Cornea

Dry Eye Syndrome, Posttraumatic Stress Disorder, and

Depression in an Older Male Veteran Population
Cristina A. Fernandez,1 Anat Galor,2,3 Kristopher L. Arheart,4 Dominique L. Musselman,5
Vincent D. Venincasa,2,3 Hermes J. Florez,2,6 and David J. Lee1
1
Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, Florida
2
Miami Veterans Administration Medical Center, Miami, Florida
3Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida
4
Department of Public Health Sciences, Division of Biostatistics, University of Miami Miller School of Medicine, Miami, Florida
5
Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, Florida
6
Department of Endocrinology and Geriatrics, University of Miami Miller School of Medicine, Miami, Florida

Correspondence: Anat Galor, 900
NW 17th Street, Miami, FL 33125;
agalor@med.miami.edu.
Submitted: January 10, 2013
Accepted: April 23, 2013
Citation: Fernandez CA, Galor A,
Arheart KL, et al. Dry eye syndrome,
posttraumatic stress disorder, and
depression in an older male veteran
population. Invest Ophthalmol Vis
Sci. 2013;54:3666–3672. DOI:10.
1167/iovs.13-11635.
PURPOSE. To evaluate whether veterans with posttraumatic stress disorder (PTSD) or
depression have differences in dry eye symptoms and signs compared to a population
without these conditions.
METHODS. Male patients aged ‡50 years with normal eyelid, conjunctival, and corneal anatomy
were recruited from the Miami Veterans Affairs Eye Clinic (N ¼ 248). We compared dry eye
symptoms (determined by the Dry Eye Questionnaire 5 [DEQ5] score) to tear film indicators
obtained by clinical examination (i.e., tear osmolarity, corneal staining, tear breakup time,
Schirmer’s, meibomian gland quality, orifice plugging, lid vascularity) between patients with
PTSD or depression and those without these conditions. Student’s t-tests, v2 analyses, and
linear and logistic regressions were used to assess differences between the groups.
RESULTS. DEQ5 scores were higher in the PTSD (mean ¼ 13.4; standard error [SE] ¼ 1.1; n ¼
22) and depression (mean ¼ 12.0; SE ¼ 0.8; n ¼ 40) groups compared to the group without
these conditions (mean ¼ 9.8; SE ¼ 0.4; n ¼ 186; P < 0.01 and P ¼ 0.02, respectively). More
patients in the PTSD and depression groups had severe dry eye symptoms, defined as a DEQ5
score ‡ 12 (77% and 63% vs. 41%; P < 0.01 and P ¼ 0.02, respectively). No significant
differences in tear film indicators were found among the three groups. Multivariable logistic
regression indicated that a PTSD diagnosis (odds ratio [OR] ¼ 4.08; 95% confidence interval
[CI] ¼ 1.10–15.14) and use of selective serotonin reuptake inhibitors (OR ¼ 2.66; 95% CI ¼
1.01–7.00) were significantly associated with severe symptoms.
CONCLUSIONS. Patients with PTSD have ocular surface symptoms that are not solely explained
by tear indicators. Identifying underlying conditions associated with ocular discomfort is
essential to better understand the mechanisms behind ocular pain in dry eye syndrome.
Keywords: depression, posttraumatic stress disorder, dry eye syndrome, veterans

