Correlation of CPAP, BiPAP, and AutoPAP use with intraocular
pressure in patients with sleep apnea and glaucoma.
1
B.S. ,
2
M.D. ,and
2
M.D.
Daniel J. Watson
Anita Vin
Shuchi Patel
1 Loyola University Chicago, Stritch School of Medicine, Maywood, IL
2Department of Ophthalmology, Loyola University Chicago Stritch School of Medicine, Maywood, IL
Introduction and Purpose
Background Continued
Introduction
Several studies have shown that obstructive sleep apnea (OSA) is related to
pathology of the eye. Correlations between OSA and floppy eyelid syndrome,
primary open angle glaucoma (POAG), normal tension glaucoma (NTG),
nonarteritic anterior ischemic optic neuropathy (NAION), papilledema, and
keratoconus have all been shown [4,12]. Our research team is interested in the
relationship between obstructive sleep apnea and glaucoma (GLC). Evidence
has shown that people with sleep apnea are more likely to have glaucoma and
people with glaucoma are more likely to have sleep apnea [12]. OSA results in
impaired oxygen supply to the optic nerve. This results in neuropathy and
degeneration of retinal ganglion cells in the nerve fiber layer with concomitant
loss of vision. Recently, there has been some controversy over whether or not
positive airway pressure (PAP) used to treat OSA raises intraocular pressure
[1,2,6,7,8]. Intraocular pressure (IOP) is currently the only modifiable risk factor
for glaucoma. High intraocular pressure inhibits blood flow and trophic factors
needed to support the optic nerve and retinal ganglion cells. In this study, we
looked at different positive airway pressure machines and how they affected the
IOPs of patients with both OSA and GLC (POAG + NTG) and in patients with
just OSA. No previous research study has measured IOPs of patients with both
OSA and GLC while on PAP therapy.
positive pressure. The EPAP is a therefore a lower pressure level that tries to relieve this
discomfort. BiPAP machines also have spontaneous (S) or timed (T) cycling between IPAP
and EPAP.
[3] AutoPAP- automatic positive airway pressure machines modulate the pressure
administered during the night so that only the minimum pressure is used to maintain an
open airway. Maximum and minimum pressures are programmed into the machine.
Purpose
By understanding the effects of different positive airway pressure machines on
intraocular pressure, we can better manage patients who have been diagnosed
with both sleep apnea and glaucoma. If our study happens to find that one
machine increases intraocular pressure less, then perhaps the treatment
modality for patients with both sleep apnea and glaucoma needs to be modified
to prevent raised intraocular pressure and further progression of glaucoma.
Background
Figure 1.
Sleep Apnea
Obstructive sleep apnea is
characterized by the loss of pharyngeal
muscle tone and the collapse of the soft
palate or base of tongue into the airway
during sleep (see figure 1) [12]. The
prevalence of sleep apnea is 2 to 9% of
the population if defined by patients
having at least one clinical symptom and
an apnea/hypopnea index (AHI) of >5
[9, 5]. If just defined by an AHI >5, prevalence is 20% for the general population and it
is estimated that 26% of adults are at high risk for OSA [9] Risk factors, symptoms,
and complications of sleep apnea are listed below in Table 1.
Table 1.
Risk Factors
Symptoms
Untreated Complications
Obesity
Hypertension
Hypothyroidism
Anatomically narrowed
airways
- Large neck circumference
- Alcohol/ sedatives before
sleep
- History of cigarette use
- Snoring
- Waking with a snort or
while gasping or coughing
- Told by others hold breath
or stop breathing during
sleep
- Daytime somnolence
- Morning Headaches
- Weight Gain
- Depression
Cardiovascular:
- arrhythmias
- hypertension
- autonomic dysfunction
- vascular dysregulation
- atherosclerosis
Kidneys: nephritic syndrome
Liver: hypoxic hepatitis
Central Nervous System:
stroke
-
Testing and Diagnosis
Sleep apnea is detected with overnight sleep studies also called
polysomnography. The Epworth Sleepiness Scale is also a good measure of
symptoms associated with sleep apnea where 0-9 points are normal and 10+ out
of 24 points are considered abnormal. Diagnosis of sleep apnea is based on the
apnea/hypopnea index (AHI) or the respiratory disturbance index (RDI). Apneas
are defined as the complete cessation of breathing for greater than 10 seconds.
