Journal of Critical Care (2012) 27, 537541

Ventilation

Exposure keratopathy in sedated and ventilated

patients,
Hisham Jammal FRCSEd a,, Yousef Khader PhD b , Wisam Shihadeh MD a ,
Laila Ababneh MBBS a , Ghazal AlJizawi MBBS c , Arqam AlQasem MBBS c
a

Department of Ophthalmology, Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan
Department of Community Medicine, Public Health and Family Medicine, Jordan University of Science and Technology,
Irbid 22110, Jordan
c
Department of Ophthalmology, King Abdullah University Hospital, Irbid, 22110, Jordan
b

Keywords:
Chemosis;
Exposure;
Jordan;
Keratopathy;
Lagophthalmos;
Sedated;
Ventilation

Abstract
Purpose: The purpose of this study is to determine the frequency of exposure keratopathy in sedated/
mechanically ventilated patients in the intensive care unit and its risk factors.
Materials and Methods: This is a prospective cohort study including all patients admitted to an adult
intensive care unit department between March and October 2010 who were sedated and mechanically
ventilated. Patients were examined by an ophthalmologist 1 to 5 days after commencing ventilation and
subsequently every day. Examination included assessment of lid position, conjunctival edema (chemosis),
and corneal changes.
Results: Of the 74 patients included in the study, 57% had exposure keratopathy. Fifty-four percent of
patients developed chemosis, and 31% of patients developed lagophthalmos. Frequency of exposure
keratopathy differed significantly according to degree of chemosis and lagophthalmos (P b .0001);
lagophthalmos was also significantly related to chemosis (P b .0001). For lagophthalmos score of 3, the
odds ratio of association with higher exposure keratopathy score was 136 (95% confidence interval [CI],
14.97-1242.6); for lagophthalmos score of 2, it was 14.4 (95% CI, 2.67-77.2). For any edema, the odds
ratio of association with exposure keratopathy was 5.50 (95% CI, 2.02-15.00).
Conclusion: The frequency of exposure keratopathy in sedated/mechanically ventilated patients is high
with lagophthalmos and chemosis as the main risk factors.
2012 Elsevier Inc. All rights reserved.

1. Introduction

None of the authors has conict of interest with the submission.

No nancial support was received for this submission.
Corresponding author. Tel.: +962 795312811; fax: +962 27200621.
E-mail address: hishamjammal@hotmail.com (H. Jammal).

0883-9441/$ see front matter 2012 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.jcrc.2012.02.005

Exposure keratopathy is a well-recognized clinical entity

and is associated with neuroparalytic disorders, reduced
muscle tone, mechanical eyelid disorders, and abnormalities
of globe position [1]. Sedated patients in the intensive care
unit (ICU) receiving mechanical ventilation are at risk for

538
exposure keratopathy [2-7] and, subsequently, infectious
keratitis [8-12], which can lead to devastating effects on
vision [8,10]. The development of keratopathy has been
linked to many risk factors, such as incomplete eyelid closure
(lagophthalmos) and conjunctival edema (chemosis).
To date, investigations studying the frequency and risk
factors of corneal involvement in ICU patients have
reported variable results in part due to different denitions
of keratopathy and whether patients were mechanically
ventilated. For example, supercial keratopathy was present
in 40% of 50 randomly selected ICU patients of whom
90% were intubated [3]. In comparison, of 143 mechanically ventilated patients whose stay exceeded 1 week, only
20% were found to have ocular disorders, but the frequency
increased with continuous sedation (35%) [4]. In addition,
not all studies have addressed supercial punctuate
keratopathy in the assessment [13]. Early and less severe
forms of exposure such as supercial punctuate keratopathy
have been found to correlate with increased corneal
epithelial permeability [14] and corneal epithelial barrier
dysfunction [15].
This prospective observational study was conducted to
determine the frequency of exposure keratopathy and its
associated factors among sedated patients on mechanical
ventilation not receiving any form of prophylactic eye care.

2. Methods
The study was conducted at the adult ICU of King
Abdullah University Hospital, Jordan, from March 2010 to
October 2010. King Abdullah University Hospital is a
tertiary referral center with an ICU capacity of 12 beds.
All adult patients who had been admitted to the ICU for
mechanical ventilation for at least 24 hours during the study
period and who had no spontaneous blink reex were
included. The total number included in this study was 74. All
patients received intravenous infusion of fentanyl and/or
midazolam according to the level of sedation except 3
patients with head injury and no brain stem reexes who
were not sedated. Patients with known preexisting ocular
conditions, acute ocular, or orbital trauma and those with a
recent admission to the ICU were excluded. Verbal consent
was obtained from the admitting ICU consultant. The
approval of the institutional review board committee was
obtained before study commencement.
Our intent was to examine all patients by an ophthalmologist at least 24 hours after commencement of ventilation and
subsequently every day, although in some patients, this was
longer than 24 hours. The examination included assessment
of lagophthalmos, chemosis, and corneal changes. The
corneal surface was stained with a single drop of sodium
uoresceine and then assessed using a portable slit lamp with
a cobalt blue lter (Kowa SL-14; Kowa Company Ltd,
Tokyo, Japan). Corneal epithelial changes were classied

