ADDITIONAL EXPERIMENTS 
To Determine the Lesion 
IN 
Quinine Blindness. 
By G. E. de SCHWEINITZ, M.D., 
Of Philadelphia. 
With Photo Micrographic Studies by William M. Gray, M.D. 
\Reprinted from American Ophthalmological Society Transactions, 1891.] [Reprinted from American Ophthalmological Society Transactions, 1891.] 
ADDITIONAL EXPERIMENTS TO DETERMINE 
THE LESION IN QUININE BLINDNESS. 
By G. E. de SCHWEINITZ, M.D., 
OF PHILADELPHIA. 
With Photo-micrographic studies by William M. Gray, M.D. 
A communication presented to the College of Physicians of 
Philadelphia, November, 1890,* contained the results of some 
experiments which I had made in the endeavor to determine the 
lesion in quinine blindness. A brief summary of this research 
is the following: Quinine given hypodermically to dogs in 
quantities varying from one grain to four grains to the pound, 
produces blindness in from three to fourteen hours, the earliest 
appearance of the amaurosis after the injection being three 
hours. The blindness remained practically complete in one 
animal for twenty-nine days after a single injection of 3! grains 
to the pound ; in one there was a slight return of vision after 
thirty-six hours of blindness. The effects of the drug were ob- 
tained more quickly and more surely with quin, bimur. carbami- 
dat. than when the bisulphate was used. A dose exceeding 
3| grains to the pound produced death ; one animal perished 
from a dose of three grains to the pound ; and one dog resisted 
11 grains of quinine to the pound given on two successive 
days, but succumbed when a third similarly proportioned dose 
was administered. With two exceptions the animals suffered 
from other symptoms in addition to the blindness, viz : vomiting, 
* Transactions of College of Physicians of Phila., 1890; also Ophthalmic Review, Feb- 
ruary, 1891. 2 
Schweinitz : Additional Experiments to 
or staggering gait, or paraplegia, or convulsions. The two ex- 
ceptions became blind without any general symptoms, and 
in one of these the most noted microscopical changes were found. 
The ophthalmoscopic picture in these animals was in all in- 
stances similar to that which has been noted in human beings, 
suffering from quinine amaurosis. In one there was complete 
obliteration of the vessels in the disc; in another, blurring of the 
edges of the papilla. In all the pupils were immovably dilated. 
The microscope did not discover any very coarse lesions except 
in one dog, in which the central vein was plugged with a clot, and 
in the transverse cuts of the smaller veins white thrombi were 
visible. In other nerve entrances there was some dilatation of 
the vessels. In the transverse cuts of the optic nerve there was 
some increase of the connective tissue, and a curious appear- 
ance was the spreading apart of the individual nerve-fibrils as if 
the tissue was oedematous. There was no true atrophy demon- 
strable by Weigert's method, even in the nerve of a dog blind for 
twenty-nine days. Chiasms, retinas, and choroids were normal. 
In sections from the cuneus there was remarkable dilatation of 
the pericellular lymph spaces, with degeneration of the proto- 
plasm of the cells. From these results it became evident that 
toxic doses of quinine could produce thrombosis in the central 
vein, and that, as negative evidence, neither neuritis, nor atrophy 
in the true sense of the word, was present in an animal blind 
for nearly a month (although the disc was quite white and 
the vessels threads), but that there appeared to be a species of 
oedema between the optic nerve and chiasm. 
Certain additional evidence is desirable, viz. : 
(1) Can the same results be produced with salts of quinine 
other than with those composed of the bimuriate of quinine com 
bined with the carbamide of urea, and will all of these results 
be apparent in animals so poisoned that blindness, unaccom- 
panied by general symptoms, is the sole effect ? 
(2) Will the prolongation of the quinine blindness produce 
true atrophy ? . 
(3) Is the production of thrombosis or embolism to be 
expected in severe cases ? 
(4) Is the apparent degeneration of the brain cells the result 
of the hardening process, or due to a lesion from the drug ? Determine the Lesion in Qziinine Blindness. 
3 
I. In the first research, the effect of the quin, bimur. car- 
bamidat. was found to be more pronounced than the ordinary 
bisulphate of quinine, although it was shown that the latter 
was active. Since then in a number of instances I have 
produced blindness by using quinine dissolved with the aid of 
tartaric acid or dilute hydrochloric acid, and have used qui- 
nine from several different sources. It is needless to detail 
these experiments. The results were the same as those already 
published. In regard to the second portion of the first query, 
an affirmative answer may be given, as the detailed research 
presently to be given will show, as it will also answer the other 
questions. One experiment is detailed. 
Experiment. Black dog, weight 15 pounds, was given 30 
grains of bisulphate of quinine at 4.15 p. m., October 28, 1890, 
previous examination having shown normal fundus oculi, pupil 
reactions, and cornea. 
