A VALUABLE EXPERIMENT BEARING UPON 
SYMPATHETIC OPHTHALMIA WITH A CRIT- 
ICAL REVIEW OF THE SUBJECT. 
BY 
ROBERT L. RANDOLPH, M.D., 
ASSISTANT OPHTHALMIC AND AURAL SURGEON TO THE JOHNS HOPKINS HOSPITAL AND TO THE 
PRESBYTERIAN EYE AND BAR HOSPITAL, BALTIMORE ; OPHTHALMOLOGIST TO THE 
BALTIMORE AND OHIO RAILROAD. 
Reprinted from the Archives of Ophthalmology, Vol. xxi., No. 3, 1S92. A VALUABLE EXPERIMENT BEARING UPON 
SYMPATHETIC OPHTHALMIA WITH A CRIT- 
ICAL REVIEW OF THE SUBJECJ> 
By ROBERT L. RANDOLPH, M.D., 
ASSISTANT OPHTHALMIC AND AURAL SURGEON TO THE JOHNS HOPKINS HOSPITAL AND TO THE 
PRESBYTERIAN HYE AND EAR HOSPITAL, BALTIMORE ; OPHTHALMOLOGIST TO THE BALTI- 
MORE AND OHIO RAILROAD. 
IT is seldom that we meet a case where all the conditions 
are favorable for thoroughly testing the truth of the 
infectious origin of sympathetic ophthalmia, and I am 
satisfied that the case here reported, together with the 
laboratory experiment, form a valuable supplement to my 
earlier work on this subject. 
The following typical case of sympathetic ophthalmia 
came to the Presbyterian Eye and Ear Hospital early last 
summer. 
J. M., forty-one years old, farmer; while endeavoring to digout 
a large stone deeply imbedded in the earth, a piece of the pick 
broke off and flew into his right eye. This was on June 1, 1891. 
He kept on, however, with his work though seeing very indis- 
tinctly with the wounded eye. He was not conscious of any pain 
at the time. He continued regularly at his farming for three 
days longer, when pain and dimness of sight compelled him to 
rest. He came to the hospital on the fifth day. At this time he 
had only light-perception left in the wounded eye. The eye was 
exceedingly sensitive to the touch. He remained in the hospital 
three days, and left with directions what treatment to follow, and 
with the understanding that he should return in case the pain 
persisted. After he had been at home six weeks, and suffering 
all the time, his good eye began to show signs of sympathy, 
Reprinted from the Archives of Ophthalmology, Vol. xxi., No. 3, 1892. 368 
Robert L. Randolph. 
photophobia, lachrymation, and dimness of vision, and according 
to his account he could not see a horse a hundred yards away. 
Before this he possessed unusally acute vision. His family 
physician treated him with blisters and cold applications to eye, 
and sight improved. Thursday, August 13th, he came to the 
hospital again, and the condition of his eyes was as follows : 
In the injured eye light-perception was gone. Eyeball very 
sensitive to touch. At the point of the wound, the sclera was 
injected, cornea clear, pupillary margin entirely bound down by 
adhesions to anterior capsule. His good eye had a vision of 2V0 • 
The anterior capsule showed abundant inflammatory deposits 
upon its surface, together with numerous evidences of old iritis 
all around the pupillary margin. Indeed, it was difficult to make 
out the fundus with any distinctness on account of the general 
dirty appearance of the lens. He complained of great pain in 
forehead and in the region behind the nose. He was persuaded 
to have the eye enucleated, and I prepared to have everything 
ready to make cultures from the vitreous and anterior chamber. 
The eye was removed, and after sterilizing with a hot knife a 
point at the corneo-scleral junction not far from the wound, I 
entered the anterior chamber with a spade-knife, which had been 
sterilized by passing it several times through an alcohol flame. I 
withdrew the knife and followed it with a platinum wire loop, which 
was stirred up in the anterior and posterior chambers of the eye, 
and smear cultures on agar were made, also three Esmarch tubes. 
These tubes were subjected to the proper temperature in an 
oven for as long as ten days, and not a sign of growth showed it- 
self. Prof. Welch, Dr. Flexner, and myself each examined cover- 
slips made from the vitreous and anterior chamber, but discovered 
no organisms. 
I then obtained a rabbit, and made a small opening into the 
anterior chamber with an iridectomy knife. I may add that all 
the instruments were thoroughly sterilized. An iris-forceps was 
introduced into the anterior chamber of the enucleated eye, and 
a regular iridectomy was performed. I found the iris very hard 
to pull away from its adhesions to the lens capsule, but managed 
to draw out and cut off a good-sized piece of the iris. This lat- 
ter was then forced into the anterior chamber of the rabbit's eye, 
and moved about several times in the chamber, and partly drawn 
out and left. 
