ARTICLE
Prevalence and Risk Factors of Dry Eye Disease Among a Hospital-Based Population in Southeast China Jinyang Li,
M.D., Ph.D.,
Ke Zheng,
M.D., O.D.,
Li Sun,
Zifeng Deng, M.D., Jingwei Zheng, and Wei Chen, M.D., Ph.D.
Objective: To investigate the prevalence of dry eye disease (DED) and distribution of associated risk factors among a hospital-based population. Methods: In this cross-sectional study, we collected detailed information of clinically defined moderate-to-severe patients with dry eye among a consecutive hospital-based population, including age trend, gender structure, frequency of symptoms, and distribution of associated environmental/ occupational risk factors. Results: Of 6,657 consecutive outpatients aged older than 20 years, symptomatic dry eye presented in 635 subjects (9.54%). Five hundred thirty-two of these 635 subjects (7.99%) were clinically diagnosed as defined DED that combined with positive signs. Women (10.41%) were significantly higher than men (5.21%) (P,0.001). Overexposure to visual display terminal was a major risk factor for DED among young men and women (56.2%). Our study also found occupational conditions with the risk of exposure to adverse environment made up over half of all 532 patients with dry eye. The use of contact lenses was closely associated with DED in young women, and history of ocular surgeries might be another factor associated with DED in old people. One hundred sixtythree of 371 female patients with dry eye (43.9%) were associated with hormonal changes. The incidence of meibomian gland dysfunction– related DED increased gradually with age. There were only 10 patients with dry eye (1.9%) associated with Sjögren syndrome, and all of them were women. Conclusions: Environmental and occupational factors were strongly associated with DED and constituted the major proportion in a hospitalbased population. A classification of DED based on the distribution of risk factors was recommended for clinical use. Key Words: Dry eye disease—Prevalence—Risk factor—Hospital-based population. (Eye & Contact Lens 2015;41: 44–50)
D
ry eye disease (DED) is one of the most frequent conditions in ophthalmology practice. According to the International Dry Eye Work Shop in 2007, DED is a multifactorial disease of tears and ocular surface that results in symptoms of discomfort, From the Department of Cornea and Ocular Surface Diseases, School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, China. Supported by a research grant 81170820 from National Natural Science Foundation of China. The authors have no conflicts of interest to disclose. Address correspondence to Wei Chen, M.D., Ph.D., School of Ophthalmology and Optometry, Wenzhou Medical University, 270 Xueyuan West Road, Wenzhou, Zhejiang 325027, China; e-mail: chenweimd@hotmail. com Accepted May 1, 2014. DOI: 10.1097/ICL.0000000000000064
44
M.D.,
Huixiang Ma,
M.D., Ph.D.,
M.D.,
visual disturbance, and tear film instability with potential damage to the ocular surface.1 It is important for clinicians to understand the integrated impact of physiological and ergonomic factors that are responsible for the development of DED. There were many studies2,3 that presented that environmental and occupational factors could affect ocular surface and cause dry eye symptoms. For example, exposure of visual display terminal (VDT) was reported to have a strong association with DED.4,5 As summarized by Wolkoff,2 identified environmental, occupational, and personal risk factors associated with dry eye symptomatology were listed, including aging, hormonal changes, contact lens (CL) wear, visual display unit work, cigarette smoking, ocular surgeries, systemic medication, indoor pollutants, low humidity, high room temperature, and so on. Therefore, various risk factors, especially environment- and occupation-related factors, seem to be highly associated with the occurrence and development of dry eye symptoms. The reported prevalence of dry eye syndrome varied because there are different standards of selected patients, questionnaires, cutoff of objective tests, and diagnostic criteria.6–10 In other words, even under the same diagnostic criteria, prevalence of DED may change along with sex, age, race, geography, education level, profession, and other risk factors. Therefore, selection of different study population could dramatically influence the final results and conclusions. For most epidemiologic studies achieved using questionnaires, one of the major limitations is usually lack of objective tests. In that case, the participants in those studies, such as seniors, office workers, and school students cannot show clinically diagnosed DED and fail to further classify different subtypes. Moreover, some important risk factors of DED may be ignored in studies restricted to a certain crowd of participants. A hospitalbased study could comprehensively embrace various crowds of participants with different risk factors of DED. However, there were few studies that paid close attention to present the proportion and association of each risk factor in a hospital-based population; nevertheless, it offered obvious advantages in convenience, high response rate, and complete identification of all cases. Moreover, analysis of data of clinically diagnosed DED from consecutive outpatients can provide global impression for clinicians to help determine diagnosis and classification and to realize the most important risk factors in clinic. To the best of our knowledge, no study has been designed to observe the prevalence and related risk factors of DED from consecutive outpatients. This study focused the investigation on the prevalence of DED and distribution of associated risk factors in a large-scale, cross-sectional hospital-based population. Eye & Contact Lens Volume 41, Number 1, January 2015
Copyright @ Contact Lens Association of Opthalmologists, Inc. Unauthorized reproduction of this article is prohibited.
Eye & Contact Lens Volume 41, Number 1, January 2015
MATERIALS AND METHODS Study Population In this hospital-based cross-sectional study, consecutive outpatients aged older than 20 years presenting with various ophthalmic problems to a tertiary eye hospital from May 1 to May 16, 2010 were included and screened for dry eye. Subjects were excluded from the study if they exhibited any active infection of the eye, active ocular allergy, evidence of lid deformity or abnormal lid movement disorder, pregnancy or lactation, evidence of ocular chemical or thermal burn, pterygium extending onto the cornea, and ocular surgeries within 6 months of the screening. This research was approved by the Wenzhou Medical University Review Board, Wenzhou, Zhejiang, China, and was performed in accordance with the Tenets of the Declaration of Helsinki. The patients were aware of the privacy policy of the hospital that states that information released for publication would not include patient identifiers.
Assessment of Dry Eye Each participant took a dry eye symptom questionnaire consisting of eight symptoms involving questions on feelings of dryness, grittiness or sandy, burning, redness, sticky, watery or tearing, crusting or discharge on the lashes, and stuck shut in the morning.9 When a participant indicated the presence of any symptom, the respondent was asked to indicate the frequency of occurrence ranging rarely, sometimes, often, or constantly. Subjects were considered symptomatic when at least one of the symptoms of the questionnaire was experienced often or all the time.5 The participant had the presence of either a previous clinical diagnosis of DED or severe symptoms were screened and assigned to the dry eye consulting room for a detailed questionnaire which was modified from dry eye questionnaires11 and objective tests. The data collection included age, sex, occupation, physiological status of menopause or postmenopause, lifestyle factors (e.g., cigarette smoking, VDT use), systemic medical history (e.g., diabetes mellitus, rheumatoid arthritis, thyroid disease, Parkinson disease), history of dry mouth/nose, ocular history (e.g., ocular surgery [OS], use of CL, and dye drops), and current use of systemic medications (e.g., oral contraceptives and hormonal preparations). Suspicious dry eye–related risk factors that derived from the previous literature were recorded, including the use of VDT more than 4 hr per day, wear of soft or rigid CL for a minimum of 8 hr daily, inveterate cigarette smoking, and driving more than 2 hr everyday. All participants were required to answer if the symptoms aggravated when their eyes exposed to the following types of environmental factors: excessive wind, swimming pool, dust, pollen, cooking fume, cigarette smoke, air conditioning/heating, and aircraft cabin. Three Chinese doctors (J.L., L.S., and H.M.) translated questionnaires from English into Chinese, and back-translated by native English speakers from Chinese to English. The translation was verified by W. Chen to avoid discrepancies resulting from cultural differences. The standard order of eye examinations was as follows: tear film breakup time test (TBUT), corneal and conjunctival fluorescein staining, Schirmer test (ST), and slit-lamp examination for assessment of the meibomian gland. The subjects were required to remove CLs at least 2 hr before examination and not to use artificial tears within 2 hr of screening. Each of assessments was at 10-min intervals to minimize reflex tearing and ocular surface changes secondary to testing. © 2014 Contact Lens Association of Ophthalmologists
Risk Factors of DED in Southeast China Tear film breakup time test and fluorescein staining were performed by using a dry fluorescein strip to touch the inferior palpebral conjunctiva lightly. The tear film was observed with a slit lamp with a cobalt blue filter after asking the patient to blink several times. The time, in seconds, between the last blink and the first desiccation spot was recorded. The mean of three of these recordings, taken after one single instillation of a drop of fluorescein, was registered as TBUT. Fluorescein staining of the cornea and lissamine green staining of the exposed interpalpebral conjunctiva were both graded on a scale from 0 (no staining) to 3 (confluent staining) according to the method of van Bijsterveld12 (score range, 0–9). Schirmer test without anesthesia was performed by placing a precalibrated standard strip (Sno strips, Chauvin, Montpellier, France) temporally in each of the lower temporal fornix and noting the extent of wetness on the strip after 5 min. During this time, the participants were instructed to look slightly upward and blink normally. The eyelid margins, meibomian gland orifices, and the meibomian gland secretions were carefully examined for signs of meibomian gland dysfunction (MGD). According to the criteria by Bron et al.,13 diagnosis of MGD included one or more of the following: (1) absent, viscous, or waxy white secretion on digital expression, (2) presence of greater than two lid margin telangiectases, and (3) plugging of greater than two gland orifices. Sjögren syndrome (SS) was defined as the presence of dryness of mucous membranes (mouth, throat, nose, or vagina) combined with history of rheumatoid arthritis or systemic lupus erythematosus and laboratory manifestations. Both SS and MGD were recorded as either present or absent.
