results Of 5825 subjects who participated (90.7% response rate), 4881 (83.8%) had fundus photographs gradable for AMD. Early, intermediate and late AMD were present in 2003 (41.0%), 879 (18.0%) and 42 (0.86%) participants. The age-standardised prevalence of early, intermediate and late AMD was 40.4% (95% CI 39.6% to 41.2%), 17.6% (95% CI 17.0% to 18.2%) and 0.79% (95% CI 0.65% to 0.95%), respectively. Total AMD was more prevalent in men than in women (62.8% vs 57.1%).
Conclusions AMD is an important public health concern for rural southern China, and the prevalence of AMD was higher in men than in women.
- prevalence
- age-related macular degeneration
- Rural China
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Introduction
Age-related macular degeneration (AMD) is a leading cause of visual loss in elderly in Western countries.1 2 Increasing population-based studies of AMD have been performed in Caucasian and Asians in the past decades, and it is estimated that 196 million people would be affected by this disease in 2020 worldwide. Significant differences in the epidemiology of AMD have been found between regions and populations. A meta-analysis by Wong et al 1 reported that cases of early and any AMD were more prevalent in Europe and North America than in Asia. Furthermore, wide variations of AMD prevalence have been reported between different Asian ethnicities.3
China has the largest population worldwide, accounting for more than one-fifth of the world’s population. There are approximately 1.33 billion people living in mainland China alone, with over two-thirds living in rural areas.4 Furthermore, millions of Chinese people have emigrated to Western countries as well as other Asian countries. Therefore, an accurate estimation of the epidemiological characteristics of AMD in China provides essential information for health policy planning and health service delivery in China but also in other developed countries.
There were only three studies on the prevalence of AMD in mainland China, namely the Beijing Eye Study (BJES), Handan Eye Study (HDES) and Jiangning Eye Study (JNES). No study has been conducted in rural southern China to date.5–7 These studies reported considerably different prevalence on both early (1.4% in BJES, 3.0% in HES and 9.5% in JNES) and late AMD (0.2% in BJES, 0.1% in HDES and 1.0% in JNES). Two of these studies (BJES and HDES) were conducted 10 years ago. Therefore, an up-to-date study will allow us to validate these findings and to understand and assess the magnitude of the disease. The present study describes the age-specific and gender-specific prevalence of AMD in a rural southern Chinese population, making comparisons with other populations.
Methods
Study population
The Yangxi Eye Study is an expanded part of the 2014 China Nine-Province Survey, which was a population-based study of visual impairment, blindness and common eye diseases in adults aged 50 years and older living in rural China. Yangxi is a rural county, situated in western Guangdong Province, and the population of Yangxi was estimated to be 513 802 in 2012. We selected Yangxi district for the survey as it has a socioeconomic profile that is representative of the rural area of Guangdong as a whole. Based on data from the Residence Administrative Committee, the sampling frame was constructed using geographically defined clusters of approximately 1000 individuals (population aged 50 years or older accounts for approximately 20%). Villages with less than 500 individuals were combined and with more than 1500 individuals were subdivided. Each geographically defined cluster was treated as a basic sample unit, and using this method 268 basic sampling units were created. Twenty-eight clusters from which more than 5600 eligible subjects could be recruited were randomly selected.
The study fieldwork was carried out from August to November in 2014. Eligible subjects were recruited according to the protocol of the 2014 China Nine-Province Survey. In brief, individuals aged 50 years or older who had been living in the selected districts for at least 6 months were considered eligible at the time of recruitment. Door-to-door visits were conducted by the recruitment team with the help of the village registers, and participants were enumerated by address, name, gender, data of birth, education level and spectacle usage.
Written informed consent was obtained from all participants at the time of examination. The study was approved by the Zhongshan Ophthalmic Center Institutional Review Board and the tenets of the Declaration of Helsinki were observed.
Study procedures
An examination site was set up in each selected basic sample unit and eligible participants were verified using their identity cards. A standard questionnaire was conducted by trained interviewers to collect information about general medical history, current medication use, ophthalmic history and education level.
Eye examinations were performed by ophthalmologist according to a standardised protocol that included autorefraction, visual acuity measurement, slit lamp microscopic examination and direct ophthalmoscopy. Fundus photography was undertaken in all participants for each eye using a digital non-mydriatic fundus camera (FundusVue, Crystalvue, Taoyuan City, Taiwan), corresponding to ETDRS standard field 1 (centred on the optic disc) and field 2 (centred on the fovea).8 Pupils were dilated using compound tropicamide eye-drops as necessary.