In one week's time, with the exception of a slight blush about Experiment Bearing upon Sympathetic Ophthalmia. 
369 
the wound, the rabbit's eye showed no evidence of disease, and 
in two weeks this injection had faded entirely away, and only a 
slight prolapse of the iris at this point gave any evidence of the 
operation. The cornea remained clear throughout, and the pro- 
lapsed iris was simply the result of the manipulation, and in no 
way interfered with the functions of the eye,-just what we some- 
times see in cataract-operation without iridectomy. During the 
operation I took pains to bruise the tissues about the incision, 
thus imitating, as far as possible, the conditions peculiar to a 
penetrating wound of the eye. 
One cannot read the literature of this subject for a single 
year without being struck by the want of certainty that exists 
as to its exact nature, and I mean that this has been the 
case every year even since Deutschmann's experiments. The 
solution proposed by Deutschmann and the history of his ex- 
periments are praiseworthy, and few scientific articles may be 
read with more interest by all medical men than his contribu- 
tion to the pathogenesis of sympathetic ophthalmia. Let 
me review briefly his experiments. 
The earlier experiments of Deutschmann were made with 
the spores of the aspergillus fumigatus, and consisted in 
making repeated injections of a suspension of this organism 
into the corpus vitreum of a rabbit. Choroido-iritis followed 
the first injection, and at the end of four weeks, or a few 
days after the fourth injection, he discovers choroido-iritis 
and opacities in the vitreous of the fellow-eye. The animal 
is killed, and the microscopic examination confirms the 
diagnosis. Evidences of inflammation are seen throughout 
the inoculated eye. Interstitial inflammation of the optic 
nerve extending up to the chiasm, with an involvement of 
the latter, is seen, the process passing on down to the other 
eye by way of its optic nerve. The iris and ciliary region 
of the sympathetically affected eye were not examined. 
The posterior half of the eyeball shows abundant signs of 
inflammation in round-cell infiltration. He concluded 
therefore that a sympathetic inflammation may be produced 
in one eye by the introduction of infectious matter into the 
other eye, and that the track of this inflammation is along 
the optic nerve and its sheaths, Inasmuch, however, as he 370 
Robert L. Randolph. 
regarded the inflammation resulting from the inoculation 
with the aspergillus fumigatus as the result of chemical irrita- 
tion, and knowing that such irritation is rarely, if ever, con- 
cerned in the production of sympathetic ophthalmia, he 
resorted to the pus organism for the inoculating material. 
He injects two or three drops of a suspension of staphylo- 
coccus aureus into the vitreous of one eye. The animal dies 
of meningitis on the third day. To avoid this complication, 
he uses a very dilute suspension of the same organism and 
experiments on five rabbits. Only one of the animals gives 
a negative result, negative in so far that after remaining alive 
for several weeks no change was observed in the fellow eye. 
Meningitis does not occur in any of these cases, but all 
the rabbits die of general infection at periods ranging from 
five or six days to three weeks. As regards the microscopic 
examination, round-cell infiltration with micrococci were to 
be found in both optic nerves and chiasm and in the pos- 
terior half of second eye ; a typical case of sympathetic 
ophthalmia, he concludes, in all but one feature, namely, in 
the non-participation of the iris and ciliary region of the 
second eye. And the reason the iritis is absent is because 
the animal dies before the organisms have time to reach the 
anterior portion of the eye. 
In reading the account of these experiments one is forcibly 
struck with their simplicity ; and in these five experiments 
the result of each one never fails to confirm the result of the 
foregoing, so that after coming to the end of Deutschmann's 
work one feels that there is strong reason to believe that the 
theory is proven. I doubt whether any scientific problem 
in pathology has ever been proven so smoothly. 
The nature of sympathetic ophthalmia has always been 
an interesting topic of discussion among ophthalmologists, 
and when Deutschmann's work appeared in 1882 it can be 
imagined with what satisfaction the account of his experi- 
ments was read and how generally they were accepted. 
As is always the case in experimental pathology, any spe- 
cial solution of a problem is subjected to verifying tests at 
the hands of different observers. Such has been the fate of 
this class of work for years, and it is no uncommon thing to Experiment Bearing upon Sympathetic Ophthalmia. 
371 
find what seemed a valuable discovery fall into disrepute 
simply because it could not stand the test in the hands of 
others. And such a course is right, as any one can readily 
see. The explanation of any phenomenon in medicine only 
becomes valuable when that explanation can be verified by 
others than the originator. The things in the science of 
medicine which remain are those things which have been 
proven by many, both in the laboratory and in the hospital, 
and the things which have been discarded and are forgotten 
are those things which have been found worthless except 
possibly in the hands of one man. 