H. Jammal et al.
according to Mercieca et al [5]: grade 0, no erosion; grade 1,
punctuate epithelial erosions involving the inferior third of
the cornea; grade 2, punctuate epithelial erosions involving
more than the inferior third of the cornea; grade 3,
macroepithelial defects; grade 4, stromal whitening in the
presence of epithelial defect; grade 5, stromal scar; and grade
6, microbial keratitis. A patient was considered to have
exposure keratopathy if any eye had a grade greater than 0.
Chemosis was graded as either no edema (1), edema without
dellen (2), or edema with dellen (3) (modied from Ezra et al
[16]). Lagophthalmos was graded as lids opposed (1),
conjunctiva visible (2), or cornea visible (3) [17].
Daily examination continued until the end of the study,
when one of the following occurred: development of
signicant corneal changes (grades 3-6), extubation, recovery of spontanous blinking, discharge from the unit, or death.
Other data collected included sex, age, indication for
admission, duration of stay (time between admission and
discharge or death), and the outcome of admission (death or
discharge to another unit).
The ICU at our hospital did not have a protocol for eye
care, and an ophthalmologist was normally consulted upon
the nding by the nursing staff of any gross lid or conjunctival abnormality. Therefore, in this study, no ocular
lubrication, taping, or other means of prophylactic measures
were used for any of the patients (ie, no prophylactic eye care
in regard to exposure keratopathy). After data were collected,
a lubricating antibiotic ointment was prescribed by the
examining ophthalmologist.

2.1. Statistical analysis

Descriptive statistics are reported as mean (SD) for
continuous variables and frequencies for categorical factors.
Comparisons between categorical factors were analyzed by 2
and Fisher exact tests and / b for ordinal categories.
Regression analysis was carried out to determine the odds
ratios (ORs) for signicant covariates and factors associated
with the exposure keratopathy score. All statistical analysis
was conducted using PASW 19 (SPSS, Inc, Chicago, Ill), with
a P value of less than .05 considered statistically signicant.

3. Results
A total of 74 sedated and ventilated patients in the ICU
(28 females) were examined by an ophthalmologist. The
mean (SD) of their age was 51.3 (22.0) years (median, 52.5
years). Duration of stay was 12.7 days (SD, 11.28; range,
1-51 days).
Twenty-nine patients (39%) were examined 1 day after
commencement of ventilation; 32 (43%), 2 days after
commencement of ventilation; and the rest (18%), 3 to 5
days after commencement of ventilation. Thirty-eight
patients (51%) died in ICU, and the remainder were
discharged to another unit.

Exposure keratopathy in sedated and ventilated patients

Table 1

Frequency of chemosis and lagophthalmos

Score

Chemosis (%)

Lagophthalmos (%)

1
2
3

34 (46)
35 (47)
5 (7)

51 (69)
7 (9)
16 (22)

Exposure keratopathy score

1

Age (y)
b50
15 (43) 10 (29) 4 (11) 4 (11)
50
17 (44) 7 (18) 11 (28) 1 (2)
Sex
Male
19 (41) 9 (19) 10 (22) 4 (9)
Female
13 (46) 8 (28) 5 (18) 1 (4)
Indication for admission
Cardiopulmonary 9 (43) 6 (28) 4 (19) 1 (5)
CVA
7 (47) 2 (13) 4 (26) 1 (7)
Medical
3 (25) 3 (25) 3 (25) 1 (17)
Neurosurgical
3 (60) 1 (20) 1 (20) 0 (0)
Trauma
10 (48) 5 (24) 3 (14) 1 (5)
Duration of stay (d)
12
16 (35) 11 (24) 12 (26) 4 (9)
N12
16 (57) 6 (21) 3 (11) 1 (4)
Time to examination (d)
1
12 (42) 9 (31) 6 (21) 1 (3)
2
15 (47) 7 (22) 4 (13) 3 (9)
3-5
5 (38) 1 (8)
5 (38) 1 (8)
Outcome
Death
14 (37) 7 (18) 11 (29) 4 (11)
Transfer
18 (50) 10 (28) 4 (11) 1 (3)
Data are expressed as n (%).

