12 Behavior, Aging, and the Nervous System

Moreover, if we compare the means for the extremes in the
ages studied, namely, those under twenty-one and those over
fifty years of age, we find that the older group definitely has a
longer pupillary latency (0.273 sec.) than the younger group
(0.238 sec.). Comparing the means of these two groups, a
highly significant t value of 3.92 was found with 34 degrees of
freedom. The probability that the two populations would have
the same mean would be less than 1 in 1000.

If we compare the original pupil size and aging, we find that
with aging, the pupil diameter decreases. Statistically, this may
be expressed by a Pearsonian r of -0.55, a regression line
y = 0.36x-++7.5, a chi-square of 11.20 (df = 1; p<.001).

The average latency of response to original pupil size in dark-
ness shows a negative relationship.

A possible relationship between latency of response and myopia
with mydriasis has been brought to our attention in five cases
which we have studied. In each instance, regardless of age, the
latency period has been longer than 0.260 sec. Whether these
longer latency periods have occurred by chance or not will have
to be determined by further studies.

Longer latency period in pupillary constriction as a possible
correlate of nerve conduction disease was introduced to us by a
physician, who, himself, was the victim of Charcot-Marie-Tooth
disease, a progressiye disorder that symmetrically affects only
the distal muscles of the legs and occasionally the arms. It is
associated with pathologic changes in the anterior horn cells,
peripheral neuromuscular units, posterior columns and frequently
other tracts of the spinal cord including the pyramidal (Baker,
1962). Our patient showed, at the age of fifty-one, a pupillary
latency period of 0.299 sec.

CONCLUSIONS

1) A method is described for measuring pupillary contraction
latency period regardless of initial absolute pupil diameter.

2) Pupillary contraction latency period increases with age.
The data presented show that the normal pupil, as usually found
in healthy young people, has a shorter latency than is found in
older normal subjects.


Latency of Pupillary Reflex to Light Stimulation 3

Kumnick (1956) stated that the latency period of pupil con-
striction is not affected by increasing age® but is affected sig-
nificantly by the pupillary conditions of restitution and decay
of restitution at certain age levels.

METHOD

The over-all features of the instrumentation used for pupil
latency measurements are shown in the block diagram of Figure
2 and the photograph of Figure 3. The basic instrument is the
Electronic Pupillograph (10, 14). It consists of a scanner, an am-
plifier-detector assembly and a stimulator.

The scanning unit is a rotating drum with slits in its periphery
through which a light beam is projected. This beam is divided
into two identical paths which scan both irises in rectangular
patterns, comprised of twelve horizontal lines, at a rate of sixty
times per second. A Wratten 87C filter placed between the
drum and the eye renders the scanning light invisible to the dark-
adapted person. The light of the two scanning beams is reflected
onto two photoelectric cells. The outputs of these cells are
amplified in two identical channels and converted into DC analog
voltages, whereby the voltage amplitudes are proportional to the
largest horizontal diameters of the pupils.

The stimulator lamp energy is reflected from a mirror located
just above the optical path of the infrared scanning unit. The
same mirror is used to reflect a dim, red fixation light which is
placed on the ceiling above the scanner at a distance of four feet.
The line of regard and the direction of the stimulating light beam
are 15° above horizontal.

The Grass Photic Stimulator (model PS-2) provided a high
intensity flash of approximately one million peak candle power
for 10 microseconds. The flash was seen by the left eye only,
while measurements of latency period were obtained from the
consensually reacting right pupil. For these measurements, the
derivative of the Electronic Pupillograph scanner voltage was
used rather than the analog voltage which represents the pupil

* Kumnick noted means of initial latency of pupil constriction to be 0.200 for age
group 7.5—15.0 years; 0.222 for 18.1—28.2 years; 0.226 for 30.5—52.7 years; 0.226 for
704-908 years.



8 Behavior, Aging, and the Nervous System

Age in Years

14-20
21-30
31-40
41-50
51-60

61+

RESULTS

Our sample consisted of 86 persons ranging from 14 to 67 years
of age (Table 1). The average latency period in these subjects

TABLE 1
AcE oF Susyects use IN THIS EXPERIMENT

No. of Subjects

15

7

10

22

20

2
N=86

was 0.252 second, with a range from 0.214 to 0.314 second
(Figure 7). It should be noted that the true latency periods are
somewhat shorter than the values indicated in this communica-
tion. The latency period as determined in this experiment was
the time interval from the start of stimulation to the moment
when pupillary contraction had reached a speed of 3.5 mm. per

Medion Age

‘Average Latency (rs)
8

L
os Cr a a ae
AGE

Figure 7. Scattergram of average pupil latency periods by age.


Latency of Pupillary Reflex to Light Stimulation 5

diameter. The derivative voltage, representing the velocity of
the pupil, was used as the following description indicates.

