7 Ways Sleep Apnea Affects Ocular Health

Almost everyone has either seen or is aware of the scene in Star Wars where Darth Vader holds out his hand and uses the Force to strangle a commander while Vader states, “I find your lack of faith disturbing.” Imagine this same thing happening to someone hundreds of times per night for 10 to 60 seconds.

Then you might say, “I find your lack of faith in the effects of sleep apnea disturbing.”

Sleep apnea is a serious health concern that is widely underdiagnosed and undertreated due to the high costs and uncomfortable circumstances of sleeping labs and polysomnography (PSG) testing (the gold standard to diagnose sleep apnea). Eighty percent of men and 90% of women go undiagnosed.¹ Its prevalence in the general population ranges extensively from 2% up to 24%.

Obstructive sleep apnea is the most common type of sleep apnea and accounts for 84% of all sleep apneas. The obstruction originates from the soft tissue of the throat that collapses and causes decreased air and oxygen flow leading to a hypoxic blood state. Risk factors for obstructive sleep apnea (OSA) include age, gender (occurs in 24% of men vs. 9% in women), smoking, race (African Americans are 2.5 times higher risk), and a neck circumference of over 19 inches (occurs in 34% of NFL linemen).¹

OSA not only has detrimental systemic health sequelae, it can also affect ocular health in many ways. It is our duty as optometrists to examine for these ocular effects and diseases that can be consequences of undiagnosed and/or untreated OSA.

Glaucoma (especially normal-tension glaucoma)
Uncontrolled Type 2 Diabetes
Floppy Eyelid Syndrome (FES)
Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION) and Retinal Vein Occlusion (RVO)
Papilledema
Central Serous Chorioretinopathy (CSR)
Keratoconus
Glaucoma

The proposed mechanism of OSA influencing glaucoma is related to blood flow to the optic nerve head (ONH). In OSA, low oxygenated blood reaching the ONH could be insufficient to properly maintain nerve health. This is similar to the how hypotension, especially nocturnal hypotension, can lead to difficult to control normal tension glaucoma.

Historically, the evidence of association between OSA and glaucoma have been widely varied and inconclusive. In order to strengthen the expected association, a vast meta-analysis was performed. The analysis scoured informational databases and found 312 relevant studies about OSA and glaucoma. Shi et al. then performed a rigorous screening to come up with the final 16 studies included in the analysis, which totalled over 2 million participants.² The researchers found a positive correlation with prevalence of glaucoma in patients with OSA.

The researchers calculated the statistically significant hazard ratio based on a 95% confidence interval for each type of study examined. They found the hazard ratios to be 1.67, 1.96, and 1.41 for the single retrospective cohort study, six case-control studies, and nine cross-sectional studies, respectively (i.e. a hazard ratio of 2.0 would mean there is a two times higher likelihood of glaucoma in OSA patients). The cohort study also found that patients with glaucoma were 12.9% more likely to have OSA.²

While a prospective cohort study could confirm these result, this analysis gives clinicians a better understanding and backing to recommend a sleep study and PSG in patients with glaucoma, especially normal-tension glaucoma.

Diabetes

Duration of diabetes and blood sugar control, specifically HbA1c values, are known factors to influence the likelihood of diabetic retinopathy. A drop of 1% in A1c values can reduce the risk of diabetic retinopathy by nearly 30%. Furthermore, obesity is significantly more common in both patients with type 2 diabetes and OSA, which may be why independent studies have shown the prevalence of OSA in patients with type 2 diabetes range as high as 58 to 86%.³

A study was performed to determine the relationship of OSA on A1c values, specifically OSA during rapid eye movement (REM) and non-rapid eye movement (NREM) sleep. The study included 115 subjects and used the apnea-hypopnea index (AHI), Oxygen desaturation index (ODI) and microarousal index (MAI) as measures of OSA. AHI is defined as the total number of obstructive apneas and hypopneas per hour of sleep. In order to qualify as an apnea, cessation of airflow had to be greater than or equal to 10 seconds or a 50% drop in magnitude of ventilation signal to be considered hypopnea. OSA was defined as AHI 5 (mild 5-14, Moderate 15-29, and severe 30).