Definition and grading of AMD lesions
The Clinical Classification of Age-Related Macular Degeneration, developed by the Beckman Initiative for Macular Research Classification Committee,9 which has been previously used in the AMD Preferred Practice Pattern guidelines by the American Academy of Ophthalmology,10 was consequently chosen as the system for grading AMD lesions in the present study.
Drusen was classified based on size into small drusen (≤63 µm), medium drusen (63–125 µm) and large drusen (>125 µm). Retinal pigmentary abnormalities were defined as any hyperpigmentary or hypopigmentary abnormalities associated with medium or large drusen but not associated with other known disease entities. Neovascular AMD lesions were considered as the presence of subretinal or subretinal pigment epithelium (RPE) haemorrhages, neurosensory detachment, RPE detachment or a disc scar within the macular area. Geographic atrophy was defined as a sharply discrete region of dropout of the RPE with an area of at least 175 µm in diameter, exposing choroidal vessels. Based on the above definitions, the five-stage classification scale for AMD was summarised below.
No apparent ageing changes were defined as no visible drusen and no AMD pigmentary abnormalities. Normal ageing change was defined as only small drusen without AMD pigmentary abnormalities, which is not believed to represent increased risk of late AMD developing. Early AMD was defined as medium drusen without AMD pigmentary abnormalities. Intermediate AMD was defined as large drusen and/or any AMD pigmentary abnormalities. Late AMD was defined as neovascular AMD and/or geographic atrophy, which is also consistent with the definition of Wisconsin Age-Related Maculopathy Grading System.
Two trained graders classified each image independently based on a standard protocol. The results were considered as the grading outcome if two graders agreed with each other, otherwise the images were sent to a senior grader for further verification and the grading results were considered as the final outcome. The interobserver agreement between two graders was weighted kappa (0.80) for the AMD classification.
Statistical analysis
Overall, age-specific and sex-specific prevalence of AMD and its individual signs was assessed. For participants with AMD signs only in one eye or asymmetric AMD severity in two eyes, the prevalence of AMD was estimated according to the worse eye. Age-standardised prevalence with 95% CIs of AMD and AMD lesions was calculated using direct standardisation of the study population to the world population in 2010 (http://www.census.gov/population/international/data/idb) to compare with the findings from other population-based studies. Χ2 tests and Mann-Whitney U test were used to compare the characteristics between genders as well as different age groups. All data analyses were performed using Stata V.12.0 software.
Results
Based on the data from the Residence Administrative Committee, 6844 subjects were identified as aged 50 years and older at the time of examination. Among these, 6425 were eligible (409 had moved away from their original residences, 7 had died and 3 were non-existent according to village registers) and 5825 (90.7% response rate) took part in the study.
Out of the 5825 participants, 4495 had fundus photographs of both eyes, 386 had fundus photographs for only one eye, and 944 did not have fundus photographs taken or poor-quality photographs of both eyes, leaving 4881 participants with fundus photographs of acceptable quality for grading AMD. Demographic characteristics of this study population are shown in online supplementary tables 1 and 2. The mean age of subjects included in the final analysis was 66.0±10.0 years. Women accounts for 50.9% of the study population, and the mean age of men and women was 66.6±9.51 and 65.4±10.5, respectively, with a statistical significance (p<0.001).
Table 1 shows the crude prevalence of early, intermediate, late and any AMD was 41.0%, 18.0%, 0.9% and 59.9%, respectively, in all participants. Male participants had a higher prevalence of intermediate, late and any AMD overall (20.6% vs 15.5%, 1.2% vs 0.6%, and 62.8% vs 57.1%, respectively). The prevalence of intermediate and late AMD increased with age in the whole study sample (p<0.05). After age standardisation against the world population data (2010 census), the prevalence of early, intermediate, late and any AMD was 40.4% (39.6% to 41.2%), 17.6% (17.0% to 18.2%), 0.8% (0.65% to 0.95%) and 58.7% (57.9% to 59.5%), respectively, in all participants.
Age-specific and sex-specific prevalence of age-related macular degeneration (AMD)
Large drusen was present in 701 (14.4%) participants, with the highest prevalence (15.9%) in those 273 participants who were 70 years or older. Large drusen was more prevalent among older participants than younger participants, both in women (p=0.032) and overall (p=0.021). These differences remained after adjusting for age. Men were more likely to have large drusen (15.6% vs 12.9%, p=0.004). RPE pigmentary abnormalities were present in 134 (2.7%) of all the participants, and men were also more likely to have RPE pigmentary abnormalities before and after adjusting for age (4.4% vs 1.1%, p<0.001, and 5.1% vs 1.2%, respectively) (table 2). Late AMD was present in 42 (0.86%) participants, and neovascular AMD was more prevalent than geographic atrophy, with 29 (0.59%) participants diagnosed with neovascular AMD and 13 (0.27%) participants diagnosed with geographic atrophy.
