13.

14.

15.

16.

17.

18.

19.

20.

2l.

22.

23.

24,

25.

26.

Sutton JR, Coats G, Gray GW, Mansell AL, Powles ACP,
Zahoruk R. Retinal studies at 446 torr ina hypobaric
chamber. Aviat Space Environ Med 1980; 51:407-408.

Eysel UT. Susceptibility of the cat's visual system to
hypoxia, hypotonia and circulatory arrest. Pflugers Arch
1978; 375:251-6.

Alder VA, Constable IJ. Effect of hypoxia on the maintained
firing rate of retinal ganglion cells. Invest Ophthalmol vis
Sci 1981; 21:450-6,

Enroth-Cugell C, Goldstick TK, Linsenmeier RA. The contrast
sensitivity of cat retinal ganglion cells at reduced oxygen
tensions. J Physiol 1980; 304:59-81.

Noell WK. Site of asphyxial block in mammalian retinae. J
Appl Physiol 1951; 3:489-500.

Linsenmeier RA, Mines AH, Steinberg RH. Effects of hypoxia
and hypercapnia on the light peak and electroretinogram of
the cat. Invest Ophthalmol 1983; 24:37-46.

Linsenmeier RA. Effects ef light and darkness on oxygen
distribution and consumption in the cat retina. J Gen
Physiol 1986; 88:521~42,

Steinberg RH. Monitoring communications between
photoreceptors and pigment epithelial cells: effects of
"mild" systemic hypoxia. Invest Ophthalmol 1987; 28:1888-
1904.

McFarland RA, Evans JN, Halperin MH. Ophthalmic aspects of
acute oxygen deficiency. Arch Ophthalmol 1941; 26:886-913,

Merceir A, Perdriel G, Sole P, Chevaleraud J, Graveline g.
Glaucoma incidence and significance in aviators. Aerospace
Med 1964; 35:567-71.

Payne BF. Glaucoma as an aviation hazard. Aerospace Med
1962; 33:1328-31.

Dieckert JP, O'Connor PS, Schacklett DE, Tredici TJ, Lambert
HM, Fanton JW, Sipperley JO, Rashid ER. Air travel and
intraocular gas. Ophthalmology 1986; 93:642-5,

Hanscom TA, Diddie KR. Mountain travel and intraocular gas
bubbles. Am 7 Ophthalmol 1987; 104:546.

Anderson DR. The mechanisms of damage of the optic nerve.
In: Krieglstein GK, Leydhecker W, eds. Glaucoma Update II.
New York: Springer-Verlag, 1983:89-93.

17

i


Table 3a. Means of two indices (mirror and asym.) that measure the
a@ifference between the superior and inferior hemifields (see
text) for six subjects with glaucoma (gl.) and for twelve
age-matched controls (contr.) by whether the test was done at
ground level or at a simulated altitude of 10,000 ft.

Mirror Asym.
Test Condition gl. contr. gl. contr.
Ground 256.2 61.5 214.7 50.4
10,000 ft. , 250.5 59.0 216.0 48.1

|

Table 3b. Results of MANOVAs, repeated measure design, for the within-
subject effect of altitude (ground level or at 10,000 ft.)
and the between-subject effect of glaucoma (with or without
glaucoma) on two indices (mirror and asym.) that measure the
difference between the superior and inferior hemifields (see
text). Shown are the F values (1, 16 Gegrees of freedom) and
Probabilities (p) that differences observed were due to

chance.
Variable
Factor Mirror . Asym.
Glaucoma 12.67, p<.001 19.32, p<.001
Altitude 0.33, p=.575 <.001, p=.950
Interaction 0.05, p=.827 .05, p=.818

SS

Two measures which indicated how subjects responded to the
testing procedure were the short-term fluctuation and the time to
complete the test. Short-term fluctuation is an output of the
Humphrey STATPAC. It measures the consistency of the subjects!’
responses during a single test session by thresholding 10 pre-
selected points a second time. The means of the short-term
fluctuation and time to complete the test are shown in table 4a.
Subjects with glaucoma took more time to complete the visual
field test and were more variable in their thresholds than
controls. Results of the MANOVA failed to show any effect of
altitude on these variables (table 4b).

11


ST

Partial or complete loss of consciousness occurs at about
20,000 feet but this can occur sooner in unacclimatized
individuals?. Also, exercise has produced loss of consciousness
at altitudes as low as 15,000 feet*. Carbon monoxide and
alcohol, which might be acquired by smoking and drinking, reduce
the body's ability to use what oxygen is available and would be
expected to produce the above events at lower altitudes?.

