Journal of

Clinical Medicine
ArticleCharacteristics of Individuals with Dry Eye
Symptoms without Clinical Diagnosis: Analysis
of a Web-Based Survey
Ryutaro Yamanishi 1 , Miki Uchino 1, *, Motoko Kawashima 1 , Yuichi Uchino 1 , Norihiko Yokoi 2
and Kazuo Tsubota 1
1
2*

Department of Ophthalmology, Keio University School of Medicine, Tokyo 160-8582, Japan;
b763_er@a7.keio.jp (R.Y.); motoko-k@a3.keio.jp (M.K.); uchino@z2.keio.jp (Y.U.); tsubota@z3.keio.jp (K.T.)
Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto 606-8566, Japan;
nyokoi@koto.kpu-m.ac.jp
Correspondence: uchinomiki@keio.jp; Tel.: +81-3-3353-1211; Fax: +81-3-3359-8302



Received: 15 April 2019; Accepted: 15 May 2019; Published: 21 May 2019

Abstract: Currently, the available treatment for dry eye disease (DED) varies. The present study
aimed to investigate the characteristics of undiagnosed DED and patient-based self-care managementfor DED based on a web-based survey performed for Tear’s Day in Japan; 1030 participants (301
women) responded; 155 participants (72 women) had a clinical diagnosis of DED. We defined
undiagnosed DED (n = 116; 54 women) as those with DED symptoms, as evaluated by a frequently
used questionnaire despite not having a clinical diagnosis. A multivariate adjusted model indicatedthat younger age (odds ratio (OR), 0.97 for each one-year decrease; 95% confidence interval (CI),
0.95–0.99), female sex (OR, 2.12; 95% CI, 1.28–3.50), and prolonged visual display terminal usage(OR, 1.12; 95% CI, 1.04–1.21) were risk factors for undiagnosed DED. To investigate the efficacy ofself-care management for DED, a sub-analysis was conducted. The number of self-care methods used
was significantly higher among women than men. For undiagnosed DED, those with less than three
self-care methods had a significantly worse Dry Eye-related Quality-of-Life Score compared withthose with diagnosed DED. This study revealed risk factors for undiagnosed DED; individuals withthose risk factors need to be clinically assessed and should not rely solely on self-care.
Keywords: dry eye disease; undiagnosed dry eye disease; risk factor; self-care

1. Introduction
Dry eye disease (DED) is a multifactorial disease of the tears and ocular surface [1]. Symptoms of
DED vary and include irritation, dryness, ocular fatigue, foreign body sensation, pain, heavy sensation,brightness, discharge, and fluctuating visual disturbances [2–4]; such symptoms can significantly
affect quality of life [4,5]. Previous studies have shown that DED is more prevalent in women than inmen, and various factors underlying this sex-specific difference have been speculated [5–7]. Adverse
effects of DED contribute to a substantial economic burden, with indirect costs comprising the largest
proportion of the overall cost, due to a substantial loss of work productivity [4]. For instance, DED
impairs work performance among office workers, which may lead to a substantial loss to industry [8].
Untreated, DED may become chronic and progressive [5]; therefore, the economic effects of untreated
DED should not be ignored.

