ETIOLOGY AND PATBOLOGY OF SYMPATHETIC 
OPHTHALMIA. 
By Charles Zimmermann, M. D., 
Milwaukee, Wis. 
Reprinted from The Medical and Surgical Reporter, August 17,1895. ETIOLOGY AND PATHOLOGY OF SYMPATHETIC OPHTHALMIA.* 
CHARLES ZIMMERMANN M.D., MILWAUKEE, WlS. 
In recent years the pathology of sympa- 
thetic ophthalmia has been the subject of 
numerous careful investigations by prom- 
inent ophthalmologists which, however, 
resulted in quite contradictory opinions. 
Deutchmann gave the experimental proof 
of what Mackenzie (A Practical Treatise 
on the Diseases of the Eye, 4th ed.p. 597) 
tonght fifty years ago, that “ the chief 
medium through which sympathetic 
opthalmitis is excited, is the union of the 
optic nerves, ” with the conclusion that 
the microorganisms from the infected eye 
apparently enter the optic track in four 
different ways: 1st, from the perichoroi- 
dal space; 2nd, directly from the choroid 
into the pial sheath of the optic nervee 
3rd, from the sheathes of the central 
vessels along their branches which radiate 
into the optic nerve, into the pial sheaths 
and the intervaginal space; 4th, sometimes 
probably from Tenon’s capsule. (Deutseh- 
mann : On Ophthalmia migratoria.) 
Others, who did not succeed in obtaining 
the same results, consider it still an open 
question; and yet others, with Schmidt- 
Rimpler (v. Grczfe’s Arch. 38.1.) as re- 
presentative, adhere to a modification of 
the old theory advanced by Heinrich 
Mueller, that the ciliary nerves convey the 
disease from the first to the second eye. 
Deutschmann with Leber {von Grcefe's 
Arch. 27) also acknowledges this, but only 
for the sympathetic irritation which is a 
reflex neurosis and an entirely different 
disease, independent of sympathetic or, as 
he calls it, migratory ophthalmia. The 
former is permanently cured by removal 
of the diseased eye, whereas sympathetic 
ophthalmia is not influenced, by it at all. 
Both diseases, however, may coexist in the 
same eye but perfectly independent of 
each other, or one may precede the other. 
The sympathetic irritation is not a 
milder form of sympathetic inflammation, 
as has been supposed, although eyes 
which cause sympathetic ophthalmia may 
also produce sympathetic irritation. 
As pointed out by Schweigger, there is 
no typical form of sympathetic ophthal- 
mia; it is only a diagnosis of probability. 
This may reach almost certainty, if a nor- 
mal eye becomes diseased after an affec- 
tion of the first eye, under conditions 
which, according to experience, deserve 
some value: the form of disease of the 
first eye; that of the second eye; and the 
interval between both, generally of from 
two weeks to four months. Schirmer 
{von Grcefe's Arch., 38. 4), gave a critical 
review on sympathetic ophthalmia of the 
publications of the last years and came to 
♦Read at the Wisconsin State Medical Society 
June 19,1895. the conclusion which Albrecht von Groefe, 
I860, pointed out, that an inflammation of 
the uveal tract is necessary to produce a 
sympathetic affection. And it is only by 
the development of irid-ocyclitis that 
sympathetic ophthalmia may be aroused 
by intraocular tumors, formation of bone 
in the choroid, incarceration and laceration 
of the ciliary body or iris, and that this 
inflammation is due to infection. In sub- 
conjunctival ruptures of the globe the 
irido-cyclitis is to be attributed to an in- 
vasion of microbes by minimal lesions of 
the conjunctiva, or if it sets in later by 
small defects of the scar, perhaps only 
abrasions of the epithelium (Wagenmann, 
von Grcefe's Arch., 34. 4). That infec- 
tion must occur was clearly demonstrated 
in a case of intraocular cysticercus of 
Pincus (von Grcefe’s Arch., 40. 4), which 
in fourteen years had brought about ex- 
tensive degeneration of the globe with 
dislocation of the lens, without disturbing 
the second eye. After extraction of the 
lens the wound did not heal well and be- 
came infected, producing severe irido- 
cyclitis and, after eight weeks, serious- 
plastic uveitis of the other eye. 
Aseptic perforating wounds, as for in- 
stance in operations, heal without reac- 
tion, whereas minimal quantities of mi- 
crobes, brought in contact with them, 
cause severe inflammations, and this in- 
flammation of the uveal tract represents 
the relation between injury and sympa- 
thetic ophthalmia. 