ry eye syndrome (DES) is one of the most common ocular
D conditions in the United States, with approximately 1.7
million men aged 50 and older affected.1,2 This number is
projected to increase to over 2.8 million by 2030.2 The most
common symptoms of DES include irritated, gritty, scratchy, or
burning eyes; sensation of something in the eyes; watery eyes;
and blurred vision.3 Because of these symptoms, DES has been
shown to negatively impact one’s quality of life and emotional
well-being.4 DES may also pose difficulties in daily tasks, such as
reading, working, using a computer, or driving.5 These
physical, mental, and social limitations due to DES have ignited
research regarding the associations between DES and specific
mental health diagnoses.
Preliminary studies investigating the association between
mental health and DES in Western populations have used
administrative databases to define DES.6,7 However, recent
studies on Asian populations have used symptoms in addition
to clinical indicators to measure DES, with mixed results. For
example, Li et al. found that Chinese patients with depression
and anxiety reported more dry eye symptoms, but did not differ
in clinical measurements (i.e., Schirmer test 1, tear breakup
time [TBUT], and corneal fluorescein staining) from a control
group.8 Similarly, Kim et al. documented that depression scores
in a geriatric Korean population were correlated with dry eye
symptoms, but not with TBUT or Schirmer test score.9
Conversely, Wen et al. reported a greater prevalence of dry
eye symptoms and clinical measurements (i.e., Schirmer test 1,
TBUT, and corneal fluorescein staining) in Chinese individuals
with depression and anxiety disorders.10
To the authors’ knowledge, no studies to date have
investigated the relationship between DES, as defined by
objective measures, and depression or anxiety in a Western
population. More specifically, the association between DES and
posttraumatic stress disorder (PTSD) has never been examined.
PTSD is defined briefly as experiencing the following symp-
toms, lasting for at least 1 month: experience of a traumatic
event; intrusive recollection of the event; avoidance/numbing;
and hyperarousal.11 In addition, significant emotional distress