Dry Eye Definition Symptomatic dry eye was defined as the presence of at least one symptom that ranked as often or constantly. Clinically diagnosed dry eye was defined according to the Japanese dry eye diagnostic criteria as follows: (1) the presence of qualitative or quantitative disturbance of the tear film on one or both eyes (ST, ,5 mm or TBUT, ,5 sec), (2) presence of conjunctivocorneal epithelial damage on one or both eyes (score of fluorescein staining above three points), and (3) presence of dry eye symptomatology. The presence of all the above criteria was necessary for diagnosis of definite DED.1
Data Analysis All analyses were performed with Statistical Package for the Social Sciences software (Version 13.0, SPSS Inc., Chicago, IL). Pearson or linear-by-linear chi-square tests were performed to test for an association between demographic variables (age, gender, and frequency of symptoms and risk factors). Cochran–Mantel– Haenszel chi-square test for categorical variables adjusting for age. A P,0.05 was considered statistically significant, and the 95% confidence intervals (CIs) were tabulated. The data analyses were performed by a statistician who was masked to whether the data came from a normal subject or a patient with dry eye.
RESULTS Population Demographics Of 6,657 consecutive outpatients aged older than 20 years, symptomatic dry eye present in 635 subjects (9.54%). Five hundred thirty-two of these 635 subjects were clinically diagnosed as defined DED that combined with positive signs. The prevalence 45
Copyright @ Contact Lens Association of Opthalmologists, Inc. Unauthorized reproduction of this article is prohibited.
Eye & Contact Lens Volume 41, Number 1, January 2015
J. Li et al. TABLE 1. Age Groups, y
Total (n=6,657) DED (n=532)
21–30 31–40 41–50 51–60 61–70 .70
Dry Eye Risk Factors
Prevalence of Dry Eye According to Age Groups
1,339 1,269 1,100 1,094 913 942
Pre, %
Pa
95% CI
7.62 11.35 10.27 7.77 7.12 2.44
0.572 ,0.001 0.002 0.767 0.295 ,0.001
0.752–1.179 1.289–1.926 1.096–1.694 0.760–1.230 0.669–1.146 0.180–0.419
102 144 113 85 65 23
The percentage of selected risk factors in 532 patients with clinically diagnosed DED was shown in Figure 2, including VDT use (VDT, 56.2%), menopause (30.6%), drive (25.8%), MGD (15.4%), CL use (13.2%), cigarette smoking (10.7%), and SS (1.9%). Physiological status of menopause/postmenopause was found in 163 of 371 female participants (43.9%), which represented a large proportion of women with clinically diagnosed DED. There were 76 participants having a history of OS (14.3%), comprised of cataract (n=21), glaucoma (n=10), pterygium (n=12) and vitreoretinal (n=11), and laser corneal surgeries (n=22). According to the univariate analysis, risk factors associated with age trend in participants with clinically diagnosed dry eye were OS, VDT, drive, CL, and MGD (P,0.005, linear-by-linear x2 test; Table 3). Exposed risk factors of VDT, drive, and CL were more common among young people with dry eye, instead OS and MGD were in the elderly. In men, risk factors of drive and smoking were associated with an increased percentage as compared with women (42.9% and 34.2% in men vs. 18.3% and 0.5% in women; P,0.001, Pearson x2 test; Table 4). Wearing contact lens was found to be significantly associated with clinically diagnosed DED in women (15.9% in women vs. 6.8% in men; P=0.004, Pearson x2 test; Table 4). There were no gender differences among other exposed risk factors in participants with clinically diagnosed dry eye.
Age differences by x2 test.
a
P , 0.05 was considered statistically significant. CI, confidence interval; DED, dry eye disease; Pre, prevalence.
of clinically diagnosed DED was 7.99% in all consecutive outpatients. The prevalence was significantly higher in patients aged 31 to 50 years (P,0.005) and significantly lower in age group of over 70 years (P,0.001), which demonstrated an inverted U-shaped relationship; the relative peaks were located on age group 31 to 40 years (Table 1). The mean age of DED patients was 42.26614.91 years, and 69.74% were women. As shown in Table 2, the prevalence of women (10.41%) was significantly higher than men (5.21%) (P,0.001; 95% CI, 0.390–0.573). In all age groups, the prevalence of women was significantly higher except the age groups above 61 years (P,0.005). After adjusting for age, women still had significantly increased prevalence compared with men (P,0.001).
Environmental and Occupational Risk Factors Frequency of Symptoms
By completing the analysis of occupations, conditions with the risk of exposure to adverse environment made up over half of all 532 patients with dry eye, which consisted of computer operators, office workers, scientists, drivers, cooks, teachers, students, doctors, nurses, fishers, retirees, administrators and government officer, and others with fine visual tasks. As shown in Figure 3, there were 241 of 532 participants (45.3%) with clinically diagnosed DED who reported sensory eye irritation when exposed to excessive wind, which was followed by air conditioning/heating (28.7%), cigarette smoke (23.8%), cooking fume (20.7%), aircraft cabin (14.1%), and swimming pool (13.2%). Only 11 of 507 and 16 of 312 patients experienced sensory irritation when exposed to environment of pollen and dust.
Among 635 participants of this survey, there were quite a few differences in the distribution of each dry eye symptom by frequency of response. Figure 1 showed the proportion of subjects who reported often to constant ocular symptoms. The results demonstrated that participants with clinically diagnosed DED (with positive signs) complained of burning most often (58.5% of 532 subjects). Watery or tearing, in contrast, was reported most frequently (49.5% of 103 subjects) in symptomatic participants with dry eye (without positive signs). They were both followed by grittiness (55.5% and 48.5%, respectively) and dryness (54.1% and 47.6%, respectively). There were significant differences in self-reported sensation of burning between the two groups (P,0.05, Pearson x2 test). TABLE 2.
Prevalence of Dry Eye According to Gender
Men Age Groups, y 21–30 31–40 41–50 51–60 61–70 .70
Women
N
DED
Pre, %
N
DED
Pre, %
Pa
95% CI
645 625 567 425 391 439
35 39 37 19 21 10
5.43 6.24 6.53 4.47 5.37 2.28
694 644 533 669 522 503
67 105 76 66 44 13
9.65 16.30 14.26 9.87 8.43 2.58
0.004 ,0.001 ,0.001 0.001 0.075 0.761
0.351–0.820 0.232–0.502 0.278–0.634 0.253–0.723 0.360–1.055 0.381–2.024
Gender
Total (n=6,657)
DED (n=532)
Pre, %
Pa
95% CI
Men Women
3,092 3,565
161 371
5.21 10.41
,0.001
0.390–0.573
Gender differences of different age groups by x2 test.
a
P , 0.05 was considered statistically significant. CI, confidence interval; DED, dry eye disease; Pre, prevalence.
