Sleep apnea syndrome (SAS) is characterized by cessation of breathing during sleep.

This is known as periods of apnea.

Clinically, apnea is defined as complete cessation of breathing for more than 10 seconds in adults.

Normally, when an individual is awake, the upper airway remains patent, allowing airflow to the lungs, except for momentary closures during swallowing and speech.

In some individuals, however, the pharyngeal lumen may become obstructed during sleep.

Sleep apnea syndrome describes two major sleep-related clinical problems: central sleep apnea and obstructive sleep apnea (OSA).

Central sleep apnea is caused by the loss of ventilatory effort controlled by the nervous system.

OSA is caused by upper airway obstruction. However, the mechanisms underlying these different types of sleep apnea are likely to overlap.The prevalence of sleep-disordered breathing is approximately 2% in women and 4% in men between 30 and 60 years of age.

The majority of patients with SAS are diagnosed with OSA.

OSA is the most common form of sleep apnea.

OSA is characterized by the physical obstruction of the airway. This can result from a variety or combination of anatomical factors; i.e.: enlarged tonsils, enlarged uvula, increased tongue size and abnormal craniofacial morphology.

Genetics have also been found to be a factor in what causes Sleep Disorders.

In individuals with OSA, numerous sleep-related obstructive breathing events can occur throughout the night.

In mild cases, there can be 5–15 episodes per hour and in severe cases more than 30 episodes per hour.

These respiratory disturbances may lead to hypoxia and hypercapnia, which can trigger arousal from sleep by increasing ventilatory drive. As a result of this sleep disruption, excessive daytime sleepiness is the most common presenting complaint.

Other symptoms of sleep apnea may include loud snoring, not feeling well-rested in the morning, chronic fatigue, falling asleep at inappropriate times of day, morning headaches, recent weight gain, limited attention span, memory loss, poor judgment, personality changes, and lethargy.

These symptoms can significantly decrease quality of life and increase the risk of accidents.

Unfortunately, sleep apnea may go undiagnosed for years.

This is most likely because the people themselves may not remember the episodes of apnea.

For this reason, it is often the patient’s spouse, bed partner, roommate or family member who may witness the periods of apnea, alternating with arousals and accompanied by loud snoring.

However, it is important to note that although snoring is the most common complaint associated with sleep apnea, most patients who snore do not have sleep apnea.

Therefore, patients reporting symptoms of SAS should be referred to a sleep center for an overnight sleep study.

SAS is usually diagnosed by overnight polysomnography, including simultaneous electroencephalography (EEG), electromyography (EMG), electrocardiography (ECG), an electro-oculogram (EOG), and oximetry, airflow through the mouth and nose, and thoracic and abdominal respiration by plethysmography.

From the overnight sleep study, the number of obstructive breathing events per hour can be determined.

This calculation is commonly called the respiratory disturbance index (RDI) or more specifically, the apnea-hypopnea index (AHI), which represents the sum total of apneas, hypopneas and respiratory arousals per hour of sleep.

The RDI value is used to diagnose and grade the severity of the sleep apnea.

Risk factors for SAS include upper airway abnormalities, male gender, alcohol use, snoring, obesity (especially of the upper body), and a neck circumference of more than 17 in. in men or 16 in. in women.

Sadly, in the United States, with the increased prevalence of obesity in children and adolescence, we are beginning to see symptoms of sleep apnea at an earlier age.

Treatment of SAS can range from conservative methods such as oral appliances, to moderate intervention such as continuous positive airway pressure (CPAP), to more radical approaches, including surgical removal of anatomic obstructions. Since SAS is treatable, early recognition of the symptoms of this sleep disorder is crucial.

Recent evidence in the literature suggests that the eye may help us identify individuals who suffer from undiagnosed SAS.

Reported ophthalmic findings in patients with SAS may include floppy eyelid syndrome, non-arteritic anterior ischemic optic neuropathy, and glaucoma.