Exposure keratopathy score

0

Table 2 Exposure keratopathy scores in relation to patient and

eye factors

Table 3 Exposure keratopathy scores in relation to chemosis

and lagophthalmos
Variable

Thirty-one percent of patients developed lagophthalmos,

whereas 54% of patients had some degree of chemosis
(Table 1). Forty-two patients (57%) had exposure keratopathy (Table 2), although there was no signicant association
of exposure keratopathy in regard to any of the variables
listed in Table 2. No eyes developed infectious keratitis.
However, the frequency of exposure keratopathy differed
signicantly according to degree of chemosis (P = 2.8 10-8)
(Tables 3 and 4). Likewise, the frequency of exposure
keratopathy differed signicantly according to degree of
lagophthalmos (P = 1.1 10-15). Patients with incomplete lid
closure had a much higher frequency of keratopathy than
patients with closed lids (100% vs 37%). In addition, patients
with the cornea visible had much higher exposure keratopathy
scores compared patients in whom only the white of the eye
was visible.
Lagophthalmos was also signicantly related to chemosis
(P = 2.4 10-11). Although lids were opposed in most
patients (97%) with no chemosis, they were only opposed in

Variable

539

4
2 (6)
3 (8)
4 (9)
1 (4)
1 (5)
1 (7)
1 (8)
0 (0)
2 (9)
3 (6)
2 (7)

Chemosis
None
22 (65) 8 (23) 4
Edema without
10 (29) 9 (26) 8
dellen
Edema with dellen
0 (0)
0 (0) 3
Lagophthalmos
Lids opposed
32 (63) 13 (25) 6
White of eye visible 0 (0)
3 (43) 4
Cornea visible
0 (0)
1 (7) 5

(12) 0 (0) 0 (0)

(23) 5 (14) 3 (8)
(60) 0 (0)

2 (40)

(12) 0 (0) 0 (0)

(57) 0 (0) 0 (0)
(31) 5 (31) 5 (31)

Data are expressed as n (%).

45% of patients who had chemosis (Table 4). The cornea was
visible in 40% of patients with chemosis and in none of those
with no chemosis. There was also a high correlation between
the 2 variables (0.60-0.96) depending on how the correlation
was calculated.
For a lagophthalmos score of 3 (cornea visible), the OR of
association with higher exposure keratopathy score was 136
(95% condence interval [CI], 14.97-1242.6; P = .000013);
for a lagophthalmos score of 2 (white of eye visible), the OR
was 14.4 (95% CI, 2.67-77.2; P = .002) (lagophthalmos
score of 1 was used as reference). For any degree of
chemosis, the OR of association with exposure keratopathy
was 5.50 (95% CI, 2.02-15.00; P = .001).

4. Discussion
In this study, exposure keratopathy occurred in 57% of
patients. In previous prospective studies in which patients
did not receive prophylactic eye care, the rate of exposure
keratopathy ranged from 37.5% to 50% (Table 5). This
nding stresses the fact that exposure keratopathy is still
underappreciated in ICU patients. This is the highest rate of
exposure keratopathy reported in the literature to the
authors' knowledge.
Of the risk factors assessed, keratopathy was signicantly
associated with lagophthalmos and chemosis, both of which

Table 4 Cross-tabulation severity of chemosis and

lagophthalmos

1 (3)
3 (9)
1 (8)

Lagophthalmos

2 (5)
3 (8)

Lids opposed
White of eye visible
Cornea visible

Chemosis
None

Edema without
dellen

Edema with
dellen

33 (65)
1 (14)
0 (0)

18 (35)
6 (86)
11 (69)

0 (0)
0 (0)
5 (31)

540

H. Jammal et al.

Table 5 The frequency of exposure keratopathy in previous

prospective studies in which patients did not receive
prophylactic eye care
Study

No. of Study
Exposure
keratopathy patients population
enrolled
(%)

Hernandez and Mannis,

1997 [3]
Mercieca et al, 1999 [5]
Ezra et al, 2005 [13]
McHugh et al, 2008 [6]

40%

50

42%
54%
37.5%

26
24
18

United
States
UK
UK
UK

were highly correlated with each other. Lagophthalmos has

been reported as a main risk factor in previous studies [4-6]. In
particular, we found that corneal involvement was more
severe when the lagophthalmos was higher. Nevertheless,
keratopathy occurred in 37% of patients with no lagophthalmos, indicating that other risk factors might be involved, such
as low Glasgow Coma Scale, signicant metabolic derangement [3], and multisystem failure [4]. In some patients, a small
degree of lagophthalmos can be missed [2]; therefore, it is
crucial to carefully asses the degree of eyelid closure.
Exposure keratopathy was also associated with chemosis, and corneal involvement was more severe when chemosis was worse. Keratopathy was still present in 35% of
patients who did not have chemosis, but all those patients
exhibited lagophthalmos.
The study showed a relationship between chemosis and
lagophthalmos, a nding that has not been described in
previous studies. Most likely, chemosis in these patients
develops from uid imbalance and positive pressure
ventilation, and although it is known that the development
of lagophthalmos is due to sedation and paralysis, there may
be a contribution from chemosis due to mechanical interference with lid closure.
Our study did not demonstrate any signicant association between keratopathy and the outcome of admission in
terms of survival. Previous studies [3,4] demonstrated the
association between keratopathy and more severe critical
illness but not the nal outcome of patient admission.
Intensive care unit patients can develop severe illness and
survive, or they may die early in the course of admission
depending on the cause.
Several protection mechanisms of the ocular surface exist.
The tear lm is essential in maintaining a normal functioning
ocular surface through various mechanical and chemical
processes [18]. Eyelid blinking serves to spread tears over
the ocular surface, thereby reducing tear evaporation. Eyelid
closure during sleep also reduces tear evaporation and
protects the corneal epithelium from mechanical insults as
well as from microorganisms. During sleep, eyelid closure is
maintained by active contraction of the orbicularis oculi.
Patients undergoing mechanical ventilation with sedation
in ICUs are exposed to a variety of factors, which predispose