The study concluded with a multivariate, linear regression model that revealed REM AHI was independently associated with increasing levels of A1c (P < 0.008). They found no such association with NREM AHI (3). Since most of our REM sleep occurs later in the night and apnea events lasted nearly 30 seconds longer during REM sleep, the study urged the use of CPAP machines for greater than four hours (mean CPAP wear time was 3.6 hours). “Seven hours of CPAP use would cover more than 85% of REM sleep and would be associated with a decrease in HbA1c by as much as 1%.”³

It is prudent to always discuss lifestyle modifications with diabetic patients, especially weight loss in obese type 2 diabetics. I usually like to tell patients to try smaller portion sizes, drink water instead of sugary drinks, and exercise on a regular basis, even if it is just light walking for 30 minutes. Now we have one more way we can help our diabetics control their Alc levels.

Floppy Eyelid Syndrome (FES)

Digitally manipulating eyelids should be a part of every clinicians slit lamp routine and can easily uncover FES. Patients with FES may complain about such things as dryness, irritation, redness, and discharge, especially in the morning. Patients may only complain about symptoms on one eye and if the clinician sees unequal SPK, they should inquire about the patient’s preferred sleeping position (i.e. I only sleep on my right side could explain OD SPK and symptoms).

OSA tends to more severe in FES patients and is reported in 96% of patients with the FES diagnosis.⁴

NAION/RVO

NAION is caused by blood flow loss to the optic nerve head resulting in the classic altitudinal VF defect and disc edema with hemorrhaging. It occurs unilaterally, but if the underlying cause is not determined the patient is at high risk for it affecting the second eye. Studies of patient cases have shown that 71% of patients with NAION also have OSA, thus patients should be scheduled for a polysomnogram test to rule out OSA. More urgent causes such as high risk medications and other vascular diseases should be investigated with higher precedence (GCA should always be ruled out first).

RVO is a common cause of vision loss worldwide; conversely, branched retinal vein occlusions (BRVO) can be caught in routine, asymptomatic patients. Most people will notice a central RVO as painless vision loss upon awakening. RVO can be associated with OSA by the same mechanism as described below in central serous chorioretinopathy.

Papilledema

The proposed mechanism of action of papilledema secondary to OSA is due to the increase in CO2 in the blood. High CO2 levels results in dilated vessels and increased pressure which leads to the swelling of the optic disc. Patients with comorbid OSA and papilledema have shown improvement or even complete resolution of papilledema with CPAP therapy.

It is prudent to note that idiopathic intracranial hypertension (IIH) is common in overweight females and obesity is a risk factor for OSA. Idiopathic intracranial hypertension commonly presents as swollen, bilateral optic nerve heads. In order to diagnosis as IIH, other causes must be ruled out, and this includes OSA.

Central Serous Chorioretinopathy

Obstructive sleep apnea is found in nearly two-thirds of patients with the diagnosis of CSR according to a recent small prospective study.⁵ Another study, which reviewed charts of 117 patients and found 61 patients with CSR, found 61.1% of CSR patients to be at high risk for sleep apnea (based on a standardized survey administered via phone).⁶

The proposed mechanism which is shared by both CSR patients and OSA patients includes increased oxidative stress which produces superoxide radicals, platelet aggregation and hypercoagulability. Oxidative stress from OSA can produce more epinephrine which results in choroidal vasoconstriction and hyperpermeability of the choriocapillaris which then leads to CSR.

Studies have also shown a correlation between levels of plasma epinephrine and macular thickness in CSR. Superoxide radicals lower the levels of antioxidants which causes vessel endothelium damage.⁵ It would be interesting to see what affects antioxidant supplementation has on chronic CSR and the many systemic effects of OSA.