Copyright 2013 The Association for Research in Vision and Ophthalmology, Inc.
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 DES, PTSD, and Depression in Older Male Veterans
and functional impairment must be present. Even though PTSD
is categorized as an ‘‘Anxiety Disorder’’ in the Diagnostic and
Statistical Manual for Mental Disorders, it is a unique disorder
with regard to its clinical symptomatology, presentation, and
treatment protocol.12 Furthermore, there is scant research
evaluating potential links between psychiatric disorders and
DES.6 As both PTSD and depression have been associated with
systemic inflammation,13,14 and DES with local inflamma-
tion,15–17 it is possible that inflammation may serve as a link
between these entities.
Veterans are a unique population with distinctive physical
and psychiatric comorbidities, including a higher prevalence of
PTSD and depression compared to the general population.18–20
Using administrative databases, we found that male and female
US veterans had a DES prevalence of 19% and 22%,
respectively, and those with PTSD or depression had a higher
likelihood of having a dry eye diagnosis.6,7 The objective of the
current study was to augment the existing DES literature by
evaluating associations between a symptoms-based DES
diagnosis and objective parameters of DES among male
veterans with and without PTSD or a depression diagnosis.
Additionally, we explored whether elevated C-reactive protein
(CRP) levels were associated with depression or PTSD among
male veterans with and without DES to study whether systemic
inflammation could be a possible link between psychiatric
disorders and DES.
METHODS
Study Population
The Miami Veterans Affairs (VA) Institutional Review Board
reviewed and approved the prospective examination of
patients for this study, which was conducted in accordance
with the principles of the Declaration of Helsinki. Patients
were recruited from the Miami VA Eye Clinic (October 2010–
December 2011). Patients were seen in the eye clinic by an
ophthalmologist or optometrist for a variety of concerns,
including refractive issues, cataract evaluation, and retinal
pathology. Inclusion criteria included having normal eyelid,
conjunctival, and corneal anatomy. Patients were not eligible to
participate if they were female; were under 50 years of age;
used contact lenses; used any ocular medication (with the
exception of artificial tears/topical cyclosporine); or had
human immunodeficiency virus, sarcoidosis, graft-versus-host
disease, a collagen vascular disease, an active external ocular
process (e.g., keratitis), or any history of refractive surgery or
cataract surgery within the last 3 months. Patients were
prescreened by eye care practitioners, and eligible subjects
were informed about an opportunity to participate in a 1-day
research study with the purpose of evaluating tear film
function. Potential subjects were told that the goal of the
study was to understand why some individuals had tear
dysfunction while others had healthy tears. This script was
drafted specifically to mitigate possible selection bias and
recruit patients with and without DES. Interested patients were
scheduled for a research visit, at which time informed consent
was obtained.
The sample was divided into three groups: depression only,
PTSD only, and those without either diagnosis. We excluded
participants who had a diagnosis of both depression and PTSD
(n ¼ 15) in order to study each diagnosis separately.
Data Collection
For each individual, demographic information, medical history,
and psychiatric and medication information were collected.
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IOVS j May 2013 j Vol. 54 j No. 5 j 3667
Demographic information, health status, medical history,
psychiatric diagnoses (e.g., PTSD and depression), and
medication information were gathered via a chart review of
the VA administrative database. Specifically, lifetime and
current PTSD and depression diagnoses were coded using
the International Classification of Disease-9 (ICD-9) by the
patient’s treating physician. Current antidepressant and anti-
anxiety medication use was categorized by drug category.
Antidepressants were categorized as selective serotonin
reuptake inhibitors (SSRIs), other, or none. This categorization
was used due to small sample sizes in the non-SSRI categories;
antidepressant medications included in the ‘‘other’’ group
included serotonin and norepinephrine reuptake inhibitors
(SNRIs), aminoketones, and piperazinoazepines. Even though
SSRIs and SNRIs are similar in their inhibition of reuptake of
serotonin, SNRIs are a distinct therapeutic class because these
agents also block the reuptake of norepinephrine, and were
thus classified in the ‘‘other’’ group. Similarly, antianxiety
medication use was categorized as benzodiazepines, other, and
none. Other antianxiety medications included atypical anxio-
lytics and antihistamines (i.e., only when used for anxiety
treatment purposes).
The validated five-item Dry Eye Questionnaire (DEQ5) was
administered to all patients.21 The DEQ5 comprises questions
regarding the frequency and intensity of dry eye symptoms,
such as eye discomfort, eye dryness, and watery eyes. The total
score ranges from 0 to 22, with a score of zero indicating no
dry eye symptoms and a score of 22 indicating that the subject
experiences the most frequent and intense symptoms. Based
on previous validation studies, the presence of mild symptoms
was defined as a score ‡ 6, and the presence of severe
symptoms score was defined as a score ‡ 12.21
The ocular surface examination, in the order performed,
consisted of tear osmolarity (measured once in each eye;
TearLAB, San Diego, CA), TBUT (measured twice in each eye
and averaged per eye), conjunctival and corneal staining
(punctuate epithelial erosions [PEE]; range, 0–5),22,23 Schirm-
er’s strips with anesthesia,23 and morphologic and qualitative
eyelid and meibomian gland information. For the TBUT, a
fluorescein strip (Fluorets; Laboratoire Chauvin, Aubenas,
France) was wetted with the application of one drop of
nonpreserved saline to the lower one-fourth of the strip.
Excess fluid was gently removed such that the saturated tip
delivered approximately 3 to 5 lL liquid sodium fluoride
(NaFl). With the patient gazing up, the examiner introduced
the NaFl into the lower fornix. Starting with the right eye,
timing was stopped upon visualization of the first break (one
or more black [dry] spots) appearing in the precorneal tear
film or after 15 seconds had elapsed. The procedure was then
repeated for the left eye. Morphologic information collected
included the degree of eyelid vascularity (0 ¼ none; 1 ¼ mild
engorgement; 2 ¼ moderate engorgement; 3 ¼ severe
engorgement)24 and the presence of inferior eyelid meibomian
orifice plugging (0 ¼ none; 1 ¼ less than one-third lid
involvement; 2 ¼ between one-third and two-thirds involve-
ment; 3 ¼ greater than two-thirds lid involvement). Meibum
quality was graded on a scale of 0 to 4 (0 ¼ clear; 1 ¼ cloudy; 2
¼ granular; 3 ¼ toothpaste; 4 ¼ no meibum extracted).25 For
each participant, data from the worst eye were used.
C-Reactive Protein
Blood samples were obtained from each patient and analyzed
for plasma concentrations of high-sensitivity CRP. For the CRP
analysis, we excluded participants with CRP levels greater than
10 (n ¼ 22; 9%), as this level indicates an acute rather than a
chronic inflammatory process.26
 DES, PTSD, and Depression in Older Male Veterans IOVS j May 2013 j Vol. 54 j No. 5 j 3668