October 29. Partially blind. Runs with nose stretched out 
and apparently finding his way by the sense of smell; frequently 
butts his head against objects, as one whose field of vision 
is deficient. Ophthalmoscope. Pupils widely dilated. Cornea 
not anaesthetic. No evident change in the color of the disc or 
caliber of the veins; arteries smaller than on previous day. 
Thirty additional grains of quinine injected. 
October 30. Dog entirely blind, but not deaf. Slight verti- 
cal nystagmus. Pupil dilated. No anaesthesia of cornea. 
Ophthalmoscope. No change in veins ; arteries small. 
November 17. Daily record of animal's condition omitted, 
which may be summarized as gradual shrinking of the arteries, 
loss in color of disc, and contraction of veins. No general 
symptoms occurred, and on this date (November 17, 1890) discs 
entirely white ; arteries not distinguishable. Only faint traces 
of the lower veins in each eye. 
December 25. There has been practically no change in the 
animal. During the last day or two, however, there appears to be 
some return of sight, as he now avoids certain objects in 
the room and fails to promptly respond to the ordinary tests. 
The ophthalmoscope shows no new changes in the fundus. 
December 26. Fifteen additional grains of quinine admin- 
istered. 4 
Schweinitz : Additional Experiments to 
December 29. Dog apparently completely blind. Ophthal- 
moscope. In each eye the discs entirely white, only the lower 
temporal veins being visible. The position of the arteries is 
marked by faint white threads. The animal was killed, and the 
eyeballs, optic nerves, chiasms, and entire brain were placed in 
Mueller's fluid and prepared with the utmost care for section. 
Some days later a normal dog was similarly killed and the same 
organs removed and placed in Mueller's fluid for comparison. 
The specimens, which were removed for microscopic exam- 
ination, were sectioned for the microscope by Dr. William M. 
Gray, and from the sections thus obtained the accompanying 
photo-micrographs prepared. The following are the results of 
the microscopic examination : (Fig. 1, Pl. I, is the normal optic 
entrance.) 
At the point of entrance of the central vessels - the vessel 
infundibulum - a cup has been formed somewhat similar to 
the excavation seen in glaucoma. This cup is partly filled 
by a fine granular substance, a portion of which is arranged 
in threads holding in its meshes a few blood corpuscles. A 
little below the cupped entrance is a dense plug of this 
granular substance. Below this plug the central vessel is seen, 
the walls of which are somewhat thickened, and its lumen almost 
entirely filled by a connective tissue growth composed of fine 
reticular fibrous connective tissue, small spindle cells with 
long processes, and small round cells. (Fi g. 2, Pl. I). Scattered 
through this structure and in relation to the cells is a small 
quantity of pigment. Running through the center of this mass 
of tissue which fills the vessel there is a small capillary arteriole, 
narrow at its upper extremity, but at its lower fourth suddenly 
expanding to at least double the size of the upper portion 
(Fig. 3, Pl. II, high power). To one side of the upper extremity 
of this capillary vessel is an irregularly-shaped space, formed in 
the connective tissue filling the large vessels. This space con- 
tains a few blood corpuscles and seemingly is lined by endothe- 
lium, a few nuclei being seen around the edge (Fig. 3, Pl. II). 
At its upper extremity this space leads off into a series of 
branching capillary vessels, which run into and are lost in the 
surrounding nerve tissue. At the lower portion of the large 
occluded central vessel there is a blood sinus which also leads Plate I. 
Figure i. Optic nerve entrance of the normal dog. [X 75-] 
Figure 2. Quinine-dog nerve entrance, showing cupping and 
occluded vessel. [X 100.] Plate II 
Figure 3. Same section as figure 1, showing the tissue filling the ves- 
sel, capillary arteriole running through the centre of the 
tissue, and the large cavity formed in it. [X 250 ] 
Figure 4. Ciliary ganglion from quinine-dog, showing above part of 
the oculo-motor nerve, and springing from the ganglion 
short ciliary nerves. [Weigert's stain.] Plate III. 
Figure 5. Normal optic nerve of a dog. [X 125, Weigert's stain.] 
Figure 6. Optic nerve of a dog, blind from the effects of quinine for 
two months, showing atrophy and degeneration. 
[X 125, Weigert's stain.] Determine the Lesion in Quinine Blindness. 
