Applying the evidence on OSA and glaucoma

The two disorders can exist concomitantly. Is it time the work-up for one includes the other?

By Ahmad A. Aref, MD

	About the Author
	Ahmad A. Aref, MD, is an anterior segment/glaucoma specialist and assistant professor at the Illinois Eye & Ear Infirmary, University of Illinois at Chicago Department of Ophthalmology and Visual Sciences. His e-mail is aaref@uic.edu. Disclosure: Dr. Aref has no financial relationships to disclose.

Obstructive sleep apnea (OSA) affects approximately 15% of the US population, and the prevalence is trending upward because of rising rates of obesity in the aging population.¹ Ocular associations of OSA include nonarteritic ischemic optic neuropathy (NAION), floppy eyelid syndrome, blepharochalasis, keratoconus and papilledema. Recently, several studies have suggested that OSA may increase the risk of glaucomatous optic neuropathy.² This article examine some of these recent studies and provides take-home pearls for clinical patient care.

Sleep apnea definition

The repetitive collapse of the upper airway, which leads to transient disruptions in sleep and transient hypoxemia, characterizes OSA. OSA significantly increases the risk of life-threatening systemic events such as cerebrovascular accident, myocardial infarction and cardiac arrhythmia,³ but OSA often goes undiagnosed due to its generalized and non-specific symptoms, which include night-time snoring, daytime sleepiness and generalized impaired daytime function.

A definitive diagnosis of OSA typically requires night-time sleep signal monitoring (polysomnography). Treatment with a continuous positive air pressure (CPAP) mask has proven effective in maintaining upper airway patency during sleep and reducing the risk of deleterious consequences of OSA (Figure 1).⁴

SLEEP APNEA AND GLAUCOMA

OSA and optic nerve perfusion

The repetitive airway collapse and associated hypoxemia characteristic of OSA may lead to sporadic perfusion abnormalities of the optic nerve and subsequent glaucomatous optic neuropathy. A definitive association between the two disorders would represent a meaningful finding and help to risk stratify individuals for glaucoma diagnosis. A cohort study out of Taiwan found that patients with OSA were 1.67 times more likely than controls to be diagnosed with open-angle glaucoma in five years.⁵

In this study, investigators used data from a population-based Taiwanese database maintained by the Taiwan National Health Research Institute to investigate the risk of open-angle glaucoma diagnosis within a five-year period after initial diagnosis of OSA compared to a control group. After adjusting for several medical and demographic factors, including number of outpatient visits for ophthalmologic care, the authors reported that patients diagnosed with OSA were on average 1.67 times more likely than controls to be diagnosed with open-angle glaucoma within five years.

When interpreting the results of this study, it is important to note the investigators made an initial diagnosis of OSA only after a positive polysomnography study. Furthermore, they made a diagnosis of glaucoma only in cases that went on to treatment with topical IOP-lowering medicines. These two methodological features decreased the chances of false diagnoses and increased the validity of the study, suggesting that OSA may indeed be an independent risk factor for the development of glaucoma.

Figure 1. The CPAP device – for continuous positive airway pressure – has proven effective in maintaining upper airway patency at night in patients with obstructive sleep apnea.

Glaucoma cohorts and association with OSA

Studies of glaucoma patient cohorts have also borne out an association with OSA. A 2010 study out of France reported on the polysomnography results of 31 glaucomatous patients that admitted to snoring on interview.⁶ The investigators reported positive polysomnography results in 49% of the subjects, suggesting an increased prevalence of OSA among glaucomatous individuals. They suggested that clinicians ask glaucoma suspects about the presence of snoring and, conversely, sleep therapists ask their patients if they have a history of POAG, and if so, should undergo all-night sleep recording to explore for OSA.

Although most studies reporting on the potential association between OSA and glaucoma indicate a likely link, a few studies have revealed differing results. Joshua Stein, MD, MS, and his team at University of Michigan Kellogg Eye Center performed a retrospective, longitudinal cohort study examining the association between the two disorders in a large managed care network database.⁷ In that investigation, the incidence of glaucoma did not differ between individuals with or without a diagnosis of OSA. Similarly, Christopher Girkin, MD, MSPH, and colleagues at the University of Alabama⁸ found no additional adjusted risk for a history of OSA in a Veterans Affairs population of patients with newly diagnosed glaucoma.

Importantly, the two US studies based the diagnoses of OSA and glaucoma on ICD-9-CM billing codes as the care provider completed them, unlike the previously mentioned Taiwan study,⁵ which required a polysomnogram or other formal sleep study to establish the diagnosis of OSA. However, diagnoses in the US studies may have been coded in error, limiting the conclusions we may draw from them.

Challenges of diagnosing both disorders

Given the slowly progressive and relatively asymptomatic nature of both OSA and glaucoma, clinical detection of either disorder in the known presence of the other may be challenging. A few recent studies have revealed results promising to aid us in this regard.

Investigators in Spain performed a cross-sectional study to determine whether the presence of floppy eyelid syndrome (FES) – which they defined as easily evertible eyelids and the presence of papillary conjunctivitis, in patients with known OSA – may represent a predictor of glaucomatous optic neuropathy.⁹ The group reported a glaucoma prevalence of 5.33% in OSA patients without FES vs. 23.07% in OSA patients with FES. These results suggest that FES represents a clinical predictor of possible glaucoma in patients with OSA.