TABLE 1. Demographic Information of the Study Population

No Depression/PTSD PTSD* Depression* P Value

Sample size, n (%) 186 (75) 22 (9) 40 (16) –

Age, mean (SE) 69.5 (0.7) 66.8 (1.9) 66.3 (1.4) 0.08
Race, n (%)
White 133 (72) 11 (50) 28 (70) 0.36
Black 47 (25) 11 (50) 11 (28)
Other 6 (3) 0 (0) 1 (2)
Ethnicity, n (%)
Hispanic 51 (27) 7 (32) 10 (25) 0.85
Non-Hispanic 135 (73) 15 (68) 30 (75)
Smoking status, n (%)
Never 51 (28) 9 (41) 9 (22) 0.11
Former 107 (58) 10 (45) 19 (48)
Current 27 (15) 3 (14) 12 (30)
Self-reported health status, n (%)
Excellent 12 (7) 4 (19) 2 (5) 0.16
Good 108 (58) 10 (48) 19 (48)
Fair 54 (29) 5 (24) 13 (32)
Poor 11 (6) 2 (9) 6 (15)
Antidepressant medication use, n (%)
SSRI 18 (9.7) 9 (40.9) 13 (32.5) <0.001
Other 13 (7.0) 3 (13.6) 10 (25.0)
None 155 (83.3) 10 (45.5) 17 (42.5)
Antianxiety medication use, n (%)
Benzodiazepine 11 (5.9) 5 (22.7) 9 (22.5) <0.001
Other 5 (2.7) 3 (13.6) 3 (7.5)
None 170 (91.4) 14 (63.6) 28 (70.0)
C-reactive protein, mean 6 SE (n)† 2.8 6 0.2 (170) 2.4 6 0.5 (18) 2.5 6 0.4 (32) 0.6
* PTSD/depression was assessed by the presence of an International Classification of Disease-9 (ICD-9) code for each respective disorder.
† Number smaller than sample size as patients with C-reactive protein > 10 were excluded from the analysis.

Main Outcome Measures Symptoms-Based DES Diagnosis

The main outcome measure was the comparison of dry eye
symptoms, as measured by the DEQ5, and clinical signs
between those with PTSD or depression and a group without
these comorbidities.
Statistical Analysis
Statistical analyses were performed using SPSS 19.0 (SPSS, Inc.,
Chicago, IL) and SAS 9.3 (SAS Institute, Inc., Cary, NC). T-tests
and v2 analyses were used to characterize the demographic
data. Linear models (generalized for binary data and general for
continuous data) were used to analyze the tear film indicators
obtained by clinical examination. Logistic regression analysis
was used to evaluate demographic, medical, and psychiatric
factors associated with severe symptoms. Statistical signifi-
cance was defined as P < 0.05.
RESULTS
Study Population
A total of 248 veteran men were included in this study. The
mean age was 69 years old, with the majority of the sample
being white (70%, n ¼ 172) non-Hispanic (73%, n ¼ 180)
former smokers (55%, n ¼ 126) and in self-reported good
health (56%, n ¼ 137). Demographic characteristics of the
study population are reported in Table 1.
The PTSD (mean ¼ 13.4, standard error [SE] ¼ 1.1) and
depression (mean ¼ 12.0, SE ¼ 0.8) groups had significantly
higher mean DEQ5 scores compared to the group without
these diagnoses (mean ¼ 9.8, SE ¼ 0.4; P < 0.01 and P ¼ 0.02,
respectively). These two groups also had a higher percent of
severe symptoms (as measured by a DEQ score ‡ 12)
compared to the group without these diagnoses (P < 0.01
and P ¼ 0.02, respectively). Results are reported in Table 2.
Tear Film Indicators Obtained by Clinical
Examination
Linear models (generalized for binary data and general for
continuous data) were used to analyze the tear film indicators
obtained by clinical examination. There were no significant
differences among groups with respect to tear osmolarity,
corneal staining, TBUT, meibomian gland quality, lid vascu-
larity, or meibomian gland orifice plugging in either mean
scores or cutoff definitions (Table 2). Several different cutoffs
for tear osmolarity were evaluated (308, 312, 325), but were
not found to influence the results (results shown only for
325).27
Multivariable Logistic Regression
After controlling for age, race, ethnicity, self-reported
smoking status, self-reported health status, current use of
antidepressants, current use of antianxiety medications, CRP,