46
Eye & Contact Lens Volume 41, Number 1, January 2015
Copyright @ Contact Lens Association of Opthalmologists, Inc. Unauthorized reproduction of this article is prohibited.
Eye & Contact Lens Volume 41, Number 1, January 2015
Risk Factors of DED in Southeast China
FIG. 1. Frequency of dry eye symptoms ranked as “often” or “all the time” between subjects with symptomatic and clinically diagnosed dry eye (asterisk, statistical significance, P,0.05).
DISCUSSION This study is the first large-scale, cross-sectional hospital population-based investigation of DED in China, which selected and screened all consecutive outpatients aged older than 20 years attending a tertiary eye hospital for DED during a designated time interval. Our study estimated the prevalence of DED using questionnaires and clinical tests and analyzed the association between clinically diagnosed DED and previously reported dry eye risk factors. In this study, the prevalence of symptomatic DED and clinically diagnosed DED was 9.54% and 7.99% in 6,657 consecutive outpatients, respectively, which was lower as compared with previous studies.4,7–9,14 One important reason for this difference may be strict diagnostic criteria. Patients with symtomatic dry eye screened by questionnaire were then involved with objective tests according to the Japanese dry eye diagnostic criteria, which
combined with conjunctivocorneal epithelial damage (fluorescein staining above three points) and either qualitative or quantitative disturbance of the tear film (ST, ,5 mm or TBUT, ,5 sec). Beside, unlike general population, outpatients always had clear purpose when they went to hospital. This characteristic of hospital-based population may lead to deviation of the result of dry eye prevalence. However, this cross-sectional study collected full detailed information of patients with clinically defined moderate-to-severe dry eye. The results provided global impression of DED for ophthalmologists, including age trend, gender structure, and distribution of associated environmental and occupational risk factors. Our results showed the prevalence of DED was significantly higher in patients of 31 to 50 years of age and significantly lower in the age group of above 70 years as compared with other age groups, and that presented an inverted U-shaped relationship with age trend. It was similar to the result
FIG. 2. The percentage of selected risk factors in 532 patients with clinically diagnosed dry eye distributed by sequence analysis. CL, contact lens; MGD, meibomian gland dysfunction; OS, ocular surgery; SS, Sjo ¨ gren syndrome; VDT, visual display terminal.
© 2014 Contact Lens Association of Ophthalmologists
47
Copyright @ Contact Lens Association of Opthalmologists, Inc. Unauthorized reproduction of this article is prohibited.
Eye & Contact Lens Volume 41, Number 1, January 2015
J. Li et al. TABLE 3.
Associations Between Risk Factors and Age Trend in Clinically Diagnosed Dry Eye
21–40 (n=246)
.60 (n=88)
41–60 (n=198)
Factors
Nonexposed
Exposed
Nonexposed
Exposed
Nonexposed
Exposed
Pa
VDT Drive CL MGD Smoke OS SS
72 154 185 222 221 223 240
174 92 61 24 25 23 0
102 155 193 159 173 180 195
96 43 5 39 24 18 4
59 86 84 69 80 53 87
29 2 4 19 8 35 7
,0.001 ,0.001 ,0.001 0.002 0.966 0.000 NA
Age trend by linear-by-linear x2 test.
a
P , 0.05 was considered statistically significant. CL, contact lens; MGD, meibomian gland dysfunction; NA, not available; OS, ocular surgery; SS, Sjo ¨ gren syndrome; VDT, visual display terminal. TABLE 4.
Associations Between Risk Factors and Gender in Clinically Diagnosed Dry Eye
Men (n=161)
Women (n=371)
Factors
Nonexposed
Exposed
Nonexposed
Exposed
Pa
95% CI
VDT Drive CL MGD Smoke OS SS
68 92 150 130 106 139 161
93 69 11 31 55 22 0
165 303 312 320 369 317 371
206 68 59 51 2 54 10
0.633 ,0.001 0.004 0.106 ,0.001 0.787 NA
0.754–1.592 2.222–5.026 0.198–0.760 0.916–2.444 22.971–398.958 0.545–1.585 NA
Gender differences of different risk factors by Pearson x2 test.
a
P , 0.05 was considered statistically significant. CL, contact lens; MGD, meibomian gland dysfunction; NA, not available; OS, ocular surgery; SS, Sjo ¨ gren syndrome; VDT, visual display terminal.
FIG. 3. The strength of association of various environmental exposure factors with clinically diagnosed patients with dry eye.
reported by Uchino et al.4 The explanation for low prevalence in elders might be that they were less sensitive to self-reported ocular symptoms compared with the younger patients and were more purposive to see a doctor, for example, need for cataract surgery, which may involve the loss of cases. 48
As shown in Table 2, women (10.41%) had significantly higher prevalence of DED than men (5.21%). After adjusting for age, women still had significantly increased prevalence (P,0.001). These results were agreed with most of other studies.8,9,14,15 In clinical experience, both menopausal and postmenopausal women Eye & Contact Lens Volume 41, Number 1, January 2015
Copyright @ Contact Lens Association of Opthalmologists, Inc. Unauthorized reproduction of this article is prohibited.
Eye & Contact Lens Volume 41, Number 1, January 2015 who had hormonal changes were liable to have dry eye complaints. Lots of studies16–18 suggested that sex hormones influenced ocular surface conditions through their effects on tear secretion, meibomian gland function, and conjunctival goblet cell density. In this study, 163 of 371 female participants (43.9%) who showed clinically diagnosed DED were associated with hormonal changes. The result was consistent with the large cohort study of the Women’s Health presented by Schaumberg et al.,19 which showed that 25,665 (69%) among 36,995 women with data on dry eye syndrome were postmenopausal. However, in age groups above 60 years, there was no difference in prevalence of DED between men and women. As some researchers stated,20 the reason might be progressively diminished secretion of tear with aging, so called age-related DED, that affects all exocrine glands in old people. The study of Uchino et al.4 indicated that more than 4 hr of the use of VDT was associated with an increased risk of DED (odds ratio, 1.68; 95% CI, 1.40–2.02). Our results showed that the longtime use of VDT as a risk factor was found in 299 of 532 patients with clinically diagnosed dry eye (56.2%), and notably associated with age trend, as disclosed in Table 3, which implied overexposure to VDT was a major risk factor for DED among young men and women. It has been hypothesized that excess evaporation of tear fluid because of extended blinking interval while gazing was a causative factor in VDT-associated dry eye.21,22 Beside VDT, this study showed exposure to adverse environment would elicit dry eye symptoms and signs, such as driving, smoking, excessive wind, air conditioning/heating, dust, cooking fume, and so on. Gonzalez-Garcia et al.3 reported that significant changes in comfort and the ocular surface tests were found after 2 hr of exposure to controlled adverse environment compared with indoor normal environment. It was confirmed by some basic researches focusing on the mechanism of dry eye affected by environment. Chen et al.23 indicated that an intelligently controlled environmental system, which can sustain relative humidity at a low level, induced dry eye in mice with decreased aqueous tear production and goblet cell density, increased corneal fluorescein staining, marked thinning and accelerated desquamation of the apical corneal epithelium, and upregulated apoptosis on the ocular surface. Our study also found that occupational conditions with risk of exposure to adverse environment made up over half of all 532 patients with dry eye. There was a discrepancy compared with the study performed by Sahai and Malik14 that showed farmers/laborers were most afflicted with dry eye, followed by the group designated “others with high exposure” consisting of computer operators, drivers, salesmen, field workers, mechanics, and cooks. Because Wenzhou is one of the most economically developed cities in mainland China, farmers represent a relatively small minority, instead office workers and businessmen are a majority. Furthermore, occupational structure from consecutive outpatients can better reflect the actual situation. Above all, particularly novel in this research were the findings that environmental and occupational factors were the main cause of DED in a hospital-based population. This study also analyzed other dry eye–related risk factors extracted from the previous published literature, including CL use, OS, MGD, and SS. As we all know, the reflex stimulation of tear secretion is due to lid and eye friction, environmental temperature, and trigeminal activity, etc. Sensory block or neurodeprivation can be secondary to CL use, OS, diabetes, and so on. Our results indicated that wearing CL was closely associated with clinically © 2014 Contact Lens Association of Ophthalmologists