to the development of exposure keratopathy. Heavy sedation

impairs blinking reex and orbicularis contraction leading to
incomplete lid closure, increased tear evaporation, and exposure of the corneal surface.
Positive end-expiratory ventilation [19] and increased
vascular permeability [4] have been implicated in causing
conjunctival edema and, subsequently, impaired eyelid
closure. With excessive tear evaporation, many of the protective tear functions are lost, and the corneal epithelium
becomes desiccated and compromised. Epithelial defects
nally develop and predispose to bacterial infections. Few
bacteria can penetrate an apparently normal corneal epithelium, making infectious keratitis a devastating complication in such patients. Corneal perforation can occur, and
treatment with therapeutic penetrating keratoplasty carries less
favorable prognosis than optical corneal grafting [20]. The
source of infection is usually from tracheal secretions splashed
onto the eye during tracheal suction [8,9]. No previous studies
have estimated the true frequency of keratitis, and only case
reports have been published about such cases [9-11]. In our
prospective study, patients were started on lubricating antibiotic eye ointment for epithelial defects, which would, subsequently, reduce the rate of keratitis and might explain why
none of our patients developed bacterial keratitis. It is also
possible that, with implementation of more careful tracheal
suctioning, to avoid contamination of the cornea with
respiratory pathogens, keratitis has become less observed in
ICU patients.
Intensive care unit patients, who suffer from a critical
illness, are vulnerable to ocular morbidity due to other
factors not relating directly to corneal exposure. Ocular
examination, if neglected or carried out quickly, may miss
important signs that can help in the diagnosis, management
of the patient, and avoidance of long-term visual complications. Furthermore, regularly prescribed ophthalmic medications, such as antiglaucoma drops, may be forgotten to be
prescribed by the admitting physician in the context of an
acute admission to the ICU.
Several studies have been reported that compare different
methods of eye protection in ICU patients [16,21-24] or
describe algorithms to follow in the ICU [17,25], but it
appears that such protocols are not always followed [25] in
many units, including our ICU.
Exposure keratopathy and subsequent complications
should be further highlighted and stressed to ICU physicians
and nursing staff. The staff should be trained to carefully
assess the ocular surface. McHugh et al [6] found that ICU
physicians can screen for exposure keratopathy using only a
penlight and a blue lter with reasonable sensitivity and
specicity. Training should also include the use of proven
measures to prevent exposure keratopathy. A recent metaanalysis [26] showed that moisture chambers and lubricating
ointments are simple and efcient methods for the prevention
of exposure keratopathy in ICU patients. We recommend
that staff should promptly report critical signs such as a large
epithelial defect, a white patch on the cornea, or a severely

Exposure keratopathy in sedated and ventilated patients

congested eye, as all these signs might indicate that infective
keratitis is present.
There are some limitations to our study. Patients with
previous ocular problems were excluded based on the
absence of such history in the medical record. Such
previously unidentied problems, especially ocular surface
disease and dryness, could be present and account for some
of the positive ndings. Surviving patients were not followed
up in our study after they were transferred to the ward. Doing
this would have revealed information on the progress and
outcome of ocular problems. Despite the fact that no patients
developed keratitis, no long-term follow-up for visual
impairment was carried out to nd out the total burden of
the problem of exposure keratopathy in those patients.
Several factors were not tested in our analysis (eg, depth of
sedation), and there was likely some ination of the ORs in
the ordinal regression due to the nature of the data.
In conclusion, exposure keratopathy in sedated and mechanically ventilated patients continues to occur at a signicant
rate. The main risk factors were lagophthalmos and chemosis.
Lagophthalmos was also found to be highly correlated to
chemosis. Protocols on proper eye care in the ICU exist, but in
many units, they are not followed. Further follow-up is needed
to document long-term corneal complications.

Appendix A. Supplementary data

Supplementary data to this article can be found online at
http://dx.doi.org/10.1016/j.jcrc.2012.02.005.

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