THE PHYSIOLOGICAL ATT ION 
/•' OF 
Belladmna ami its Alkaloid, Atropia, 
ON THE EYE. 
BY P. D. KEYSER, A.M., M.D.. 
SiaiOTCON 11) TUB W ILLS E Y E Hv>$riTAL, P.HILA. ; OpfclTH Ai.MIC SURG»ON TO THE HoiJSK 
ob Correction. Phil a. Ophthalmic StrRGR<*v to the Mkdicai. Department op 
the German Society, Phila.: Member of the PhilaoelpHta County 
Medical S cjBty, The Pennsylvania 3tatb Medical Society, The 
AMRIiU an MttM0ALASsocrATlO.\, THBLNTKKNAlH»»AL 0pllTHAL* 
MoLOvilCALCoMJKKSs, Kx-PkeSIDENTOB THE MElHC.O*CHI- 
RU ROIC At SOCfETY, FELLOW OP THE AMERICAN 
- Academy of Medicine, Honorary Fel- 
low of the Medical S<vntrY op 
Delaware, Ktcm Etc.,’ 
P H I.LA D E L PH I A : 
1 <s 7 x . THE PHYSIOLOGICAL ACTION OF BEL 
LADONNA AND ITS ALKALOID, 
ATROPIA, ON THE EYE. 
An Address read by invitation before the Medical 
Society of the State of Delaware, at Dover, 
June 12tli, 1877. 
[Reprinted from the Medical and Surgical Reporter.] 
It has been known, for a very long time, that 
when belladonna was taken inwardly in large 
doses, the pupils of the eyes would become 
dilated and the vision affected. Charles Ilimly, 
taking advantage of this fact, made a local 
application of it in the eye, to prevent the ad- 
hesion of the iris to the anterior capsule of the 
lens, and occlusion of the pupil in cases of 
iritis. C. v. Graefe, the father of the great 
oculist A. v. Graefe, followed up the same idea, 
and applied it in scrofulous and rheumatic in- 
flammationsofthatorgan. Also Prof. M.Langen- 
beck used it, with success, to dilate the pupil in 
cataract operations, to prevent injury to and 
adhesions of the iris, as well as to combat any 
inflammation arising from the operation. 
Since this first introduction of the use of 
belladonna, locally, in the eye, it, or its alkaloid, 
atropia, has become the sovereign remedy in 
most of the diseases of that part, just as opium 2 
or its alkaloid, morphium, is the sovereign 
remedy in most cases of pain. 
In former times, a decoction of the leaves 
was applied over the eyes ; then the extract was 
made from the plant and the root, and it came 
into use by rubbing it over the eyebrow and 
on the temple, as well as dissolving some in 
water, and dropping it in the eye ; but in the 
present time the alkaloid, or active principle, 
“atropia,” has been extracted, and is now 
almost universally used. 
Atropia, being almost insoluble in water, is 
made into a sulphate by dissolving it in ether 
or alcohol, and adding, very carefully, sulphuric 
acid until saturation only, without excess of 
acid. It is crystallized by evaporation, and 
washed from excess of acid by ether or alcohol, 
then re-dissolved and re-crystallized until per- 
fectly pure. 
This sulphate of atropia is easily soluble in 
water, and has become one of the most import- 
ant remedies, not only to the ophthalmologist, 
but also to the general practitioner, for hypo- 
dermic injections, etc. 
The use of this salt in solution, as an eye 
wash, has become so general, that almost every- 
body prescribes and recommends it for every 
and all troubles of the eye. Druggists pre- 
scribe it over their counters continually. It is 
not to be supposed that such persons know any- 
thing of its action, whether good or bad, upon 
the eye; but there are, no doubt, many physi- 
cians, who, following the course recommended 3 
by some writer or friend who has found it bene- 
ficial in some cases, prescribe, daily, collyria and 
ointments containing either belladonna or atro- 
pia, to dilate the pupils, or to relieve inflamma- 
tion, without knowing its true physiological 
action on the eye. 
It will be my pleasure, therefore, to lay 
before you this afternoon, in brief, the results 
of some of the anatomical and physiological 
researches upon this subject that have been 
brought to light by the great workers of the 
day, among whom I may mention Muller, 
Manz, von Graefe, Bonders, Bowman, Arlt, 
Helmholtz, Stellwag, Leber, Krause, Ilenle, 
Kolliker, Luschka, etc. 
