Sympathetic Pupillary Activity in Infants

(1)

Sympathetic

Pupillary

Activity

in Infants

Netanel Laor, M.D., Amos D. Korczyn, M.D., and Pinchas Nemet, M.D.

From the Department ofPhysiology and Pharmacology, Sackler School ofMedicine, Tel-Aviv University, and the Department of Ophthalmology, Ichilov Municipal Government Hospital, Tel-Aviv, Israel

ABSTRACT. In an attempt to learn the contribution of the sympathetic system to smaller pupillary size in infants, pupillary responses were tested to agents acting on this

system in 12 infants and 23 young adults. Phenylephrine dilated the pupils of both groups by the same ratio, with infants’ pupils reaching a lesser diameter. The responses to cocaine and hydroxyamphetamine were lower in children.

It is concluded that in the first months of life the post-ganglionic sympathetic nerve releases less norepinephrine. This may be due to a lower number of sympathetic neurons.

The post-synaptic apparatus may not be fully developed in

infants. Pediatrics, 59: 195-198, 1977, SYMPAThETIC NERVOUS

SYSTEM, DENERVATION SUPERSENSITIVITY, EYE, PUPIL.

ocular sympathetic system in infants and

compared them to responses in young controls.

MATERIALS AND METHODS

. Subjects

Twelve subjects aged 3 to 6 months and 23

young adults aged 17 to 20 years were included in

this investigation. Subjects were healthy

non-smokers. Permission to carry out this study was

obtained from the volunteers or legal guardians.

Methods

During the first yearof life the pupillary size of

infants is small. A common explanation of this

phenomenon is that mechanical factors (i.e.,

mesenchymal trabeculae at the anterior angle)

prevent dilatation.’ This explanation is unlikely

because the pupil changes in size continuously,

e.g., in response to change in illumination, and

because it can reach a diameter of 9 mm when

mydriatics are applied. The mechanism of this

relative miosis in infants may be significant and

could be used as a model for other autonomic

functions.

In an attempt to learn whether neural factors

are responsible for this phenomenon, we have

tested pupillary responses to agents acting on the

Apparent pupillary size was measured by

direct comparison with a series of circles with

diameters of 2.0 to 9.0 mm, increasing at 0.5-mm

intervals. With this method, a trained observer

can easily reach an accuracy of ± 0.5 mm.

Examinations were done in a room with light

coming through the window. All observations

were made during the morning in early summer

in the Tel-Aviv area when the sky was not

clouded. The luminosity in the room was 200 lx.

All subjects were awake at the time of the study.

They faced away from the window and were

fixating at the distance.

(Received February 3; revision accepted for publication

April 16, 1976.)

ADDRESS FOR REPRINTS: (A.D.K.) Department of

Physi-ology and Pharmacology, Sackler School of Medicine,

(2)

Cocaine

MR=

maximal pupillary diameter after mydriatics

pupillary diameter in nontreated eye

DISCUSSION

TABLE I

196

SYMPATHETIC

PUPILLARY

ACTIVITY

PUPILLARY DIAMETERS AND MYDRIATIC RATIOS BEFORE AND AFTER DRUGS AFFECTING THE SYMPATHETIC NERVOUS SYSTEM

Drug Age Group Pupil Size (mm)

Size ±SD Mydria Size tric Ratio ±SD Control Infants Young adults 3.7 0.5 4.6#{176} 0.8 -Phenylephrine Infants Young adults 6.8 0.6 8.3#{176} 0.7 1.9 1.8 0.3 0.2 Cocaine Infants Young adults

5.0 . 0.9

8.4#{176} 0.7 1.3 1.8#{176} 0.1 0.2 Hydroxyamphetamine #{176}Significantly different Infants Young adults

rom the value for i

5.8 0.7

8.2#{176} 0.8

nfants at P < .01.

1.5 1.8#{176}

0.1 0.2

The drugs used were 10% phenylephrine, 5%

cocaine, and 1% hydroxyamphetamine. All drugs

were given as eye drops, 0.05 ml into one

conjunc-tival sac, while the other eye served as a

con-trol.

Measurement of pupillary size was taken

during one hour or more and the maximal size

was then recorded. Each drug was given on a

different day.

In order to compare the pupillary responses to

the different drugs that we used, the mydriatic

ratio (MR) was defined as follows:

Cocaine dilated all pupils, but affected infants

to a significantly lesser degree. The

post-treat-ment diameters were 5.0 ± 0.9 mm and

8.4 ± 0.7 mm for infants and young adults

respectively. Following cocaine the difference

between the pupillary size of infants and young

subjects therefore increased. This is shown by the

fact that the MR was significantly higher for

young adults than for infants (1.8 ± 0.2 and

1.3 ± 0.1 respectively).

Statistical analysis consisted of Student’s t-test,

and results were considered significantly different

when P values were below 0.01.

RESULTS

Pupillary

Size at Rest

The pupillary diameter of the infants was

3.7 ± 0.5 mm (mean ± SD) and that of the older

subjects 4.6 ± 0.8 mm. The difference is

statisti-cally significant. The mean pupillary size of males

and of females in each age group was similar.

Phenylephrine

Following phenylephrine instillation, all pupils

dilated, reaching diameters of 6.8 ± 0.6 mm and

8.3 ± 0.7 mm for the infants and young adults

respectively. This difference is statistically

signif-icant. The MR of the two groups were not

significantly different, being 1.7 ± 0.3 mm and

1.8

± 0.2 mm respectively.

