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Clinical science
The relationship between floppy eyelid syndrome and obstructive sleep apnoea
  1. MªJesús Muniesa1,2,
  2. Valentín Huerva1,2,
  3. Manuel Sánchez-de-la-Torre2,3,
  4. Montserrat Martínez2,3,
  5. Carmen Jurjo1,2,
  6. Ferran Barbé2,3
  1. 1Ophthalmology Department, Hospital Universitari Arnau de Vilanova, Lleida, Spain
  2. 2Institut de Recerca Biomèdica de Lleida, Lleida, Spain
  3. 3Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), Madrid, Spain
  1. Correspondence to MªJesús Muniesa Royo, Department of Ophthalmology, Hospital Universitari Arnau de Vilanova, Avenue Alcalde Rovira Roure,  Lleida 80 25198, Spain; mariajesus.muniesa{at}gmail.com

Abstract

Purpose To determine the prevalence of eyelid hyperlaxity and floppy eyelid syndrome (FES) in obstructive sleep apnoea (OSA), and the presence of OSA in FES.

Participants One-hundred and fourteen patients who had been consecutively admitted for OSA evaluation and 45 patients with FES in which sleep studies were recorded.

Methods Subjects underwent eyelid laxity measurement, slit-lamp examination and polysomnography.

Results Eighty-nine patients were diagnosed of OSA. Fourteen patients with OSA had FES (16%) and 54/89 (60.67%) had eyelid hyperlaxity. Two of the 25 non-OSA patients had FES (8%) and 8 of 25 (32%) had eyelid hyperlaxity. There was a significantly higher incidence of eyelid hyperlaxity in OSA than in non-OSA patients (p=0.004). Thirty-eight of the 45 patients with FES were diagnosed of OSA (85%) and 65% had severe OSA.

Conclusions OSA might be an independent risk factor for eyelid hyperlaxity and severe OSA is common in patients with FES.

  • Eye Lids

https://doi.org/10.1136/bjophthalmol-2012-303051

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    Introduction

    Floppy eyelid syndrome (FES) is an often underdiagnosed disorder of unknown pathogenesis that is characterised by lax upper eyelids that are easily distorted and everted with minimal traction, a soft and foldable tarsus, and chronic papillary conjunctivitis of the upper palpebral conjunctiva.1 ,2 Since the initial description by Culbertson and Ostler in 1981,1 one of the most consistently reported associations with FES is that of obstructive sleep apnoea (OSA).3 ,4 OSA is characterised by recurrent, complete or partial, upper airway obstructions during sleep and it is usually diagnosed by overnight polysomnography.5 OSA is associated with a high incidence of cardiovascular and neurovascular diseases.6 Woog was the first to specifically identify this important association between FES and OSA in three patients in 1990.7 The prevalence of FES in the OSA population varies from 2%8 ,9 to 32%4 according to the reported series. A few investigations have raised the question of the frequency of OSA in patients with FES.3 ,10 As FES and OSA are independently associated with obesity, male sex and increasing age, it is unclear whether OSA and FES are causally associated, whether they merely share common risk factors or whether they have a common pathophysiological cause.

    The aim of this study was to establish the relationship between these two entities. The primary objective was to determine the prevalence of FES and eyelid hyperlaxity in a group of patients referred for suspected OSA. The second objective was to determine the presence of OSA in patients who had been previously diagnosed with FES in the oculoplastic unit.

    Material and methods

    Subjects

    The time period for patient inclusion was from September 2008 to January 2011. For the first objective, we included 114 patients consecutively admitted for OSA evaluation at the Arnau de Vilanova University Hospital and the Santa Maria Hospital, Lleida, Spain, who agreed to undergo an ophthalmologic examination. For the second objective, 45 patients with diagnosed FES made by an oculoplastic consultant (MJM), were subjected to overnight polysomnography to detect OSA. The protocol and informed consent were approved by the Ethics Committee of our hospital. All the subjects authorised the use and disclosure of protected health information. Patients who had undergone any type of surgical procedure to their eyelids or who had suffered from any type of ocular trauma or abnormality that could have affected their eyelid functions were excluded from the study.

