OBSTRUCTIVE SLEEP APNEA AND GLAUCOMA
INTRODUCTION:
Obstructive Sleep Apnea (OSA) is
a condition characterized by recurrent complete or partial interruption of
breathing due to functional occlusion or collapse of upper airway during sleep.
This leads to apnea or hypopnea and subsequent hypoxia.
There are 2 components of OSA:
·
Apnea: Indicates obstruction of airflow at the
level of the oropharynx for atleast 10 seconds.
·
Hypopnea: Reduction of airflow by atleast 30%,
associated with arousal or oxyhemoglobin desaturation by atleast 3%.
Apnea/hypopnea index (AHI) is the
number of such events per hour.
OSA has been defined as an AHI
>5 with daytime hyper-somnolence or an AHI >15 with/without symptoms.
A prevalence of OSA of 7-20% in
men and 2-28% in women above 20 years of age has been reported.
OSA has been positively
associated with hypertension, cardiovascular and cerebrovascular disease,
pulmonary hypertension and overall mortality.
OSA has been reported with ocular
conditions such as: floppy eyelid syndrome, papilledema, Non-Arteritic Anterior
Ischemic Optic Neuropathy (NAAION), glaucoma, idiopathic intracranial
hypertension, diabetic retinopathy, geographic atrophy, Age Related Macular Degeneration,
retinal vein occlusion and Central Serous Retinopathy.
OSA AND GLAUCOMA:
The association of OSA with
glaucoma was first reported by Walsh and Montplaisir (1982). They described 5
patients from 2 generations of a family having OSA and glaucoma. The severity
of glaucoma was directly related to the severity of OSA. Later Mojon, Onen,
Marcus and others reported positive association of OSA and glaucoma. Lin et al reported a 1.67 times
higher risk of developing open angle glaucoma among OSA patients. However,
Geyer and also Girkin did not find any increased prevalence of glaucoma in OSA
patients. Kremmer reported 2 patients with OSA who had progression of their
glaucoma despite lowering of their intra-ocular pressure (medically and
surgically). Subsequently, they were started on continuous positive airway
pressure (CPAP) and there was a halt in their visual field (VF) defects.
PATHOPHYSIOLOGY OF GLAUCOMA IN
OSA:
(1) Hypoxia: Optimal cellular
function in all living cells is dependent on an adequate oxygen supply.
Neuronal cells are particularly vulnerable due to their higher metabolic rates
and oxygen consumption. OSA causes hypoxia, leading to oxidative stress and
inflammation by increasing the reactive oxygen species and inflammatory
markers. These biochemical mediators cause mitochondrial dysfunction in retinal
ganglion cells (RGCs) and ultimately apoptosis.
Apnea/hypopnea causes decreased
arterial oxygen saturation and increased carbon-dioxide saturation during
sleep. This results in transient hypoxia and increased vascular resistance in
body tissues. In ocular tissues this results in reduction of ocular perfusion
pressure and decreased oxygenation to the optic nerve which ultimately leads to
Glaucomatous Optic Neuropathy (GON).
(2) Vascular factors: OSA causes
cell wall changes in the carotid artery and plaque formation. The resultant
arterial narrowing reduces the blood supply to the optic nerve head (ONH) and
retina. Intermittent hypoxia causes an increase in the sympathetic nervous
activity in the body leading to vasoconstriction and systemic hypertension.
Raised autonomic activity during the daytime will cause autonomic dysfunction
which alters cerebral and ocular circulation at night.
During sleep, there is a normal
decrease in the sympathetic tone and blood pressure in the body. However,
ocular perfusion pressure is kept stable due to an increase in the episcleral
venous pressure around the eye during supine posture. Therefore, any elevation
in the sympathetic activity and autoimmune dysfunction may alter the ocular
perfusion pressure at night time.
Hypoxia also reduces the
vasodilator agent nitric oxide (NO). Conversely, the vasoconstrictor agent
endothelin-1 increases in this situation. Endothelin-1 has been found to be
higher in OSA and normal tension glaucoma (NTG) patients; this causes severe
impairment of vasodilator response of blood vessels.
Hypoxia induced Endothelin-1 and NO
imbalance in OSA causes vascular dysregulation and affects blood flow of ONH
and retina.