Hypopneas are partial airway collapse with 30-50% reduction in airflow
accompanied by at least a 3-4% decrease in oxygen saturation or arousal. The
AHI is the number of apnea and hypopnea episodes per hour whereas the RDI
includes the number of respiratory event related arousals in addition to apneas
and hypopneas per hour. An AHI of <5 is considered normal, 5-15 is mild OSA,
15-30 is moderate OSA, and >30 is severe OSA [12].
Figure 2.
Treatment
Treatments for OSA include weight
loss, dental devices, sleep position
restriction, and surgery. The most
common treatment, however, is
positive airway pressure (PAP) therapy.
Positive air pressure acts like a splint
to prevent collapse of the airway during
sleep (see figure 2). There are many
different PAP machines each with their
own features:
[1] CPAP- continuous positive airway pressure machines administer the same
pressure level measured in cm of H2O during the use of the machine
[2] BiPAP- bi-level, biphasic, or variable positive airway pressure machines
administer different pressure levels during inspiration (IPAP) and expiration
(EPAP). The greatest discomfort reported by patients is trying to exhale against
Methods
CPAP, BiPAP, and AutoPAP machines can have different features that improve patient
comfort by modulating the pressure administered. RAMP- is a feature that gradually
increases the administered pressure to the prescribed pressure over a period of time after
therapy is initiated to allow the patient to fall asleep. EPR- exhalation pressure relief, is a
feature that transiently decreases pressure while a patient exhales but still maintains the
prescribed pressure throughout therapy. C-flex, A-flex, and Soft-X are all different types of
EPR. PAP machines also can have air humidifiers that can heat, cool, or maintain the air
at room temperature. Machines can also be used with different facemasks. These include
nasal, nasal pillow, nasal prong, oral, hybrid (nasal and oral), or full face.
Glaucoma
Table 2.
Risk Factors
-
Increased intraocular pressure
Aging
Glaucoma in first degree relative
Race (higher in African Americans)
Suspicious optic nerve appearance
(cupping or asymmetry)
- Thin Corneas
- High myopia (nearsightedness)
-
Diabetes
Hypertension
Eye injury or surgery
History of steroid use
Migraine headaches
Peripheral vasospasm
Sleep related breathing
problems
- Gender (males more
likely)
Symptoms
- Generally
symptomless
until the
disease has
progressed
significantly
- 50% of nerve
loss can occur
without loss of
vision
Untreated
Complications
- Loss of
vision
- Peripheral
vision is lost
first and
then central
vision
Glaucoma is a group of diseases characterized by a progressive degeneration of retinal
ganglion cells and the optic nerve. High intraocular pressure is often the cause of retinal
ganglion cell damage due to compression of blood vessels and axons transporting trophic
factors to support them [13]. However, other pathologies that inhibit blood supply to the
cells and the optic nerve are also implicated in glaucoma including obstructive sleep
apnea [4]. Prevalence of glaucoma is 2% of the population >40 years old. It is estimated
that in 2010, 44.7 million people worldwide were affected by primary open angle glaucoma
with 8.4 million resulting in bilateral blindness. These numbers are projected to be 58.6
million and 11.2 million in the year 2020 [10].
Increased intraocular pressure is a
Figure 3.
contributing factor to the
development of glaucoma. The most
common cause of increased IOP is
the excessive production or
inadequate drainage of aqueous
fluid in the eye. Aqueous fluid is
produced by the ciliary epithelium
and travels from the posterior
chamber to the anterior chamber
through the pupil (see figure 3).
Drainage of aqueous fluid occurs
through two routes: trabecular or
uveoscleral. The trabecular
meshwork is a loose fibrous
connective tissue found at the
iridocorneal angle which allows
drainage of aqueous into Schlemm’s canal and then into the scleral veins. Drainage
through the uveoscleral pathway is through the muscle fibers of the ciliary body into the
scleral veins [13]. Average eye pressures are around 15mmHg while normal pressures
are considered to be below 21mmHg. Pressures of 22mmHg have been shown to cause
8.6 times more damage than 21mmHg [11]. There are three major types of glaucoma.
Angle-closure glaucoma (ACG) occurs when the iridocorneal angle is obstructed
preventing the drainage of aqueous fluid. Primary open angle glaucoma (POAG) occurs
when the iridocorneal angle is free from obstruction but IOPs are high and optic nerve
changes and vision loss are detected. Normal tension glaucoma (NTG) is when IOPs are
in the normal range but optic nerve changes and vision loss are still detected [13].
Figure 4.