J. Clin. Med. 2019, 8, 721; doi:10.3390/jcm8050721

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J. Clin. Med. 2019, 8, 721

2 of 13Moreover, self-care methods for DED have been introduced; however, there have been no reports
evaluating the efficacy and differences among the numbers and types of self-care and the symptomsof DED. Individuals attempt to cope with DED symptoms using various methods and tend to findpersonalized ways [9]. Because many self-care methods are available, to provide more standardized
eye treatment and self-care methods, Tear Film-Oriented Therapy (TFOT) has been established inJapan. TFOT for DED treatment is based on the characteristics of the breakup pattern of fluorescein,and targets supplementation for insufficient components of the ocular surface [2,10]. The specifictherapy corresponds with unique breakup patterns. To maximize the effect of TFOT, physician visits
are essential; accordingly, ocular evaluation by a physician may improve self-care methods.
Many individuals complain about severe DED symptoms, but more than half have not beenclinically diagnosed as having DED [11]. As the characteristics of patients with undiagnosed DED(severe symptoms of DED without a clinical diagnosis) and the associated risk factors remain unclear,
there is a need to better understand the factors regarding undiagnosed DED.
In 2017, the Japanese Dry Eye Society enacted 3 July as Namida no Hi (Tear’s Day), with theaim of spreading awareness regarding the importance of tears, to the public at large [12]. In 2018,
we performed a web survey to evaluate the demographic characteristics of undiagnosed DED andthe relationship with self-care methods for relieving DED symptoms. In particular, this study aimed
to investigate the characteristics of and the risk factors for undiagnosed DED, and to compare thefindings with patient-based self-care management of DED.
2. Materials and Methods
2.1. Study Participants
We enrolled participants who were willing to complete our web survey; participants were froma registered population of the digital researching company Macromil Incorporated (Tokyo, Japan).
Among the 1,200,000 panels, 5000 participants who used a visual display terminal (VDT) during
work were randomly selected. We distributed invitation mail to 5000 panels, without introducing theaim of the study. First consecutive 1030 were enrolled in the present study. The survey participantsacquired the equivalent of $0.60 for compensation. The information obtained in the survey included
age, sex, marital status, offspring status (does or does not have any children), annual household income(<$40,000 per year, $40,000–$59,999 per year, or ≥$60,000), VDT usage hours during work, contact lens(CL) use, smoking history, and symptoms and diagnosis of DED.
This study followed the tenets of the Declaration of Helsinki. The Institutional Review Board ofHaneginomori Eye Clinic, Tokyo, Japan, approved the protocol prospectively (ethical approval no.
17009; date: 24 April 2017). Web-based informed consent was obtained from all of the participants
after an explanation of the nature and possible consequences of the study.
2.2. Dry Eye Disease Symptoms
We evaluated severe DED symptoms using one of the most frequently used questionnaires for
epidemiological studies [13]. The questions used for the evaluation of severe DED symptoms were as
follows: (1) “How often do your eyes feel dry (not moist enough)?” and (2) “How often do your eyes
feel irritated?”. Possible answers to the two questions concerning symptoms included “constantly”,“often”, “sometimes”, or “never”. Severe DED symptoms were defined as both dryness and irritation,either constantly or often, as previously reported [13].

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3 of 132.3. Diagnosis of Dry Eye Disease
Diagnosed DED was defined as a prior diagnosis of DED. Undiagnosed DED was defined assevere DED symptoms without a physician diagnosis of DED. Non-DED was defined as meeting
neither criteria [2].
2.4. Dry Eye-Related Quality-Of-Life Score
The Dry Eye-related Quality-of-Life Score (DEQS) is a questionnaire developed by the Japanese
Dry Eye Society [14]. This questionnaire enabled us to evaluate the effect of DED on patients’ daily lives,
is often used to evaluate patient-reported symptoms, and is easily used in routine clinical practice [14].
The total score range ranges from 0 to 100, with higher values corresponding to a lower quality of life.
The DEQS consists of two components, namely: bothersome ocular symptoms and impact of daily
life. The former component includes six contents, as follows: foreign-body sensation, dry sensation in
the eyes, painful or sore eyes, ocular fatigue, heavy sensation in the eyelids, and redness in the eyes.
The latter component includes nine contents, as follows: difficulty opening eyes, blurred vision when
watching something, sensitivity to bright light, problems with eyes when reading, problem with eyes
when watching television or looking at a computer or cell phone, feeling distracted because of eye
symptoms, eye symptoms affect work, not feeling like going out because of eye symptoms, and feelingdepressed because of eye symptoms.
2.5. Self-Care Methods for Dry Eye Disease
To study self-care management for DED, the self-care methods that participants used when theyfelt dry eye symptoms were evaluated. The self-care methods used in the questions were as follows: useof over-the-counter eye drops [15], increase in blinking [16], use protection glasses from dryness [17],use of a warm compress [18], sleeping longer [19], exercise [20], use of oral supplements [15], deep,
relaxing breathing [21], and improved eyelid hygiene using eye shampoo [22]. The questions could beanswered “yes” or “no”. In addition, the number of self-care methods used was counted (ranging
from 0 to 9).
2.6. Statistical Analysis
All of the analyses were performed using Statistical Package for Social Sciences (SPSS) Statistics,
version 25.0 (IBM Corp., Armonk, NY, USA). Descriptive statistics were used to describe thecharacteristics of the study population, stratified by sex and subtype of DED diagnosis (non-DED,
undiagnosed DED, and diagnosed DED). Using a logistic regression model, we calculated the odds
ratios (ORs) and 95% confidence intervals (CIs) of undiagnosed DED and diagnosed DED comparedwith that of the non-DED group, along with the relevant risks. Firstly, we performed univariate
analyses to determine the relationships with each factor. Secondly, we performed multi-adjustment
analyses with age, sex, and statistically significant factors identified in univariate analyses. In thesecond analyses, participants were divided into two groups based on the number of self-care methods
used (<3 and ≥3), and were then compared. An unpaired t-test was used for the continuous variables(age, DEQS, and VDT hours), and the chi-squared test was used for the categorical variables. Two-tailed
p values of <0.05 were considered to indicate a statistically significant difference.
3. Results
Among the randomly selected 5000 participants using VDTs during work, the first consecutive
1030 participants took part in the survey. The participant age ranged from 20 to 69 years, and there were729 men and 301 women. The male participants were significantly older than the female participants(49.6 ± 0.4 years vs. 40.1 ± 0.6 years; p < 0.001). The DEQS was higher (worse) in women than in men(17.9 ± 0.7 vs. 24.6 ± 1.2; p < 0.001), and the VDT hours during work were longer in women than in men(6.6 ± 0.1 hours vs. 7.1 ± 0.2 hours; p = 0.02). Women used CL significantly more frequently comparedJ. Clin. Med. 2019, 8, 721