The effect of ao! visual system

Hypoxia can affect a variety of threshold measures. At
about 4,000 feet the absolute dark adapted rod threshold
increases until, at 16,000 feet, about twice as much light as at
sea level is needed for a threshold response>. Ernest and Kril1®
and others have found that the cone as well as rod threshola@ is”
Titicreased:"~Hécht et al.’ found that lights tend to appear dim,
and brightnéss discrimination becomes obviously reduced at about
8,000 feet. Reduction in brightness discrimination becomes much
more “iid?kead’ ‘at 15,000 feet where contrast must be about twice as
great as at sea level for threshold. Similar results have been
reported by Kohfeld®. on the other hand, Kobrick et al.? failed
to find a reduction in contrast sensitivity even at 25,000 feet.

Visual acuity (VA) can become diminished at about 8,000 feet
and at 177000 feet it approaches only about 50% of what it was at
“sea level, but these changes occur only in low levels of
illumination. With good illumination no VA changes are seen up
to 18,000 feet?°,

The visual fields remain grossly normal until about 20,000
feet, after which there is a constriction of the peripheral
field, an enlargement of the blind spot, and a development of
central scotomas!1, With more sensitive testing, visual field
defects can be found at lower altitudes. Angioscotomas (areas of
relative insensitivity around the arterioles of the normal
retina) start to enlarge at about 12,000 feet and continue to
enlarge until, at about 21,000 feet, the entire visual field is
obliterated except for a region 8-10 degrees about the macula?!,

Effects hypox: n the eye

Direct retinal damage, mainly in the form of hemorrhages,
has occurred in mountain climbers. At about 17,000 feet the disc
became hyperemic, the retinal blood vessels dilated and became
tortuous, and there was about a 50% incidence of retinal
hemorrhages!?, However, these studies on mountain climbers
involved elevations and durations far in excess of what is
experienced aboard civilian airplanes. Furthermore, the exercise
associated with climbing raised blood pressure and increased
oxygen demands. In a study using a hypobaric chamber at 14,500

2



Nakagawara VB. The relevance of vision defects in the
medical certification of civilian airmen. In: Goss DA,
Edmondson LL. eds. Proceedings of the 1988 Northeastern
State University Symposium on Theoretical and Clinical
Optometry. Northeastern State University, Tahlequah, Ok.
1988:59-71.

Heijl A, Lindgren G, Olsson J. Normal variablility of
static perimetric threshold values across the central visual
field. Arch Ophthalmol 1987; 105:1544-9,

Balazsi GA, Rootman J, Drance SM, Schulzer M, Douglas GR.
The effect of age on the nerve fiber population of the human
optic nerve. am J Ophthalmol 1984; 97:3760-6.

Sommer A, Enger Cc, Witt K. Screening for glaucomatous field
with automated threshold perimetry. Am J Opthalomol 1987;
103:681-4,

Anonymous. Guide for Aviation Medical Examiners. us Dept
of Transportation, Federal Aviation Administration. Oct.
1981:62-66.

18 ‘YXU.8. GOVERNMENT PRINTING OFFICE: 1991 - 561-020/20698



We selected 10,000 feet as our simulated test altitude
because this would provide a margin of error in determining if
visual field changes would be expected at altitude conditions
more typical of commercial flight in pressurized aircraft (about
8,000 feet). General aviation pilots may fly to 12,500 feet
without supplemental oxygen or pressurization but this altitude
was not selected in this study to preclude unnecessary risk to
the subjects. A simulated altitude of 10,000 feet did not have
an effect on any of the eight visual field variables we measured.

Our results argue against any increased restrictions in the
medical standards used by the FAA to medically certify civilian
pilots with glaucoma. Although the Guide for Aviation Medical
Examiners?! does not automatically disqualify pilots from any
class of license because of glaucoma, an ophthalmological
consultation is required if the Iop is greater than or equal to
24 mm Hg or if there is a Pressure difference greater than or
equal to 5 mm Hg between the two eyes. If the ophthalmological
report documents that pressures are under control and there is
little or no field loss, the pilot may be certified. our results
showed that field loss revealed by testing at ground level did
not increase with a brief exposure to an altitude greater than
that experienced by most general aviation and commercial pilots.
This was equally true both for older subjects with and without
glaucoma and for younger normal subjects.

Current FAA medical certification policy does not appear to
put pilots or passengers with glaucoma at risk for disease
progression. Under short-term exposure to mild hypoxia, we could
find no short-term change in visual field thresholds. Therefore
we would not expect altitude to cause any long-term progression
in glaucomatous damage.