Testing and Diagnosis
Diagnosis of glaucoma is made when
changes in the optic nerve are
visualized such as an increased cupto-disc ratio, asymmetry of cupping
between eyes, hemorrhage of optic
disc, pigment and rim changes, and
retinal nerve fiber layer thinning (see
figure 4). Diagnosis is made after a
dilated fundus exam to visualize the
optic nerve, applanation tonometry to
measure IOPs, gonioscopy to visualize the iridocorneal angle, perimetry to assess the
visual field, and retinal nerve fiber layer analysis.
Treatment
Treatment for glaucoma is usually through the use of eye drops. Beta blockers,
prostaglandin analogues, alpha-adrenergic agonists, and carbonic anhydrase inhibitors
either reduce the production of aqueous fluid or increase its drainage. Patients with
severe glaucoma can undergo various surgeries and procedures aimed at lowering
intraocular pressure.
Acknowledgements: This work was supported by the Richard A. Perritt Charitable Foundation and the Illinois Society for the
Prevention of Blindness.
Study Design
Patients seen in the glaucoma clinic found to also have been diagnosed with OSA were
recruited for this study. They wore a CPAP, BiPAP, or AutoPAP machine during a 2 hour
session in which intraocular pressure measurements were made. Five pressure
measurements were taken in sequence with each patient:
Discussion Continued
Figure 7.
1. Seated
2. After lying supine for 15 min
3. Supine immediately after 30 min of PAP therapy
4. Remaining supine for 15 min after PAP therapy cessation
5. After returning to the seated position for 15 min.
Inclusion criteria was greater than 18 years of age, diagnosed with OSA on PAP therapy,
and a normal anterior chamber with an open angle.
Exclusion criteria was younger than 18, inability to provide informed consent, any
abnormality that prevented reliable applanation tonometry, angle closure glaucoma, and
central sleep apnea. Surgeries and concomitant use of drops were not exclusion criteria.
This study was approved by the institutional review board and the human research
protection program.
Figure 5 (above)
& 6 (below).
Data Collection
Intraocular pressure measurements were taken via two methods:
Perkins and Tono-Pen. The Perkins tonometer is a handheld version of
the Goldmann tonometer (figure 5) which is considered the gold
standard for IOP measurements. The Tono-Pen (figure 6) is handheld
instrument that gives a digital pressure reading with a confidence
interval. Both are forms of applanation tonometry which involves
contact with the front of the eye after administration of a topical
anesthetic drop.
Figure 7 shows the delicate interplay between GLC, OSA, and PAP therapy. Sleep
apnea causes vascular dysregulation which can cause ischemic damage to the optic
nerve. PAP therapy can prevent the ischemic episodes of OSA but may also increase
intraocular pressure which damages the optic nerve by decreasing axonal transport of
trophic factors and cutting off blood supply. It has been proposed that PAP therapy
increases intraocular pressure by first raising intrathoracic pressure and intracranial
pressure. The rise in intracranial pressure increases venous circulation pressure and
reduces aqueous humor outflow subsequently resulting in increased intraocular
pressure [2, 4, 13].
Summary
• Glaucoma (GLC) is a group of diseases that result in optic nerve damage
Anticipated / Preliminary Results and
Discussion
Preliminary Data
Due to ongoing status of this study, only general observations of the data can currently be
made. Recruitment and data gathering are still in process in order to obtain statistical
significance or non-significance.
Anticipated Results
1. We expect there to be an increase in intraocular pressure
after PAP therapy.
Preliminary data has shown an increase in intraocular pressures after PAP therapy. Other
studies have shown a significant increase in IOPs after PAP therapy. Concern was first
reported by Alvarez-Sala, et al. in 1992 and followed with a study by the clinicians in 1994.
They found a significant increase in IOP in patients with primary open angle glaucoma
(POAG) but no significant increase in non-glaucomatous (non-GLC) subjects. Recently,
Kiekens, et al. 2008 and Pepin, et al. 2010 reevaluated the correlation between CPAP
therapy and an increase in IOP. Both research teams studied non-GLC patients recently
diagnosed with OSA and each found a significant increase in IOPs. However, the studies
had contradicting conclusions: Kiekens, et al. reported that CPAP machines may be
involved in the increase of IOP and Pepin, et al. reported that CPAP machines restore
normal IOP rhythms and that the dangers of CPAP use can be discarded [1,2,6,7,8].
