Obstructive Sleep Apnea and Floppy Eyelid Syndrome: An Eye Opener

INTRODUCTION

Obstructive sleep apnea (OSA) is characterized by periodic, partial, or complete obstruction in the upper airway during sleep resulting in intermittent hypoxia and hypercapnea which further triggers repetitive arousal from sleep in order to reestablish airway patency.¹ Our understanding of the pathophysiology and clinical implications of OSA has come a long way since its discovery in 1965.¹ A meta-analysis by Franklin and Lindberg² inferred that the prevalence of OSA is about 22% (4-50%) and has been increasing over the years due to improved diagnostic modalities and changes in the criteria and grading of severity of the illness. The diagnosis of OSA is ascertained by polysomnography which aims at identifying nocturnal obstructive events and the subsequent changes in blood oxygen. The severity of OSA is primarily based on apnea-hypopnea index (AHI), calculated as the number of obstructive events per hour of sleep.¹ Treatment modalities for OSA include lifestyle modifications, positive airway pressure (PAP) therapy, oral appliances, and palate-pharyngeal surgeries. OSA is noted to be frequently associated with various other diseases.³ Most commonly observed associations comprise of cardiovascular diseases like systemic hypertension, coronary artery disease, arrhythmias, and ischemic stroke; respiratory diseases, such as chronic obstructive pulmonary disease (COPD) and bronchial asthma; metabolic disorders including diabetes mellitus, dyslipidemia, gout, and obesity; gastrointestinal disorders (gastroesophageal reflux disorders and chronic liver disease); psychiatric disturbances including depression, anxiety, and insomnia; and ophthalmologic conditions like glaucoma, floppy eyelid syndrome (FES), and keratoconus.^2-5

Recent studies have suggested that OSA can be suspected based on presence of ocular disorers.⁶ First discovered in 1981, FES is one such ophthalmic disorder which has been found to be associated with OSA. FES is characterized by lax upper eyelids that evert effortlessly on elevation, a soft and foldable tarsus, and a chronic papillary reaction (conjunctivitis) of the upper palpebral conjunctiva.⁶ There is growing literature to suggest that OSA is the most frequently associated systemic disease with FES. Various theories have been put forward to explain the underlying pathophysiology linking the two disorders, like repeated mechanical trauma due to pressure from sleeping on one side and chronic inflammation attributed to hypoxia further exacerbated by reperfusion injury causing connective tissue weakness.⁷

Studies have been conducted to look into the prevalence of OSA in FES and vice versa. The prevalence of OSA in patients with FES was observed to be as high as 96% and the prevalence of FES in patients with OSA has been reported to be anywhere between 2 and 33%.⁷ An Indian study by Tyagi et al.⁸ identified that among 81 patients with FES, 60 (74.1%) had significant values on Berlin questionnaire; 24.1% of these patients were confirmed on polysomnography.

In the current study, we aimed at evaluating the prevalence of OSA in patients with a confirmed diagnosis of FES. We also explored the willingness for further evaluation and management of OSA.

MATERIALS AND METHODS

This is a retrospective cross-sectional study conducted in a freestanding sleep clinic in Chennai from 2015 to 2018. Patients who were diagnosed with FES at an ophthalmic care hospital and referred to the sleep clinic for evaluation of suspected OSA were included in the study.

RESULTS

The study was conducted from January 2015 to December 2018. During this period, 51 patients with FES were referred consecutively to the sleep clinic and all of them were included in the study. All the referrals were males and the mean age was 49.8 ± 13.4. One of the patients had ENT related complaints and was referred to otolaryngorhinologist, and excluded from analysis. Two patients had their polysomnography done elsewhere before presenting to our clinic. Based on clinical assessment of the remaining 48 patients, all of them required sleep studies (46 patients required Level III polysomnography, one patient required level I polysomnography, and one required level I polysomnography with MSLT). Of these 48 patients who were prescribed PSGs, 12 (24%) were unwilling to undergo sleep study as they were disinclined to accept the possible association of OSA and FES and/or could not afford additional testing. Risk factors such as weight gain (15.7%) and comorbidities including hypertension (13.7%) and diabetes mellitus (11.8%) were addressed and reinforced.

Of the 38 patients who underwent polysomnography, 36 (94.8%) were found to have OSA (Table 1). Only one of these patients followed up and accepted continuous positive airway pressure (CPAP) therapy (Flowchart 1). The patient is not a resident of Chennai and had not come for a follow up thereafter. The patient had not responded to our attempts of communication.