15


Each subject visited the research facility three times.
Each visit was spaced no less than two days and no more than

three weeks apart. Table 1 outlines the tests performed at each
visit.

a

Table 1. Tests that were performed at each of three visits.

Visits Tests

1 physical and vision examinations
screening fields out of chamber

2 preliminary fields in chamber
dilated fundus examination

3 experimental fields in chamber

aS

At the first visit, we explained to each applicant the test
procedures and obtained a signed informed consent form. In order
to eliminate potential subjects who may have had a physical or
visual abnormality that would interfere with testing, the
following procedures were performed at the first visit:

1. the physical examination;

2. vision examination including a subjective refraction,
funduscopy through an undilated pupil, slit lamp examination
of the anterior segment and tonometry;

3. visual field testing of both eyes (referred to as screening
fields) with the central 24-2 threshold program.

At the conclusion of these procedures, the applicant was either
dismissed or provisionally accepted into the study pending the

outcome of the dilated fundus examination which was done at the
second visit.

One eye of each subject was selected for further testing.
In glaucoma subjects, we selected the eye that had the more
clearly delineated depression unless the field loss was extensive
in both hemifields in which case we selected the eye with the
lesser field loss. One member of each pair of controls had their
dominant eye tested while the other member had the non-dominant


The effects of hypoxia on glaucoma

What is the evidence that hypoxia may have a significant
effect on glaucomatous visual fields? High altitude might be
expected to exacerbate glaucoma in at least two ways-~by changing
intraocular pressure (IOP), or by reducing PO2 in blood delivered
to the optic nerve.

The literature on the effect of atmospheric pressure on IOP
is inconsistent. Mercier et al.2? reported that in a low
pressure chamber simulating 10,000 feet, normal subjects as well
as treated and non-treated glaucoma subjects showed a decrease in
IOP of about 3-5 mm Hg which continued even into descent.
However, Merci.r et al.?? also reported that Furaya and Bucalossi
found increases in IOP on ascent.

Payne?? gives arguments but no data that IOP would not be
expected to change with altitude because the eye is an enclosed
globe of fluid. On the other hand, when gas bubbles are in the
eye (for example after injections of a slow dissolving gas such
as perfluoropropane for retinal detachment surgery), ascent by

airplane** or by car in the mountains®® can greatly increase IOP.

Epidemiologic data are also available. Payne23 reported
that W.A. Arzabe found no difference in the prevalence of
glaucoma in Bolivia (about 3%) for individuals living at about
10,000 feet compared to those living near sea level. Mercier et
al.?2 examined 1048 eyes of civilian and military flying
personnel and found glaucoma in 2.7%, although their main
criterion for glaucoma was a pressure over 21 mm Hg. Fighter,
bomber, and test pilots had more glaucoma (3.8%) than other
civilian and military categories (1.6%). This finding suggested
to these authors the possibiliy that certain flight conditions
might increase IOP or otherwise aggravate glaucoma, but they did
not elaborate on this.

Whether or not hypoxia is a likely candidate for
accelerating the progression of glaucoma or temporarily
increasing field loss may depend on whether naturally occurring
hypoxia has any role in the etiology of open angle glaucoma. An
hypoxic etiology for glaucoma is still maintained as possible by
some, but they are in the minority. Anderson? suggests that
individuals who are abnormally susceptible to optic nerve damage
from high IOP may have faulty autoregulation of the blood supply
to the optic nerve head.

The primary study that supports the hypothesis that hypoxia
can exacerbate field loss typical of glaucoma may be Evans and
McFarland!], in which they note that the loss of visual field
caused by the enlargement of angioscotomas during hypoxia follows
very closely the pattern of field loss due to glaucoma. Since
that study, visual field testing devices have become much more

4


feet for 24 hours, no retinal hemorrhages were seen in spite of a
period of maximal exertion’3. Thus, no retinal hemorrhages would
be expected at the low altitude experienced in civilian air
travel.

Eyse114 has determined for the cat that, during anoxia,
electrical signals from the various components of the visual
system die out over time in the following order: retina (ERG b-
wave) first, followed by visual cortex, superior colliculus,
lateral geniculate nucleus, and lastly optic tract. Eysel
suggested that the extreme sensitivity of the retina to anoxia is
due to its greater 0, consumption/tissue weight for its degree of
blood perfusion than other structures such as the cortex.