Risk Factors of DED in Southeast China diagnosed DED in young women, and history of OS might be another factor associated with DED in old people. Meibomian gland dysfunction was considered to be the leading cause of DED, especially for Asians.24 In this study, the prevalence of MGD-related DED was 15.4%, which was associated with age trend. It indicated that the incidence of MGD-related DED increased gradually with age. There were only 10 SS-related DED in this study, and all of them were women, which suggested that SS-related DED account was for only a small portion of clinically diagnosed DED. It was reported that the female gender and older age were known risk factors for SS.25 Our result was consistent with the study by Nelson et al.26 that found that 1.3% of Medicare patients had a primary diagnosis of SS or dry eye. A general consensus on the mechanistic classification of DED has defined two main subtypes: aqueous-deficient and evaporative dry eye. However, in addition, clinical differentiation of the two subtypes mentioned above was indefinite because patients with DED may have both phenotypes.27 According to this study, if the classification of DED based on distribution of risk factors could be proposed for clinical practice, this simplified classification would include: environmental and occupational, hormonal, neurodeprivation-induced, MGD-related, age-related, SS-related, and others. It was similar to the classification proposed on the Eighth Congress of the International Society of Dacryology and Dry Eye in Madrid,28 but more concise and easy to remember, moreover, we added subtype of environmental and occupational DED as a major portion in clinic. Limitations and potential biases of this study should be noted. Firstly, the cross-sectional design of study prevents inferring causality, but the risk factors that we identified were consistent with those found in cohort studies and clinical trials. Secondly, in this single-center research, the data derived from only one hospital may have introduced selection bias. Thirdly, influence of some risk factors was not analyzed due to lack of collection. For example, it was hard to draw conclusions about relationship of systemic diseases such as diabetes and the use of systemic medications between with DED independently from the present data. Also influence of the use of eye drops might be ignored, because there were sorts of eye drops used by patients in this study, including preservative containing and free, artificial tears, and others (e.g., glaucoma medications). It was difficult to determine whether the use of eye drops (such as artificial tears) reduced or contributed to dry eye symptoms because of toxicity of preservative after long-term treatment. However, this article focused on the analysis of characteristic of consecutive outpatients with dry eye who met diagnostic criteria, regardless of severity and treatment. Finally, this was a cross-sectional, single-hospital population-based study; therefore, it may have selection bias, and further multicentered studies with various time points were required to verify the results. In conclusion, the strengths of our study included the large sample of clinically diagnosed DED selected from consecutive outpatients and the evaluation of clustering of risk factors. We demonstrated that environmental and occupational factors were strongly associated with DED and constituted the major proportion in a hospital-based population. A classification of DED based on distribution of risk factors was recommended for the clinical use. REFERENCES 1. The definition and classification of dry eye disease: Report of the definition and classification subcommittee of the international dry eye workshop (2007). Ocul Surf 2007;5:75–92.
49
Copyright @ Contact Lens Association of Opthalmologists, Inc. Unauthorized reproduction of this article is prohibited.
J. Li et al. 2. Wolkoff P. “Healthy” eye in office-like environments. Environ Int 2008;34: 1204–1214. 3. Gonzalez-Garcia MJ, Gonzalez-Saiz A, de la Fuente B, et al. Exposure to a controlled adverse environment impairs the ocular surface of subjects with minimally symptomatic dry eye. Invest Ophthalmol Vis Sci 2007;48: 4026–4032. 4. Uchino M, Schaumberg DA, Dogru M, et al. Prevalence of dry eye disease among Japanese visual display terminal users. Ophthalmology 2008;115: 1982–1988. 5. Tong L, Waduthantri S, Wong TY, et al. Impact of symptomatic dry eye on vision-related daily activities: The Singapore Malay Eye Study. Eye (Lond) 2010;24:1486–1491. 6. Albietz JM. Prevalence of dry eye subtypes in clinical optometry practice. Optom Vis Sci 2000;77:357–363. 7. Uchino M, Nishiwaki Y, Michikawa T, et al. Prevalence and risk factors of dry eye disease in Japan: Koumi study. Ophthalmology 2011;118: 2361–2367. 8. Jie Y, Xu L, Wu YY, et al. Prevalence of dry eye among adult Chinese in the Beijing Eye Study. Eye (Lond) 2009;23:688–693. 9. Lin PY, Tsai SY, Cheng CY, et al. Prevalence of dry eye among an elderly Chinese population in Taiwan: The Shihpai Eye Study. Ophthalmology 2003;110:1096–1101. 10. Lee AJ, Lee J, Saw SM, et al. Prevalence and risk factors associated with dry eye symptoms: A population based study in Indonesia. Br J Ophthalmol 2002;86:1347–1351. 11. Begley CG, Chalmers RL, Mitchell GL, et al. Characterization of ocular surface symptoms from optometric practices in North America. Cornea 2001;20:610–618. 12. van Bijsterveld OP. Diagnostic tests in the Sicca syndrome. Arch Ophthalmol 1969;82:10–14. 13. Bron AJ, Benjamin L, Snibson GR. Meibomian gland disease. Classification and grading of lid changes. Eye (Lond) 1991;5:395–411. 14. Sahai A, Malik P. Dry eye: Prevalence and attributable risk factors in a hospital-based population. Indian J Ophthalmol 2005;53:87–91.
50
Eye & Contact Lens Volume 41, Number 1, January 2015 15. McCarty CA, Bansal AK, Livingston PM, et al. The epidemiology of dry eye in Melbourne, Australia. Ophthalmology 1998;105:1114–1119. 16. Mathers WD, Stovall D, Lane JA, et al. Menopause and tear function: The influence of prolactin and sex hormones on human tear production. Cornea 1998;17:353–358. 17. Krenzer KL, Dana MR, Ullman MD, et al. Effect of androgen deficiency on the human meibomian gland and ocular surface. J Clin Endocrinol Metab 2000;85:4874–4882. 18. Connor CG, Flockencier LL, Hall CW. The influence of gender on the ocular surface. J Am Optom Assoc 1999;70:182–186. 19. Schaumberg DA, Buring JE, Sullivan DA, et al. Hormone replacement therapy and dry eye syndrome. JAMA 2001;286:2114–2119. 20. Wang HF, Fukuda M, Shimomura Y. Diagnosis of dry eye. Semin Ophthalmol 2005;20:53–62. 21. Acosta MC, Gallar J, Belmonte C. The influence of eye solutions on blinking and ocular comfort at rest and during work at video display terminals. Exp Eye Res 1999;68:663–669. 22. Tsubota K, Nakamori K. Effects of ocular surface area and blink rate on tear dynamics. Arch Ophthalmol 1995;113:155–158. 23. Chen W, Zhang X, Zhang J, et al. A murine model of dry eye induced by an intelligently controlled environmental system. Invest Ophthalmol Vis Sci 2008;49:1386–1391. 24. Nichols KK, Foulks GN, Bron AJ, et al. The international workshop on meibomian gland dysfunction: Executive summary. Invest Ophthalmol Vis Sci 2011;52:1922–1929. 25. Bell M, Askari A, Bookman A, et al. Sjogren’s syndrome: A critical review of clinical management. J Rheumatol 1999;26:2051–2061. 26. Nelson JD, Helms H, Fiscella R, et al. A new look at dry eye disease and its treatment. Adv Ther 2000;17:84–93. 27. Bron AJ, Yokoi N, Gafney E, et al. Predicted phenotypes of dry eye: Proposed consequences of its natural history. Ocul Surf 2009;7:78–92. 28. Murube J, Nemeth J, Hoh H, et al. The triple classification of dry eye for practical clinical use. Eur J Ophthalmol 2005;15:660–667.
Eye & Contact Lens Volume 41, Number 1, January 2015
Copyright @ Contact Lens Association of Opthalmologists, Inc. Unauthorized reproduction of this article is prohibited.