For the better understanding of the action of 
belladonna on the iris, I will follow, principally, 
Stellwag, and necessarily translate and quote 
very much that has been said by this eminent 
authority upon this subject 
The iris contains circular and radiary mus- 
cular fibres. The circular fibres form a smooth, 
ring-like muscle, located around the pupillary 
part. This muscle is called the “ sphincter 
pupillae,” and contracts the pupil. The radiary 
fibres do not form a continuous muscle, but 
extend from the ciliary border in a radiary 
manner, and are inserted into the circular fibres 
by slender fasciculi. These fibres serve to di- 
late the pupil, and the muscle is called the 
“dilatator pupillae.” See Fig. 1. 
The iris is influenced by four nerves: the 4 
third (oculomotor), the fifth (trigeminus), the 
sympathetic and the optic. 
Fig. 1 
a. Circular fibres of the Sphincter pupillse. 
b. Radiary fib-es of tne Dilatator pupillse. 
(From Kolliker.) 
“ The sphincter pupillas and the ciliary mus- 
cle are supplied with branches of the third nerve, 
which pass through the ciliary ganglion, and 
form, with the other ciliary nerves, four main 
bundles of fibres, which reach to the ciliary 
body and separate in a quadrant of the ciliary 
muscle and sphincter pupillse muscle. The 
dilator pupil'ae and the vascular muscles of the 
iris are influenced by motoric fibres of the 
sympathetic. These fibres originate in the 
medulla oblongata, run downward in the 5 
anterior column of the spinal cord, enter the 
anterior roots of the two lower neck and upper 
breast nerves, unite with the sympathetic, and 
pass with it upward through the superior cervi- 
cal ganglion. The fifth nerve supplies the iris 
with sensible fibres. 
“ The optic nerve has only an indirect action 
on the iris, inasmuch as the iris contracts when 
light falls on the retina. The ciliary nerves 
(branches of the third, fifth and sympathetic) lie 
in the outer layer of the choroid, in the lamina 
fusca, and run through many little knots, the 
so-called intra-ocular ganglia” (Schweigger). 
Fio. 2. 
Ganglion cells and nerve fibres found in the Choroid. (Schweigger.) 
“ These ganglia officiate as centres, because 
conditions of excitation of the sensible nerves 
can be reflected on the motoric nerves without 
the brain or spinal cord partaking thereof. On 
these ganglia the atropia acts” (Stellwag). 
The action of atropia is of a twofold nature ; 
it dilates the pupil and paralyzes the accommo- 
dation. After the proper length of time of 6 
action of the agent, the dilatation of the pupil 
is a maximum, the iris recedes until only a 
small seam is perceived; it remains perfectly 
immovable, and does not react either on reflex 
irritation, contrast of light or consensual action 
as accommodative impulse. Stellwag says that 
“ this powerful dilatation is hardly attainable 
through the paralysis of the sphincter pupillae 
alone ; there must be some active power present, 
which drives the blood out of the iris back into 
the posterior uveal tract; and this power is 
developed through the contraction of the dila- 
tator pupillae and vascular muscles. A proof 
of which is, that in complete paralysis of the 
oculomotor nerve the pupil is only half dilated, 
and if atropia is put into the eye at this stage 
the dilatation becomes greater, showing that 
through the atropia a particular power is 
brought into action that can still dilate the 
pupil/’ 
“It remains now the question, If, from the- 
above expressed facts, it can alone be explained 
by the sole contraction of the dilatator pupillse V' 
“The dilator lies on the posterior border of 
the iris, and consists of an evenly formed, thin 
layer of smooth, muscular tissue; the larger 
vessels of the iris lie before it (i.e., anteriorly). 
If it contracts alone the pupil is dilated, but 
the vessels are not compressed. The retreating 
iris forms a small but thick fold. This fold is 
not found, however, by a thoroughly dilated 
pupil. If we examine the iris by a contracted 
and a completely dilated pupil, we do not find 7 
it thicker in the latter (dilated) state than in 
the former, a proof that the vascular muscles 
have also contracted.” 
Rossbach and Frohlich, in their experiments 
with atropine on rabbits, noticed that very 
weak solutions (three to six millionths of a 
gramme) caused contraction instead of dilata- 
tion of the pupil, through irritation of the ends 
of the oculomotor nerve. In somewhat stronger 
solutions the ends of the oculomotor nerve 
became paralyzed and the pupil dilated slightly. 