The rare occurrence of sympathetic 
ophthalmia in panophthalmitis, the se- 
verest form of infectious inflammation, 
seems to be in apparent contradiction to 
these observations,especially since Schmidt- 
Ilimpler proved by cultures the presence 
of staphylococcus pyogenes aureus in an 
eye affected with panophthalmitis for four 
weeks, and Schirmer in a case of metasta- 
tic panophthalmitis of three weeks dura- 
tion. This has been utilized as an impor- 
tant argument against Deutsehmann’s 
theory. There are, however, some cases of 
sympathetic ophthalmia after panophthal- 
mitis observed lately by Schirmer, 
Scheffels and Deutschmann. The latter 
{Beitrage z. Aug. 10 p. 50) assumes with 
Leber, that in panophthalmitis the micro- 
organisms are removed with the flow of 
pus out of the perforated globe, or are de- 
stroyed by the profuse suppuration, and 
with Gifford, that the lymph-channqls be- 
come obstructed by the accumulation of 
puss and fibrinous products, thus imped- 
ing the migration of micro-organisms. In 
those cases in which panophthalmitis 
creates sympathetic ophthalmia, Schirmer 
surmises a mixed infection with the hypo- 
thetical coccus of Sattler,which ordinarily 
is destroyed by the more virulent staphylo- 
coccus. Deutschmann suggests instead 
of the coccus any bacterium which is more 
apt to follow the tract of the optic nerve, 
than the staphylococeus pyogenes is in 
man. 
Such a mixed infection is also to be sup- 
posed in sympathetic ophthalmia after 
gonorrhceic and tuberculous iritis, as in all 
the cases so far published a corneal perfor- 
ation occurred which allowed the invasion 
of other microbes. 
The sympathetic inflammation of the 
second eye appears in two forms: Sym- 
pathetic uveitis in its various fashions and 
localizations, and papillo-retinitis. Both 
may be combined; often the latter may 
not be visible on account of opacities of 
the media, especially when associated with 
choroiditis. Schirmer mentions only five 
cases in which papillo-retinitis preceded 
the uveitis, and thinks that papillo-retin- 
itis alone is very rare and gives a much 
better prognosis than uveitis. Its depend- 
ence on the sympathizing eye was shown 
by the fact, that after enucleation it healed 
rapidly, though not at once as in sympa- 
thetic irritation. From this Schirmer in- 
fers that it is produced by toxines, and 
if caused by micro organisms the inflam- 
mation will spread to the uveal tract. 
Deutschmann found that neuritis and 
neuroretinitis of the second eye are more 
frequent than formerly supposed. The 
examination of human eyes which have 
been removed after they had given rise to 
sympathetic ophthalmia, revealed that 
neuritis and perineuritis were the rule. 
The discs of Dentschmann’s rabbits were 
reddened and under the inner medullary 
stripe four to five yellow prominent 
choroidal spots of the size of a pin’s head 
owing to circumscribed round cellinfiltra- 
tions of the choroid. 
As a typical ophthalmoscopic picture of 
sympathetic ophthalmia, Hirchberg (C. 
Bl. F. A. 1895, p. 80) describes light 
foci in the periphery, slightly resembling 
the specific patches, which may also be 
observed in the eye first affected. Casper 
{Klin. Mon. f. Aug. 1895, p. 179) saw an analogous condition in a case of sympa- 
thetic disseminated choroiditis. 
Sympathetic inflammation of the uveal 
tract appears as iritis serosa, iritis plastica, 
irido-cyclitis, plastica or maligna, irido- 
choroiditis, or they may pass from one into 
the other. All three parts of the uvea 
are generally affected, as autopsies have 
shown, but often during life the condition 
of the choroid cannot be ascertained. 
The disease mostly starts in the iris, but 
it may also advance from behind forward. 
If uveitis posterior or anterior are primary, 
the explanation by the migration theory 
is: Through the perichoroideal space, 
perhaps from the posterior pole of the 
globe along the sheathes of the long ciliary 
vessels the microbes or their toxines may 
rapidly advance to the anterior portion of 
the uveal tract and display earlier the 
clinical symptoms, before the process at 
the optic disc becomes noticeable. The 
serous iritis is not as malign as the plastic 
uveitis which shows a tendency to re- 
lapses, always leaving the eye in a worse 
condition than before, and mostly ends in 
atrophy of the globe. 
Sympathetic ophthalmia does not set in 
before fourteen to eighteen days after the af- 
fection of the first eye, generally in four to 
six weeks. A maximum interval cannot be 
set down as a rule, but the longer the in- 
termediate time the more the probability, 
that the disease of the second eye is of an 
idiopathic nature. A phthisical eye with- 
out any signs of irritation does not cause 
sympathetic ophthalmia. If after several 
years an affection of the second eye occurs, 
the first eye has never been quiet, or it 
shows some recent inflammation, either by 
a new infection or a revival of micro-or- 
ganisms, which have been latent like 
spores, or from time to time increase to 
such an extent that they cause a new in- 
flammation. 