Such striking and uniform results as those which attended 
the experiments of Deutschmann would seem to promise an 
easy confirmation, and it was almost with this conviction 
that I entered upon the experiments published in these 
Archives three years ago (vol. xvii., 187-213). The first 
parallel experiments of Deutschmann's work were made by 
Dr. H. Gifford,1 of Omaha, who at the time he was engaged 
in this work was serving as one of Horner's assistants in 
Zurich. I shall not go into an account of his experiments 
in detail, but will simply state that after repeating Deutsch- 
mann's experiments on seventeen rabbits, he failed on any 
point to confirm the work of the latter. Eighteen months 
later I commenced my own work on this subject, and after 
spending many months in a series of thirty experiments I 
obtained nothing but negative evidence from Deutschmann's 
point of view. 
For the first few months I used dogs as subjects, as I sup- 
posed they would be less likely to succumb to the effects of 
a general infection, and in consequence would enable me to 
follow out more accurately the theory, and my results 
proved that I was right, as none of the animals, with the 
exception of one case, showed any evidence of constitutional 
disturbance. Until this time the character of my work had 
differed in only one point from that of Deutschmann, namely, 
in the fact that mine were made on dogs. Thinking that 
this difference might impair the value of my work as a 
control of that of Deutschmann, I concluded to repeat his 
1 Ibid., vol. xv., 281-295. 372 
Robert L. Randolph. 
experiments on rabbits. This line of experiments consisted 
of fifteen in number, and they resulted just as did the first 
series; in other words, at no time during the life of the 
animal could any sympathetic disturbance be detected in 
the second eye, and though an ophthalmoscopic examina- 
tion was made every day the fundus of the second eye never 
indicated the slightest departure from the normal, and I 
may add that the microscopic examination only served to 
strengthen this state of the case. 
My work then, so far as verifying the results of Deutsch- 
mann's experiments, resulted negatively. As I remarked in 
my previous work on this subject, the microscope always 
showed infiltration of the intraocular end of the infected 
eye. A moment's glance was sufficient to tell me that. 
The excess of the nuclei present over what is seen in the 
normal condition was too apparent to be mistaken, but any 
noticeable progress of this increased nucleation for more 
than a short distance from the eye was never observed. 
Mazza 1 experimented also upon rabbits and guinea-pigs, 
but reports only failures from Deutschmann's point of view. 
Nor did this observer notice any change in the second eye 
with the ophthalmoscope. In those animals that had died 
of meningitis cocci were to be found in the optic nerve and 
its sheaths. 
And finally I would call attention to the work of Lim- 
bourg and Levy 2 of Strassburg. These experimenters in- 
oculated twenty-five rabbits and seventeen guinea-pigs after 
the method of Deutschmann. As the changes in the inocu- 
lated eye resembled precisely those observed in my own 
experiments, I shall only allude to the condition of the 
second eye. To use their words " as regards any changes in 
the second eye which could be looked upon as sympathetic, 
none were observed with the exception of a very doubtful 
hyperaemia of the fundus. The examination for organisms 
was in every case negative." Their work simply confirms my 
own. It is surprising that the authors after finishing such 
a valuable piece of work did not feel themselves justified in 
1 Bericht ubet den VII. Internal. Ophthal. Congr., zu Heidelberg, 1888. 
2 Archiv. f. experiment. Path. u. Pharmak., Bd. xxxviii., S. 153-166. Experiment Bearing upon Sympathetic Ophthalmia. 
373 
drawing any further conclusion than as follows : " It fol- 
lows from these experiments how difficult a thing is the 
experimental investigation of this question." 
It would seem that Limbourg and Levy were so influenced 
by Deutschmann's views as to distrust their own work, and 
yet their experiments were far more exhaustive than those 
of the latter. Even if they did not feel warranted in ex- 
pressing in so many words their doubts as to the value of 
Deutschmann's work, they certainly had a right to conclude 
that it is impossible by the method employed to produce a 
sympathetic ophthalmia in a rabbit. 
As regards the discovery of organisms in an eye which 
has been enucleated for fear of sympathetic disease in the 
other eye, experience differs widely, and even this point is 
too often decided in the negative to admit it as an addi- 
tional support of the germ theory of the disease. Deutsch- 
mann rarely failed to find organisms in an eye enucleated 
to avoid sympathetic trouble, and though I have examined 
at least a score of such eyes I have succeeded in detecting 
organisms in but one case, and that was when the injury 
dated only two weeks back, a fact which has led me to 
conclude that the very questionable agency of micro-or- 
ganisms in the production of sympathetic ophthalmia is ren- 
dered more unlikely when the sympathetic disturbance makes 
its appearance from two to six months after the injury. 