Still stronger solutions increased the dilatation 
by irritating the sympathetic and the dilatator 
pupillae; and on the use of very strong solu- 
tions the sympathetic and dilatator pupillae 
were paralyzed, so that the pupil contracted 
somewhat from its extreme dilatation. 
They found that atropine has the contrary 
action on the pupil of a frog to that of man or 
warm-blood animals. It contracts it instead of 
dilating, and physostigmin (the active princi- 
ple of the calabar bean) dilates the pupils. 
I have made some very careful experiments 
with the sulphate of atropia and sulphate of 
eserine (physostigmin) on the eyes of the frog j 
and my experience does not accord with that of 
Rossbach and Frohlich. I found that the 
action of these salts was not different in this 
case from that in man and warm-blood animals, 
except that the dilatation from atropia was so 
slight, and remained such a short time, that it 
could hardly be observed. It required the 
closest attention and scrutiny. In making my 8 
experiments, I found that simply dropping 
the solution of either atropine or eserine on 
the eye, gave not the least action. I then intro- 
duced a probe behind the lid and held it off 
from the ball, while my assistant, Dr. Thomas 
II. Fenton, let a drop of the solution I was 
using fall in the cul-ie-sae made by the probe. 
Weak solutions of either salt did not give any 
reaction, but from a solution of sulphate of 
atropia of four grains to the ounce of water, a 
•very slight dilatation was observed. From a 
solution of eserine, of the same strength, 
marked contraction took place in a short time, 
with considerable irritation in the eye, causing 
him to wink often, then close it and rub it with 
his fore leg. The contraction of the pupil did 
not remain but for a few minutes, although it 
reached a very marked degree in that short 
time. The frog felt the toxical effects for over 
an hour, exhibited by great spasmodic breath- 
ing, then closing the eyes and remaining 
motionless for a time, then again spasmodic 
action of the respiratory organs. 
A peculiarity which we noticed in the eyes 
without any drops was, that in the morning, 
until about 9 o’clock, the irides were somewhat 
contracted; then they slightly dilated until 
about 11 o’clock, when they began to contract, 
and remained in this condition until 2 p m., 
when dilatation took place until about 3 or 4 
o’clock; then a slight contraction occurred till 
toward evening, when they beg in to dilate 
again, and by night were widely expanded. 9 
A solution of atropia, gr.iv ad. 3j dropped in 
the eye of a pigeon, did not produce the least 
dilatation of the pupil; but, after eserine, of the 
same strength, there was in two minutes great 
spasmodic action of the lids, and contraction of 
the pupil, which, in four minutes, reached its 
maximum, the pupil being as small as a pin’s 
point, and death occurred in half an hour. 
I also tried the action of both these salts on 
chickens, and did not see any effect, except that 
the eserine created a temporary irritation and 
congestion of the conjunctiva. 
Giguel has observed, that “ when a not too con- 
centrated solution of atropine is injected under 
the skin, in the neighborhood of the eye, dilata- 
tion of the pupil of that side only takes place. 
In some cases when a concentrated solution 
(xff) was used, its action was noticed in the 
pupil of the other side, but never by a weak so- 
lution.” lie coincides with Potain, that the one- 
sided mydriasis following a hypodermic injec- 
tion of atropine in the peri-orbital region is the 
result of reflex action in the benumbing of the 
peripheric ends of the trigeminus. But when 
the mydriasis is double, it shows direct action 
from the centre. He recommends the hypo- 
dermic injection of atropine for facial neuralgia, 
to be made in the immediate neighborhood of 
the diseased nerve. 
Beside the dilatation of the pupil, there takes 
place, on the use of atropia, loss of accommoda- 
tion, and the condition of refraction is generally 
reduced somewhat below the standard measure, 10 
which is found in complete rest of the apparatus 
of accommodation. This is particularly the 
case if it is put in the eye in strong solutions, 
or at short intervals. 
It has a twofold action on the eye. It irri- 
tates the sympathetic, belonging to the motoric 
nerves of the dilator and vascular muscles, and 
paralyzes the motoric nerves of the sphincter 
pupillae (contractor) and ciliary muscles. 