Prevalence and Risk Factors of Dry Eye Disease Among a Hospital-Based Population in Southeast China Jinyang Li,
M.D., Ph.D.,
Ke Zheng,
M.D., O.D.,
Li Sun,
Zifeng Deng, M.D., Jingwei Zheng, and Wei Chen, M.D., Ph.D.
Objective: To investigate the prevalence of dry eye disease (DED) and distribution of associated risk factors among a hospital-based population. Methods: In this cross-sectional study, we collected detailed information of clinically defined moderate-to-severe patients with dry eye among a consecutive hospital-based population, including age trend, gender structure, frequency of symptoms, and distribution of associated environmental/ occupational risk factors. Results: Of 6,657 consecutive outpatients aged older than 20 years, symptomatic dry eye presented in 635 subjects (9.54%). Five hundred thirty-two of these 635 subjects (7.99%) were clinically diagnosed as defined DED that combined with positive signs. Women (10.41%) were significantly higher than men (5.21%) (P,0.001). Overexposure to visual display terminal was a major risk factor for DED among young men and women (56.2%). Our study also found occupational conditions with the risk of exposure to adverse environment made up over half of all 532 patients with dry eye. The use of contact lenses was closely associated with DED in young women, and history of ocular surgeries might be another factor associated with DED in old people. One hundred sixtythree of 371 female patients with dry eye (43.9%) were associated with hormonal changes. The incidence of meibomian gland dysfunction– related DED increased gradually with age. There were only 10 patients with dry eye (1.9%) associated with Sjögren syndrome, and all of them were women. Conclusions: Environmental and occupational factors were strongly associated with DED and constituted the major proportion in a hospitalbased population. A classification of DED based on the distribution of risk factors was recommended for clinical use. Key Words: Dry eye disease—Prevalence—Risk factor—Hospital-based population. (Eye & Contact Lens 2015;41: 44–50)
D
ry eye disease (DED) is one of the most frequent conditions in ophthalmology practice. According to the International Dry Eye Work Shop in 2007, DED is a multifactorial disease of tears and ocular surface that results in symptoms of discomfort, From the Department of Cornea and Ocular Surface Diseases, School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, China. Supported by a research grant 81170820 from National Natural Science Foundation of China. The authors have no conflicts of interest to disclose. Address correspondence to Wei Chen, M.D., Ph.D., School of Ophthalmology and Optometry, Wenzhou Medical University, 270 Xueyuan West Road, Wenzhou, Zhejiang 325027, China; e-mail: chenweimd@hotmail. com Accepted May 1, 2014. DOI: 10.1097/ICL.0000000000000064
44
M.D.,
Huixiang Ma,
M.D., Ph.D.,
M.D.,
visual disturbance, and tear film instability with potential damage to the ocular surface.1 It is important for clinicians to understand the integrated impact of physiological and ergonomic factors that are responsible for the development of DED. There were many studies2,3 that presented that environmental and occupational factors could affect ocular surface and cause dry eye symptoms. For example, exposure of visual display terminal (VDT) was reported to have a strong association with DED.4,5 As summarized by Wolkoff,2 identified environmental, occupational, and personal risk factors associated with dry eye symptomatology were listed, including aging, hormonal changes, contact lens (CL) wear, visual display unit work, cigarette smoking, ocular surgeries, systemic medication, indoor pollutants, low humidity, high room temperature, and so on. Therefore, various risk factors, especially environment- and occupation-related factors, seem to be highly associated with the occurrence and development of dry eye symptoms. The reported prevalence of dry eye syndrome varied because there are different standards of selected patients, questionnaires, cutoff of objective tests, and diagnostic criteria.6–10 In other words, even under the same diagnostic criteria, prevalence of DED may change along with sex, age, race, geography, education level, profession, and other risk factors. Therefore, selection of different study population could dramatically influence the final results and conclusions. For most epidemiologic studies achieved using questionnaires, one of the major limitations is usually lack of objective tests. In that case, the participants in those studies, such as seniors, office workers, and school students cannot show clinically diagnosed DED and fail to further classify different subtypes. Moreover, some important risk factors of DED may be ignored in studies restricted to a certain crowd of participants. A hospitalbased study could comprehensively embrace various crowds of participants with different risk factors of DED. However, there were few studies that paid close attention to present the proportion and association of each risk factor in a hospital-based population; nevertheless, it offered obvious advantages in convenience, high response rate, and complete identification of all cases. Moreover, analysis of data of clinically diagnosed DED from consecutive outpatients can provide global impression for clinicians to help determine diagnosis and classification and to realize the most important risk factors in clinic. To the best of our knowledge, no study has been designed to observe the prevalence and related risk factors of DED from consecutive outpatients. This study focused the investigation on the prevalence of DED and distribution of associated risk factors in a large-scale, cross-sectional hospital-based population. Eye & Contact Lens Volume 41, Number 1, January 2015
Copyright @ Contact Lens Association of Opthalmologists, Inc. Unauthorized reproduction of this article is prohibited.
Eye & Contact Lens Volume 41, Number 1, January 2015
MATERIALS AND METHODS Study Population In this hospital-based cross-sectional study, consecutive outpatients aged older than 20 years presenting with various ophthalmic problems to a tertiary eye hospital from May 1 to May 16, 2010 were included and screened for dry eye. Subjects were excluded from the study if they exhibited any active infection of the eye, active ocular allergy, evidence of lid deformity or abnormal lid movement disorder, pregnancy or lactation, evidence of ocular chemical or thermal burn, pterygium extending onto the cornea, and ocular surgeries within 6 months of the screening. This research was approved by the Wenzhou Medical University Review Board, Wenzhou, Zhejiang, China, and was performed in accordance with the Tenets of the Declaration of Helsinki. The patients were aware of the privacy policy of the hospital that states that information released for publication would not include patient identifiers.
Assessment of Dry Eye Each participant took a dry eye symptom questionnaire consisting of eight symptoms involving questions on feelings of dryness, grittiness or sandy, burning, redness, sticky, watery or tearing, crusting or discharge on the lashes, and stuck shut in the morning.9 When a participant indicated the presence of any symptom, the respondent was asked to indicate the frequency of occurrence ranging rarely, sometimes, often, or constantly. Subjects were considered symptomatic when at least one of the symptoms of the questionnaire was experienced often or all the time.5 The participant had the presence of either a previous clinical diagnosis of DED or severe symptoms were screened and assigned to the dry eye consulting room for a detailed questionnaire which was modified from dry eye questionnaires11 and objective tests. The data collection included age, sex, occupation, physiological status of menopause or postmenopause, lifestyle factors (e.g., cigarette smoking, VDT use), systemic medical history (e.g., diabetes mellitus, rheumatoid arthritis, thyroid disease, Parkinson disease), history of dry mouth/nose, ocular history (e.g., ocular surgery [OS], use of CL, and dye drops), and current use of systemic medications (e.g., oral contraceptives and hormonal preparations). Suspicious dry eye–related risk factors that derived from the previous literature were recorded, including the use of VDT more than 4 hr per day, wear of soft or rigid CL for a minimum of 8 hr daily, inveterate cigarette smoking, and driving more than 2 hr everyday. All participants were required to answer if the symptoms aggravated when their eyes exposed to the following types of environmental factors: excessive wind, swimming pool, dust, pollen, cooking fume, cigarette smoke, air conditioning/heating, and aircraft cabin. Three Chinese doctors (J.L., L.S., and H.M.) translated questionnaires from English into Chinese, and back-translated by native English speakers from Chinese to English. The translation was verified by W. Chen to avoid discrepancies resulting from cultural differences. The standard order of eye examinations was as follows: tear film breakup time test (TBUT), corneal and conjunctival fluorescein staining, Schirmer test (ST), and slit-lamp examination for assessment of the meibomian gland. The subjects were required to remove CLs at least 2 hr before examination and not to use artificial tears within 2 hr of screening. Each of assessments was at 10-min intervals to minimize reflex tearing and ocular surface changes secondary to testing. © 2014 Contact Lens Association of Ophthalmologists
Risk Factors of DED in Southeast China Tear film breakup time test and fluorescein staining were performed by using a dry fluorescein strip to touch the inferior palpebral conjunctiva lightly. The tear film was observed with a slit lamp with a cobalt blue filter after asking the patient to blink several times. The time, in seconds, between the last blink and the first desiccation spot was recorded. The mean of three of these recordings, taken after one single instillation of a drop of fluorescein, was registered as TBUT. Fluorescein staining of the cornea and lissamine green staining of the exposed interpalpebral conjunctiva were both graded on a scale from 0 (no staining) to 3 (confluent staining) according to the method of van Bijsterveld12 (score range, 0–9). Schirmer test without anesthesia was performed by placing a precalibrated standard strip (Sno strips, Chauvin, Montpellier, France) temporally in each of the lower temporal fornix and noting the extent of wetness on the strip after 5 min. During this time, the participants were instructed to look slightly upward and blink normally. The eyelid margins, meibomian gland orifices, and the meibomian gland secretions were carefully examined for signs of meibomian gland dysfunction (MGD). According to the criteria by Bron et al.,13 diagnosis of MGD included one or more of the following: (1) absent, viscous, or waxy white secretion on digital expression, (2) presence of greater than two lid margin telangiectases, and (3) plugging of greater than two gland orifices. Sjögren syndrome (SS) was defined as the presence of dryness of mucous membranes (mouth, throat, nose, or vagina) combined with history of rheumatoid arthritis or systemic lupus erythematosus and laboratory manifestations. Both SS and MGD were recorded as either present or absent.