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 DES, PTSD, and Depression in Older Male Veterans IOVS j May 2013 j Vol. 54 j No. 5 j 3669

TABLE 2. Ocular Surface Symptoms and Tear Film Parameters in Study Population by Presence of Depression and PTSD

Mean Cutoff Definitions

Comparisons, P Comparisons, P

Tear Film Parameters* Mean (SE) No PTSD/Depression PTSD % (SE) No PTSD/Depression PTSD

DEQ5 Score ‡ 12
No PTSD/depression 9.8 (0.4) 40.9 (3.6) – –
PTSD 13.4 (1.1) <0.01 77.3 (8.9) <0.01
Depression 12.0 (0.8) 0.02 0.33 62.5 (7.7) 0.02 0.24
Tear breakup time Value < 5 s
No PTSD/depression 7.6 (0.3) 38.2 (3.6) – –
PTSD 6.3 (0.1) 0.21 50.0 (10.7) 0.29
Depression 6.6 (0.7) 0.21 0.80 50.0 (7.9) 0.17 1.00
Schirmer’s Value < 5 mm
No PTSD/depression 10.9 (0.5) 21.0 (3.0) – –
PTSD 10.6 (1.7) 0.85 22.7 (8.9) 0.85
Depression 13.2 (1.2) 0.09 0.21 7.5 (4.2) 0.06 0.67
Lid vascularity Grade > 1
No PTSD/depression 0.8 (0.1) 22.0 (3.0) – –
PTSD 0.5 (0.2) 0.08 13.6 (7.3) 0.37
Depression 0.6 (0.1) 0.06 0.81 10.0 (4.7) 0.09 0.67
Tear osmolarity Value > 325 mOsm†
No PTSD/depression 309.8 (1.1) 11.7 (2.4) – –
PTSD 309.5 (3.2) 0.93 4.8 (4.6) 0.35
Depression 309.8 (2.3) 0.10 0.94 10.0 (4.7) 0.76 0.49
Corneal staining Grade > 1
No PTSD/depression 1.0 (0.1) 23.8 (3.1) – –
PTSD 1.3 (0.2) 0.14 40.9 (10.5) 0.09
Depression 1.2 (0.2) 0.21 0.67 27.5 (7.1) 0.62 0.28
MG quality Grade > 1
No PTSD/depression 1.5 (0.1) 42.4 (3.6) – –
PTSD 1.2 (0.2) 0.38 31.8 (9.9) 0.35
Depression 1.6 (0.3) 0.57 0.26 42.5 (7.8) 0.99 0.44
MG orifice plugging Grade > 1
No PTSD/depression 1.0 (0.1) 29.2 (3.3) – –
PTSD 1.2 (0.2) 0.44 40.9 (10.5) 0.26
Depression 1.0 (0.2) 0.83 0.43 25.0 (6.8) 0.60 0.20
MG, meibomian gland.
* More severe value of the two eyes.
† Results did not change when the cutoff value was changed to 308 or 312 mOsm.

and psychiatric diagnosis (e.g., PTSD or depression), PTSD DISCUSSION

diagnosis (odds ratio [OR] ¼ 4.02; 95% confidence interval
[CI] ¼ 1.10–15.14), SSRI use (OR ¼ 2.66; 95% CI ¼ 1.01–
7.00), and never smoker (versus current smoker; OR ¼ 3.11;
95% CI ¼ 1.11–8.75) remained significant predictors of a
symptoms-based DES diagnosis. Results are illustrated in Table
3.
C-Reactive Protein
No significant differences in CRP levels were found between
the group without any psychiatric diagnoses (mean ¼ 2.8; SE ¼
0.2) and the depression group (mean ¼ 2.5; SE ¼ 0.4; P ¼ 0.45)
or the PTSD group (mean ¼ 2.4; SE ¼ 0.5; P ¼ 0.45), nor was
there a significant difference between the PTSD and depres-
sion groups (P ¼ 0.88). The inclusion of CRP levels in the
models shown in Table 2 did not alter the significance of the
results (data not shown). Additionally, CRP levels were not
significantly associated with severe dry eye symptoms in our
multivariable model (Table 3).
Our results demonstrate that within our population, a
diagnosis of PTSD or depression was associated with DES
severity when measured using a symptom-based instrument.
However, measurements of objective tear film parameters
could not explain the degree of symptoms. These findings are
similar to those reported by Li et al.8 and Kim et al.,9 who also
found no differences in tear parameters in those with
depression or anxiety. Understanding mechanisms behind
ocular discomfort is a vital first step in alleviating morbidity
for DES suffers. While abnormal tear film indicators are
important in the pathway of ocular pain, our study and
others28,29 confirm that other factors must be important as
well, based on the poor correlations between the symptoms
and signs of DES.30 Our study suggests that having a psychiatric
disorder independently affects the symptoms of DES. However,
while we postulated that inflammation may be a potential link
between the two entities, we were not able to demonstrate
differences in CRP levels between the groups.