Being on the frontline of health care, eye care practitioners are likely to be the first health care professionals to see the general public.

For this reason, it is essential for eye care professionals to recognize patients with symptoms of sleep apnea and refer them to a sleep specialist. Similarly, sleep medicine specialists who treat SAS should refer their patients for appropriate ophthalmic evaluation.

In this review article, we describe each of the reported ocular complications associated with SAS. It is our hope that an increased awareness of the possible connection between SAS and ocular disease will promote cross-referrals between ophthalmic clinicians and sleep medicine specialists, resulting in improved patient outcomes.

Floppy eyelid syndrome (FES) was first described in 1981 by Culbertson and Ostler.

It is an under-diagnosed disorder of unknown pathogenesis that is characterized by lax upper eyelids that readily evert on elevation, a soft and foldable tarsus, and a chronic papillary reaction (conjunctivitis) of the upper palpebral conjunctiva.

Papillary conjunctivitis is defined as inflammation of the conjunctiva that presents as raised, vascularized areas (papillae).

Additional clinical findings may include eyelash ptosis, aponeurotic blepharoptosis and chronic corneal lesions, such as punctate epithelial keratopathy and corneal ulceration.

In addition, a number of ocular and systemic diseases have been reported in association with FES, including keratoconus, blepharochalasis and dermatochalasis, tear film abnormalities and meibomian gland dysfunction, hyperglycemia, and mental retardation.Conjunctival papillae presenting as raised, vascular areas.

FES was originally seen in overweight males that presented with rubbery, easily everted upper eyelids; however, the condition has also been reported in females and non-obese patients.

A growing body of literature suggests that FES may be associated with OSA.

2.1.1. Pathophysiology

The pathophysiology of FES centers on the elastin located within the tarsal plate of the upper eyelid. Although the tarsal collagen appears normal in patients with FES, histopathologic studies using special stains, immunohistochemistry, and electron microscopy demonstrate a significant decrease in the amount of tarsal elastin. Other theories about the pathogenesis of FES include tear film disorders, meibomian gland abnormality including cystic degeneration, squamous metaplasia of the orifice, and atrophy of acini.

2.1.2. Signs and symptoms

FES may present with symptoms of nonspecific irritation, foreign body sensation, mucoid discharge, dryness, redness, photosensitivity, and eyelid swelling. Many of these symptoms seem to be worse in the morning; it is speculated that one pathogenic mechanism of FES is through contact between the palpebral conjunctiva and pillow during sleep. Some reports suggest that in patients with FES, the worse floppy eyelid corresponds to the side of the body upon which the patient lies during sleep, and that there is also a preference for sleeping on one’s stomach.

2.1.3. Diagnosis

Ophthalmic clinicians may employ several measures to diagnose FES, including gross examination, slit lamp biomicroscopy, and tear film/lacrimal testing. Direct external examination with palpation may uncover laxity of the lids.

A loose upper eyelid is easily everted when pulled superiorly toward the eyebrow because the soft, rubbery tarsal plate can be folded upon itself. With chronic FES, the tarsal plate area may appear atrophic on biomicroscopy.

Under biomicroscopy, the pre-corneal tear film, which is composed of lipids, electrolytes, and protein containing aqueous fluid and mucins, can be evaluated.

The tear film serves several functions. In addition to its primary action of lubricating the ocular surface, it is used as a waste removal system, as well as a defense mechanism for the cornea. The tear layer also provides anti-microbial protection.Under normal circumstances, aqueous tears are secreted by the lacrimal gland, spread over the entire cornea by lid blinking, and then cleared from the eye into the nose through the nasolacrimal drainage system, which includes the superior and inferior puncta and canaliculi, the lacrimal sac, and nasolacrimal duct.