DISCUSSION

The association of OSA with metabolic and vascular disorders has been extensively studied and well accepted.³ Vascular involvement of the eye, such as diabetic retinopathy, retinal vein, and arterial disorders have been clearly associated with OSA⁷ and few other ophthalmologic disorders, such as glaucoma have also been noted to have a significant association. In this study, we explore the association between FES and OSA and further the feasibility of simple screening by Ophthalmologists to refer patients appropriately for further evaluation in a sleep clinic.

Though various studies have explored the association between the two diseases, the definitive underlying pathophysiology linking the two is yet to be explained. One of the probable explanations is that rubbing of the eyelids against the pillows causes mechanical trauma and is common in patients with OSA as they tend to sleep on their sides.^7,10,11 Another theory suggested is that hypoxia (during sleep) and sudden reperfusion (on awakening) may damage the tarsal plate and initiate a papillary reaction.⁷ Alternate explanations include poor eyelid-to-globe apposition, inflammation of the Meibomian glands or Demodex eyelid infestation. A possibility of genetically transmitted disease has also been considered.^7,10,11

Previous studies^12-14 have observed a male predominance with regards to concurrence of FES and OSA, which has been reestablished in our study. As observed in previous studies,^12-14 hypertension, weight gain, and diabetes mellitus were common comorbidities among the patients which may worsen the prognosis of FES in such patients.¹³

In our study, significant proportion of the patients were not ready to undergo the sleep study or commence treatment despite being diagnosed and explained the consequences of untreated OSA. A qualitative analysis by Shaw et al.¹⁵ aimed at assessing the knowledge, beliefs, and attitudes toward OSA evaluation and treatment observed that misconception with regards to OSA and its evaluation might prevent people from early diagnosis and treatment. Patients may relate their symptoms like snoring and daytime sleepiness to their lifestyle and working conditions and may not perceive them as symptoms of a disease condition. This may also signify that although they are aware that the sedentary nature of their lifestyle and unhealthy habits contribute to chronic conditions, such as obesity and cardiovascular disease, they seem to underestimate or fail to see the correlation to OSA.¹⁶

It is noteworthy that out of 36 patients diagnosed with OSA, 20 had severe OSA, but only one of these patients accepted treatment with PAP. Studies have evaluated the barriers of acceptance and adherence to PAP therapy. Various factors including cost of CPAP, limited insurance coverage, inability to tolerate the device, inconvenience of nightly use, lack of knowledge on the use, fear of social judgment, and lack of awareness regarding OSA have been recorded in these studies.^17,18 A study by Yang et al.¹⁹ observed that CPAP acceptance reduces with age. Another study by Lee et al.²⁰ stated that CPAP counseling prior to ordering a sleep study might be prudent to better manage patient expectations.

Several studies conducted across many countries have concurred the poor knowledge and awareness regarding OSA and its associations even among medical professionals.^21-24 A comforting prospect in this study was that ophthalmologists were able to effectively screen patients for OSA with simple screening questions about snoring and daytime hypersomnolence. Knowledge about OSA and its association with disorders specific to their domain helped the physicians treat patients more holistically and consequently improve the overall prognosis.

A previous Indian study had looked into the prevalence of systemic disorders like OSA in FES.⁸ In our study, we had taken a step further and tried to assess how many patients were willing to undergo relevant assessment and further management. But our study is not devoid of limitations. One of the limitations is the small sample size, which could be due to the fact that FES is not a very common diagnosis and also a frequently overlooked entity, and no further statistical analysis was possible due to the small sample size. Presence of male participants alone could denote a possible selection bias when it comes to screening for OSA. Possibility of effects of confounding factors like gender, comorbidities, hypertension, obesity, etc. was not ruled out. Poor follow up was one of the major limitations of the study. This could be a reflection of lack of awareness with regards to OSA and its consequences. Future studies with bigger sample size of prospective designs are warranted to better understand the impact of the confounding factors, causes for poor follow up, and influence of treatment of OSA on the patients with FES.

CONCLUSION

Ophthalmologists should consider systemic disorders, such as OSA while evaluating patients with FES. Simple screening questions seem to have a high yield in appropriately identifying patients with OSA which was confirmed by portable sleep studies in most of these patients. The proportion of patients with FES having OSA is significant and most of them had moderate or severe OSA. Educating the patients and making them understand the association remains a challenge and can only be improved with increasing awareness among the Ophthalmologists and general public on the importance of treating coexisting OSA.

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