    Medical and ophthalmic examination

    All subjects underwent a full medical and ophthalmic history. The slit-lamp examinations and lid laxity assessments were performed by the same ophthalmologist (MJM), who was blind to the results of sleep study. The ophthalmological examination included visual acuity, slit-lamp examination with anterior segment analysis and ophthalmoscopy. Eyelid examination was conducted specifically to evaluate eyelid laxity and obtain an FES diagnosis. Horizontal distraction from the globe was assessed as described by Iyengar and Khan11and measured in millimetres. We used this simple method of quantifying lid laxity using a ruler to measure the horizontal distraction of the lid from the globe. Lid distraction >5 mm for upper lids and >6 mm for lower lids was considered as significant and indicative of increased laxity.12 The results were dichotomised for the purpose of analysis as increased laxity were present or absent. In the absence of standardised evaluation, we chose consensus criteria upon which to score the laxity in three groups: group 1 was normal laxity; group 2: asymptomatic eyelid hyperlaxity. Patients were defined as having eyelid hyperlaxity if either lid was graded positive for increase in laxity8; and group 3: FES defined as easily evertible lids and papillary conjunctivitis in the same upper eyelid, which is the clinical definition of FES.1 Different grades of FES were included in this group. Easy lid eversion was characterised by elastic upper lids that became easily distorted and everted with minimal superolateral traction.9 ,10

    Sleep studies

    Diagnosis of OSA was reached on the basis of either conventional polysomnography or of a cardio-respiratory sleep study. All the sleep studies were analysed manually at each participating centre using standard criteria.13 The sleep score was performed by technicians not involved in the study. The polysomnographies included continuous recording of neurological variables: EEG (C3/A2 and C4/A1), electro-oculogram and electromyogram. Breathing variables were scored according to the flow tracing provided by a nasal cannula and thermistor. Thoraco-abdominal motion was measured with thoracic and abdominal bands. Oxygen saturation was recorded with a finger-pulse oximeter. The cardio-respiratory sleep study included, at the minimum, continuous recording from the nasal cannula, thoraco-abdominal motion, oxygen saturation and body position. Apnoea was defined as an absence of airflow for at least 10 s and hypopnoea was defined as a clear (50%) airflow reduction for at least 10 s, with a drop in oxygen saturation of at least 4% or an arousal. OSAs were defined as the absence of airflow in the presence of chest or abdominal wall motion. The apnoea–hypopnoea index (AHI) was calculated according to the average number of episodes of apnoea plus hypopnoea per hour of sleep or recording time. OSA was excluded when the AHI was AHI<10−1. OSA severity was scored as mild when the AHI was between 10 and 20 h−1<20, moderate when it was between 20 and 30−1, and severe when the AHI>30−1.13

    Statistical analysis

    Continuous variables were reported as the mean±SD, and the IQR using the Wilcoxon rank sum test. Categorical variables were reported as percentages and were compared using the χ2 or Fisher exact test. CIs for the proportion of patients with FES in the OSA group and OSA in the FES group were based on an exact binomial test. The association between eyelid hyperlaxity and OSA was evaluated by logistical regression. A p value of <0.05 was considered statistically significant. Age- and body mass index (BMI)-adjusted models were also estimated.

    Results

    One hundred and fourteen patients were consecutively admitted for OSA evaluation by polysomnography or cardio-respiratory sleep study. A categorisation of these patients based on reported clinical findings is presented in table 1. Eighty-nine patients were diagnosed with OSA (78%) and 25 of 114 patients were considered non-OSA patients or controls (22%). As expected, subjects with OSA were significantly older and had a higher BMI than control patients but there was no significant difference in gender and other medical conditions. Among the patients with OSA, 9/89 had mild OSA (10.1%), 24/89 had moderate OSA (26.9%) and 56/89 had severe OSA (62.9%). Fourteen patients (16%) diagnosed with OSA had FES. Eleven of 14 patients with FES (78.57%) had severe OSA, 2 patients had moderate OSA and 1 patient had mild OSA. The percentage of FES in patients with severe OSA reached 20%. Two of the 25 non-OSA patients were diagnosed with FES (8%). The difference of prevalence of FES in OSA patients (16%) and in non-OSA patients (8%) was not statistically significant. None of the FES patients had experienced spontaneous lid eversion when sleeping. The findings of these patients with FES are presented in table 2.