Dyes such as fluorescein, rose bengal and lissamine green are used to establish an aqueous tear deficiency. One common way of measuring tear clearance is to measure the tear break-up time (TBUT). Using fluorescein, the TBUT can be measured. It is evaluated by placing a drop of fluorescein into the inferior fornix, asking the patient to close his eyes, then to open them and keep them open. The examiner then measures the number of seconds (after opening) until the tear film breaks. Rose bengal and lissamine green dyes are also used to evaluate ocular surface integrity. These dyes stain mucus, degenerating cells, and dead cells of the corneal epithelium.
In addition, a Schirmer test can be performed. During this test, a bent piece of Whatman No. 41 filter paper is placed in the lower conjunctiva, and the amount of tearing on the filter paper is recorded in millimeters. A positive Schirmer result is less than 5 mm after 5 min, indicating a compromised tear layer.

The differential diagnoses of FES include the vernal, atopic, superior limbal, and giant papillary keratoconjunctivitities, as well as nocturnal lagophthalmos. A detailed history and proper ophthalmic workup can rule out these masqueraders.

2.1.4. Treatment

The goal of treatment of FES is to protect the ocular surface during sleep. Topical management centers upon the frequent instillation of artificial tears and ocular lubricants. In the event of significant corneal or conjunctival compromise, such as superficial punctate keratitis, a broad-spectrum antibiotic ophthalmic ointment, such as erythromycin, can be prescribed.Surgical intervention is usually reserved for those patients who do not benefit from topical treatment. Horizontal lid shortening is a surgical technique in which the loose lid is resected and shortened, thus preventing spontaneous eversion during sleep.

2.1.5. FES and SAS

Both FES and specifically OSA syndrome have similar patient profiles—middle aged, obese men. A common thread that may link FES to OSA is a defect in elastic tissue. In FES, tarsal elastin is affected; in OSA, palatine elastin is affected.

In a case series, Mojon et al. determined the prevalence of eyelid, conjunctival, and corneal findings in patients referred for polysomnography because of suspected SAS.

Seventy-two out of 80 patients received an ophthalmic examination, videokeratography, general neurologic and laboratory examinations, and sleep studies, which were interpreted and graded according to the RDI.

In this study, the Spearman rank correlations between the RDI and tear film break-up time (distribution of an adequate tear film), eyelid distraction distance, presence or absence of blepharoptosis (a drooping eyelid), floppy eyelids, lacrimal (tear producing) gland prolapse, keratoconus (irregular protrusion of the cornea), and corneal endothelial dystrophy were calculated.

The presence or absence of symptoms of ocular irritation was also correlated with the RDI. Each correlation was controlled for age and body mass index.

The authors concluded that SAS was significantly associated with reduced tear film break-up time, floppy eyelids, and lacrimal gland prolapse. According to the RDI, 61% (44 out of the 72) of the patients with these ocular findings had SAS.

In addition, the RDI correlated positively with the eyelid distraction distance (P=0.05), presence or absence of floppy eyelids (P=0.01), and lacrimal gland prolapse (P=0.01). However, the RDI correlated negatively with tear film break-up time (P=0.02). Thus, the authors were unable to confirm previous studies that reported a high prevalence of corneal involvement in floppy eyelid syndrome.
In another study, Robert et al. set out to establish the frequency of FES or other palpebral and ocular abnormalities in patients with sleep disorders.

The sample consisted of 69 patients with sleep disorders, of which 46 had been diagnosed with OSA syndrome, 16 with untreated apneas and seven with heavy snoring without apneas. The control group consisted of 45 patients with neither SAS nor palpebral troubles.

The authors found an association between upper eyelid hyperlaxity (chi-squared test P=0.001) and OSA. They also identified one case of papillary conjunctivitis and two cases of punctate epithelial keratitis. In addition, the authors found an abnormal elasticity in patients with OSA syndrome, supporting the theory of a disorder of elastin fibers. However, this remains to be proven histologically []. Like Mojon et al, the authors were not able to establish any significant prevalence of corneal involvement. Thus, they concluded that OSA was associated with upper eyelid hyperlaxity, but not FES.