Following instillation of this drug, all pupils

dilated. The maximal diameter reached was

significantly higher for young subjects than for

infants (8.2 ± 0.8 mm and 5.8 ± 0.7 mm

respec-tively). The relative dilatation was also

signifi-cantly greater in young adults (MR = 1.8 ± 0.2

mm and 1.5 ± 0.1 mm respectively).

The results are summarized in Table I and

Figures 1 and 2.

The pupil is under the antagonistic influences

of the sympathetic and parasympathetic parts of

the autonomic nervous system. In an attempt to

explain the relative miosis in infants we have

examined the function of the ocular sympathetic

in normal infants and compared the findings to

our results2 in young adults.

The first possibility tested was that the

post-synapticreceptors of the dilator muscle of the iris

are hyposensitive to norepinephrine. Instillation

of phenylephrine, a direct a-adrenergic stimulant,

dilated the pupils of infants and young adults by

at Viet Nam:AAP Sponsored on September 8, 2020

www.aappublications.org/news

(3)

5

-F

4

-I.

- - _

F henyteph.

Cocaine

Resting

diam.

OH-amphet

M.R.

3 YOUNG

ADULTS

I

INFANTS

Ph enyLeph.

Cocai

ne

OH-ctmphet.

E

V 0. 0.

10

-

YOUNG ADULTS

c::

INFANTS

FIG. 1. Pupillary size before and after various drug treatments in young adults and in infants. Pupillary diameters (mm) are plotted on the ordinate. For details, see text.

(4)

198

SYMPATHETIC

PUPILLARY

ACTIVITY

a similar ratio (Table I). This is the result expected

if the post-synaptic receptors have a normal

response to norepinephrine. However, the

possi-bility of hyposensitivity is not ruled out by this

finding because even after this treatment the

pupils were still less mydriatic in infants.

The small size of pupils in infants, relative to

the size of the eyes, could result from a lower

concentration of norepinephrine in the vicinity of

their receptors. This could be due to either

smaller release or greater inactivation of the

neurotransmitter. Cocaine is known to block the

neural re-uptake of norepinephrine. If indeed the

difference between the pupillary diameters of

infants and young adults were due to an altered

re-uptake or intraneuronal inactivation (e.g., by

mono-amine oxidase) then this difference would

be expected to be abolished by cocaine. In fact,

cocaine exaggerated the difference between

infants and young adults (Table I). A similar

decrease in the response to cocaine was found by

us in old subjects2 and was explained by the

assumption that this group had a lower

sponta-neous release of norepinephrine. Thus, if infants

had less spontaneous norepinephrine release,

cocaine could increase sympathetic activity only

by little, whereas in young adults with higher

initial norepinephrine release, cocaine would

cause a higher build-up of norepinephrine

concentration in the vicinity of the receptors.

Decreased response to cocaine may also indicate

decreased re-uptake ability by infant sympathetic

neurons. However, if this were the major or sole

explanation, infant pupil size should have been

larger than that of adults. It is therefore

concluded that sympathetic terminals discharge

less norepinephrine in infants (and in old subjects)

compared to young adults. In infants, it is possible

to account for this small rate of norepinephrine

release by assuming that sympathetic nerves have

not yet fully developed. If this is the case, then

hydroxyamphetamine, an indirect-acting

sympa-thomimetic, would be expected to produce a

smaller effect in infants. This is exactly what we

found (Table I).

Our results are therefore consistent with the

assumption that in infants the development of the

sympathetic nervous system is still functionally

incomplete. Anatomical findings support this

view. In infants, there is a smaller number of

neurons in spinal roots3 and of myelinated fibers

in the paravertebral sympathetic chain.4

Simi-larly, the excretion of norepinephrine increases

with age until adolescence5 as does the

concentra-tion of dopamine-$-hydroxylase in the serum.6

The sympathetic post-ganglionic nerves are the

main site where inactivation of norepinephrine

takes place. Thus, if the sympathetic endings

were not developed in infants, as just suggested,

we would expect to observe supersensitivity to

norepinephrine or phenylephrine78 as

demon-strated in old subjects.2 For example, when

phenylephrine was applied, the rate of

inactiva-tion would be smaller in infants and therefore its

effect should have been exaggerated. The fact

that we have not observed this supersensitivity to

phenylephrine in infants (Table I) may indicate

that the smooth muscle is limited in its reaction to

direct a-adrenergic agonists. This may be due to

immaturity of the receptors or the contracting

mechanism. We cannot test this possibility

further with our methods.

REFERENCES

1. Duke-Elder WS: Textbook of Ophthalmology. London,

Henry Kimpton, 1942, vol 1, pp 368-369.

2. Korczyn AD, Laor N, Nemet P: Sympathetic pupillary activity in old age. Arch Ophthalmol 94:1905, 1976.

3. Gardner F: Decrease in human neurons with age. Anat

Rec 77:529, 1940.

4. Appenzeller 0, 0gm G: Myelinated fibers in human paravertebral sympathetic chain: Quantitative study on white rami communicantes. J Neurol Neurosurg Psychiatry 33:777, 1963.

5. K#{228}rkiNT: The urinary excretion of noradrendine and adrenaline in different age groups, its diurnal

van-ation and the effect of muscular work on it. Acta Physiol Scand 39:52, 1956.

6. Freedman U, Ohuchi T, Goldstein M, et al: Changes in

human serum dopamine-beta-hydroxylase activity

with age. Nature 236:310, 1972.

7. Korczyn AD: Adrenergic denervation supersensitivity.

Adv Neurol 9:113, 1975.

8. Korczyn AD: Denervation supersensitivity in Homer’s syndrome. Ophthalmologia 170:313, 1975.

(5)

1977;59;195

Pediatrics

Netanel Laor, Amos D. Korczyn and Pinchas Nemet