    View this table:
    Table 1

    Categorisation of patients admitted for OSA evaluation, based on reported clinical findings

    View this table:
    Table 2

    Data of patients admitted for OSA evaluation with floppy eyelid syndrome

    Eyelid hyperlaxity was observed in 60.67% (54/89) of the patients with OSA, and in 32% (8/25) of the non-OSA patients (p=0.0125). This significance remained when adjusted for age and BMI (3.06, 95% CI 1.04 to 9.78, p=0.0474).

    Forty-five patients with diagnosed FES were subjected to overnight polysomnography to detect OSA. A categorisation of these patients based on reported clinical findings can be seen in table 3. Thirty-eight of the 45 patients (84.4%) with FES were diagnosed with OSA. Mild OSA was diagnosed in 8% (3/38) of these patients with FES, moderate OSA in 26.3% (10/38) and severe OSA in 65.7% (25/38).

    View this table:
    Table 3

    Categorisation of FES patients, based on reported clinical findings

    Discussion

    In this study, the incidence of eyelid hyperlaxity was significantly higher in OSA than in non-OSA patients and this significance remained after adjusting for age and BMI. These results suggested that OSA might be an independent risk factor for eyelid hyperlaxity. However, the prevalence of FES in OSA patients was not significant, although the prevalence of FES between patients with severe OSA reached 20%. To the best of our knowledge, this study is the largest cohort of FES patients (n=45) used to detect OSA diagnosed by polysomnography, the international criteria for OSA diagnosis.14 Among patients with FES, the prevalence of OSA reached 85% and most of them had severe OSA. This prevalence contrasts with the prevalence of OSA in the general population estimated to be 2% to 5% in middle-aged populations,15 and with the prevalence of OSA in obese population, estimated at 40%.16 Therefore, this association between OSA and FES appears not to represent an epiphenomenon only. McNab3 reported a cumulative series of 50 FES patients of whom 48 (96%) had a history of sleep disturbed breathing, and 26 of the 27 patients undergoing polysomnography were confirmed to have OSA. Ezra et al10 studied OSA in 102 patients with FES using the Epworth daytime somnolence score, which is a method not considered valid for OSA diagnosis.

    The reported prevalence of FES in OSA varies in different studies. The range of reported rates of FES prevalence (2.3–32%) includes studies by Robert et al,8 1/46, 2.2%; Karger et al,9 1/44, 2.3%; McNab,3 3/20, 15%; Kadyan et al,12 28/89, 31.5%.%; Mojon et al,4 14/44, 32%; and Chambe et al,17 23/89, 25.8%. A consensus has clearly not been reached. Kadyan et al12 used only oximetry, which is a method not considered valid for OSA diagnosis,14 McNab et al3 had a very low patient sample size and Monjon et al4 lacked any adjustment for age or BMI. Karger et al9 used polysomnography for OSA diagnosis and showed an association between subjectively easy eversion and OSA when they studied 15 non-OSA patients and 44 OSA patients, but their findings lost statistical significance when they adjusted for age and BMI. Our results were comparable to the results of a recent study by Chambe et al17 with 89 patients with OSA diagnosed with overnight respiratory polygraphy and 38 non-OSA patients, in which FES prevalence was 15.8% in non-OSA patients and 25.8% in OSA population (not significant), with a significant correlation between OSA severity and FES and eyelid laxity. So, the present study features one of the largest cohort of non-treated OSA patients diagnosed using a method considered valid for OSA diagnosis,14 which has been used to detect FES.