Much effort has been devoted to determine which retinal
layers are most sensitive to hypoxia. This is of particular
interest to the present study because glaucoma involves damage to
retinal ganglion cells and their axons.

Single-cell recording from cat ganglion cells has shown no
changes until the percent oxygen breathed was reduced to under
10%79-16, In humans this would.correspond to an altitude of
15,000 feet. Alder et al.}5 found that 67% of the ganglion cells
showed an increase in spontaneous activity before an eventual
decrease (suggesting the loss of inhibition from earlier retinal
cells that must be less resistant to hypoxia). On the other
hand, Noel1+” reported that a large b-wave can still be seen in
man following black-out, indicating that early retinal processes
might not be impaired first.

Linsenmeier et al.1819 report that, in the cat, tissue PO,
reaches a minimum at some point in the outer retina. During
darkness, this PO, gradient across the receptors becomes even
steeper due to 0) consumption by mitochondria deep in the
receptor layer, which are most active in the dark. Linsenmeier!?
and Steinberg24 suggest that the steep PO, gradient in the dark
makes the receptor outer segments relatively hypoxic and the
metabolic rate decreases as a protective measure. This may
explain why McFarland et al.?! and Hecht et al.’ found that the
dark adapted threshold is so sensitive to hypoxia. A very small
decrease in PAO, causes the already relatively hypoxic rod
receptors to decrease their responsiveness to light to conserve
02.

Clearly, many of the effects of mild hypoxia on the visual
nervous system can be explained by receptor dysfunction alone.
These effects are measured with great sensitivity by
electrophysiological techniques. However, this does not preclude
an effect of mild hypoxia on other parts of the visual system.
Although it has been difficult to measure these effects in the
past, they might be revealed by the highly sensitive visual field
testing techniques available today.

3


10.

11.

12.

REFERENCES

Siesjo BK, Johannsson H, Ljunggren B, Norberg K. Brain
dysfunction in cerebral hypoxia anda ischemia. In: Plum F
ed. Brain Dysfunction in Metabolic Disorders. New York:
Raven Press. 1974: 74-112.

DeHart RL, ed. Fundamentals of Aerospace Medicine,
Philadelphia: Lea & Febiger, 1985: 93,

McFarland RA. The effects of altitude on pilot performance.

In: Hannisdahl B, Sem-Jacobsen CW, eds. Proceedings of XVII

International Congress on Aviation ana Space Medicine. Oslo:
Universitetsforlaget, 1968: 96-108.

Ernsting J, Stewart wk. Hypoxia and altitude. In: Gillies
GA, ed. A Textbook of Aviation Physiology. London: Pergamon
Press, 1965: 209-13,

McFarland RA. Human factors in relation to the development
of pressurized cabins. Aerospace Med 1971; 42:1303-18.

Ernest JT, Krill AE. The effect of hypoxia on visual
function: psychophysical studies. Invest Ophthalmol 1971;
10:323-28.

Hecht Ss, Hendley CD, Frank SR, Haig C. Anoxia and brightness
discrimination. 7 Gen Physiol 1946; 29:335-51,

Kohfeld DL. An evaluation of visual contrast sensitivity
measures. In: Eberts RE, Eberts CG, eds. Trends in
ergonomics/ human factors II. Amsterdam: Elsevier, 1985:83-
9

Kobrick JL, Crohn E, Shukitt B, Houston cs, Sutton JR,
Cymerman A. Operation Everest II: lack of an effect of
extreme altitude on visual contrast sensitivity. Aviat Space
Environ Med 1988; 59:160-4.

McFarland RA, Halperin MH. The relation between foveal
visual acuity and illumination under reduced oxygen tension.
J Gen Physiol 1940; 23:613-30.

Evans JN, McFarland RA. The effects of oxygen deprivation on
the central visual field. Am 7 Ophthalmol 1938; 21:968-80,.

McFadden DM, Houston CS, sutton JR, Powles ACP, Gray

GW, Roberts RS. High-altitude retinopathy. JAMA 1981;
245:581-86.

16


subjects with those of the older control subjects constituted our
study of age-dependent effects of altitude on visual fields.

We solicited paid volunteers to participate in the study
through private optometry and ophthalmology practices and by
placing ads in the local newspapers. To be selected as a
subject, an applicant had to fulfill all of the following
conditions:

1. pass a medical examination equivalent to a FAA class-three
physical which is required to obtain an airman medical
certificate (with supplemental EKG, spirometry, urinalysis,
and a hearing test);

2. have corrected visual acuity of 20/30 or better in at least
one eye;
3. be free of any non-glaucomatous retinal lesions that would

be likely to cause a defect in the central 30 degrees of the
visual field;

4. be able to respond reliably to the visual field testing,
i.e. the false positive and false negative rates needed to
be less than 33% and fixation losses less than 20%;

5. be able to be clearly classified as either having glaucoma
or being free of glaucoma as defined below.