4 of 13with the usage among men (16.6% vs. 48.2%; p < 0.001). In addition, the number of self-care methods
for DED was significantly higher among women than among men (1.6 vs. 1.8; p = 0.02; Table 1).
Table 1. The distribution of the study population.

Demographic Characteristic

Age (year), mean ± SD
DEQS
Summary score, mean ± SD
Bothersome ocular symptoms, mean ± SD
Impact of daily life, mean ± SD
Marital status: married n (%)
Offspring status: does have any children n (%)
Annual household income n (%)<$40,000 per year
$40,000–$59,999 per year≥$60,000 per year
VDT hours during work (hrs), mean ± SD
CL use, n (%)
History of smoking, n (%)
The number of self-care methods mean + SD

Men
n (%)

Women
n (%)

729 (70.8)301 (29.2)

49.6 ± 0.4

40.1 ± 0.6<0.001 a17.9 ± 0.7
9.0 ± 0.3
8.9 ± 0.4502 (68.9)
436 (59.8)

24.6 ± 1.2
13.1 ± 0.5
11.4 ± 0.7
111 (36.9)
86 (28.6)<0.001 a
0.002 a<0.001 a<0.001 b<0.001 b<0.001b94 (12.9)
145 (19.9)
430 (59.0)
6.6 ± 0.1
121 (16.6)
202 (27.7)
1.6 (0.0)87 (28.9)51 (16.9)
116 (38.5)
7.1 ± 0.2
145 (48.2)
47 (15.6)
1.8 (0.1)

p Value0.02 a<0.001 b<0.001 b
0.02 a

DEQS—Dry Eye-related Quality of Life Score; VDT—visual display terminal; CL—contact lens; SD—standard
deviation. a an unpaired two-tailed test; b the chi-square test.

The demographic data for DED diagnosis subgroups are shown in Table 2. One hundred andfifty-five participants (15.0%; 83 men and 72 women) were categorized as having diagnosed DED.
One hundred and sixteen (11.3%; 62 men, 54 women) were categorized as having undiagnosed DED(Figure 1). A younger age was more prevalent in the undiagnosed DED group than in the diagnosed
DED group (p = 0.002). The frequency of female sex was not significant between the undiagnosed
DED and diagnosed DED groups (p = 0.99). The DEQS was worse in the undiagnosed DED groupthan in the diagnosed DED group, although the difference was not statistically significant (p = 0.06).
The DEQS subscale score for bothersome ocular symptoms was significantly higher in the undiagnosed
DED group compared with that in the diagnosed DED group (p < 0.001). The prevalence of othervariables (marital status, offspring status, annual household income, VDT hours during work, CL use,and smoking history) were not significantly different between the groups (Table 2).

