dry eye disease ( des ) is a major tear deficiency disorder which causes discomfort , visual disturbances , and tear film instability with potential damage to the ocular surface .
the tear film and ocular surface form a complex and stable system that can lose its equilibrium through multiple disturbing factors . despite the gain in knowledge of pathogenic factors of des acquired in the past decades
, there has been considerable discrepancy in the reported prevalence worldwide , mainly due to lack of consensus on appropriated diagnostic criteria and differences in the parameters and research methodology applied .
two large population - based studies suggested that about 7.8% of american women and 4.7% of men aged 50 years and older had des [ 3 , 4 ] . in a study conducted in melbourne , australia ,
des was diagnosed in subjects over 40 years old as 10.8% by rose bengal staining , 16.3% by schirmer 's test , 8.6% by tear breakup time , 7.4% with two or more signs , and 5.5% with severe symptoms of des not attributed to hay fever .
risk factors for two or more signs included age and self - report of arthritis .
a large study used questionnaires to investigate the prevalence of des in canada in all age groups . in
the 13,517 returned questionnaires ( 55% aged 2150 years , 60.7% were women ) , 28.7% respondents reported des .
those reporting severe des were predominantly women , with a ratio of 46  :  1 .
some population - based studies investigating the prevalence and risk factors of des in china have been published [ 718 ] .
therefore , it is difficult to assess the overall prevalence of des in china . based on the current published data , the present study utilized systematic review and meta - analysis with an aim to estimate the overall pooled prevalence of des in china .
the epidemic characteristics of des such as prevalence in different geographic regions , genders , and age groups were also explored .
to obtain regional epidemiologic data , we searched medline ( from january 1 , 1946 , to october 31 , 2013 ) , embase ( from january 1 , 1950 , to october 31 , 2013 ) , the cochrane central register of controlled trials ( up to 2013 , issue 10 ) , chinese biological medicine ( january 1 , 1978 , to october 31 , 2013 ) , china national knowledge infrastructure ( january 1 , 1979 , to october 31 , 2013 ) , wan fang data ( january 1 , 1982 , to october 31 , 2013 ) , and chongqing vip database ( january 1 , 1982 , to october 31 , 2013 ) using the free combinations of the terms  dry eye , 
the corresponding authors or first authors of the publications were contacted if additional information was needed , results were unclear , or relevant data were not reported .
the review and analysis were guided to be conducted by the prisma statement for preferred reporting of systematic reviews and meta - analysis .
reports potentially eligible for inclusion in this systematic review and meta - analysis had to meet the following criteria : population - based studies , authentic , written either in english or in chinese , and being able to provide sufficient information to estimate the pooled prevalence of and risk factors for des .
population - based study needed to meet the following criteria : ( i ) the study populations need to be scrutinized with regard to all characteristics of the cohort before one can compare their results and ( ii ) the study populations need to be from special samples except hospital .
if more than one study was based on the same population sample , the study with better quality was included .
we excluded studies that were on the duplicate population groups but of lower quality and those that had participants drawn from a particular occupation or population and those that did not satisfy one or more inclusion criteria .
the literatures were searched independently by two researchers ( lei liu and yi - zhou sun ) .
data were extracted from each article using a standardized form which included the first author , publication year , region or province , age range , sample size , diagnostic criteria , prevalence definition , response rage , and quality of the studies ( in a score of 15 ) ( table 1 ) .
odds ratio ( or ) was analyzed using revman version 5.0 ( review manager , copenhagen : the nordic cochrane centre , the cochrane collaboration , 2010 ) statistical software package .
multivariate analyses to test the individual association of each variable with the overall pooled prevalence estimate using meta - regression analyses were performed by comprehensive meta - analysis software version 2.0 ( biostat , englewood cliffs , nj , usa ) .
all meta - analyses were evaluated for heterogeneity using the chi - square based i test and q test .
i estimated the percentage of the total variance in all of the data under consideration that was related to heterogeneity .
if a moderate or high level heterogeneity was observed , random - effects meta - analysis was performed by the dersimonian and laird method , except when using fixed - effects models .
assessment of publication bias was done by inspecting a funnel plot and using egger 's and begg 's test .
the flow chart showing how the identified published studies were included in the meta - analysis was demonstrated in figure 1 .
, only 12 studies [ 718 ] ( table 1 ) met the inclusion criteria and were included in the meta - analysis .
the pooled prevalence of des was 17.0% ( 95% ci : 9.9%27.4% ) ( i = 49.9% ,  q = 0.99 ,  p
< 0.001 ) in overall population ( figures 2(a ) and 2(b ) , table 2 ) .
the pooled prevalence rate in female individuals was significantly higher than that in males ( 21.6% versus 15.6% ) ( or : 1.41 , 95% ci : 1.311.52 , and p < 0.001 ) ( figures 2(c ) and 2(d ) , table 2 ) .
no significant difference was found in prevalence rate between urban china and rural china ( 15.3% and 21.3% , resp . , or : 1.06 , 95% ci : 0.971.17 , and p = 0.205 ) ( figures 3(c ) and 3(d ) , table 2 ) .
the prevalence rates , however , were found to be remarkably variable in different geographic regions in china .
northern china had significantly higher prevalence than southern china ( 17.9% versus 16.1% ) ( or : 1.97 , 95% ci : 1.782.04 , and p < 0.001 ) ( figures 3(a ) and 3(b ) , table 2 ) . compared with central china which had a prevalence rate of 10.3% ,
eastern china and western china showed significantly higher prevalence rate ( 12.8% and 31.3% , resp . ) ( or : 2.62 and 1.38 , resp . , and p < 0.001 ) ( table 2 ) .