Age-specific and sex-specific prevalence of large drusen and RPE pigmentary abnormalities in the Yangxi Eye Study
The results of multivariate-adjusted logistic regression analyses of risk factors for the development of AMD are shown in online supplementary table 3. Men was a significant risk factor for the development of intermediate AMD (OR, 1.44, 95% CI 1.23 to 1.69), late AMD (OR, 2.46, 95% CI 1.15 to 5.24) and any AMD (OR, 1.20, 95% CI 1.06 to 1.36), and older age was significantly associated with both early and any AMD (per 10-year increase, OR, 1.13, 95% CI 1.03 to 1.24, and OR, 1.14, 95% CI 1.05 to 1.24, respectively).
Comparisons with other population-based studies
Comparisons of the prevalence of large drusen and RPE pigmentary abnormalities with other populations are illustrated (figures 1 and 2). The total prevalence of large drusen was similar with that reported in the Chinese American Eye Study (CHES) and the Beaver Dam Eye Study.11 12 Furthermore, it was higher than that of Blue Mountain Eye Study (BMES) and the BJES, and lower than that in Los Angeles Eye Study and Shipai Eye Study conducted in Taiwan.7 11 13 14 A comparison between different population-based studies indicates that the prevalence of RPE pigmentary abnormalities in the present study was similar to the Hisayama Eye Study performed in Japan, but lower than studies conducted in the USA and Australia.12 15 16 Interestingly, the prevalence was also lower than that reported by other studies conducted in China (figure 2).
Comparison of age-specific prevalence of large drusen (≥125 µm) in different population-based studies. BDES, Beaver Dam Eye Study; BJES, Beijing Eye Study; BMES, Blue Mountain Eye Study; CHES, Chinese American Eye Study; LAES, Los Angeles Latino Eye Study; SPES, Shipai Eye Study; YXES, Yangxi Eye Study.
Comparison of age-specific prevalence of retinal pigment epithelium abnormalities in different population-based studies. BMES, Blue Mountain Eye Study; CHES, Chinese American Eye Study; HDES, Handan Eye Study; HS, Hisayama Eye Study; LAES, Los Angeles Latino Eye Study; SPES, Shipai Eye Study; YXES, Yangxi Eye Study.
Table 3 summarises the crude and age-standardised prevalence of late AMD in previous studies of Chinese populations. The study population was found to have a similar age-standardised prevalence of late AMD compared with Chinese Americans in the Multi-Ethnic Study of Atherosclerosis (0.8% vs 0.7%),17 but a higher prevalence compared with the BJES and the HDES as well as the CHES.6 7 12 The prevalence of late AMD in this rural Chinese population was found to be lower than an urban Chinese population of the JNES and the Shipai Eye Study in Taiwan. When compared with non-Chinese populations, the age-specific prevalence of late AMD in this study was similar to that of the Hisayama Eye Study in Japan, but lower than that of BMES in Australia and Beaver Dam Eye Study in America.
Comparison on prevalence of late age-related macular degeneration in Chinese population
Discussion
This population-based study reports on the prevalence of AMD in rural China and shows the age-standardised prevalence of early, intermediate and late AMD was 40.4%, 17.6% and 0.8%, respectively. Men were more likely to have AMD and AMD lesions than women (62.8% vs 57.1% for any AMD, p<0.001; 15.6% vs 12.9% for large drusen, p=0.004; 4.4% vs 1.1% for RPE pigmentary abnormalities, p<0.001). This southern rural Chinese population had a higher prevalence of late AMD compared with previous findings in a northern rural Chinese population,6 but a lower prevalence than that in an urban Chinese population of China and Taiwan.5 13 18
This study used a new AMD grading system that is valuable in predicting the risk of late AMD and improving care and communication between eye care providers.9 As previous studies used different definitions for classifying early and intermediate AMD, it is difficult to compare the prevalence findings for these two grades in the present study. Considering large drusen and RPE pigmentary abnormalities have been identified as key risk factors for predicting the progression of AMD9 and used as main reference indexes both in the Clinical Classification of Age-Related Macular Degeneration and Wisconsin AMD grading systems,9 we compared the prevalence of large drusen and RPE pigmentary abnormalities as surrogates of early AMD with other population-based studies. It has long been perceived that AMD is more common in Caucasians compared with Asians1 6; however, in the present study we found the total prevalence of large drusen to be higher in this Chinese population than in Caucasians from the BMES.15 This finding is in line with another report of a similar higher prevalence of large drusen in a Chinese American population as compared with the BMES.12 The present study also shows that the prevalence of RPE pigmentary abnormalities, another important lesion of AMD, was lower in this Chinese population than in Caucasians from the America and Australia,15 19 but similar with Japanese Asians.16