Ohlmann 1 records recently having examined thirty eyes 
enucleated to avoid sympathetic disturbance, and in not a 
single one did he find organisms. 
It should be remembered that sympathetic ophthalmia is 
a very rare disease. I can safely say that, in by far the 
majority of cases where I have performed enucleation, it has 
been on an eye which had been sightless for many months, 
certainly for many weeks and frequently for years, and this 
I feel sure has been the experience of most ophthalmic 
surgeons. In other words, enucleation is practised almost in- 
variably as a precaution against the disease, and when we 
consider how all-pervading organisms are, is it not strange 
that, if they are really factors in this disease, they do 
1 Archiv. f. Augen., Bd. xxii., I. Robert L. Randolph. 
374 
not begin their work sooner, or is it not stranger still that 
in the majority of cases they accomplish nothing? When 
we consider the fact that organisms have almost certainly 
been introduced into all eyes which have been destroyed by 
penetrating wounds, and furthermore that a large number 
of such patients have carried these sightless eyes for a long 
time,-when we consider this, there remains a striking lack 
of anything like cause and effect between the opportunity 
offered the organisms to do their work and the actual occur- 
rence of the disease. These remarks though are simply by 
the way, for I do not desire to pronounce myself positively 
against the infectious origin of the disease. 
As to the experiments on rabbits, guinea-pigs, and dogs, 
the weight of evidence goes to show that not only is there 
no analogy between the disease, as seen in man and these 
animals, but that sympathetic ophthalmia cannot be pro- 
duced in these animals through the agency of the staphy- 
lococcus, and that consequently such a character of experi- 
ments can throw no positive light on the subject. 
It is unaccountable how Deutschmann discovered in every 
case such uniform conditions of neuritis extending along 
both optic nerves including the chiasm. Professor Deutsch- 
mann, no doubt, rejects the possibility of having mistaken the 
normal for the pathological condition, but I would again, as 
in my former work, emphasize the fact, that there is no ques- 
tion about the difficulty of differentiating unless one has at 
hand sections of a nerve which are known to be normal, and 
with which we can compare the supposed pathological section. 
The rabbits, it will be remembered, all die at the end of 
two or three weeks, and in consequence the chief distin- 
guishing feature of a neuritis at this stage is the increase in 
nuclear elements, and upon this point we must mainly rely 
in making our diagnosis. Changes in the nervous bundles 
are not readily demonstrable features of a neuritis of three 
weeks' duration. And though one will invariably detect an 
increased number of nuclei at the intraocular end of the 
infected eye, one will be astonished to find on comparing 
such a section with a normal eye what an enormous number 
of nuclei are present in the latter (physiological condition). Experiment Bearing upon Sympathetic Ophthalmia. 
375 
But, apart from this, in the light of all the control work 
that has been put upon this subject, and with nothing but 
negative results, it seems unreasonable to look upon the 
infection theory as demonstrated by the experiments of 
Deutschmann as anything yet awhile but an idea. 
And finally, to return to my experiment in the laboratory. 
It seems to me that this is a most valuable test of the question 
as to what rdle bacteria play in the production of the dis- 
ease. We have here an undoubted case of sympathetic 
ophthalmia, and if bacteria in the injured eye gave rise to 
the sympathetic trouble, it is reasonable to suppose that the 
means employed to discover them would have been success- 
ful, and that the experiment on the rabbit would at least 
have suggested something which might be regarded as posi- 
tive evidence. 
The reasonableness of the infectious origin of sympathetic 
ophthalmia no doubt accounts for the general acceptance of 
the theory, but we ought to recollect that this theory owes 
almost its entire support to a few experiments with the pus 
organism. And if there is an organism which we might 
almost predict would not produce the disease it is the pus 
organism. Purulent inflammation of the eyeball, in a word 
" panophthalmitis," where the pus organisms are most abun- 
dant, as a rule do not give rise to sympathetic ophthalmia. 
As I have said before, I do not wish to be regarded as 
absolutely arrayed against the infection theory, but 
against the theory only so far as the pus organism is con- 
cerned. There are many organisms about which we know 
nothing, with which it might be possible to produce the dis- 
ease in animals ; and, again, sympathetic ophthalmia may 
have its own specific organism. 
It is possible too that the disease is not of bacteric origin, 
but that an organism of some other class may be present. 
And again, we have strong reason for believing that the 
lower animals do not have sympathetic ophthalmia, just 
as they do not have many other diseases peculiar to the 
human race. 
The experiment here recorded I regard as strong proof 
against the views set forth in the work of Deutschmann. Ttbe Unicherbocher press 
g. p. putnam's sons 
Nbw York