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Table 2. The distribution of the study population among dry eye categories.
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Non DED
Undiagnosed DED
Diagnosed DED
n (%)
n (%)
n (%)
p value**
Table 2. The distribution of the study population among dry eye categories.
758 (73.7)
116 (11.3)
155 (15.1)
Age (year), mean ± SD
± 0.4 Undiagnosed
41.8
± 0.9
± 0.9
0.002 aNon47.8
DED
DED
Diagnosed45.7
DED
Women, Characteristicn (%)
175 (23.1)
54 (46.6)
72 (46.5)
0.99 bp Value **Demographic
n (%)
n (%)
n (%)
DEQS
758 (73.7)
116 (11.3)
155 (15.1)
Summary score, mean ± SD
14.6 ± 0.5
37.3 ± 2.0
32.2 ± 1.8
0.06 aBothersomeAge
ocularsymptoms,
mean ± SD
7.60.4± 0.2
19.8 ± 0.7
16.0 ± 0.7(year),
mean ± SD
47.8 ±
41.8 ± 0.9
45.7 ± 0.9
0.002 a<0.001 a
Impact of Women,
daily life,nmean
7.0 ± 0.3
17.5 ± 1.4
16.2 ± 1.1(%) ± SD
175 (23.1)
54 (46.6)
72 (46.5)
0.99 b 0.47 a
Marital status:DEQS
married, n (%)
463 (61.1)
62 (53.4)
88 (56.8)
0.59 bSummarymean ± nSD
14.6400± 0.5
37.3 ± 2.0
32.2 ± 1.8
0.06 a 0.49 b
Offspringstatus:score,
no children,(%)(52.8)
55 (47.4)
67 (43.2)
Bothersome
ocular symptoms,mean
7.6 ± 0.2
19.8 ± 0.7
16.0 ± 0.7<0.001 a0.82 b
Annual householdincome, n(%) ± SD
Impact <$40,000/yearof daily life, mean ± SD
7.0 ±
0.3
17.5
±
1.4
16.2
±
1.1
0.47 a127 (16.8)
26 (22.4)
28 (18.1)b
Maritalstatus:married,n(%)
463(61.1)
62(53.4)
88(56.8)
0.59$40,000–$59,999/year
143 (18.9)
23 (55.0)30 (19.4)bOffspring≥$60,000/year
status: no children, n (%)
400 (52.8)
55(47.4)
67(43.2)
0.49
414 (54.6)
57 (49.1)
75 (48.4)
Annual household income, n (%)
0.82 bVDT hours during work (hours),
6.6 ± 0.1
7.2 ± 0.2
0.08 a<$40,000/year
127 (16.8)
26 (22.4)7.7 ± 0.2
28 (18.1)
mean ± SD$40,000–$59,999/year
143 (18.9)
23 (55.0)30 (19.4)
CL use, n (%)
164 (21.6)
41 (35.3)
61 (39.4)
0.50 b≥$60,000/year
414 (54.6)
57 (49.1)
75 (48.4)
Historyofsmoking,n(%)
186(24.5)
22(19.0)
41(26.5)
0.14 bVDT hours during work (hours),
a
6.6
±
0.1
7.7
±
0.2
7.2
±
0.2
0.08
DED—dry eye disease;
DEQS—Dry Eye-related Quality of Life Score; VDT—visual display terminal; CL—contact lens; SD—mean ± SDb squaretwo-tailed test. b thestandard deviation.
**analysis
DED and diagnosed
CL use,n (%) between undiagnosed
164 (21.6)
41 (35.3)DED. a an unpaired
61 (39.4)
0.50chitest
History of smoking, n (%)
186 (24.5)
22 (19.0)
41 (26.5)
0.14 bDemographic characteristic

DED—dry eye disease; DEQS—Dry Eye-related Quality of Life Score; VDT—visual display terminal; CL—contact
lens; SD—standard deviation. ** analysis between undiagnosed DED and diagnosed DED. a an unpaired two-tailed
test. b the chi square test.