“ The paralysis of the oculomotor nerve is only 
relative, it consists only for certain innervations, 
during the reaction of the muscles from other 
impulses, and during which the iris is not sen- 
sitive to reflected and consensual irritation, nor 
impulse of the will, but contracts when the in- 
traocular ganglia are directly irritated, or 
through interposition of the sensible branches 
of the fifth nerve, as is to be seen in the sudden 
contraction that takes place if paracentesis of 
the cornea is made, and the aqueous let out in 
a case where the pupil has been dilated, or if a 
strong chemical reaction is brought to bear on 
the ball in the same case. 
“ We have the same action by morbid irritation 
of the ciliary branches of the fifth nerve. It is 
constantly seen that atropia will not act in the 
least in cases of great ciliary irritation, as is 
often met with in iritis, many forms of keratitis, 
etc. It frequently occurs that, in cases where 
the pupil is well and largely dilated by the in- 
stillation of atropia, a severe ciliary irrita- 
tion will suddenly set in, a*nd cause the pupil to 
contract at once. 11 
“Really the extent of the dilatation where 
there are no posterior adhesions is the best 
barometer for the degree of ciliary irritation n 
(Stellwag). 
“ By intense irritations of the sensible ciliary 
nerve'-, spasm,of the ciliary muscles occur ; this 
still more excites the sensible ciliary nerves, 
and through these the vaso-motoric nerves, 
which increases the inflammatory condition and 
appearance. This irritation and spasm often 
occurs in hypermetropic eyes, where there is 
great strain of accommodation in acts of vision. 
The atropia relieves this spasm ; and acts 
also sedatively on the fifth nerve. Its principal 
action consists in the contraction of the vessels 
in the anterior ciliary region, and thereby 
takes its place as a true antiphlogistic.” 
“ As an antiphlogistic remedy, we have 
nothing like it in medicine ; it acts to relieve 
inflammation on a particular circumscribed 
part of the body without affecting any other 
part.'' 
Its absorption takes place through the con- 
junctiva and cornea, and soon after the instilla- 
tion it can be detected in the aqueous humor. 
If a few drops of a solution of the strength of 
2 to 4 grs. ad. is put in the eye, the pupil 
begins to dilate in 15 minutes, and reaches its 
extreme dilatation in about 30 minutes. The 
decrease of the accommodation is not simulta- 
neous with the dilatation of the iris, but begins 
to diminish only after the pupil is somewhat 
dilated ; and does not reach its fullest extent of 12 
paralysis until some hours after. After 3 or 
4 days the pupil will be somewhat smaller, and 
a slight degree of accommodation reappears ; 
but the latter is not fully re-established until 
10 and sometimes 14 days. 
The use of atropia is indicated in all cases 
where a dilatation of the pupil is necessary. 
With some few exceptions it is used in all 
diseases so long as there is any ciliary irrita- 
tion. In many cases of severe ciliary irritation 
and spasm of the muscle, a leech or two, or 
the artificial leech, on the temple, will assist the 
action of the atropia in dilating the pupil. 
A solution of the strength of four grains to one 
•ounce water is strong enough to paralyze the 
accommodation if applied often enough. Gen- 
erally one or two instillations in one day are 
sufficient; but in cases of spasm three or four 
are necessary, and sometimes it must be con- 
tinued for two or 'three days. Tn very severe 
cases I find it best t) instill a drop every five or 
ten minutes for half an hour, then wait an hour, 
when the instillation should be repeated for 
half an hour, as before. This has always relaxed 
any spasm that I have seen. 
I think it a great mistake to use stronger 
solutions, or even the pure salt, as I have seen 
practiced, for the reason that they are too irri- 
tating to the conjunctiva, causing, in a very 
short time, too great a relaxation of the vascu- 
lar muscles, thus developing a chronic form of 
conjunctivitis, and also from the probability of 
the sympathetic and dilatator becoming para- 13 
lyzed, thereby causing the pupil to contract 
agaio somewhat from its maximum dilatation. 
The use of atropia is contraindicated in cases 
where glaucoma is suspected. 
“ The greater part of the arteries of the iris 
bend direct into the veins, and these empty 
their contents almost without exception, through 
the venae vorticosa of the choroid, with which 
they are in intimate connection through the 
ciliary processes. 
