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Under Diagnosis of Floppy Eyelid Syndrome in Patients with Obstructive Sleep Apnea
Charles Bouchard MD, Sarah Maki, Bruce Gaynes OD PharmD, Ron Price, Dan Valdez, Nidhi Undevia MD
Loyola University Chicago Stritch School of Medicine
Introduction
Floppy Eyelid Syndrome (FES) is an underdiagnosed condition
characterized by an extreme laxity of the upper eyelids causing
eversion upon minimal mechanical manipulation, and chronic
papillary conjunctivitis. Other clinical findings in FES include eyelash
ptosis, aponeurotic blepharoptosis, and chronic corneal lesions. The
pathophysiology of FES is unknown, but studies have shown an
increase in matrix metalloproteinases, a decrease in elastic fibers,
and nonspecific signs of chronic inflammation4. FES is also known
to be associated with other ocular surface diseases such as
keratoconus, and the systemic diseases obesity and obstructive
sleep apnea-hypopnea syndrome (OSAHS)2.
Although many
believe FES is underdiagnosed in patients with OSAHS, a
quantitative analysis of the underdiagnosis of FES in OSAHS has
yet to be explored. This study aimed to determine the level of
underdiagnosis of FES in patients with OSAHS using historical
control values from the literature for comparison. The incidence of
Floppy Eyelid Syndrome in patients with OSAHS has been reported
by Fowler et al3 as 40%, and Chambe et al as 26-40% depending on
OSAHS severity1. Furthermore, other ocular surface diseases in
patients with OSAHS may serve to mask the true diagnosis of FES
within this population. This study aimed to investigate the degree to
which OSAHS is associated with other ocular surface diseases.
Lastly systemic diagnoses associated with OSAHS were studied to
determine which held the strongest associations with OSAHS.
Methods
Results
Results
Results
Systemic Disease Associations with OSAHS (Table 3)
Ocular Disease Association with OSAHS (Table 2)
Disease
Incidence at Loyola in Last 5
Yrs
Association with OSAHS
Odds Ratio
P value
Blepharitis
5333 pts
4.214
<0.0001
Borderline Glaucoma
6330 pts
4.127
<0.0001
Conjunctivitis in
Mucocutaneous Disease
50 pts
0.9384
0.9400
Corticosteroid- Induced
Glaucoma
73 pts
3.781
0.0007
Of the 562,585 patients from January 1st, 2007 to June 30th 2013,
Disorders of Optic Chiasm
10 pts
9.197
0.0005
11,975 had a diagnosis of OSAHS, 607 patients had a diagnosis of other
Disorders of Visual Cortex
59 pts
4.678
<0.0001
disorders of the eyelid and 445 had a diagnosis of unspecified
Glaucoma Associated with
109 pts
5.489
<0.0001
inflammation of the eyelid. The latter two diagnoses are used to code FES
Congenital Anomalies and
Systemic Syndromes
at this institution. This study confirmed an association of Keratoconus with
OSAHS OR = 3.556 (p<0.0001). This is consistent with previously
Glaucoma Associated with
106 pts
2.169
0.0828
Disorders of the Lens
published reports. Additionally, other ocular diseases were found to be
Glaucoma Associated with
352 pts
2.222
0.0001
associated with OSAHS. All ocular diseases studied with were found to be
Other Ocular Disorders
associated with OSAHS to a statistically significant degree with the
Glaucoma Stage
192 pts
3.836
<0.0001
exception of conjunctivitis of mucocutaneous disease, glaucoma
Open-Angle Glaucoma
2408 pts
3.436
<0.0001
associated with disorders of the lens, and unspecified disorders of optic
Optic Atrophy
804 pts
3.329
<0.0001
nerve and visual pathways, suggesting that various ocular diseases within
Optic Neuritis
353 pts
2.734
<0.0001
this population are more prevalent than previously thought. The various
Other Disorders of Optic
196 pts
3.757
<0.0001
Ocular diseases studied are listed in Table 2.