Dry Eye Definition Symptomatic dry eye was defined as the presence of at least one symptom that ranked as often or constantly. Clinically diagnosed dry eye was defined according to the Japanese dry eye diagnostic criteria as follows: (1) the presence of qualitative or quantitative disturbance of the tear film on one or both eyes (ST, ,5 mm or TBUT, ,5 sec), (2) presence of conjunctivocorneal epithelial damage on one or both eyes (score of fluorescein staining above three points), and (3) presence of dry eye symptomatology. The presence of all the above criteria was necessary for diagnosis of definite DED.1
Data Analysis All analyses were performed with Statistical Package for the Social Sciences software (Version 13.0, SPSS Inc., Chicago, IL). Pearson or linear-by-linear chi-square tests were performed to test for an association between demographic variables (age, gender, and frequency of symptoms and risk factors). Cochran–Mantel– Haenszel chi-square test for categorical variables adjusting for age. A P,0.05 was considered statistically significant, and the 95% confidence intervals (CIs) were tabulated. The data analyses were performed by a statistician who was masked to whether the data came from a normal subject or a patient with dry eye.
RESULTS Population Demographics Of 6,657 consecutive outpatients aged older than 20 years, symptomatic dry eye present in 635 subjects (9.54%). Five hundred thirty-two of these 635 subjects were clinically diagnosed as defined DED that combined with positive signs. The prevalence 45
Copyright @ Contact Lens Association of Opthalmologists, Inc. Unauthorized reproduction of this article is prohibited.
Eye & Contact Lens Volume 41, Number 1, January 2015
J. Li et al. TABLE 1. Age Groups, y
Total (n=6,657) DED (n=532)
21–30 31–40 41–50 51–60 61–70 .70
Dry Eye Risk Factors
Prevalence of Dry Eye According to Age Groups
1,339 1,269 1,100 1,094 913 942
Pre, %
Pa
95% CI
7.62 11.35 10.27 7.77 7.12 2.44
0.572 ,0.001 0.002 0.767 0.295 ,0.001
0.752–1.179 1.289–1.926 1.096–1.694 0.760–1.230 0.669–1.146 0.180–0.419
102 144 113 85 65 23
The percentage of selected risk factors in 532 patients with clinically diagnosed DED was shown in Figure 2, including VDT use (VDT, 56.2%), menopause (30.6%), drive (25.8%), MGD (15.4%), CL use (13.2%), cigarette smoking (10.7%), and SS (1.9%). Physiological status of menopause/postmenopause was found in 163 of 371 female participants (43.9%), which represented a large proportion of women with clinically diagnosed DED. There were 76 participants having a history of OS (14.3%), comprised of cataract (n=21), glaucoma (n=10), pterygium (n=12) and vitreoretinal (n=11), and laser corneal surgeries (n=22). According to the univariate analysis, risk factors associated with age trend in participants with clinically diagnosed dry eye were OS, VDT, drive, CL, and MGD (P,0.005, linear-by-linear x2 test; Table 3). Exposed risk factors of VDT, drive, and CL were more common among young people with dry eye, instead OS and MGD were in the elderly. In men, risk factors of drive and smoking were associated with an increased percentage as compared with women (42.9% and 34.2% in men vs. 18.3% and 0.5% in women; P,0.001, Pearson x2 test; Table 4). Wearing contact lens was found to be significantly associated with clinically diagnosed DED in women (15.9% in women vs. 6.8% in men; P=0.004, Pearson x2 test; Table 4). There were no gender differences among other exposed risk factors in participants with clinically diagnosed dry eye.
Age differences by x2 test.
a
P , 0.05 was considered statistically significant. CI, confidence interval; DED, dry eye disease; Pre, prevalence.
of clinically diagnosed DED was 7.99% in all consecutive outpatients. The prevalence was significantly higher in patients aged 31 to 50 years (P,0.005) and significantly lower in age group of over 70 years (P,0.001), which demonstrated an inverted U-shaped relationship; the relative peaks were located on age group 31 to 40 years (Table 1). The mean age of DED patients was 42.26614.91 years, and 69.74% were women. As shown in Table 2, the prevalence of women (10.41%) was significantly higher than men (5.21%) (P,0.001; 95% CI, 0.390–0.573). In all age groups, the prevalence of women was significantly higher except the age groups above 61 years (P,0.005). After adjusting for age, women still had significantly increased prevalence compared with men (P,0.001).
Environmental and Occupational Risk Factors Frequency of Symptoms
By completing the analysis of occupations, conditions with the risk of exposure to adverse environment made up over half of all 532 patients with dry eye, which consisted of computer operators, office workers, scientists, drivers, cooks, teachers, students, doctors, nurses, fishers, retirees, administrators and government officer, and others with fine visual tasks. As shown in Figure 3, there were 241 of 532 participants (45.3%) with clinically diagnosed DED who reported sensory eye irritation when exposed to excessive wind, which was followed by air conditioning/heating (28.7%), cigarette smoke (23.8%), cooking fume (20.7%), aircraft cabin (14.1%), and swimming pool (13.2%). Only 11 of 507 and 16 of 312 patients experienced sensory irritation when exposed to environment of pollen and dust.
Among 635 participants of this survey, there were quite a few differences in the distribution of each dry eye symptom by frequency of response. Figure 1 showed the proportion of subjects who reported often to constant ocular symptoms. The results demonstrated that participants with clinically diagnosed DED (with positive signs) complained of burning most often (58.5% of 532 subjects). Watery or tearing, in contrast, was reported most frequently (49.5% of 103 subjects) in symptomatic participants with dry eye (without positive signs). They were both followed by grittiness (55.5% and 48.5%, respectively) and dryness (54.1% and 47.6%, respectively). There were significant differences in self-reported sensation of burning between the two groups (P,0.05, Pearson x2 test). TABLE 2.
Prevalence of Dry Eye According to Gender
Men Age Groups, y 21–30 31–40 41–50 51–60 61–70 .70
Women
N
DED
Pre, %
N
DED
Pre, %
Pa
95% CI
645 625 567 425 391 439
35 39 37 19 21 10
5.43 6.24 6.53 4.47 5.37 2.28
694 644 533 669 522 503
67 105 76 66 44 13
9.65 16.30 14.26 9.87 8.43 2.58
0.004 ,0.001 ,0.001 0.001 0.075 0.761
0.351–0.820 0.232–0.502 0.278–0.634 0.253–0.723 0.360–1.055 0.381–2.024
Gender
Total (n=6,657)
DED (n=532)
Pre, %
Pa
95% CI
Men Women
3,092 3,565
161 371
5.21 10.41
,0.001
0.390–0.573
Gender differences of different age groups by x2 test.
a
P , 0.05 was considered statistically significant. CI, confidence interval; DED, dry eye disease; Pre, prevalence.