Hypoxia indirectly increases
intracranial pressure leading to decreased cerebral perfusion and disturbs
blood flow to the ONH, especially when associated with nocturnal systemic
hypotension.
(3) Mechanical factors: The role
of intra-ocular pressure (IOP) in OSA has not been clearly defined. However,
damage to the RGCs and ONH due to the previously mentioned factors increases
the susceptibility of these structures to even slightly elevated IOP.
Apart from the supine position at
night, obesity is associated with increased tightness around the eyeballs due to excessive intraorbital adipose tissue and
consequently, raised episcleral venous pressure. IOP increases during the apnea-hypopnea
episodes and alters the cerebral perfusion pressure.
GLAUCOMATOUS CHANGES IN OSA:
Retinal Nerve Fiber Layer (RNFL)
was found to be thinner in OSA patients and negatively correlated with AHI and
Respiratory Disturbance Index (RDI) and had a positive correlation with oxygen saturation in OSA patients.
Respiratory Disturbance (or Distress) Index reports on respiratory events during sleep (like AHI). However, it also includes respiratory-effort-related arousals (RERAs).
Incidentally, Adam did not find a
significant difference in the RNFL thickness between OSA and control patients.
However, RNFL thickness showed high variability in all quadrants in the OSA group.
OSA patients have higher inner
macula thickness compared to controls. This is attributed to hypoxia induced
swelling of the cell body, disruption of plasma membrane and alterations in
nuclear DNA.
Cup:disc ratio was found to be
higher in OSA patients (mean vertical integrated rim area= 0.67 +/- 0.4 mm3 in
OSA vs 0.55 +/- 0.29 mm3 in controls). Mean horizontal integrated rim width was
1.87 +/- 0.31 mm2 in OSA and 1.8 +/- 0.25 mm2 in controls.
Suspicious discs with
glaucomatous changes were 4 times more common in OSA compared to controls.
Choroidal thickness is altered in
OSA patients due to an imbalance between NO and endothelin-1. Lower choroidal
thickness was reported in OSA patients by Bayhan and also by Xin. However, Ozge
reported thicker choroidal measurements in OSA patients. But Karaca did not
find any difference among OSA and control groups.
Higher mean deviation (MD), lower
visual field index (VFI) and reduced retinal sensitivity have been reported in
OSA patients.
Visually evoked potential (VEP)
and pattern electroretinogram (PERG) were reported to be abnormal in a
significant number of patients diagnosed with OSA compared to zero patients in
the control group.
A few studies (Lin; Casas; Sergi)
have found IOP to be higher in OSA group (related to the increased orbital
adipose tissue content). However, Adam did not find any difference between OSA
and control groups.
A meta-analysis to study the
association of OSA with glaucoma was performed by Liu et al (2016). Based on 6
primary studies, a significant association between the 2 conditions was found.
The analysis concluded that OSA is a risk factor for glaucoma; however, further
studies are required to confirm the mechanisms of glaucoma causation in OSA.
CONCLUSION:
The association of OSA and glaucoma has not been conclusively provided by the few studies which have been performed on the subject. Although OSA is probably a risk factor for glaucoma, the diagnosis of the condition and its management is cumbersome at present.
REFERENCES:
1. Walsh JT, Montplaisir J.
Familial glaucoma with sleep apnea: A new syndrome ? Thorax. 1982;37:845-9.
2. Mojon DS et al. High
prevalence of glaucoma in patients with sleep apnea syndrome. Ophthalmology.
1999;106:1009-12.
3. Onen SH et al. High prevalence
of sleep disordered breathing in patients with primary open angle glaucoma.
Acta Ophthalmol Scand. 2000;76:638-41.
4. Geyer O et al. The prevalence
of glaucoma in patients with sleep apnea syndrome: Same in general population.
Am J Ophthalmol. 2003;136:1093-6.
5. Girkin CA et al. Is there an
association between pre-existing sleep apnea and the development of glaucoma ?
Br J Ophthalmol. 2006;90:679-81.
7. Chaitanya A et al. Glaucoma
and it’s association with obstructive sleep apnea: A narrative review. Oman J
Ophthalmol. 2016;9:125-34.