Glaucoma subjects met all of the following points while
control subjects met none of them:

a) a visual field defect typical of glaucoma, i.e. a nasal
step and/or a paracentral scotoma;

b) elevated intraocular pressure (IOP) or a history of
elevated IOP;

ec) evidence of erosion of the rim tissue of the optic
nerve apparent when viewed stereoscopically with a slit
lamp;

a) currently under treatment for glaucoma.

Procedure

Visual fields were tested with the 24-2 threshold program on
the model 630 Humphrey Field Analyzer. This program estimated
the retinal threshold at 51 points within the central 24 degrees
(including the fovea, excluding the blind spot), and two
additional points on either side of the horizontal meridian at 28
degrees on the nasal side for a total of 53 points. Thresholds
that deviated by more than five decibels (dB) from the expected
value were estimated a second time. We used the average
threshold value for all points thresholded twice. The testing
sequence took about 10 minutes per eye. To minimize fatigue we
gave subjects a short rest of approximately 30 seconds at the
five minute mark.




Subjects left the chamber after the final visual field test
and went to an examination room where visual acuity,

ophthalmoscopy, and tonometry were performed. The subjects were
then dismissed.

Data were analyzed with a repeated measures design of
multiple analysis of variance using SPSS/PC V2.0 software. The
contrast used for analysis was the difference between the "up"
and the "down" fields. The parameters used to describe the

-visual field results are defined below.

RESULTS

All points in the visual field were classified as belonging
to one of three types depending on their position. The central
point was classified as foveal, the 32 remaining innermost points
were classified as paracentral; and the outer ring of 20 points
at about 22 degrees eccentricity were peripheral.

Glaucoma.

Table 2a shows the means of the three types of points, under
various test conditions, for both glaucoma and control subjects.
For all types of points, glaucoma subjects showed lower mean
sensitivities than did controls.

i

Table 2a. Mean sensitivity for three types of points in the visual
field for six subjects with glaucoma (gl.) and for twelve
age-matched controls (contr.) by whether the test was done
at ground level or at a simulated altitude of 10,000 ft.

Fovea Paracentral Peripheral
Test Condition gl. contr. gl. contr. gl. contr.
Ground 32.8 36.4 18.7) 29.1 17.4 27.8
10,000 ft. 33.7 36.8 19.4 29.1 18.2 27.9

a


_ eye tested. Half of the glaucoma subjects and half of the

younger subjects had their dominant eye tested.

At the second visit, subjects underwent two successive
visual field tests on the selected eye. These field tests were
performed in the hypobaric chamber in order to habituate subjects
to this environment. Atmospheric pressure remained at ground
level (1290 feet) during these tests. Before each of the two
preliminary field tests, subjects waited in the chamber for 24
minutes. This was done for all ground level tests to allow the
same amount of pretest time and dark adaptation as would later be
experienced during chamber decompression and equilibration.

After preliminary field testing, we dilated the pupils of
both eyes of each subject with 1% tropicamide and performed the
following:

1. binocular indirect ophthalmoscopy,

2. slit lamp inspection of the lens and optic nerve,

3. polaroid and 35mm stereoscopic photography of the optic
nerve.

The third visit was devoted to visual field testing of the
selected eye under two conditions: at ground level and at a
simulated altitude of 10,000 feet. The test sequence was altered
so that half of the subjects were tested first at ground level
followed by testing at 10,000 feet (down-up). The other half of
the subjects were tested first at 10,000 feet followed by ground
level (up-down).

For subjects tested in the up-down sequence, the pretest
ascent and equilibration took 24 minutes. The ascent rate was
2,000 feet per minute to 6,000 feet. This was followed by a
descent to 2,000 feet at 2,000 feet per minute to check for
possible sinus and middle ear blockage. Everything ‘being normal,
the chamber was depressurized at 2,000 feet per minute to a
simulated altitude of 10,000 feet. Total ascent time, including
the ear check, was approximately 9 minutes. An additional period
of about 15 minutes was spent at 10,000 feet before the field
test to allow for equilibration of PAO). After field testing,
the pressure in the chamber was returned to ground level, this
'descent' taking about 5 minutes. An additional period of 19
minutes was spent resting, so that the total interval between
tests was always 24 minutes.