A signal coinciding with the stimulator light current is avail-
able at the External Monitor receptacle of the Grass Photic
stimulator. This signal started both the sweep circuit of a
Hughes Memoscope (model 105) and the “Start” circuit of a
Beckman Berkeley Universal Timer (model 7350). The timer
was stopped when the derivative pupil signal exceeded a pre-set
voltage level of its “Stop” circuit. The time measured from the
“Start” to the “Stop” signal was read out on a Digital Recorder
(model 1452).

Initially, a comparison of the analog signal representing the
pupil diameter and its derivative was made simultaneously to
determine which of the two signals available from the Electronic
Pupillograph was the more suitable for timing purposes. In this

0 100 ee 300 400

TIM

MILLISECONDS .

ens mi iia . am
Figure 4. Analog voltage of pupil diameter and its derivative in response to
high intensity light.



4 Behavior, Aging, and the Nervous System

PUPIL STIM,

f—~} MEMOSCOPE

TIMER

DIGITAL
RECORDER

Figure 2. Block diagram of instrumentation for pupil latency measurement.

ink
Figure 3. Photo of test apparatus.


Latency of Pupillary Reflex to Light Stimulation 7

timer was opened by the “Start” circuit when the Photo-Stimula-
tor was triggered. The gate was closed by the timer “Stop” circuit
when the voltage from the derivative signal exceeded a pre-set
level of the “Stop” circuit. The counter, in the meantime, counted
the number of cycles that passed from the crystal oscillator
through the gate at a 10,000 cycle per second rate.

The “Stop” level of the timer was pre-set so that a derivative
signal of -0.30 volts did not stop the timer, while -0.35 volts did
stop it. A voltage of -0.35 was equivalent to a pupil contraction
velocity of 3.5 mm. per second (manufacturer's specifications ).

One of the advantages of using the derivative pupil signal is
that the same “Stop” level on the timer can be used for all sub-
jects. Once the diameter of the pupil attains equilibrium (in
darkness), its derivative becomes zero and all measurements are
taken from this zero point, i.e., all measurements are independent
of the initial absolute diameter of the pupil or of the iris color.

‘igure 6. Presetting of “stop-clock” timing circuit.



AM 65-25

LATENCY OF PUPILLARY REFLEX TO LIGHT
STIMULATION AND ITS RELATIONSHIP TO AGING

Richard Feinberg, Ph. D.
Edward Podolak

Approved by Released by
Att 4 md Wd Whe
Arruur E. Wenn! M. M.S. Wurtz, M.D.
Drrecror, GCRI- Feperat Air Surcron
September 1965

FEDERAL AVIATION AGENCY

Office of Aviation Medicine
Georgetown Clinical Research Institute
Washington, D.C.



10 Behavior, Aging, and the Nervous System

TIME IN MILLISECONDS

DERIVATIVE VOLTAGE

LIGHT INTENSITY

r -1.00

Figure 8. Composite curves of average response of pupil vs. light intensity.

with the highest setting is approximately one million peak candles
measured on the axis of the parabola at a distance of 10 inches
from the glass face plate. The latency values used at each in-
tensity setting were means of 10 digital readings, a plot of which
is shown in Figure 9. The standard deviation of the readings
about each mean was approximately five milliseconds, and their
standard deviations did not vary significantly from one intensity
level to another.

LATENCY PERIOD OF PUPILLARY CONSTRICTION AND AGING

A scattergram (Fig. 7) of the average latency period by age
shows a positive relationship (r = .54) between pupillary latency
period and aging. As one grows older, his pupillary latency
period increases. A chi-square of 11.87 (each variable split at the
median) with one degree of freedom, a p<.001 shows that this
is highly significant. The slope of this increase is shown by the
regression equation y = .77x + 222.3,


Latency of Pupillary Reflex to Light Stimulation 9

second, It is obvious that this time is longer than the period of
pupillary inactivity that follows the initiation of stimulation. If
we wish to redefine latency period as the time from photic
stimulation to the first detectable response, we must re-examine
our data. Figure 5 shows that the voltage level used for a single
sample measurement was reached approximately 0.034 sec. after
the moment of first noticeable change. Though it would have
been preferable to trigger the “Stop” circuit of the counter by this
first minute voltage change, it was necessary to chose the higher
voltage in order to operate beyond the noise level of the system.
Consciously or unconsciously, most authors have run into
similar difficulties. For example, it is impossible to detect with
the unaided eye the exact moment of initiation of the contraction
movement, especially when the stimulus intensity is low and
the reactions shallow. Since, in addition, the latency period in-
creases with decreasing stimulus brightness (Lowenfeld and
Lowenstein, 1959), the large range of values for the pupillary
latency period reported by competent authors is not surprising.
The prolongation of the latency period beyond its true value
depends upon the steepness of the slope of increasing contrac-
tion velocity. For this reason mainly, we chose the maximal light
intensity conveniently available for our experiment on aging. The
values obtained on the readout of the Digital Recorder and those
marked on the Memoscope at the —0.35 volt cutoff point agreed
very well (maximal discrepancy + 4 milliseconds), and since
all of our normal subjects responded to the powerful light flashes
by reactions with steep velocity slopes, the differences between
the true latency periods and the mean times measured at the
-0.35 volt cutoff point varied only little among individuals.