An Israeli group¹⁰ reported on OCT-measured parapapillary retinal nerve fiber layer (RNFL) measurements in patients with OSA and no known glaucoma.¹⁰ Their multivariate regression analysis revealed that OSA patients tended to have thinner average, superior quadrant and inferior quadrant RNFL thickness values than controls. Sung Chul Park, MD, and colleagues at New York Eye and Ear Infirmary elucidated a functional consequence of OSA in individuals with glaucoma.¹¹ The group reported that, among other systemic vascular factors, OSA increased the risk for the development of an initial parafoveal vs. peripheral scotoma in glaucomatous individuals.

"Investigators have suggested clinicians ask glaucoma suspects about snoring.”

"We should actively interview patients with regards to symptoms of undiagnosed OSA.”

Figure 2. Automated visual field plot corresponding to the left eye of a 52-year-old woman with newly diagnosed glaucoma demonstrating a paracentral scotoma. The patient interview revealed a history of night-time snoring and daytime somnolence. Given this history and the patient’s initial paracentral scotoma, a referral for an obstructive sleep apnea work-up was initiated, and she was prescribed appropriate IOP-lowering therapy.

CLINICAL PEARLS

Discerning OSA in the patient history

Although the current literature has yet to demonstrate definitively conclusive evidence for an association between OSA and glaucoma, there exists ample support for clinical awareness by the treating ophthalmologist and corresponding practice change.

Patients with undiagnosed OSA are unlikely to volunteer a history of snoring or daytime somnolence to their ophthalmologist. So we should actively interview patients with regards to these symptoms. Often, the patient’s spouse and/or sleeping partner can provide this history. A positive response may heighten the suspicion for glaucoma, especially in the setting of other risk factors, such as increased IOP, decreased central corneal thickness, positive family history and increased cup-to-disc ratio.

In patients with known OSA, a careful ocular adnexal examination can discern the presence of FES, characterized by easily everted eyelids and papillary conjunctivitis.

OSA and FES may be markers

You may wish to undertake a lower threshold for a complete glaucoma evaluation in patients with known OSA and FES discovered on examination. We should especially try to ascertain a history for possible OSA from patients with a known diagnosis of glaucoma and progressive disease at seemingly normal IOP as well as those presenting with an initial paracentral scotoma (Figure 2) on visual field testing.

Although the benefit of referral and treatment for OSA with regards to ocular disease remains to be fully understood, the value with regards to decreasing the risk of systemic life-threatening conditions is indisputable. Ophthalmologists may play a central role in using historical and clinical clues to diagnose OSA and related glaucomatous disease, resulting in earlier treatment for overall ocular and systemic health benefits. OM

REFERENCES

1. Young T, Palta M, Dempsey J, Peppard PE, Nieto FJ, Hla KM. Burden of sleep apnea: rationale, design, and major findings of the Wisconsin Sleep Cohort study. WMJ. 2009;108:246-249.

2. Kadyan A, Asghar J, Dowson L, Sandramouli S. Ocular findings in sleep apnoea patients using continuous positive airway pressure. Eye. 2010;24:843-850.

3. Montesi SB, Bajwa EK, Malhotra A. Biomarkers of sleep apnea. Chest. 2012;142:239-245.

4. Sundar KM, Daly SE, Willis AM. A longitudinal study of CPAP therapy for patients with chronic cough and obstructive sleep apnoea. Cough. 2013;9:19.

5. Lin CC, Hu CC, Ho JD, Chiu HW, Lin HC. Obstructive sleep apnea and increased risk of glaucoma: a population-based matched-cohort study. Ophthalmology. 2013;120:1559-1564.

6. Blumen Ohana E, Blumen MB, Bluwol E, Derri M, Chabolle F, Nordmann JP. Primary open angle glaucoma and snoring: prevalence of OSAS. Eur Ann Otorhinolaryngol Head Neck Dis. 2010;127:159-164.

7. Stein JD, Kim DS, Mundy KM, et al. The association between glaucomatous and other causes of optic neuropathy and sleep apnea. Am J Ophthalmol. 2011;152:989-998.

8. Girkin CA, McGwin G Jr, McNeal SF, Owsley C. Is there an association between pre-existing sleep apnoea and the development of glaucoma? Br J Ophthalmol. 2006;90:679-681.

9. Muniesa M, Sanchez-de-la-Torre M, Huerva V, Lumbierres M, Barbe F. Floppy eyelid syndrome as an indicator of the presence of glaucoma in patients with obstructive sleep apnea. J Glaucoma. 2013 [Epub ahead of print].

10. Sagiv O, Fishelson-Arev T, Buckman G, et al. Retinal nerve fiber layer thickness measurements by optical coherence tomography in patients with sleep apnea syndrome. Clin Experiment Ophthalmol. 2013 [Epub ahead of print].

11. Park SC, De Moraes CG, Teng CC, Tello C, Liebmann JM, Ritch R. Initial parafoveal versus peripheral scotomas in glaucoma: risk factors and visual field characteristics. Ophthalmology. 2011;118:1782-1789.