In the down-up sequence, subjects first rested for 24
minutes and then were tested at ground level. Ascent and
equilibration took 24 minutes. This was followed by a visual
field test at 10,000 feet.


sophisticated and it might be expected that other subtle field
changes may be found with the relatively minor hypoxia associated
with typical flight conditions.

It is of interest to test whether eyes with glaucoma-induced
visual field defects show significant transient growth in
scotomas at elevations commonly encountered by pilots and
passengers (a maximum of about 8,000 feet within a pressurized
cabin). If this conjecture is supported, it may also be possible
that prolonged exposure to the mildly hypoxic conditions that
occur in long or repeated flights may cause a more rapid
progression of glaucomatous field defects. In addition, what may
have been measured as small, relatively safe scotomas at ground
level may enlarge and become unsafe in flight.

Hypoxia and age

The age structure of the population of licensed pilots has
changed considerably in the last 20 years. The percentage of
airmen over 50 years old has more than doubled from 9.5% in 1966
to 21.7% in 198627, Retinal sensitivity, as determined by
automated perimetry, declines with age, especially in the
periphery? + The optic nerve is also known to undergo a
reduction in the number of nerve fibers with advancing age2?.

For these reasons we also explored the possibility that age woulda
alter the effect of altitude-induced hypoxia on visual field
testing.

METHODS

This study looked for potential effects of altitude on
visual fields across two variables between subjects: glaucoma and
age. We did this by making two comparisons. First we compared
the visual fields of glaucoma subjects and age-matched controls
with respect to the possible effects of altitude. Secondly we
made a similar comparison between normal older subjects and
normal younger subjects. The data for the control group in the
first comparison were the same as those used for the older group
in the second comparison.

Subjects

For each of the six glaucoma subjects, we selected two age-
matched subjects without glaucoma (controls). All subjects in
that portion of the study were over 44 years of age (mean 58.4
years). We also tested six subjects without glaucoma under age
36 (mean 30.8 years). Comparison of the results from younger

5


THE EFFECT OF SIMULATED ALTITUDE ON THE VISUAL
FIELDS OF GLAUCOMA PATIENTS AND THE ELDERLY

INTRODUCTION

A major concern of the Federal Aviation Administration (FAA)
office of Aviation Medicine is the certification of pilot
applicants and the determination of appropriate medical standards
needed for flight safety. Glaucoma may present a special problem
because pilots with glaucoma may give visual field test results
that are acceptable at ground level but which may become
unacceptable at high altitude due to hypoxia. Another concern is
that repeated exposure to high altitudes may accelerate the
progression of glaucoma in passengers as well as pilots. Ifa
temporary increase in field loss at typical flight altitudes
could be demonstrated, then this would represent a stress on the
visual system that, with repeated or prolonged exposures, might
cause a permanent increase in visual field loss.

The present study tests whether glaucomatous and/or elderly
subjects at an atmospheric pressure simulating the high altitude
end of the typical flight environment will suffer temporary
scotomas compared with their fields at ground level.

r effect of hi ia_on th ervous system

Due to the high oxygen demands of nervous tissue!, central
nervous system effects are seen even with minimal levels of
hypoxia. The degree of these effects depends primarily on the
partial pressure of the oxygen (P02) breathed and on the length
of exposure to that pressure. fhe directly relevant factor,
however, is the partial pressure of oxygen in the arterial blood
(PAO,). PAO, is not reduced at a constant rate with increasing
altitude. At lower altitudes the reduction is small, but the
change in PAO, becomes larger above 10,000 feet. For example,
PAO, at 5,000 feet is about 79% of the sea level value; at 10,000
feet it is about 59% of the sea level value; and at 20,000 feet
it is about 33% of the sea level value’.

McFarland? has shown that mental functions start to become
impaired at about 10,000 feet. In his studies, short term memory
was first seen to decline at 8,000 to 10,000 feet with a more
rapid decline after 12,000 feet. Conceptual reasoning began
declining at about 12,000 feet with a more rapid fall at 14,000
to 16,000 feet. At about 16,000 feet disorientation,
belligerence, euphoria, and a loss of rational judgment may
occur.


a

Table 4a. Mean short-term fluctuation and mean time in minutes to
complete testing for six subjects with glaucoma (gl.) and
for twelve age-matched controls (contr.) by whether the
test was done at ground level or at a simulated altitude
of 10,000 ft.