The study also cited that an increase in plasminogen activator inhibitor 1 (PAI-1) “can lead to decreased fibrinolysis and thrombotic occlusion of the choroidal vasculature” (i.e. increased blood coagulability).⁵ They found correlating higher levels of PAI-1 in patients with OSA.⁵ While CSR often resolves on its own with limited or no consequences to vision, chronic cases should be referred for a sleep study to determine if OSA is a contributing factor.

Keratoconus

Approximately 18-20% of patients with keratoconus have OSA. However, when obesity was eliminated as a confounding factor, nonobese patients were found no more likely to have OSA than the general population.⁷. The mechanism of OSA causing keratoconus is not well understood.

It is well known that patients with keratoconus are more likely to have FES and thus a link between OSA and keratoconus can be postulated. It is hypothesized that due to FES, the cornea is at risk of mechanical trauma causing weakening of the corneal collagen. More evidence is needed to support a link between OSA and keratoconus.

Age-Related Macular Degeneration (AMD)

According to a study published from Walden University in 2017, their article is the only one investigating the link between between AMD and OSA. Their cross-sectional study used data from the 2005-2008 National Health and Nutrition Examination Survey to study the link between sleeping disorders and AMD, including advanced AMD with neovascularization and geographic atrophy. Their results suggested a link between sleep apnea and AMD.

The authors state in their conclusion that the Preferred Practice Patterns for AMD as published in 2015 by the American Association of Ophthalmology fails to state OSA as a modifiable risk factor for AMD treatment (8). With no cure for AMD and limited modifiable risk factors, it is time for the optometric community to recognize the importance of sleep on the overall health of the body and eyes.

Conclusion

This article has hopefully increased your faith in the need for action against OSA due to its life and sight threatening ramifications.

The Australian group Healthy Sleep Solutions has an easy risk calculator for OSA.

Furthermore, I hope that universities and researchers continue to spend the time and money OSA deserves to further study the effects of OSA on our patients’ health and to discover different treatment modalities. I hope that we can mimic the strong multidisciplinary approach of treatment with diabetic patients and primary care doctors with OSA sufferers and sleep professionals.

Lastly, I think it would be wise for entities like the American Association of Ophthalmology and the American Optometric Association to work cooperatively with the American Board of Sleep Medicine to update its public guidelines in the treatment and management of the ocular effects of OSA.

References

McCarthy CE. How sleep apnea affects the eye. OptometryTimes. Published October 9, 2015. Accessed January 9, 2018.
Shi Y, Liu P, Guan J, Lu Y, Su K. Association between glaucoma and obstructive sleep apnea syndrome: A meta-analysis and systematic review. PLoS ONE. 2015;10(2), E0115625.
Grimaldi D, Beccuti G, Touma C, Van Cauter E, Mokhlesi B. Association of obstructive sleep apnea in rapid eye movement sleep with reduced glycemic control in type 2 diabetes: Therapeutic implications. Diabetes Care. 2014;37(2), 355-63.
Michaud L. 5 eye issues and sleep disorders: The ocular signs of sleep apnea. Alaska Sleep Education Center. Accessed January 9, 2018.
Leveque TK, Zacks D, Chervin RD, Musch D. Prevalence of sleep apnea in patients with central serous chorioretinopathy. Investigative Ophthalmology & Visual Science, 46, Investigative Ophthalmology & Visual Science. 2005;46 Suppl S.
Yavaş G, Küsbeci T, Kaşikci M, Günay E, Doğan M, Ünlü M, Inan UÜ. Obstructive Sleep Apnea in Patients with Central Serous Chorioretinopathy. Current Eye Research. 2014;39(1), 88-92.
Skorin L, Knutson R. Ophthalmic Diseases in Patients With Obstructive Sleep Apnea. J Am Osteopath Assoc 2016; 116(8): 522–529. doi: 10.7556/jaoa.2016.105.
Nau J, Goodwin D, Griffin H, Naser D. Association Between Age-Related Macular Degeneration and Sleep-Disordered Breathing, ProQuest Dissertations and Theses. 2017.