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When physicians see a patient with floppy eyelid syndrome, they should also screen for obstructive sleep apnea-hypopnea syndrome, new research has shown.

In a small study, those with the condition -- characterized by rubbery upper eyelids -- had a 12.5-fold increased risk of obstructive sleep apnea, Daniel G. Ezra, MD, of Moorfields Eye Hospital in London, and colleagues reported in the April issue of Ophthalmology.

The findings "should encourage clinicians to be aware of the association and to direct further treatment," the researchers wrote.

Patients with floppy eyelid syndrome have very elastic upper lids that become easily distorted, with minimal lateral traction, and their eyelids can easily flip up during sleep. This, in turn, can lead to dry, irritated eyes or discharge.

Research has shown the syndrome to be associated with a variety of ocular and systemic conditions, including obstructive sleep apnea and keratoconus.

To determine the extent of those associations, the researchers conducted a case-control study of 102 patients with floppy eyelid syndrome, and matched them on the basis of age, gender, and body mass index with 102 controls from a diabetic retinopathy clinic.

Obstructive sleep apnea-hypopnea syndrome was defined either by prescription of continuous positive pressure respiratory support at night or by a score of 10 or more on the Epworth daytime somnolence scale. Keratoconus was determined using a photographic camera system assessing corneal morphology.

All patients had an upper and lower lid laxity assessment and upper lid levator function tests.

The researchers found that floppy eyelid syndrome was significantly associated with sleep apnea, as those with the eyelid condition were 12.5 times more likely to have apnea (P=0.0008). That association held even after controlling for obesity, which has been thought to be a significant confounder, the researchers said.

About a third of floppy eyelid syndrome patients had sleep apnea.

The eyelid condition was also associated with keratoconus, since floppy eyelid syndrome patients had nearly a 20-fold increased risk of the condition (OR 19.3, P<0.0001).

The researchers said rubbing the eyes, commonly seen in patients with keratoconus, could contribute to the condition.

Floppy eyelid syndrome was also significantly associated with lash ptosis (P<0.0001), dermatochalasis (P=0.02), upper lid medial canthal laxity (P=0.02), upper lid distraction (P=0.001) palpebral aperture (P=0.004), and levator function (P=0.005).

The findings indicate that sleep itself may be an important etiologic factor, the researchers said. Several mechanisms have been proposed, including reperfusion ischemia and repeated mechanical trauma leading to metalloproteinase expression and connective tissue remodeling.

The mechanical stress theory is supported by the close association with keratoconus, they added. Decreased reflexes in the central nervous system "may allow patients to tolerate extreme mechanical stress to the upper lid during sleep, which would normally cause an unaffected individual to wake and alter their sleep position."

While floppy eyelid syndrome appears to be more common in obese men in their sixth decade, the researchers said, the condition affects patients of a range of ages, body mass indices, and both genders.

Though the study was limited by a small sample size, the researchers concluded that physicians should look for these associations among their patients and treat them appropriately.