Figure 1. Participants flow chart. The participants were stratified with diagnosed history andsymptom of dry eye disease (DED). Diagnosed DED—physician diagnosis of DED (+); undiagnosed
Figure 1. Participants
flow
Theandparticipants
were stratified
history andDED—physician
diagnosisof chart.
DED (−)
severe symptomsof DEDwith(+); diagnosed
non DED—physician
symptomofofDED
dry (−)
eyeanddisease(DED).
Diagnosed
DED—physician
diagnosis of DED (+); undiagnosed
diagnosis
severesymptomsof DED(−).
DED—physician diagnosis of DED (−) and severe symptoms of DED (+); non DED—physician
Adiagnosis
logistic ofregression
model
was
used toofdetermine
DED (−) andseveresymptoms
DED (−). the risk factors for the undiagnosed anddiagnosed DED. In the multivariate-adjusted model, there was a 3% higher risk for undiagnosed
A logistic
regression
model
used
to determine
risk factors
for the undiagnosed
DED foreach decreasein oneyearwasof age(odds
ratio (OR)the= 0.97;95% confidence
interval (CI)and=
diagnosed
multivariate-adjusted
model,
there
was awork
3% higherrisk for undiagnosed
0.95–0.99;
p =DED.
0.01).InIntheaddition,
female sex and VDT
hours
duringwere significant
risk factors
DED
for each decreasein one yearof age(odds
ratio= 0.97; 95%(CI)==1.12;
0.95–
for
undiagnosed
DED (female
sex: OR
= 2.16;95%
CI(OR)= 1.31–3.33;
p = confidence
0.003; VDTinterval
hours: OR
0.99;CIp== 1.04–1.21;
0.01). In addition,sexsex
and
VDT
hours
duringwork risk
werefactors
significant
risk factors
for95%
p = 0.004).female
Femaleand
CL useweresignificant
for diagnosed
DED
undiagnosed(femalesex:
OR = 2.16;p95%
CI = CL
1.31–3.33;
0.003;95%
VDT
OR = 1.12;
95%(femalesex: ORDED= 2.45;
95% CI= 1.58–3.80;< 0.001;
use: ORp == 1.66;
CIhours:= 1.08–2.54;
p = 0.02;
CI = 3).
1.04–1.21; p = 0.004). Female sex and CL use were significant risk factors for diagnosed DED
Table(female sex: OR = 2.45; 95% CI = 1.58–3.80; p < 0.001; CL use: OR = 1.66; 95% CI = 1.08–2.54; p = 0.02;
Table 3).

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Table 3. Risk factors of undiagnosed and diagnosed dry eye disease.
Demographic
Characteristic

Undiagnosed DED

Diagnosed DED

Univariate Logistic Analysis(Compared to Non-DED)

Multivariate Logistic Analysis(Compared to Non-DED)

p Value

Univariate Logistic Analysis(Compared to Non-DED)

Multivariate Logistic Analysis(Compared to Non-DED)

p ValueAge (every one year)OR (95% CI)

0.95 (0.93–0.97)

Gender (men vs. women)
OR (95% CI)

0.97 (0.95–0.99)

0.01

0.98 (0.97–1.00)

1.01 (0.99–1.03)

0.38

2.91 (1.94–4.34)

Offspring status: does haveany children
OR (95% CI)

2.12 (1.28–3.50)

0.003

2.89 (2.02–4.14)

2.45 (1.58–3.80)<0.0010.81 (0.55–1.20)

0.68 (0.48–0.97)

0.83 (0.55–1.26)

0.39

Annual household income(every $20,000)
OR (95% CI)

0.90 (0.81–0.99)

0.96 (0.87–1.05)

0.38

1.00 (0.92–1.08)

VDT hours during work
(every one hour)
OR (95% CI)

1.15 (1.07–1.23)

1.12 (1.04–1.21)

0.004

1.08 (1.01–1.15)

1.06 (0.99–1.14)

0.07

CL use (never vs. ever)OR (95% CI)

2.01 (1.29–3.12)

1.28 (0.78–2.11)

0.33

2.35 (1.63–3.39)

1.66 (1.08–2.54)

0.02

DED—dry eye disease; OR—odd ratio; CI—confidence interval; CL—contact lens; VDT—visual display terminal.