46
Eye & Contact Lens Volume 41, Number 1, January 2015
Copyright @ Contact Lens Association of Opthalmologists, Inc. Unauthorized reproduction of this article is prohibited.
Eye & Contact Lens Volume 41, Number 1, January 2015
Risk Factors of DED in Southeast China
FIG. 1. Frequency of dry eye symptoms ranked as “often” or “all the time” between subjects with symptomatic and clinically diagnosed dry eye (asterisk, statistical significance, P,0.05).
DISCUSSION This study is the first large-scale, cross-sectional hospital population-based investigation of DED in China, which selected and screened all consecutive outpatients aged older than 20 years attending a tertiary eye hospital for DED during a designated time interval. Our study estimated the prevalence of DED using questionnaires and clinical tests and analyzed the association between clinically diagnosed DED and previously reported dry eye risk factors. In this study, the prevalence of symptomatic DED and clinically diagnosed DED was 9.54% and 7.99% in 6,657 consecutive outpatients, respectively, which was lower as compared with previous studies.4,7–9,14 One important reason for this difference may be strict diagnostic criteria. Patients with symtomatic dry eye screened by questionnaire were then involved with objective tests according to the Japanese dry eye diagnostic criteria, which
combined with conjunctivocorneal epithelial damage (fluorescein staining above three points) and either qualitative or quantitative disturbance of the tear film (ST, ,5 mm or TBUT, ,5 sec). Beside, unlike general population, outpatients always had clear purpose when they went to hospital. This characteristic of hospital-based population may lead to deviation of the result of dry eye prevalence. However, this cross-sectional study collected full detailed information of patients with clinically defined moderate-to-severe dry eye. The results provided global impression of DED for ophthalmologists, including age trend, gender structure, and distribution of associated environmental and occupational risk factors. Our results showed the prevalence of DED was significantly higher in patients of 31 to 50 years of age and significantly lower in the age group of above 70 years as compared with other age groups, and that presented an inverted U-shaped relationship with age trend. It was similar to the result
FIG. 2. The percentage of selected risk factors in 532 patients with clinically diagnosed dry eye distributed by sequence analysis. CL, contact lens; MGD, meibomian gland dysfunction; OS, ocular surgery; SS, Sjo ¨ gren syndrome; VDT, visual display terminal.
© 2014 Contact Lens Association of Ophthalmologists
47
Copyright @ Contact Lens Association of Opthalmologists, Inc. Unauthorized reproduction of this article is prohibited.
Eye & Contact Lens Volume 41, Number 1, January 2015
J. Li et al. TABLE 3.
Associations Between Risk Factors and Age Trend in Clinically Diagnosed Dry Eye
21–40 (n=246)
.60 (n=88)
41–60 (n=198)
Factors
Nonexposed
Exposed
Nonexposed
Exposed
Nonexposed
Exposed
Pa
VDT Drive CL MGD Smoke OS SS
72 154 185 222 221 223 240
174 92 61 24 25 23 0
102 155 193 159 173 180 195
96 43 5 39 24 18 4
59 86 84 69 80 53 87
29 2 4 19 8 35 7
,0.001 ,0.001 ,0.001 0.002 0.966 0.000 NA
Age trend by linear-by-linear x2 test.
a
P , 0.05 was considered statistically significant. CL, contact lens; MGD, meibomian gland dysfunction; NA, not available; OS, ocular surgery; SS, Sjo ¨ gren syndrome; VDT, visual display terminal. TABLE 4.
Associations Between Risk Factors and Gender in Clinically Diagnosed Dry Eye
Men (n=161)
Women (n=371)
Factors
Nonexposed
Exposed
Nonexposed
Exposed
Pa
95% CI
VDT Drive CL MGD Smoke OS SS
68 92 150 130 106 139 161
93 69 11 31 55 22 0
165 303 312 320 369 317 371
206 68 59 51 2 54 10
0.633 ,0.001 0.004 0.106 ,0.001 0.787 NA
0.754–1.592 2.222–5.026 0.198–0.760 0.916–2.444 22.971–398.958 0.545–1.585 NA
Gender differences of different risk factors by Pearson x2 test.
a
P , 0.05 was considered statistically significant. CL, contact lens; MGD, meibomian gland dysfunction; NA, not available; OS, ocular surgery; SS, Sjo ¨ gren syndrome; VDT, visual display terminal.
FIG. 3. The strength of association of various environmental exposure factors with clinically diagnosed patients with dry eye.
reported by Uchino et al.4 The explanation for low prevalence in elders might be that they were less sensitive to self-reported ocular symptoms compared with the younger patients and were more purposive to see a doctor, for example, need for cataract surgery, which may involve the loss of cases. 48
As shown in Table 2, women (10.41%) had significantly higher prevalence of DED than men (5.21%). After adjusting for age, women still had significantly increased prevalence (P,0.001). These results were agreed with most of other studies.8,9,14,15 In clinical experience, both menopausal and postmenopausal women Eye & Contact Lens Volume 41, Number 1, January 2015
Copyright @ Contact Lens Association of Opthalmologists, Inc. Unauthorized reproduction of this article is prohibited.
Eye & Contact Lens Volume 41, Number 1, January 2015 who had hormonal changes were liable to have dry eye complaints. Lots of studies16–18 suggested that sex hormones influenced ocular surface conditions through their effects on tear secretion, meibomian gland function, and conjunctival goblet cell density. In this study, 163 of 371 female participants (43.9%) who showed clinically diagnosed DED were associated with hormonal changes. The result was consistent with the large cohort study of the Women’s Health presented by Schaumberg et al.,19 which showed that 25,665 (69%) among 36,995 women with data on dry eye syndrome were postmenopausal. However, in age groups above 60 years, there was no difference in prevalence of DED between men and women. As some researchers stated,20 the reason might be progressively diminished secretion of tear with aging, so called age-related DED, that affects all exocrine glands in old people. The study of Uchino et al.4 indicated that more than 4 hr of the use of VDT was associated with an increased risk of DED (odds ratio, 1.68; 95% CI, 1.40–2.02). Our results showed that the longtime use of VDT as a risk factor was found in 299 of 532 patients with clinically diagnosed dry eye (56.2%), and notably associated with age trend, as disclosed in Table 3, which implied overexposure to VDT was a major risk factor for DED among young men and women. It has been hypothesized that excess evaporation of tear fluid because of extended blinking interval while gazing was a causative factor in VDT-associated dry eye.21,22 Beside VDT, this study showed exposure to adverse environment would elicit dry eye symptoms and signs, such as driving, smoking, excessive wind, air conditioning/heating, dust, cooking fume, and so on. Gonzalez-Garcia et al.3 reported that significant changes in comfort and the ocular surface tests were found after 2 hr of exposure to controlled adverse environment compared with indoor normal environment. It was confirmed by some basic researches focusing on the mechanism of dry eye affected by environment. Chen et al.23 indicated that an intelligently controlled environmental system, which can sustain relative humidity at a low level, induced dry eye in mice with decreased aqueous tear production and goblet cell density, increased corneal fluorescein staining, marked thinning and accelerated desquamation of the apical corneal epithelium, and upregulated apoptosis on the ocular surface. Our study also found that occupational conditions with risk of exposure to adverse environment made up over half of all 532 patients with dry eye. There was a discrepancy compared with the study performed by Sahai and Malik14 that showed farmers/laborers were most afflicted with dry eye, followed by the group designated “others with high exposure” consisting of computer operators, drivers, salesmen, field workers, mechanics, and cooks. Because Wenzhou is one of the most economically developed cities in mainland China, farmers represent a relatively small minority, instead office workers and businessmen are a majority. Furthermore, occupational structure from consecutive outpatients can better reflect the actual situation. Above all, particularly novel in this research were the findings that environmental and occupational factors were the main cause of DED in a hospital-based population. This study also analyzed other dry eye–related risk factors extracted from the previous published literature, including CL use, OS, MGD, and SS. As we all know, the reflex stimulation of tear secretion is due to lid and eye friction, environmental temperature, and trigeminal activity, etc. Sensory block or neurodeprivation can be secondary to CL use, OS, diabetes, and so on. Our results indicated that wearing CL was closely associated with clinically © 2014 Contact Lens Association of Ophthalmologists