    Our results suggested that OSA could be a subset of lax eyelid conditions and it would appear that once the degree of laxity reaches a certain threshold, patients run the risk of developing FES with inflammatory sequelae of the conjunctiva, cornea and tear film.18 OSA has been suggested as a possible cause for FES in a report that showed that FES could be resolved by simply making use of a continuous positive airway pressure mask.19 There are different aetiological hypotheses about the association between FES and OSA. In their initial report, Culbertson and Ostler proposed that repeated mechanical trauma was the cause of papillary conjunctivitis, but they did not offer any hypothesis to explain the associated elasticity. Netland et al20 were the first to point to abnormalities in elastic fibres, reporting a decrease in the amount of tarsal elastin. However, it still remains unclear whether this depletion of elastic fibres is causative or secondary. Schlotzer-Schrehardt et al21 demonstrated a substantial loss of elastic fibres and ultrastructural abnormalities in residual fibres, together with an increased expression of elastin-degrading enzymes in the tarsus and skin of eyelid specimens from FES patients. These changes in elastic fibres are of particular interest to those who have proposed a link between FES and OSA. It has also been observed that uvula tissue from patients with OSA undergoing uvulopharyngoplasty exhibit a loss of elastic fibres.8 ,20 ,22 These changes could explain how OSA, eyelid hyperlaxity and FES could be different manifestations of the same disease. The finding in our study of a significant association between eyelid hyperlaxity and OSA seems to support this hypothesis. Furthermore, the proposed link between OSA and FES has had quite a strong influence on the ischaemia–reperfusion theory. McNab23 claimed that an association may exist between sleeping posture and pressure on the eye, exacerbated by hypoxia, inducing ischaemia–reperfusion injury. Previous evidence confirmed that an association with sleep has been suggested because FES is commonly more symptomatic on the side the patient is used to sleeping on.24 But this association is not perfect, as we can see in the present study, and this has led to doubts being cast over the mechanical theory.25

    Clinicians should be aware of the association between FES and OSA so that underlying OSA can be detected in FES patients, and the sleep physician may be the first to detect the ocular symptoms of FES in patients with known OSA. This study confirmed that OSA is very common in FES but that FES is not so common among the general OSA population.

    The limitations of this study include possible referral bias in the populations studied. The control group in our study raises the question of whether our data for non-OSA patients are representative of the general population. Several studies12 ,17 had investigated FES prevalence in patients without OSA after these patients were recruited from a sleep unit. Kadyan et al12 showed a FES prevalence of 3.8% (1/26) in non-OSA patients, and Chambe et al17 of 15.8% (6/38). Our study presented a prevalence of 8% (2/25). These studies demonstrate that patients with OSA are significantly older and had increased BMI than patients without OSA; this suggested that our subject sample provided a good reflection of what would be observed in the general population. This could explain why the subjects were not age-matched and BMI-matched with controls.

    In conclusion, eyelid hyperlaxity is associated with OSA, independent of age and BMI, suggesting that OSA might be an independent risk factor for eyelid hyperlaxity. Moreover, FES is strongly associated with OSA. The ophthalmologist may be the first physician to admit these patients for OSA evaluation and this allows the treatment of underlying OSA in patients with FES. This is an important point because OSA has a high association with morbidity and mortality and it is also linked to hypertension, heart failure, stroke and motor vehicle accidents, and in some cases, can even result in death.13 It is important to consider routine screening of newly diagnosed FES patients for symptoms of sleep apnoea such as loud snoring or a history of apnoeic episodes and also to consider referral to a sleep specialist.

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    Footnotes

    • Contributors Arnau de Vilanova Universitary Hospital of Lleida. IRBLLeida (Reserch biomedic Institute of Lleida).

    • Funding Instituto de Salud Carlos III (FIS PS09/02224). Societat Catalana de Pneumologia (SOCAP). Sociedad Española de Neumología y Cirugía torácica (SEPAR). These organisations had no role in the design or conduct of this research.

    • Competing interests None.

    • Patient consent Obtained.

    • Ethics approval Ethics Committee of Arnau de Vilanova Universitary Hospital of Lleida.

    • Provenance and peer review Not commissioned; externally peer reviewed.

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