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Table 4 shows the distribution of the self-care methods for DED among the undiagnosed anddiagnosed DED groups. The number of self-care methods did not significantly differ between thegroups (p = 0.37). In the undiagnosed DED group, the most prevalent number of self-care methods
was two (31%); in contrast, the most prevalent number in the diagnosed DED group was one (34%).
The use of eye drops was the most common self-care method in both groups (undiagnosed, 69.0%;
diagnosed, 69.9%; p = 0.86). Fourteen participants (12.1%) in the undiagnosed DED group and 15
participants in the diagnosed DED group (9.8%) were not using any self-care methods (p = 0.55).
The stratified analysis based on the number of self-care methods (<3 or ≥3) is shown in Figure 2.
For the participants using less than three self-care methods, the DEQS was significantly worse in the
undiagnosed DED group (p = 0.002); however, there was no difference between the undiagnosed anddiagnosed DED groups who used three or more self-care methods.
Table 4. The distribution of self-care methods among undiagnosed and diagnosed dry eye disease.
Self-Care Methods

Undiagnosed DED

Diagnosed DED

p Value

The number of methods, mean + SD
The number of methods, n (%)
0
1
2≥3
Use of over-the-counter eye drops, n (%)
Increase in blinking
Use protection glasses from dryness
Use of a warm compress
Sleeping longer
ExerciseUse of oral supplements
Deep, relaxing breathing
Eyelid hygiene using eye shampoo
OthersNot doing anything

1.9 ± 0.1

2.0 ± 0.1

0.37 a0.50 b14 (12.1)
35 (30.2)
36 (31.0)
31 (26.7)
80 (69.0)
35 (30.2)
6 (5.2)24 (20.7)
42 (36.2)
4 (3.4)13 (11.2)
7 (6.0)2 (1.7)3 (2.6)14 (12.1)

15 (9.8)
52 (34.0)
37 (24.2)
49 (32.0)
107 (69.9)
38 (24.8)
12 (7.8)
36 (23.5)
71 (46.4)
12 (7.8)
13 (8.5)
13 (8.5)
0 (0.0)6 (3.9)15 (9.8)

DED—dry eye disease; SD—standard deviation; a an unpaired two-tailed test; b the chi-square test.

0.86 b0.33 b
0.39 b
0.58 b
0.09 b0.13 b
0.46 b0.45 b0.10 b0.55 b0.55 b

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8 of 13

Figure 2. Cont.

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9 of 13

Figure 2. The number of self-care methods and Dry Eye-related Quality of Life Score among undiagnosed
Figure 2. The number of self-care methods and Dry Eye-related Quality of Life Score amongand diagnosed dry eye disease. The difference in Dry Eye-related Quality of Life Score (DEQS) between
undiagnosed and diagnosed dry eye disease. The difference in Dry Eye-related Quality of Life Score
undiagnosed/diagnosed dry eye disease (DED), stratified with the amount of self-care items for DED.
(DEQS) between undiagnosed/diagnosed dry eye disease (DED), stratified with the amount of self(a) DEQS summary score; (b) DEQS bothersome ocular symptoms score; (c) DEQS impact of dailycare items for DED. (a) DEQS summary score; (b) DEQS bothersome ocular symptoms score; (c) DEQS
life score.
impact of daily life score.