LATENCY PERIOD AND LIGHT INTENSITY

Even at the high brightness levels used in this experiment, the
latency period tended to lengthen when the stimulus intensity
was reduced. Figure 8 shows the responses of the pupil to five
different flash light intensities ranging in intensity ratios from
1 to 80,

The logarithms of the relative intensities (10 log relative in-
tensity in db) are 0, 6.0, 12.0, 16.8, and 19.0. Peak intensity



6 Behavior, Aging, and the Nervous System

comparison for each flash of light from the Photic Stimulator two
traces were generated on the dual beam Memoscope face,
whereby the lower trace showed the analog voltage of the
diameter, and the upper trace its derivative. It can be seen that
the curve representing the derivative voltage has a much steeper
slope than the analog signal of the diameter. The definition with
which a single sweep can be resolved on the Memoscope is
adequate for measurements within + 3 milliseconds (Figure 5).
The readings used for this study were taken from the Digital
Recorder. For our purposes, this recorder had an accuracy of
+ 0.0001 seconds. Figure 5 also shows that the 60 cycle per
second scanning rate of the pupillograph modulates the derivative
signal.

The timer has a crystal controlled oscillator operating at a
frequency of 100,000. cycles per second; for the present ap-
plication, a 10,000 cycles per second rate was used. A gate in the

Figure 5. Definition of single sweep on memoscope.


2 Behavior, Aging, and the Nervous System

tion of contraction. Most of the investigators (Duke-Elder, 1949;
Lowenstein and Loewenfeld, 1958, 1963; Shaknovitch; Talbot,
1938; Tschirren, 1947; Walsh, 1910; Weiler, 1910) agreed that the
latency period of pupil contraction ranges from 0.2 to 0.3 second.
Some authors, however, have reported shorter latency periods; for
example, Fuchs (1903) reported 0.12 second, Dolének (1960)
0.126 to 0.295 second, and Gradle and Eisendraht (1923) 0.1875
second. At the other end of the time scale, von Arlt (1869) found
the pupillary latency period to be 0.492 second and Donders
(1864) 0.400 second.

There have been relatively few studies relating the pupillary
latency period to other physiological factors. Schlesinger (1913)
stated that it increased upon repeated stimulation; Loewenfeld
and Lowenstein (1963) have maintained that it may vary among
individuals and in the same individual under different experi-
mental conditions.

LLP.

—} Ty.

if\ | 7
ENS

P— LIGHT -—+4
TUTTE

DIAMETER IN MM —~
o

TIME IN 0.1 SEC —-

Figure 1. Diagram of pupillary reflex to light stimulus (after Lowenstein
and Loewenfeld). L.P. = Latent Period in pupillary contraction.


Latency of Pupillary Reflex to Light Stimulation 13

3) Original pupil size decreases with age.

4) A limited number of subjects with myopia coupled with
mydriasis had relatively long latency periods.

5) One subject with a nerve conduction disease was found to
have a relatively long latency period.

REFERENCES

Adler, F, H.: (1953) Physiology of the Eye. Mosby and Co., p. 195.

van Arlt, F., Jr.: (1869) Beitrag zur Kentniss der Zeitverhiltnisse bei den
Bewegungen der Iris. Graefe Arch. Ophthal. 15:294-317.

Baker, A. B., ed.: (1962) Clinical Neurology. New York, Hoeber-Harper,
pp. 1760-61.

Bender, W. R. G.: (1933) The effect of pain and emotional stimuli and
alcohol upon pupillary reflex activity. Psychol. Monogr., 44:2:1-32.

Dolének, A.: (1960) Beitrag zur Pupillographie. Ophthalmologica, 139:
76-83.

Donders, F. C.: (1864) On the anomalies of accommodation and refraction
of the eye. The New Sydenham Soc. London, 22:573-583.

Duke-Elder, Sir S. W.: (1949) Textbook of Ophthalmology, Vol. IV, pp.
371-376. ;

Fuchs, A.: (1903) Die Messung der Pupillengrésse und Zeitbestimmung
der Licht-reaktion der Pupillen bein einzelnen Psychosen und Nerven-
krankheiten. Jahrbiicher f. Psychiat., 24:326-458.

