May 26, 2017

Association of Normal Tension Glaucoma and Obstructive Sleep Apnea/Hypopnea Syndrome

Several recent studies have shown an association between moderate and severe obstructive sleep apnea/hypopnea syndrome (OSAHS), and normal tension glaucoma (NTG).  The prevalence of NTG increases with age, and is roughly 0.2% in patients aged 43 to 54 years, and 1.6% in patients over 75 years of age1.  A recent study by Lin et al.showed a prevalence of 5.7% in patients with obstructive sleep apnea of all severity, and 7.1% in patients with moderate to severe OSAHS1.  Other studies have shown an even higher prevalence of NTG, as high as 27%2.  Despite the variability in prevalence between studies, it is clear that there is a strong association between OASHS and NTG.  Why is this, and why is it important?  Our current understanding of NTG identifies risk factors for developing NTG.  These include abnormal ocular blood flow, abnormal blood coagulation, systemic hypotension, ischemic vascular diseases, and autoimmune disease1.  One possible explanation is that OSAHS creates transient hypoxemia and increased vascular resistance, which impairs optic nerve head perfusion and leads to nerve tissue injury at what would otherwise be tolerable intraocular pressures1.  Patients with OSAHS by definition suffer from five to sometimes hundreds of episodes of hypoxia and hypercapnia nightly, lasting anywhere from ten seconds up to two minutes.  These repeated episodes would then lead to repetitive nerve injury and eventually axonal death, loss of viable nerve tissue, and visual field loss.  Episodic hypoxia also leads to increased risk of hypertension, pulmonary hypertension, cardiac arrhythmias, myocardial infarction, congestive heart failure, and cerebrovascular accidents, and so NTG may represent the ophthalmic manifestations of the effects of repeated systemic hypoxia1.  It is also possible that the treatment for OSAHS may exacerbate optic nerve perfusion difficulties.  A study by Kiekens et al. showed that CPAP therapy caused additional IOP increase, particularly at night, a time when blood pressure and perfusion pressure tends to be low3.  It is particularly important to remember this association because the intraocular pressure, which has traditionally been used as a major determinant in whether or not someone has glaucoma, is normal on evaluation.  In these cases, if the clinician is not paying particular attention to the structure of the optic nerve, and specifically looking for this disorder, the diagnosis can be missed.  Untreated and unrecognized, over time this can lead to irreversible vision loss and potentially blindness.  Several studies confirm that patients with OSAHS have reduced nerve fiber layer measurements, indicating nerve tissue loss, and a high incidence of visual field defects, confirming that many of these patients may have visual impairment occurring and not be aware of a problem4,5.

So, the next time you are taking care of a patient with OSAHS, you may want to ask if they have specifically been evaluated for NTG, and consider referring them for evaluation if they have not.  Like most chronic diseases, early detection and treatment is paramount in achieving good outcomes.  Conversely, ophthalmologists evaluating patients with normal tension glaucoma should consider referral and evaluation for OSAHS, as this may be an identifiable and treatable risk factor for the disease.


1.   Normal Tension Glaucoma in Patients With Obstructive Sleep Apnea/Hypopnea Syndrome.  Lin PW, Friedman M, Lin HC, Chang HW, Wilson M, Lin MC.  J Glaucoma. 2010 Sep 16. [Epub ahead of print]

2.  Prevalence of glaucoma in patients with obstructive sleep apnoea–a cross-sectional case-series.  Bendel RE, Kaplan J, Heckman M, Fredrickson PA, Lin SC.  Eye (Lond). 2008 Sep;22(9):1105-9. Epub 2007 May 4.

3.   Continuous positive airway pressure therapy is associated with an increase in intraocular pressure in obstructive sleep apnea.  Kiekens S, Veva De Groot, Coeckelbergh T, Tassignon MJ, van de Heyning P, Wilfried De Backer, Verbraecken J.  Invest Ophthalmol Vis Sci. 2008 Mar;49(3):934-40.

4.   Moderate to severe obstructive sleep apnoea patients is associated with a higher incidence of visual field defect.  Tsang CS, Chong SL, Ho CK, Li MF.  Eye (Lond). 2006 Jan;20(1):38-42

5.  Retinal nerve fibre layer measurements are reduced in patients with obstructive sleep apnoea syndrome.  Kargi SH, Altin R, Koksal M, Kart L, Cinar F, Ugurbas SH, Ayoglu F.  Eye (Lond). 2005 May;19(5):575-9.