5 
off into the surrounding nerve tissue (Fig. 2, Pl. I). There are 
other, but smaller, sinuses or vessels passing from the main vessel 
along its entire course. In a number of the sections, both in 
the first series of quinine dogs and from the one which is under 
consideration in the present paper, the cup at the central vessel 
entrance is seen, and, protruding from the cup, masses of 
material, partly homogeneous and partly granular, containing a 
few nuclei. In one section the lower portion of this cupped 
entrance is constricted, and below the point of constriction the 
vessel rapidly expands, its lumen being filled by a finely-reticu- 
lar fibrous connective tissue, holding in its meshes a mass 
of small round cells. Here and there in this mass of tissue 
there are blood sinuses which contain a few blood cells. To 
one side of the central cup, where Mueller's fibres enter the 
nerve from the retina, there is an expanded blood vessel filled 
with a blood clot. In one dog, of the original series of quinine 
experiments, the cupping is well marked, and protruding from 
the cupped entrance is a mass of the granular and homogeneous 
material such as has been described. The entrance to the 
vessel is greatly constricted immediately after passing into the 
upper opening, and it is partly filled by the granular material. 
In one section is shown a small vessel formed of this granular 
homogeneous material which extends through the constricted 
entrance to the central vessel. Below the entrance and con- 
striction the central vessel is lost in a mass of dense fibrous 
tissue. This tissue contains numerous small blood vessels or 
channels, some of which lead off into the surrounding nerve 
tissue 
Transverse sections of the optic nerve and chiasm of the dog 
blind for two months, stained by Weigert's process, show marked 
degenerative changes. Fig. 5, Pl. Ill, represents a transverse 
cut of a normal dog's optic nerve stained by this process, while 
Fig. 6, Pl. Ill, has been prepared from a similar cut taken from the 
dog blind from the effects of quinine for two months. The con- 
trast in these two sections is well shown. In the quinine dog 
there is complete destruction of the nerve fibres, some increase 
of connective tissue, and a small amount of fatty infiltration. 
In one specimen the section has passed through the lenticular 6 
Schweinitz : Additional Experiments to 
ganglion, showing the development of the ciliary nerves and 
some slight degenerative changes in the ganglion itself (Fig. 
4, Pl. II). A section of a normal ganglion stained by Weigert's 
process compared with the ganglion from the quinine speci- 
men, prepared by exactly the same process, illustrates the 
degeneration in the fibres. The transverse sections of the 
chiasm may be compared with similar sections taken from the 
normal dog, from whence it is evident that the degenerative 
process and complete atrophy exist in all of the fibres up 
to the chiasm, in the chiasm itself, as far backward as it has 
been possible to trace the optic tracts. The dilatation of 
the pericellular lymph-spaces through the brain in the first 
series, especially in the cuneus, have been shown by a number 
of experiments to be unconnected with any action of quinine, 
being easily produced by any slight fault in the technique. 
From what has been said, it will be seen that the answer to 
the second question is that the prolongation of quinine blind- 
ness produces true atrophy. The answer to the third question 
is also affirmative, namely, that thrombosis of the central 
vessels may be expected in severe cases of the toxic action of 
this drug; while the answer to the fourth question, as has just 
been stated, is negative, as the degeneration of the brain Cells is 
the result of the hardening process, and not due to a lesion from 
the drug. 
In resume we may say in regard to the microscopical points, 
that we have thickening and changes in the walls of the central 
vessel (endo-vasculitis) ; organization of a clot, the result 
of thrombosis, an organization which has been carried on even 
to the extent of its being channeled by new vessels; widening 
of the infundibulum of the vessels as the result of the constric- 
tion of the surrounding nerve fibres, presenting appearances 
not unlike a glaucomatous excavation; and finally, practically 
complete atrophy of the visual path, including the optic nerves, 
optic chiasm, and optic tracts, as far as they could be traced. 
It seems, then, very likely that the original effect of quinine is 
upon the vaso-motor centers, producing constriction of the ves- 
sels ; that finally changes in the vessels themselves are set up, 
owing, perhaps, to an endo-vasculitis; that thrombosis may Determine the Lesion in Quinine Blindness. 
7 
occur, and that the result of all of these is an extensive atrophy 
of the visual tract. Not the least remarkable is the selective 
influence of quinine on the optic nerves and the optic tract. In 
the sections and the micro-photographs herewith presented, it 
will be seen that the ciliary and oculo-motor nerves, side by side 
with the optic nerve, are perfectly normal, and that even in the 
lenticular ganglion many of the fibres are perfectly intact, 
although others appear to have undergone a slight degeneration. 
The same, no doubt, is true of the other cranial nerves. The 
selective action of drugs is, of course, well known, the charac- 
teristic action of digitalis upon the heart being, perhaps, the 
most typical example. This, however, in addition to the well- 
known physiological action of drugs, appears to be a histo- 
logical demonstration of such affinities. Why quinine should 
produce these lesions upon the nerves of special sense 
which supply the eye and the ear, it is difficult to under- 
stand ; that it has such action is unquestioned, and here meets 
with a positive microscopic demonstration. While, no doubt, 
the original effect is in some sense due to the influence of this 
drug upon the vaso-motor centers, this cannot be the entire ex- 
planation, or we should have similar actions under the action 
of well-known vaso-motor stimulants, like ergot.