Disc
The strongest correlation of ocular disease with OSAHS was FES. The
Other Disorders of Optic
708 pts
3.126
<0.0001
association of OSAHS with FES amongst patients examined within the
Nerve
Ophthalmology clinic within the last 5 years was determined with an
Other Specified Forms of
79 pts
2.911
0.0152
OR=26.976 (P<0.0001). In comparison to historical controls, which
Glaucoma
determined a 20-40% incidence of FES in OSAHS, it was found that at
Keratoconus
251 pts
3.556
<0.0001
Loyola University Medical Center the incidence of FES among OSAHS
Papilledema
218 pts
3.801
<0.0001
patients seen in the Ophthalmology clinic was 4.33%.
Primary Angle-Closure
208 pts
2.654
0.0006
This drastic deviation from historical controls was illustrated with
Glaucoma
repeated examination of the OSAHS population, average number of
Unspecified Disorders of
25 pts
3.679
0.0574
Optic Nerve and Visual
examinations per patient= 6.116, and is consistent with published reports
Pathways
of underdiagnosis of FES in this patient population. Our study illustrated
Unspecified Glaucoma
2175 pts
4.503
<0.0001
that amongst one of the most highly associated ocular diagnosis in OSAHS
Other Causes of
124 pts
3.6
0.0003
was dry eye from tear film insufficiency OR=4.557. This finding suggests
Conjunctivitis
that FES underdiagnosis may originate from common misdiagnosis of FES
Rosacea Conjunctivitis
436 pts
4.148
<0.0001
as dry eye due to tear film insufficiency. This problem may arise due to the
Tear Film Insufficiency
4815 pts
4.557
<0.0001
similarity in symptoms and presentation of patients with either disease.
Further investigation is warranted as to whether underdiagnosis of FES is
All systemic diseases researched were found to be significantly associated with
a result of inability to recognize salient findings of the disease or an OSAHS. In the same cohort of 562, 585 patients, 3,897 patients were diagnosed with
attribution of symptoms to a more common ocular disease such as dry
diabetes mellitus type 1 and 36,185 had diabetes mellitus type 2 with OR of 5.194 (p <
eye.
A data mining procedure using ICD-9 codes for the diseases to be
studied were used to search the electronic medical record of 562,585
patients presenting to Loyola Medical Center between January 1,
2007 and June 30th 2013. The data was compiled and analysis was
preformed using a two tailed Chi squared data analysis5, alpha=0.05.
Associations with OSAHS were determined using odds ratios to
compare the incidence of each disease in patients with OSAHS
compared to the incidence of the disease in the general population.
Each systemic and ocular surface disease had one or several ICD-9
codes associated with it in the medical record which were used to
determine incidence. Notably, FES did not have a specific recognized
ICD-9 code. Therefore, the codes for unspecified inflammation of the
eyelid and other disorders of the eyelid were used to confer this
diagnosis.
Diagnosis of FES in OSAHS Patients Examined in Ophthalmology
Specifically, in order to assess the true level of under diagnosis of
Clinic (Table 1)
FES, the OSAHS population was reduced to those who had been
Incidence of
Association of OSAHS
examined in an Ophthalmology clinic in this time frame, using Incidence of
OSAHS at
OSAHS patients
and FES in OSAHS
Avg Number of
established clinic codes.
Loyola in Last
Examined in
pts Examined in
P Value
Ophthalmology
5 Yrs
Ophthalmology
Ophthalmology Clinic
Visits per Patient
From the literature the historical incidence of FES among patients
Clinic in Last 5 Yrs
Odds Ratio
with OSAHS served as a control for determining the rate of
2587 pts
26.976
<0.0001
6.116
underdiagnosis of FES at LUMC in the OSAHS population. Data 11975 pts
obtained from this retrospective review was compared to historical
Corresponding author: [email protected]
control values found in the literature.
