Correlation of CPAP, BiPAP, and AutoPAP use with intraocular

1
Correlation of CPAP, BiPAP, and
AutoPAP use with intraocular pressure
in patients with sleep apnea and glaucoma. Daniel
J. Watson B.S.1, Anita Vin M.D.2,and Shuchi Patel
M.D.2 1 Loyola University Chicago, Stritch
School of Medicine, Maywood, IL 2Department of
Ophthalmology, Loyola University Chicago Stritch
School of Medicine, Maywood, IL
Methods
Introduction and Purpose
Background Continued
Discussion Continued
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 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.
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.
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.
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. 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.
Figure 7.
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.
Glaucoma
Table 2.
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.
Risk Factors Risk Factors Symptoms Untreated Complications
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) Generally symptomless until the disease has progressed significantly 50 of nerve loss can occur without loss of vision Loss of vision Peripheral vision is lost first and then central vision
Figure 5 (above) 6 (below).
Summary
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 gt40 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.

• Glaucoma (GLC) is a group of diseases that
  result in optic nerve damage 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.

Background
Anticipated / Preliminary Results and Discussion
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 gt5

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. Ant
icipated Results
Increased intraocular pressure is a 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
Figure 3.
1. We expect there to be an increase in
intraocular pressure after PAP therapy.
9, 5. If just defined by an AHI gt5, 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.
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.
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
drainage of aqueous into Schlemms 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.
References
2. We expect AutoPAP machines to result in the
least increase in intraocular pressure compared
to CPAP and BiPAPs
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 lt5 is considered
normal, 5-15 is mild OSA, 15-30 is moderate OSA,
and gt30 is severe OSA 12.
1. Alvarez-Sala R, Díaz S, Prados C, et al.
Increase of intraocular pressure during nasal
CPAP. Chest. 1992 May101(5)1477. 2.
Alvarez-Sala R, García IT, García F, et al. Nasal
CPAP during wakefulness increases intraocular
pressure in glaucoma. Monaldi Arch Chest Dis.
1994 Dec49(5)394-5. 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 4. Dhillon S, Shapiro CM, Flanagan
J. Sleep-disordered breathing and effects on
ocular health. Can J Ophthalmol. 2007 42(2)
238-43 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 155(3)263-76. 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 Mar49(3)934-40. 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
155(2)136-43 10. Quigley HA and Broman AT. The
number of people with glaucoma worldwide in 2010
and 2020. Br J Ophthalmol. 2006
Mar90(3)262-7. 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
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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
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.
3. We expect patients with OSA and GLC to
experience the greatest increase in intraocular
pressures during PAP therapy.
Figure 4.
Testing and Diagnosis Diagnosis of glaucoma is
made when changes in the optic nerve are
visualized such as an increased cup-to-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
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. Raw Data Snapshot
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
Table 3
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.
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
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.