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 DES, PTSD, and Depression in Older Male Veterans IOVS j May 2013 j Vol. 54 j No. 5 j 3670

TABLE 3. Multivariable Logistic Regression Evaluating Factors Predictive of the Presence of Severe Dry Eye Symptoms (Defined as a Dry Eye
Questionnaire 5 Score ‡ 12)

Variable OR 95% CI P Value

Age, y 0.99 0.96–1.03 0.75

Race
Black/white 1.02 0.46–2.24 0.97
Other/white 2.56 0.39–17.06 0.33
Ethnicity
Non-Hispanic/Hispanic 0.80 0.38–1.68 0.56
Smoking status
Former/never 1.74 0.67–4.57 0.26
Never/current 3.11 1.11–8.75 0.03
Self-reported health status
Good/poor 0.66 0.20–2.18 0.50
Fair/poor 1.76 0.50–6.20 0.38
Excellent/poor 3.37 0.60–18.80 0.17
Antidepressant category
SSRI/none 2.66 1.01–7.00 0.05
Other/none 2.41 0.84–6.89 0.10
Antianxiety category
Benzodiazepine/none 1.67 0.55–5.04 0.36
Other/none 0.67 0.13–3.48 0.63
Psychiatric diagnosis
PTSD/none 4.08 1.10–15.14 0.04
Depression/none 1.16 0.46–2.89 0.76
C-reactive protein 0.94 0.81–1.08 0.37

There are several potential reasons that may explain why
veterans with depression report more dry eye symptoms, but
do not have measurable tear film disturbances greater than
those of veterans without depression. First, it has been well
established that depression and pain often coexist.31 For
example, the Medical Outcomes Study found that patients with
depression tended to have greater bodily pain, worse physical
functioning, and worse perceived current health compared to
patients without depression.31 Similarly, Katon et al. found that
those with depression or anxiety, in addition to a chronic
medical illness, reported significantly higher numbers of
medical symptoms compared to those with a medical illness
only.32 In addition, studies using a variable pressure dolorim-
eter found that individuals who are depressed have the same
pain sensitivity as control subjects but report higher levels of
pain. 33 However, it is important to note that in our
multivariable model, depression did not remain an indepen-
dent predictor of dry eye symptoms.
Depression and PTSD share many similarities, and the above
mechanisms may play a role in the relationship between PTSD
and ocular surface symptoms.11,31–40 However, individuals
with PTSD have unique attributes, such as amplified emotional
reactions and arousal and increased attention when faced with
pain-related or threatening stimuli,11,41 which may lead to an
increased focus on pain, sensitivity to painful stimuli, and
amplification of the pain experience.42,43
In our study, even though we did not find a difference in
CRP levels between the three groups, inflammation is another
potential mechanism that may link PTSD and depression to
DES symptoms. Patients with PTSD and depression are known
to have higher levels of inflammatory markers in the blood,
including increased CD4:CD8 ratios and CRP, Intercellular
Adhesion Molecule 1 (ICAM-1), TNFa, IL-1, and IL-6 lev-
els.13,14,44–46 Patients with DES have been shown to have
elevated levels of these markers in the tears and conjunctivae,
including infiltration of CD4þ lymphocytes into the conjunc-
tival epithelium15–17 and increased levels of IL-1b, IL-2, IL-6, IL-
8, IFN-c, and TNF-a in the tears and conjunctival epitheli-
um.47–51 It is not known, however, whether a higher burden of
systemic inflammatory cells and soluble mediators translate
into higher symptoms on the ocular surface. Given our
negative findings regarding CRP levels, futures studies can
consider exploring other proteins such as IL-1b or IL-6 as
potential links between DES and mental illness.
Consistent with prior studies, SSRI use was significantly
associated with DES.10,52 The association between antidepres-
sants and ocular discomfort is not clear, but there are a few
potential explanations. The anticholinergic side effects of
antidepressants, especially SSRIs, have long been acknowl-
edged to exert ocular reactions, including dry eye symp-
toms.10,53–56 In addition, serotonin receptors have been
identified in the corneal and conjunctival epithelium,17,57 and
serotonin has been previously isolated from human tears.58 It is
possible that altered levels of serotonin due to antidepressant
treatment can affect the sensitivity thresholds of corneal
nerves, given that serotonin has been found to the affect the
sensitivity, threshold, and function of peripheral nerves.59,60
Inconsistent with previous cross-sectional epidemiologic
studies, we found that participants who had never smoked
reported more dry eye symptoms compared to current
smokers.61–63 However, two longitudinal incidence studies
found no association between smoking and DES,52,64 whereas
one prospective case series found that smokers had more
damage to their lipid layer of precorneal tear film compared to
nonsmokers.65 Therefore, it is possible that temporality issues
intrinsic to cross-sectional designs, including the present study,