As the definition of late AMD in this study corresponds to the definition in the Wisconsin AMD grading system, the prevalence of late AMD was comparable with previous studies. After age standardisation with the 2000 world population, the prevalence of late AMD was 0.8% among this rural Chinese population, which was most similar to that of Chinese Americans in the Multi-Ethnic Study of Atherosclerosis.17 This prevalence was lower compared with Caucasians in the BMES15 and the Beaver Dam Eye Study,11 and is consistent with other reports that the prevalence of late AMD was lower in ethnic Chinese than in Caucasian populations.6 20 But for the subtypes of late AMD, we found that the ratios of neovascular AMD to geographic atrophy was a little higher than white populations, which was consistent with previous studies.21 22 The possible reasons maybe lie in that we did not differentiate polypoidal choroidal vasculopathy (PCV) from neovascular AMD, and PCV has been known to be more prevalent in Asians compared with whites.22 23 This suggests there are racial differences that are significant for explaining the AMD epidemiological pattern. The present study also finds there is a lower rural prevalence for late AMD in comparison to that in the urban areas of China,5 Taiwan13 18 and Singapore,3 which suggests that regional development may account for different AMD characteristics in the Chinese population. This finding is in keeping with the results of the HDES conducted in northern rural China.8
The logistic regression analysis shows male is a risk factor for AMD compared with female, which was consistent with several previous studies that demonstrated a higher AMD prevalence in men compared with women.6 13 16 19 Although the exact pathogenesis remains unclear, several hypotheses have been proposed. First, this sex disparity may be partly explained by the higher frequency of cigarette smoking among Asian men than women.6 16 Smoking has been consistently identified as a risk factor for presence and progression of AMD.24 Second, exogenous oestrogen use (such as oral contraceptive use and hormone replacement therapy) in women may be a protective factor for AMD lesions as has been previously reported.19 Experiments have shown that oestrogen may protect against increasing sub-RPE deposits and prevent Bruch’s membrane from thickening.25 Other factors have also been proposed to be involved, such as different degrees of sunlight exposure26 and dietary intake of n-3 polyunsaturated fat,27 aside from obvious genetic variation and anatomic differences.28
Strengths of this study lie in the population-based study design with large sample size, high response rate (90.7%) and the use of a standardised protocol complementing the widely recognised AMD grading classification system. The limitations of this study are as follows. First, although the new AMD grading system used in this study is quite compatible with other traditional grading system and is valuable in predicting the risk of late AMD, head-to-head comparison of results between the present study and previous landmark studies might be limited. Second, the data on other potential confounders such as genetic factors and smoking status were unattainable from the survey. Thus, we could not sufficiently evaluate the influence of these factors on AMD prevalence in this sample. Third, consistent with previous studies, the prevalence of AMD is underestimated in participants due to dense cataract formation, from whom we could not acquire gradable fundus photographs.
Conclusions
This study presents the findings of age-specific and gender-specific AMD prevalence in a rural southern Chinese population. The results indicate that AMD may be a significant public health concern for rural southern China, with a higher prevalence in men than in women. This study provides essential prevalence data and insight for health service planning and delivery in China, and especially in rural China, where the majority of the population resides.
Acknowledgments
The authors thank ORBIS International North Asia for supporting the work.
References
Footnotes
Contributors Conception and design of the study (MH, JZ); analysis and interpretation (GJ, XD, WX); writing of the article (GJ, WW, WY); critical revision of the article (LA, XX, MH, JZ); data collection (GJ, XD, WX, LW, XH, OX, RL, WW); administrative, technical or logistic support (XX, MH, JZ).
Funding This work was supported by National Institute of Hospital Administration, Chinese National Health and Family Planning Commission under ORBIS International North Asia (Beijing, China) contract no 1541. MH receives support from Fundamental Research Funds of the State Key Laboratory in Ophthalmology, Science and Technology Planning Project of Guangdong Province 2013B20400003. MH receives support from the University of Melbourne at Research Accelerator Program and the CERA Foundation. The Centre for Eye Research Australia receives Operational Infrastructure Support from the Victorian State Government.
Competing interests None declared.
Patient consent Obtained.
Ethics approval Zhongshan Ophthalmic Center Institutional Review Board Sun Yat-sen University.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Original data are available on request. Please contact the corresponding author for further information.
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