“ The pressure of the circulation in the eye is 
regulated in the normal condition partly by the 
contractile walls of the vessels, and partly by 
the elasticity of the ball, which extends in equal 
proportion. If more arterial blood flows into 
the eye, more venous blood is forced out, thus 
regulating the circulation. In this way the 
intraocular pressure and tension remain always 
an equal standard. If, however, from some 
cause, the eyeball loses its elasticity, it will 
not be in a condition to regulate the circulation 
as formerly. The consequence thereof will be, 
that by a temporary arterial increase the fresh 
blood cannot be pressed out with rapidity 
enough to keep the intraocular pressure at the 
normal standard, and then a slight choking of 
the veins will take place, causing an increase of 
tension in the ball. 
“ Hard eyeballs, with little elasticity, are 
often found in advanced age in connection with 
dilated atheromatous vessels, and in some cases 
it is habitual from birth, being hereditary in 
some families. Bulbs of this kind can take but 14 
little active action ini the circulation of the eye, 
while the want of the proper elasticity can be 
the cause of much trouble. 
“ From the rigidity of the capsule the lamina 
cribrosa is extended, and gradually gives way, 
and presses back under the increased intra- 
ocular tension, thus causing the excavation in 
the disk as seen in glaucoma. 
“ By continued pressure the vessels passing 
obliquely through the sclera are eventually ob- 
literated ; the meshes in the lamina cribrosa 
become reduced and the main stems of the 
central veins compressed. From this the exca- 
vation will be the cause of a still greater chok- 
ing of the vessels and an increase of the intra- 
ocular pressure; the greater part of the blood 
will try to relieve itself through the anterior 
ciliary veins which pass straight through the 
sclerotica, and whose calibre is not at first 
affected by the pressure, but become enlarged 
by the increased flow through them. 
“We therefore see that eyes of greater than 
normal tension are disposed to glaucoma; and 
in such cases glaucoma often arises by outward 
influences of the slightest kind, as by any inter- 
ference in the circulation of the eye, etc.” 
(Stellwag). 
As before mentioned, the action of atropia 
causes the blood to be driven out of the iris, 
back into the posterior uveal tract, and thereby 
an overfilling, and choking of the vessels of 
the choroid can take place, with the develop- 15 
ment of glaucoma in persons whose eyes are so 
disposed. 
From this we see that there is danger in the 
instillation of atropia in the eyes of persons 
when there is an abnormal hardness of the ball. 
By long continued use of atropia in the eye, 
the sympathetic fibres become somewhat weak- 
ened, and the blood vessels cannot perform 
their proper function. They become suddenly 
enlarged, pain sets in, and the conjunctiva and 
episcleral tissue become swollen and inflamed. 
Naturally, in such a condition, the use of atropia 
must be discontinued, and a light astringent or 
chlorine water used for a time. I have seen 
some persons of extreme scrofulous diathesis 
who could not bear the least particle of atropia 
without its being combined with chlorine water, 
or a very weak solution of sulphate of zinc. 
Care should be taken to see that the solution 
of atropia used is perfectly clear and neutral. 
Sometimes the salt is not thoroughly washed, 
and it contains some excess of acid, which 
causes irritation. Solutions of atropia beoome 
cloudy and flocky on standing, from collections 
of free particles of carbon that get in it during 
manufacture, etc., and should be filtered or 
renewed. 
In its use, some naturally passes, with the 
tears, through the lachrymal duet into the nose 
and down the throat; and on continued use 
symptoms of poisoning appear, as dryness of 
the mouth, bitter taste, headache, excitement, 
fever, etc.; to remove which quickly, one or 16 
two hypodermic injections of i to £ gr. of 
morphium should be made, in the temple or 
arm. 
Great care should be taken in its use by 
small children and infants. It is not advisable 
to allow the parents or others to apply this ex- 
ceedingly dangerous remedy to such patients, 
for they are likely either to put in too much, or 
to let it run down the face into the mouth, and 
thus seriously, and perhaps fatally, poison the 
child. I have seen some cases of infants and 
very small children, where not the least parti- 
cle of atropia could be used without toxic symp- 
toms, while the extract of belladonna, in weak 
solutions, could be made to answer very well. 
In examining eyes, and using atropia, it 
should not be forgotten that, when the pupil is 
dilated, the accommodation is paralyzed, and 
the vision reduced; it is well to inform the 
patient of this fact, otherwise they are apt to 
become alarmed, and- run from physician to 
physician, in their anxiety and worriment, fear- 
ing they are going blind from what has been 
dropped in their eyes.