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 DES, PTSD, and Depression in Older Male Veterans
may play a role in the conflicting results. However, it is also
possible that nonsmokers are more health conscious, thus may
be more aware of or more prone to report physical health
symptoms. Future studies should utilize prospective studies
and objective measurements, such as cotinine, to validate self-
reported smoking status.
A major limitation of this study is that we did not use
clinical interviews or other validated dimensional measures to
categorize patients as having depression or PTSD, but instead
relied upon documentation of these conditions in the medical
record via ICD-9 codes. Due to the nature of this retrospective
chart review, it is uncertain whether these diagnoses originally
came from a clinician (e.g., psychiatrist) interview or a
standardized measure. Future studies should use validated
measures to assess for current mental illness. Similarly, as
pharmacy information was collected retrospectively, we did
not have detailed information about the length of time on
medication to examine its dose–response effects on DES
symptoms. Because we grouped patients who were taking
psychotropic medications due to small sample sizes, we were
unable to examine the effects of medications besides SSRIs and
benzodiazepines on dry eye symptoms. Furthermore, the
stability of the DES measurements could not be assessed in
this study, as tear film indicators obtained by clinical
examination were measured at only one time point.
Despite these limitations, this is the first study to confirm
that while a symptom-based DES diagnosis was more prevalent
in veterans with PTSD and depression seen in an eye clinic,
clinical tear film measurements were not notably different from
those without these diagnoses. This suggests that the etiology
of DES symptoms extends beyond tear dysfunction. Since
ocular discomfort is the main cause of DES morbidity, future
studies using validated metrics for systemic abnormalities are
needed to examine additional factors that drive ocular pain
(e.g., local and/or systemic nerve dysfunction). This informa-
tion may provide new directions in the evaluation and
treatment of DES. In the meantime, given the known morbidity
of DES symptoms with respect to physical and mental well-
being, the presence of ocular surface discomfort should be
evaluated in veterans with depression and PTSD. This is
especially warranted due to the new influx of veterans
returning from the war in Afghanistan, the Middle East, and
elsewhere.
Acknowledgments
We thank Bozorgmehr Pouyeh, Gail Lewis, and Ashley Katsikos for
their assistance with the implementation of this study.
Supported by a grant from the Veterans Affairs Medical Center
(AG) and with unrestricted funds from Research to Prevent
Blindness, New York, New York.
Disclosure: C.A. Fernandez, None; A. Galor, None; K.L.
Arheart, None; D.L. Musselman, None; V.D. Venincasa, None;
H.J. Florez, None; D.J. Lee, None
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