Quite a number of cases are published in 
which sympathetic ophthalmia broke out 
within three to four weeks after preventive 
enucleation, optico-ciliary neurotomy or 
neurectomy. In two of Nettleship’s cases 
enucleation was performed one to two days 
after the injury, but the latter had ex- 
tended also to the orbit and caused inflam- 
mation of the orbital tissues, and this gave 
rise to the sympathetic affection seven and 
five weeks afterwards. When the sympa- 
thetic ophthalmia exists before enucleation 
even in a slight degree, the latter does not 
prevent its malignity. It has been 
anatomically proven, that both ends of the 
optic nerve after neurotomy become again 
united and that a regeneration of the 
ciliary nerves takes place in that way, 
that from the central stumps numerous 
twigs grow into the sclera and the sen- 
sibility returns. Therefore if the ciliary 
nerve theory is wrong and the optic nerve 
exclusively conveys the virus or sympath- 
etic ophthalmia, then, according to 
Scheffels, {Klin. Mon. f. Aug. 1890) 
an early and thorough resection of the 
optic nerve must prevent sympathetic 
ophthalmia in all cases. Should the 
latter occur only in one case of resection 
rightly performed, the whole theory of 
migration through the optic nerve falls to 
the ground. Trousseau observed such 
a case of sympathetic ophthalmia with 
ensuing blindness two mouths after resec- 
tion of the optic nerve of 4 to 5mm. 
length. 
Deutschmann, presupposing a reunion 
of the stumps, considered this question of 
such principal importance, that he under- 
took new experiments for its explanation. 
{Beitraege, hft 10). A piece of 
three to four mm. of the left optic nerve 
of rabbits, which was 14 mm. long from 
the chiasma to the globe, was resected, 
i.e. the 4-5 to 3-5 part of the whole length, 
corresponding to Schweigger’s claim for 
effectual neurectomy of ten mm. of the 
human optic nerve, which measures 
38 mm. Two months later one animal 
died accidentally. Immediately after death 
he injected of a Pravaz’s syringe of In- 
dia ink into the subdural space of the 
skull, and 15 minutes afterward India ink 
was found in the intervaginal space of the 
whole right optic nerve. The ends of the 
left optic nerve were connected by a tract 
of connecting tissue 2 mm. long, in which 
as well as in both ends India ink was seen 
down to the globe. Ilis deductions were: 
Eesection of the optic nerve permanently 
destroys the nervous conduction, but the 
nerve ends become reunited by connective 
tissue. It communicates with the cen- 
tral and peripheral vaginal spaces and 
leads the lymph current from the brain 
to the bulbar end more slowly and not as 
readily as in the normal vaginal space, 
but without essential difficulty ” (p. 27). 
He further assumes,that microbes or their 
toxines may proceed against the lymph 
current from the globe to the chiasma as well as the India ink did with the lymph 
current to the globe. At the instance of 
these experiments Wagenmann (v. Grcefe's 
Arch. 41, i, p. 182) modified the regular 
resection by thorough cauterization of the 
peripheral end of the resected optic nerve 
in order to increase the protection un- 
doubtedly furnished by neurectomy, but 
leaves the proof to later experiments. 
Velhagen [Arch. f. A. 29,No. 14) imitated 
Deutschmanu’s experiment, but with op- 
posite results. Staining fluid injected 5 
weeks after neurectomy into the arachnoi- 
dal space under high pressure did not ooze 
from the central optical stump, which was 
tightly sealed by cicatrical tissue. He infers 
from this, that, if the mode of cicatrization 
in man is similiar to that in rabbits after 
neurectomy, no micro-organisms from the 
interior of the globe can enter the central 
optical sheath after a lapse of time suf- 
ficient for cicatrization. 
The migratory theory has met with op- 
position mostly by Schmid t-Rimpler (l.c.), 
who observed two cases of sympathetic 
ophthalmia, one and a half years after 
optico-ciliary neurectomy, and mentioned 
as the chief point, that no micro-organ- 
isms were found in the resected piece nor 
in the globe which was afterwards enu- 
cleated, so that no micro organisms could 
have migrated to the other eye. Norden- 
sen, Berry, Ayers, Alt, Randolph, Kuhnt, 
Ohlemann, Greef, Uhthoff, Schirmer did 
not find micro-organisms in the eyes 
which had been removed after sympathetic 
ophthalmia had taken place. Positive in 
regard to bacteria in enucleated eyes were 
the investigations of Limbourg, Levy, 
Sattler, Snellin, Leber, Abraham, Story, 
Angelucci, Basevi, Secondi, Waldispuehl, 
Berry, and Finlay, who used Knapp’s ma- 
terial. Deutschmann found micro-organ- 
isms in all cases observed in three years 
after publication of his monograph. 