4. Discussion
4. Discussion
DED imposes a substantial economic burden, with indirect costs comprising the largest proportion
imposesa substantial
burden,with indirect
costs comprising
the impact
largestof theDED
overallcost, due
to a markedeconomic
loss of work
productivity
and a considerable
negative
proportion
thepotentiallyoverall cost,
due to a marked
loss ofwork
and aetconsiderableonphysical ofandpsychological
function[4].
For productivity
instance, Uchino
al. reported negativethat theimpactonphysicalandpotentiallypsychological
function[4].
For
instance,
Uchinoetal.
reported
annual productivity loss owing to DED was estimated to be $6160 per employee when measured bythat production,
the annual productivity
owing whento DEDwas estimatedbe Based$6160 onpera previous
employeesurvey
when
total
and $1178 perloss
employeecalculated
by wageto[23].
measuredby
total
production,
and
$1178
per
employeewhencalculated
by
wage
[23].
Based
on a
of 4393 Japanese office workers, 26.1% experienced DED symptoms, although only 10% of the workers
previous
surveyof
4393
Japanese
officeworkers,26.1%
experienced
DED
symptoms,
althoughonly
had a previous clinical diagnosis of DED [24]. Work performance was worse in participants with DED
10% of the but
workers
hadclinicala previous
clinicalof DEDwith[24].those
Workwith
performance
was worse[8].
insymptoms
without
diagnosis
ofdiagnosis
DED compareda clinical diagnosis
participants
withDED
symptoms
butwithout
clinicaldiagnosisofDED
compared
with
those
with
Therefore, appropriate treatment and management for such individuals is of paramount importance.aclinicaldiagnosis[8]. Therefore,
appropriate treatment
andmanagement
forfactors
such individuals
is of
In thepresent analysis,
the multivariate-adjusted
model
indicatedthat risk
for undiagnosed
paramount
importance.
DED
includeda younger age, female sex, and VDT hours. The multivariate analysis showed a 3%Inthepresent
analysis, DED
the multivariate-adjusted
model
indicatedrisk tofactorsforincrease in risk of undiagnosed
for each one year decreasein age;this is inthat
contrast
The Tearundiagnosed
DED
includeda younger
female(TFOS
sex, and
VDTIIhours.
multivariate
analysisFilmand OcularSurface
Society
Dry Eyeage,
Workshop
DEWS)
report,The
showingthat increasing
showeda3%
increaseinriskofundiagnosed
DED
for
each
one
year
decrease
in
age;
this
is
in
contrast
age is a risk factor for DED, although it is unclear whether the DED was diagnosed or undiagnosed
[25].
to
The
Tear
Film
and
Ocular
Surface
Society
Dry
EyeWorkshop
(TFOS
DEWS)
II
report,showing
According to the White Papers and Reports 2009–2010 conducted by the Japanese Ministry of Health,that increasing
age is[26],a riskfor DED,although
it is unclear
whetherthehousehold
DED was diagnosedorLabor,and Welfare
thefactor
averageincomeper household
as wellas permember by
undiagnosed[25].
According
to
the
White
PapersandReports
2009–2010
conducted
bytheJapanesehouseholder age was the highest in the 50–59-year age group ($76,550) and lowest in the ≤29-year
Ministry
Health, Moreover,Labor, andthe grows
averageincome perwith
householdas wellperagegroupof($29,890).
theWelfare
average[26],incomein accordancehouseholder
age,asuntilhouseholdby householder
age wasthe highest
in the 50–59-year
age
group
($76,550) lessandreaching
themember
50–59-year
group. We thus
speculatethat younger
individuals
have
comparably
lowestinthe≤29-yearage
group($29,890).
Moreover,the
averageincomegrows
inaccordancewithmoney than older individuals, and there is a correspondingly greater impact regarding the cost ofhouseholder age, until reaching the 50–59-year group. We thus speculate that younger individuals
have comparably less money than older individuals, and there is a correspondingly greater impact