Fluctuation Time
Test Condition gl. contr. gl. contr.
Ground 1.7 1.3 11.1 9.2
10,000 ft. 1.9 1.4 10.9 9.5

Le

LL SS

Table 4b. Results of MANOVAs, repeated measure design, for the within-
subject effect of altitude (ground el or at 10,000 ft.)
and the between-subject effect of glaucoma (with or without
glauco! on short-term fluctuation and mean time in minutes
to complete testing. Shown are the F values (1, 16 degrees
of freedom) and probabilities (p) that differences observed
were due to chance.

Variable
Factor Fluctuation Time
Glaucoma 4.49, p=.050 7.63, p=.014
Altitude 2.02, pe-175 0.07, p=.801
Interaction 0.02, p=.895 1.32, p=.267

a ed

Age_study

The 12 normal older subjects, used as age-matched controls
for the glaucoma study, were compared to six younger subjects to
investigate any possible age-dependent effect of altitude on the
visual field. Mean sensitivities of the three types of points in
the visual field are shown in Table 5a for young and old subjects
by condition of the experimental test (at ground level or at
10,000 ft.). The MANOVAs (table 5b) showed that older subjects
had lower sensitivities than younger subjects for peripheral and
paracentral points. Foveal thresholds were equal for the two
groups. Altitude had no effect on these sensitivities.

12


Table 6a. Mean short-term fluctuation and mean time in minutes to
complete testing for six subjects less than 36 years of
age (young) and for twelve subjects over 45 years of age

i (older) by whether the t was done at ground level or at

i a simulated altitude of 10,000 ft.

Fluctuation Time
Test Condition young older young older
4 Ground 1a 1.3 8.9 9.2
10,000 ft. 1.0 1.4 8.8 9.5

1 a
|

Table 6b. Results of MANOVAs, repeated measure design, for the
within-subject effect of altitude (ground level or at
10,000 ft.) and the between-subject effect of age (<36 or
>45 years old) on the mean short-term fluctuation and mean
time to complete t: ing. shown ‘e the F values (1, 16
degrees of freedom) and probabilities (p) that differences
' observed were due to chance.

/ Variable

; ' " Factor Fluctuation Time

Age ” s.94,  pe.027 1.75,  p=.205
Altitude 0.39, p=.543 0.49, p=.495
Interaction 1.83, p=.191 0.88, p=.362

DISCUSSION AND CONCLUSIONS

This study is concerned with the hypothesis that the
relative hypoxia encountered in flight might temporarily increase
the size of glaucomatous field defects, making glaucoma patients
potentially unsafe as pilots. Also, if true, repeated flights
may stress the optic nerve enough to accelerate glaucomatous
field loss, a concern to passengers as well as pilots with
glaucoma.

14



ACKNOWLEDGEMENTS

The authors gratefully acknowledge Mr. J.c.
Maxey and Nikon, Inc., who provided a retinal
camera for documentation of glaucomatous changes
in the optic nerve, and Mr. B. U. Thompson and
Allergan-Humphrey, who made available a back-up
visual field analyzer. We wish to thank Ms.
Kathryn J. Wood and Ms. Susan A. Vaughan who
assisted in the examination of our test
subjects. Our sincerest appreciation to Dean I.
Dornic, O.D., Christopher Fry, 0.D., Michael J.
Hampton, O.D., Donald Ledbetter, O.D., Max D.
Venard, O.D., and Sterling S. Baker, M.D., who

provided test subjects and other support during
this study.


Technical Report Documentation Page

1, Report No. 2. Goverment Accession No. 3. Recipient’s Catalog No.

DOT/FAA/AM-91/1

4. Title and Subtitle

5. Report Date January 1991
THE EFFECT OF SIMULATED ALTITUDE ON THE VISUAL FIELDS

OF GLAUCOMA PATIENTS AND THE ELDERLY 6. Performing Organization Code

8. Performing Organization Report No.

7. Author's) Van B. Nakagawara, O.D.; George W. Fulk, O.D-,
Ph.D.; Roger W. West, O.D., Ph.D

9. Performing Orgoni zation Name and Address 10. Work Unit No. (TRAIS)

FAA Civil Aeromedical Institute To Coa wy Ba NS
P.O. Box 25082 + Contract o .

Oklahoma City, Oklahoma 73125
: 13. Type of Report ond Period Covered

12. Sponsoring Agency Name and Address
Office of Aviation Medicine
Federal Aviation Administration
800 Independence Avenue, S.W.