Gradle, H. S. and Eisendraht, E. B.: (1923) Die Reaktionszeit der norm-
alen Pupille. Vorlaufige Mitt. Hbl. Augenheilk., 71:311.

King, G. W.: (1959) Recording pupil changes for clinical diagnosis. Elec-
tronics, 32:67.

Kumnick, L. $.: (1956) Aging and the latency and duration of pupil con-
striction in response to light and sound stimuli. J. Geront., 11:391.
Listing, J. B.: (——) Beitrag zur Physiologischen Optik. Besonderen

Abdruck, aus d. Gottingen Studien; quoted after Loewenfeld.

Loewenfeld, I. E. and Lowenstein, O.: Personal communications.

Lowenstein, O. and Loewenfeld, I. E.: (July 1959) Scoptic and photopic
thresholds of the pupillary light reflex in normal man. Amer. J. Ophthal.,
48:1, Part IL

Lowenstein, O. and Loewenfeld, I. E.: (1958) Electronic pupillography.
A new instrument and some clinical applications. Arch. Ophth. (New
York), 59:353-363.

Morone, G.: (1948) Ricerche pupillografiche nell’abbagliamento. Boll.
Oculist, 27:639-652.

Acknowledgement: We are indebted to Miss Anne Alderman for her assistance in
compiling the statistical data.



Reprinted from
BEHAVIOR, AGING AND THE NERVOUS SYSTEM
Edited by
A. T. Wetrorp, M.A., Sc.D. AND James E. Brrren, Px.D.

Cuantes.C THomas, PUBLISHER
Springfield, Illinois, U.S.A.

17

LATENCY OF PUPILLARY REFLEX TO LIGHT
STIMULATION AND ITS RELATIONSHIP
TO AGING

+ RicHarp FEeInserc AND Epwarp Popo.aK

Tas stupy is concerned with the latency period of
the pupillary contraction to light and the relationship of this la-
tency period to aging. Some findings on pupillary latency periods
related to light intensity, as well as to myopes with mydriasis and
to an individual with nerve conduction disease, are described.

Analysis of the normal light reflex into its several components
of speed and amplitude has been attempted for over 100 years.
Techniques of pupillary measurement have been varied and have
included: 1) entopic observation in which the observer subjec-
tively measured his own pupillary diameter or reactions; 2) di-
rect observation and measurement of the subject’s pupil by ruler,
scales, circles, holes, etc.; 3) photographic techniques, and, 4) pu-
pillographs using various cinematographic or electronic devices.
In 1956, Lowenstein and Loewenfeld developed the Electronic
Pupillograph which was the prototype of the instrument used in
this study. A typical curve of the signal output of the Electronic
Pupillograph is shown in Figure 1.

In 1845, Listing with entopic observations determined that the
latency period for pupillary contraction was about 0.4 second
when the eye was opened suddenly, and that the contraction
movement lasted about 0.5 second. Since then, numerous investi-
gators have made determinations of the latency period and dura-

1

* Georgetown Clinical Research Institute, Office of Aviation Medicine, Federal Aviation
Agency, Washington, D.C.





Latency of Pupillary Reflex to Light Stimulation 11

_
oa
T

RELATIVE LIGHT INTENSITY

1 1 1 J
240 250 260 270 280
TIME IN MILLISECONDS

Figure 9. Means of pupillary latency vs. relative light intensity (one sub-
ject).



14 Behavior, Aging, and the Nervous System

Ogle, K. and Burke, D.: Comparison of pupillary and visual light thresholds
in the periphery. (Presentation at the 1963 Colloquium on the Pupil.,
N.Y.C.

Shaknovitch, V. R.: Cinematographic investigation of pupillary reaction to
convergence. J. Physiol. (USSR), 44:170-172.

Schlesinger, E.: (1913) Uber den Schwellenwart der Pupillenreaktion und
die Ausdehnung des pupillomotorischen Besirkes der Retina. Unter-
suchungen auf Grund einer neuen Methodik. Deutsch. Med. Wschr.,
163-165; Neurol. Zbl., 316.

Smith-Kline Precision Co.: (1962) Instruction Manual. Aug. 20.

Talbot, S. A.: (1938) Cinematography of the pupil. Amer. J. Physiol.,
123:200.

Tschirren, B.: (1947) Die fortlaufende Registrierung des Pupillen-reflexes.
Helv. Physiol. Pharmacol. Acta, 5:C57-C58.

Walsh, F. G.: (1910) Clinical Neuroophthalmology. Williams & Wilkins,
pp. 152-154,

Weiler, K.: (1910) Untersuchungen der Pupille und der Irisbewegungen
beim Menschen. Berlin. Also Zeitschr. Ges. Neurol. Psychiat. I1:101-274.