The support of the Richard A Perritt Charitable Foundation is acknowledged
0. 0001) and 8.115 (p < 0.001) respectively. Essential HTN was found to have a high
correlation OR = 9.391 (P < 0.0001). Consistent with well documented reports, obesity
held the highest association with OSAHS, OR = 20.21 (p<0.0001). Sicca syndrome, a
consequence of Sjogrens syndrome, also was found to be correlated OR= 3.182
(P<.00001). Rosacea was found to be correlated as well OR=3.812 (P<0.0001), but to a
lesser extent. Lastly, complications of transplant, both solid organ and bone marrow
were found to be associated with OSAHS. Our results showed that systemic diseases
such as diabetes type 1 and 2, hypertension, and obesity carried the strongest
associations with OSAHS. This is consistent with previously published knowledge on
the association of OSAHS with obese patients who often share hypertension and
diabetes as comorbidities. The association with diabetes type 1 prompts additional
investigation on this association.
Disease
Incidence at Loyola
in Last 5 Yrs
Association with
OSAHS Odds Ratio
P Value
Benign Intracranial
HTN
409
3.266
<0.0001
Complication of
Bone Marrow
Transplant
561 pts
1.701
0.0183
Complication of
Transplanted
Organ
277 pts
6.667
<0.0001
DM Type 1
3897 pts
5.194
<.0001
DM Type 2
36,185 pts
8.115
<0.0001
Essential HTN
89,156 pts
9.391
<0.0001
Obesity
29,293 pts
20.21
<0.0001
Rosacea
3,274 pts
3.812
<0.0001
Sicca Syndrome
728 pts
3.182
<0.0001
Conclusion
1. Not surprisingly the strongest association between OSAHS and
systemic disease belonged to obesity. Other comorbidities associated
with obesity were also found to be correlated highly with OSAHS.
2. OSAHS was determined to be statistically significantly associated with
all ocular surface diseases studied excluding Conjunctivitis of
Mucocutaneous Disease, Glaucoma Associated with Disorders of the
Lens, and Unspecified Disorders of Optic Nerve and Visual Pathways.
3. The strongest ocular disease association belonged to FES OR=26.976.
4. This study confirmed a high level of underdiagnosis of FES, 4.33%, in
patients with OSAHS when compared to established historical values,
20-40%. This level of under diagnosis was illustrated even with
repeated
Ophthalmology
clinic
visitation;
average
number
Ophthalmology clinic visits per patient= 6.116.
5. Our data prompts further investigation of the relationship of FES to
OSAHS and the true cause of underdiagnosis. These future studies will
work to increase awareness of FES among ocular physicians, gain
further understanding of common pathophysiology which link these two
disease entities, and improve the quality of ocular care in this growing
patient population.
References
1. Chambe J. Laib S. Hubbard J. Erhardt C. Ruppert E. Schroder C. Malan A. Bourcier T.
Bourgin P.: Floppy eyelid syndrome is associated with obstructive sleep apnea: a prospective
study on 127 patients. Journal of Sleep Research. 21(3):308-15, 2012 Jun.
2. Ezra, Daniel G., Michèle Beaconsfield, Mano Sira, Catey Bunce, Richard Wormald, and
Richard Collin. "The Associations Of Floppy Eyelid Syndrome: A Case Control Study."
Ophthalmology 117.4 (2010): 831-838. Print.
3. Fowler, Amy M., and Jonathan J. Dutton. "Floppy Eyelid Syndrome As A Subset Of Lax
Eyelid Conditions: Relationships And Clinical Relevance (an ASOPRS Thesis)." Ophthalmic
Plastic & Reconstructive Surgery 26.3 (2010): 195-204. Print.
4. Schlotzer-Schrehardt, U, M Stojkovic, C Hofmannrummelt, C Cursiefen, F Kruse, and L
Holbach. "The Pathogenesis Of Floppy Eyelid Syndrome Involvement Of Matrix
Metalloproteinases In Elastic Fiber Degradation." Ophthalmology 112.4 (2005): 694-704.
Print.
5. GraphPad Prism version 5.00 for Windows, GraphPad Software, San Diego California USA