the meta - analysis data covered eight provincial / municipality / autonomous regions as shown in figure 4 .
the pooled or was 3.34 ( 95% ci , 2.684.16 ) ( i = 15% ,  p < 0.001 ) for elder age ( 60 years ) .
the pooled or was 1.15 ( 95% ci , 1.041.27 ) ( i = 12% ,  p = 0.005 ) for female gender .
in addition , diabetes also showed a significant risk factor for des and the pooled or was 3.82 ( 95% ci , 2.685.46 ) ( i = 10% ,  p < 0.001 ) .
there was no significant publication bias in this meta - analysis ( p < 0.05 for both egger 's test and begg 's test ) .
to our knowledge , the present study is the first meta - analysis of des in mainland china .
population - based studies evaluating the prevalence of des differ in the definitions , diagnostic criteria for des , selection of the study population , and the methodology applied ( questionnaires and/or objective tests ) .
not surprisingly , there is a discrepancy in the prevalence between our data and findings in other asian regions and countries .
the shihpai eye study found that 33.7% ( 459/1361 ) of individuals aged 65 years in taiwan were symptomatic , as defined by the reporting of one or more dry eye symptoms often or at all times . in yongin , korea ,
the adjusted prevalence of dry eye disease was 33.2% in 657 subjects aged 65 years or older .
a japanese study found that 21.6% of the female individuals aged 40 years or over were diagnosed with dry eye disease or severe symptoms , significantly higher than their male counterparts ( 12.5% ) .
report suggested that the prevalence of des increased with age , which is consistent with our meta - analysis .
our findings verified that the elder population ( over 60 years of age ) had higher prevalence of des than the younger population .
however , some published studies based on regional population in china did not find any prevalence difference between males and females [ 7 , 1317 ] .
the pooled prevalence in our study showed significantly higher prevalence in female subjects , consistent with majority of studies . a larger number of des cases were identified in individuals with diabetes , particularly those with type 2 diabetes .
our meta - analysis illustrated significantly higher prevalence of des in diabetes patients , which is consistent with other studies [ 30 , 31 ] .
the prevalence of diabetes has been increased dramatically with the rapid economic growth and the improved quality of life in china over the last thirty years .
much attention should be paid to prevent ocular surface disorder in the people with diabetes .
other risk factors for des ( e.g. , alcohol , smoking , computer use , contact lens wear , and systemic or ocular medications ) were initially included in the present study but were excluded because the pooled or was not able to be calculated as a result of insufficient information provided .
western china and northern china had significantly higher prevalence when compared with central , eastern , and southern china , possibly because of the difference in the climate conditions and geographic characteristics in these regions .
qinghai - tibetan plateau of western china is characterized with high altitudes , long hours of sunlight , and strong ultraviolet radiation , which may contribute to the high prevalence .
other climate conditions including low humidity and draft were believed to be related to des , which may partially be an explanation of the higher prevalence in northern china . although the pooled prevalence in rural china seemed to be higher than in urban china , the difference was not statistically significant after meta - regression .
further investigation is needed . because the findings in pooled prevalence of des had moderate i , we did meta - regression to analyze and verify the results to avoid substantial heterogeneity .
although pooled prevalence of des in mainland china was derived in the present study , there are some limitations .
firstly , the pooled prevalence data was estimated using meta - analysis , rather than prevalence in a single national population - based study .
secondly , china is a vast country geographically with 34 provincial - level administrative units ( 23 provinces , 4 municipalities , 5 autonomous regions , and 2 special administrative regions ) .
our study only included data from 12 units , which may be inaccurate to represent the pooled prevalence of the whole country .
more regional epidemiologic studies are warranted , particularly those units with no published data , so that a more accurate picture of prevalence in china can be drawn .
lastly , our data should be updated as a result of the emerging new data .
compared with some of the other asian regions and countries , the pooled prevalence of des in mainland china was lower .
there is remarkable discrepancy in the prevalence in different geographic regions in china , with western and northern china presenting higher prevalence , possibly because of the difference in the climate conditions and geographic characteristics .
female , elder individuals , and patients with diabetes seemed to be more vulnerable to des .
more studies focusing on chinese populations in regions without epidemiologic data are of great value .
 
 purpose . to evaluate the pooled prevalence rate and risk factors of dry eye symptoms ( des ) in mainland china 
 . methods . all the published population - based studies investigating the prevalence of des in china were searched and evaluated against inclusion criteria . a systematic 
 review and meta - analysis were performed . results . 
 twelve out of the 119 identified studies were included in the meta - analysis . 
 the pooled prevalence of des in china was 17.0% . 
 female individuals , subjects living in the northern and western china , and over 60 years of age had significantly higher prevalent rates ( 21.6% , 17.9% , 31.3% , and 34.4% , resp . ) compared with their counterparts . 
 patients with diabetes were also found to be more vulnerable to des . 
 conclusions 
 . the pooled prevalence rate of des in mainland china was lower than that in other asian regions and countries . 
 a remarkable discrepancy in the prevalence in different geographic regions was noted . 
 aging , female gender , and diabetes were found to be risk factors for des in china . 
1. Introduction
2. Methods
3. Results
4. Discussion
5. Conclusions