2. We expect AutoPAP machines to result in the least increase
in intraocular pressure compared to CPAP and BiPAPs
and retinal ganglion cell loss. The only modifiable risk factor of glaucoma is
intraocular pressure (IOP).
• Obstructive sleep apnea (OSA) is the cessation of breathing during sleep
due to the loss of oropharyngeal muscle tone and collapse of the airway.
• Positive airway pressure (PAP) splints open the airway during sleep to
prevent collapse. There has been controversy over whether or not PAP
therapy increases IOPs.
• We measured IOPs during PAP therapy with 3 different machines on
patients with GLC and OSA or just OSA. This is the first study to measure
IOPs of patients with both GLC and OSA while on PAP therapy.
• We report our anticipated results and preliminary data. We expect there to
be an increase in intraocular pressure after PAP therapy; AutoPAP machines
to increase IOPs the least compared to CPAPs and BiPAPs; and patients with
both OSA and GLC to experience the greatest increase in intraocular
pressure during PAP therapy.
References
1. Alvarez-Sala R, Díaz S, Prados C, et al. Increase of intraocular pressure during nasal CPAP. Chest.
1992 May;101(5):1477.
AutoPAP machines modulate the pressure administered during the night so that only the
minimum pressure is used to maintain an open airway. This is the first study to compare
intraocular pressure measurements between CPAPs, BiPAPs, and AutoPAPs.
2. Alvarez-Sala R, García IT, García F, et al. Nasal CPAP during wakefulness increases intraocular
pressure in glaucoma. Monaldi Arch Chest Dis. 1994 Dec;49(5):394-5.
3. We expect patients with OSA and GLC to experience the
greatest increase in intraocular pressures during PAP therapy.
4. Dhillon S, Shapiro CM, Flanagan J. Sleep-disordered breathing and effects on ocular health. Can J
Ophthalmol. 2007; 42(2): 238-43
Alvarez-Sala 1992 and 1994 have already reported significant increases in intraocular
pressure among patients with glaucoma after PAP therapy. We believe patients with both
OSA and GLC will have increases beyond these findings because patients with OSA have
more connective tissue flexibility which may allow for a greater increase in intrathoracic
pressure and subsequently increased intracranial pressures and intraocular pressure.
6. Kiekens S, DeGroot V, Coeckelbergh T, et al. Continuous positive airway pressure therapy is
associated with an increase in intraocular pressure in obstructive sleep apnea. Invest Ophthalmol Vis
Sci. 2008 Mar;49(3):934-40.
Raw Data Snapshot
Table 3
3. Antonescu-Turcu A and Parthsarathy S. CPAP and Bi-level PAP therapy: new and established
roles. Resp Car. 2010 Sep; 55(9):1216-28
5.Epstein LJ et al. Clinical guideline for the evaluation, management and long-term care of obstructive
sleep apnea in adults. J Clin Sleep Med. 2009 Jun 15;5(3):263-76.
7. Melki L, Haller, M, Pepin JL, et al. Sleep apnea and intraocular pressure: effects of continuous
positive airway pressure treatment. Invest Ophthal Vis Sci 2005; 46: E-Abstract 4834
8. Pepin JL, Chiquet C, Tamisier R, et al. Frequent loss of nyctohemeral rhythm of intraocular
pressure restored by nCPAP treatment in patients with severe apnea. Arch Ophthalmol. 2010 Oct;
128(10): 1257-63
9. Punjabi NM. The epidemiology of adult obstructive sleep apnea. Proc Am Thorac Soc. 2008 Feb
15;5(2):136-43
10. Quigley HA and Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br
J Ophthalmol. 2006 Mar;90(3):262-7.
Table 3 shows data from 5 patients enrolled in the study. The number furthest left
corresponds to the pressure measurements described in the methods section above. The
values are given first for the right eye (Tono-Pen, Perkins) then for the left eye. All patients
had OSA and their GLC status is listed along with their machine type and settings.
11. Sommer A, Tielsch JM, Katz J, Quigley HA, Gottsch JD, Javitt J, Singh K. Relationship between
intraocular pressure and primary open angle glaucoma among white and black Americans. The
Baltimore Eye Survey. Arch Ophthalmol. 1991 Aug;109(8):1090-5.
12. Waller EA, Bendel RE, Kaplan J. Sleep disorders and the eye. Mayo Clin Proc. 2008 Nov; 83(11):
1251-61
13. Weinrab RN and Pen TK. Primary open-angle glaucoma. Lancet. 2004 May; 363: 1711-20