Washington, D.C. 20591 14. Sponsoring Agency Code

15. Supplementary Notes

This work was performed under task AM-A-89-PHY-144

16. Abstract
This study tests whether mild “hypoxia, that is typically encountered in civilian
aircraft, causes temporary visual field defects in elderly persons or temporarily
increases pre-existing defects in persons with glaucoma. The central 24-2 program
on the Humphrey automated perimeter was used to test visual fields in three groups
of subjects: six with glaucoma, 12 age-matched controls all of whom were over 44
years of age, and six normal subjects under age 36. Visual fields were tested at
ground level and at 10,000 feet in an alternating sequence. A repeated measures
design of multiple analysis of variance was used to analyze the data. Altitude was
found to have no effect on the visual fields of subjects with glaucoma, age-matched
normals, and younger subjects. We found no evidence to suggest a change in the
present Federal Aviation Administration standards, which allow a special issuance
certificate to persons with glaucoma who wish to obtain medical clearance to Operate
civilian aircraft. Nor have we found any evidence that should discourage glaucoma
patients from flying as passengers.

17. Key Words 18, Distribution Statement

| Mision Document is available to the public
laucoma through the National Technical
isual Fields Information Service, Springfield
‘ertification Virginia 22161

Hypoxia
19. Security Classif. (of this report) 20. Security Classif. (of this page) 21. No. of Pages | 22, Price

Unclassified Unclassified 22

Form DOT F 1700.7 (8-72) Reproduction of completed page authorized


Altitude did not affect the mean sensitivity for any type of
point. This was shown by running a separate multiple analysis of
variance (MANOVA) for each of the three outcome variables, using
a repeated measures design (table 2b).

Table 2b. Results of MANOVAs, repeated measure design, for the
within-subject effect of altitude (ground level or at
10,000 ft.) and the between-subject effect of glaucoma
(with or without glaucoma) on the mean sensitivity of three
parts of the visual field. Shown are the F values (1, 16
degrees of freedom) and probabilities (p) that differences
observed were due to chance.

Variable
Pactor Fovea Paracentral Peripheral
Glaucoma 10.28, p=.006 18.79, p=.001 17.88, p=.001
Altitude 2.96, p=.104 2.68, p=.121 1.39, p=.256
Interaction 0.33, p=.574 2.10, p=.176 1.12, p=.306

|

Glaucoma is known to affect the upper and lower hemifields
independently*°, so that glaucomatous damage accumulates in one
hemifield in advance of the other. The field, therefore, becomes
asymmetric across the horizontal meridian. Two measures of the
difference between the upper and lower hemifields were devised:
the mirror image index and the asymmetry index. The mirror image
index was the sum of the absolute values of the differences
between each point in the inferior field and its corresponding
mirror-image point in the superior field. The asymmetry index
was the absolute value of the difference between the mean
threshold of superior points and the mean threshold of inferior
points. If altitude increased glaucomatous depressions in the
visual field, these indices would increase in value for subjects
with glaucoma but not for controls.

Table 3a shows the means of these two measures by altitude.
Both indices were approximately five times larger in subjects
with glaucoma than in controls. However, there was no evidence
that altitude affected these indices (table 3b).

10


Mean sensitivity for three types of points in the visual
f. d for six subjects less than 36 years of age (young)
and for twelve subjects over 45 years of age (older) by
whether the test was done at ground level or at a
simulated altitude of 10,000 ft.

Fovea Paracentral Peripheral
Test Condition young older young older young older
Ground 36.8 36.4 31.1 29.1 30.7 27.8
10,000 ft. 36.7 36.8 31.2 29.1 30.5 27.9

|

Table 5b. Results of MANOVAs, repeated measure design, for the
within-subject effect of altitude (ground level or at
10,000 ft.) and the between-subject effect of age (<36 or
>4€5 years old) on the mean sensitivity of three parts of
the visual field. Shown are the F values (1, 16 degrees
of freedom) and probabilities (p) that differences observed
were due to chance.

Variable

Factor Fovea Paracentral Peripheral

Age 0.04, p=.845 19.39,  p<.001 8.53, p=.010

Altitude 0.13, p=.727 0.06, p=.811 0.08, p=.780

Interaction 0.69, p=.420 <.01, p=.967 0.18, p=.680

LL eS

Table 6a shows the short-term fluctuation and the time to

complete the visual fields test for both groups of subjects by

test condition and by order of testing.

Younger and older

subjects took the same length of time to complete the test and

showed equal short-term fluctuation in thresholds.

failed to affect these variables (table 6b).

Altitude