Risk Factors of DED in Southeast China diagnosed DED in young women, and history of OS might be another factor associated with DED in old people. Meibomian gland dysfunction was considered to be the leading cause of DED, especially for Asians.24 In this study, the prevalence of MGD-related DED was 15.4%, which was associated with age trend. It indicated that the incidence of MGD-related DED increased gradually with age. There were only 10 SS-related DED in this study, and all of them were women, which suggested that SS-related DED account was for only a small portion of clinically diagnosed DED. It was reported that the female gender and older age were known risk factors for SS.25 Our result was consistent with the study by Nelson et al.26 that found that 1.3% of Medicare patients had a primary diagnosis of SS or dry eye. A general consensus on the mechanistic classification of DED has defined two main subtypes: aqueous-deficient and evaporative dry eye. However, in addition, clinical differentiation of the two subtypes mentioned above was indefinite because patients with DED may have both phenotypes.27 According to this study, if the classification of DED based on distribution of risk factors could be proposed for clinical practice, this simplified classification would include: environmental and occupational, hormonal, neurodeprivation-induced, MGD-related, age-related, SS-related, and others. It was similar to the classification proposed on the Eighth Congress of the International Society of Dacryology and Dry Eye in Madrid,28 but more concise and easy to remember, moreover, we added subtype of environmental and occupational DED as a major portion in clinic. Limitations and potential biases of this study should be noted. Firstly, the cross-sectional design of study prevents inferring causality, but the risk factors that we identified were consistent with those found in cohort studies and clinical trials. Secondly, in this single-center research, the data derived from only one hospital may have introduced selection bias. Thirdly, influence of some risk factors was not analyzed due to lack of collection. For example, it was hard to draw conclusions about relationship of systemic diseases such as diabetes and the use of systemic medications between with DED independently from the present data. Also influence of the use of eye drops might be ignored, because there were sorts of eye drops used by patients in this study, including preservative containing and free, artificial tears, and others (e.g., glaucoma medications). It was difficult to determine whether the use of eye drops (such as artificial tears) reduced or contributed to dry eye symptoms because of toxicity of preservative after long-term treatment. However, this article focused on the analysis of characteristic of consecutive outpatients with dry eye who met diagnostic criteria, regardless of severity and treatment. Finally, this was a cross-sectional, single-hospital population-based study; therefore, it may have selection bias, and further multicentered studies with various time points were required to verify the results. In conclusion, the strengths of our study included the large sample of clinically diagnosed DED selected from consecutive outpatients and the evaluation of clustering of risk factors. We demonstrated that environmental and occupational factors were strongly associated with DED and constituted the major proportion in a hospital-based population. A classification of DED based on distribution of risk factors was recommended for the clinical use. REFERENCES 1. The definition and classification of dry eye disease: Report of the definition and classification subcommittee of the international dry eye workshop (2007). Ocul Surf 2007;5:75–92.
49
Copyright @ Contact Lens Association of Opthalmologists, Inc. Unauthorized reproduction of this article is prohibited.
J. Li et al. 2. Wolkoff P. “Healthy” eye in office-like environments. Environ Int 2008;34: 1204–1214. 3. Gonzalez-Garcia MJ, Gonzalez-Saiz A, de la Fuente B, et al. Exposure to a controlled adverse environment impairs the ocular surface of subjects with minimally symptomatic dry eye. Invest Ophthalmol Vis Sci 2007;48: 4026–4032. 4. Uchino M, Schaumberg DA, Dogru M, et al. Prevalence of dry eye disease among Japanese visual display terminal users. Ophthalmology 2008;115: 1982–1988. 5. Tong L, Waduthantri S, Wong TY, et al. Impact of symptomatic dry eye on vision-related daily activities: The Singapore Malay Eye Study. Eye (Lond) 2010;24:1486–1491. 6. Albietz JM. Prevalence of dry eye subtypes in clinical optometry practice. Optom Vis Sci 2000;77:357–363. 7. Uchino M, Nishiwaki Y, Michikawa T, et al. Prevalence and risk factors of dry eye disease in Japan: Koumi study. Ophthalmology 2011;118: 2361–2367. 8. Jie Y, Xu L, Wu YY, et al. Prevalence of dry eye among adult Chinese in the Beijing Eye Study. Eye (Lond) 2009;23:688–693. 9. Lin PY, Tsai SY, Cheng CY, et al. Prevalence of dry eye among an elderly Chinese population in Taiwan: The Shihpai Eye Study. Ophthalmology 2003;110:1096–1101. 10. Lee AJ, Lee J, Saw SM, et al. Prevalence and risk factors associated with dry eye symptoms: A population based study in Indonesia. Br J Ophthalmol 2002;86:1347–1351. 11. Begley CG, Chalmers RL, Mitchell GL, et al. Characterization of ocular surface symptoms from optometric practices in North America. Cornea 2001;20:610–618. 12. van Bijsterveld OP. Diagnostic tests in the Sicca syndrome. Arch Ophthalmol 1969;82:10–14. 13. Bron AJ, Benjamin L, Snibson GR. Meibomian gland disease. Classification and grading of lid changes. Eye (Lond) 1991;5:395–411. 14. Sahai A, Malik P. Dry eye: Prevalence and attributable risk factors in a hospital-based population. Indian J Ophthalmol 2005;53:87–91.
50
Eye & Contact Lens Volume 41, Number 1, January 2015 15. McCarty CA, Bansal AK, Livingston PM, et al. The epidemiology of dry eye in Melbourne, Australia. Ophthalmology 1998;105:1114–1119. 16. Mathers WD, Stovall D, Lane JA, et al. Menopause and tear function: The influence of prolactin and sex hormones on human tear production. Cornea 1998;17:353–358. 17. Krenzer KL, Dana MR, Ullman MD, et al. Effect of androgen deficiency on the human meibomian gland and ocular surface. J Clin Endocrinol Metab 2000;85:4874–4882. 18. Connor CG, Flockencier LL, Hall CW. The influence of gender on the ocular surface. J Am Optom Assoc 1999;70:182–186. 19. Schaumberg DA, Buring JE, Sullivan DA, et al. Hormone replacement therapy and dry eye syndrome. JAMA 2001;286:2114–2119. 20. Wang HF, Fukuda M, Shimomura Y. Diagnosis of dry eye. Semin Ophthalmol 2005;20:53–62. 21. Acosta MC, Gallar J, Belmonte C. The influence of eye solutions on blinking and ocular comfort at rest and during work at video display terminals. Exp Eye Res 1999;68:663–669. 22. Tsubota K, Nakamori K. Effects of ocular surface area and blink rate on tear dynamics. Arch Ophthalmol 1995;113:155–158. 23. Chen W, Zhang X, Zhang J, et al. A murine model of dry eye induced by an intelligently controlled environmental system. Invest Ophthalmol Vis Sci 2008;49:1386–1391. 24. Nichols KK, Foulks GN, Bron AJ, et al. The international workshop on meibomian gland dysfunction: Executive summary. Invest Ophthalmol Vis Sci 2011;52:1922–1929. 25. Bell M, Askari A, Bookman A, et al. Sjogren’s syndrome: A critical review of clinical management. J Rheumatol 1999;26:2051–2061. 26. Nelson JD, Helms H, Fiscella R, et al. A new look at dry eye disease and its treatment. Adv Ther 2000;17:84–93. 27. Bron AJ, Yokoi N, Gafney E, et al. Predicted phenotypes of dry eye: Proposed consequences of its natural history. Ocul Surf 2009;7:78–92. 28. Murube J, Nemeth J, Hoh H, et al. The triple classification of dry eye for practical clinical use. Eur J Ophthalmol 2005;15:660–667.
Eye & Contact Lens Volume 41, Number 1, January 2015
Copyright @ Contact Lens Association of Opthalmologists, Inc. Unauthorized reproduction of this article is prohibited.