J. Clin. Med. 2019, 8, 721

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visiting the eye clinic, thus younger individuals are less able to afford a visit to an eye clinic as a resultof the cost.
In addition, female sex was a risk factor for both undiagnosed DED and diagnosed DED. A
previous report shows an increase in DED symptoms in women, even with a similar severity of clinicalsigns and a lack of association of symptoms with signs [6]. The biological differences between men andwomen, such as sensitivity of the ocular surface and pain tolerance, and psychological and sociocultural
factors, such as self-representation of gender roles, suggest that women tend to be more symptomaticthan men [6,7].
Psychological adverse effects, including sleep disorders, are caused by VDT usage [27,28], which
may worsen work efficiency and prolonged working time; we therefore also speculate that individuals
with a prolonged working time have less time to visit an eye clinic, as most eye clinics are closed atnight and in the early morning, except for emergency services. Furthermore, a previous report showedthat office workers who spend long hours viewing VDTs develop DED [29], and the blinking rate
decreases during using VDTs [30]; thus, workers using VDTs commonly experience eye problems; thisis likely more as a result of the longer blinking interval than the decreases in tear breakup time, which
disturbs tear stability [31].
Risk factors for diagnosed DED included CL use, although CL use was not a risk factor for
undiagnosed DED. The TFOS DEWS II report mentioned that CL use can be one of the main causesof DED [25]. Participants using CL and experiencing severe DED symptoms are considered tohave a greater chance of having a DED diagnosis when visiting clinics for the purpose of obtainingprescriptions for CL.
In the present study, women exhibited significantly worse DEQS, despite using more self-caremethods compared with that of men. Typically, the relief of DED symptoms requires the use of
more self-care methods. Matossian et al. reported that women reported a lower health-related
quality of life compared with men [5]; such factors promote the use of a greater number of self-caremethods. Moreover, in participants using less than three self-care methods, the DEQS was worse in the
undiagnosed DED group than in the diagnosed DED group; we speculate that those with undiagnosed
DED may not perform self-care management appropriately. The concept of TFOT is layer-by-layer
treatment for DED, with each therapy corresponding to its target layer; this is proposed so as toassist with the supplementation of the corneal surface components that are insufficient [10]. Self-care,such as a warm compress and eyelid hygiene, are recommended for the lipid layer, and artificial
tears are recommended for the aqueous layer [10]. In addition, the specific therapy corresponds withbreakup patterns, as follows: area break or line break, punctal plug and diquafosol sodium; spot break,dimple break, and line or random break with rapid expansion, diquafosol sodium and rebamipide;and random break, Meibomian Gland Dysfunction therapy, ointment, artificial tear, hyaluronic acid,diquafosol sodium, and rebamipide [10]. Without an appropriate understanding of and information
concerning TFOT, patient-based self-care may not be properly initiated. Thus, it is possible that thoseexperiencing severe DED symptoms are more likely to visit an eye clinic and obtain information for
the appropriate management of DED.
Currently, there are various available treatment options for DED; however, even for eye
professionals, the widely diverse management options can be confusing [32,33]. The TFOS DEWS
II report summarized and recommended appropriate management and treatment for DED basedon an evidence-based review of the literature, and it encouraged education regarding DED and
its management, treatment, and prognosis [15] However, although eyelid hygiene and warm
compresses are effective self-care methods for Meibomian gland disease, compliance has not been
well characterized [15,18,34]. To maximize the effectiveness of DED treatment, self-care management
should be provided based on ocular status. Accordingly, it should be recommended that patientsshould visit an eye care physician to obtain appropriate information.
We acknowledge several limitations to the present study. Firstly, it relied on self-reporting toassess the presence of DED as either clinically diagnosed or as undiagnosed based on symptoms; noJ. Clin. Med. 2019, 8, 721

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objective examination for DED was performed. Secondly, the web survey answers were recorded
consecutively; therefore, the responses were disproportionate by age and sex. There may also havebeen a selection bias in that individuals who are interested in eye symptoms may have been more likely
to participate. There is a need for a study wherein age and sex are appropriately distributed. Lastly,
this is a cross-sectional study, thus any potential causal relationship remains unclear. For example,
there may be reverse causality among a lower DEQS and the number of self-care methods. In addition,
participants with severe symptoms may have had a lower DEQS owing to challenges implementing
self-care or inadequately employing self-care.
In conclusion, the present study revealed that a younger age, female sex, and VDT hours during
work are risk factors for undiagnosed DED. Furthermore, those in the undiagnosed DED group andthose using less than three self-care methods may perform self-care inappropriately, and thus require
professional support. Although further studies are needed to increase the understanding of theimportance of appropriate management for DED, the present results suggest the need to increase theawareness of both undiagnosed DED and appropriate self-care for DED.
Author Contributions: Conceptualization, M.U., M.K., Y.U., and N.Y.; data curation, M.U., M.K., Y.U., andN.Y.; formal analysis, R.Y. and M.U; investigation, M.U., M.K., Y.U., and N.Y.; methodology, R.Y. and M.U.;
project administration, M.U., N.Y., and K.T.; resources, M.U. and N.Y.; software, R.Y.; supervision, N.Y. and K.T.;
validation, R.Y., M.U., and M.K.; visualization, M.U., M.K., Y.U., and N.Y.; writing (original draft), R.Y. and M.U.;
Writing (review and editing), M.U., M.K., Y.U., N.Y., and K.T.
Funding: This study was a collaborative investigation of the Dry Eye Society, Tokyo.
Conflicts of Interest: Ryutaro Yamanishi, Miki Uchino, Motoko Kawashima, and Yuichi Uchino declare that they
have no conflicts of interest. Norihiko Yokoi: Consultant for Alcon Japan, Ltd.; and Rohto Co, Ltd. Kazuo Tsubota:
Consultant and research funding received from Santen Pharmaceutical Co., Ltd.; research funding received from
Kowa Company; founder of Tsubo Labo, Tokyo, Japan. The funders had no role in the design of the study; inthe collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish
the results.

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