(Staph, alb., slender bacteria, clumsy 
bacilli). Cultures made of two cases 
showed staphylococcus, pyog. aur. He 
does not infer from this the staph, to be 
the producer, but thinks that the fre- 
quency of obtaining the staph, in cultures 
is due to a mixed infection with this 
coccus. In regard to the fact, that not 
all succeeded in finding micro-organisms 
in the eye which had been enucleated on 
account of causing sympathetic ophthal- 
mia, Deutschmann 1, questions whether 
those eyes really caused sympathetic oph- 
Llial mia, the diagnosis being one of proba- 
bility only. 2d, Micro-organisms often can- 
not be found any more in eyes, in which 
they eifected great changes, creating their 
own destruction. 3d. In cases of undoubted 
sympathetic ophthalmia the interior of 
the injured eye may be free from micro- 
organisms, although it is infected, but 
they are found in the optic nerve, in the 
intervaginal space and on the surface of 
the globe. From here, i.e., from Tenon’s 
capsule the microbes may enter the inter- 
vaginal space of the optic nerve and 
migrate to the second optic nerve and 
globe, as demonstrated by recent experi- 
ments of Deutschmann, in accordance with 
Quincke and Zellweger. Deutschmann 
had used in his experiments spores of 
aspergill us fumigatus, croton oil, pus, 
then cultures of staph, pyogen. aureus 
and albus, and of streptococcus. Alt pro- 
duced sympathetic ophthalmia, with abrus 
prsegatorius — injections into one eye; 
Gayet with pus of the tear sac; Basevi 
with bacilli from enucleated human eyes, 
which had given rise to sympathetic oph- 
thalmia; Parisotti with staphylococci. 
The only track (also found by Gifford) 
between both eyes, which contained con- 
tinuously the inoculated bacilli is the in- 
tervaginal space of the optic nerves and 
their sheathes. Deutschmann had in his 
first series of thirty-five experiments 
twelve positive results, i.e., thirty per 
cent.; of the last thirty-five only two; and 
considers it as experimental luck to obtain 
positive results, emphasizing the rare oc- 
currence of sympathetic ophthalmia even 
after severe infections of human eyes. 
Ohlemann found of 556 severely injured 
eyes of Schweigger’s clinic only two which 
had given origin to sympathetic ophthal- 
mia. 
The objection has been made that the 
presence of cocci found in the optic nerves, 
the sheathes and in the intervaginal spaces 
was due to a general infection. But no 
observer ever found micro-organisms in 
the optic sheathes of patients or of animals, 
who had died from a general infection, and 
Deutschmann is of opinion, that if it ever 
should happen, which, however, is not 
probable, as then the staph, pyog. would 
be propagated by the blood vessels, not 
the lymphatics, they would be found per- 
haps in single foci, but not in continuous 
accumulations pervading the whole optic 
sheath, as in his animals. Schmidt-Kimpler’s theory of sympa- 
thetic ophthalmia is, that the irritation of 
the ciliary nerves of the injured eye gives 
only the disposition to sympathetic inflam- 
mation of the second eye by reflex dis- 
turbances of circulation and nutrition. 
The longer and the more marked these 
changes exist, the more and better pre- 
pared is the eye for the action of inflam- 
matory (bacterial or chemical) agents. 
But there is no proof that mechanical 
irritation of the ciliary nerves causes in- 
flammation of the second eye, (if there is 
no infection combined with it,) as incar- 
ceration of the iris in corneal or scleral 
wounds, or chronic glaucoma in which 
patients suffer from the most violent irri- 
tations of the ciliary nerves, or as the case 
of Pincus, (1. c.) in which an intraocular 
cysticercus kept up constant irritation of 
an eye for fourteen years, without creat- 
ing sympathetic ophthalmia before the 
infection by the operation happened. 
The migration theory explains best the 
long interval between the injury and the 
outbreak of sympathetic ophthalmia, as 
the microbes require some time to travel 
from one eye to the other. If sympathetic 
ophthalmia sets in three to four weeks 
after enucleation, the microbes had left 
the first eye at the time of enucleation, 
and are on their way on the optic nerve 
to the second eye. Deutschmann adds to 
his experiments a description of a case 
which furnishes the most valuable proof 
for his migration theory. After an iridec- 
tomy, which by infection terminated in 
phthisis bulbi, sympathetic ophthalmia of 
the other eye started with nenro-retinitis, 
afterwards opacities of vitreous, ciliary 
injection and irido-cyclitis, resulting in 
almost total blindness. The patient died 
of carcinoma of the stomach. Micro- 
organisms in both eyes, chiasma and both 
optic nerves showed that the optic nerves 
furnished the passage for their transmis- 
sion. The micro organisms were bacteria, 
the species of which could not be ascer- 
tained. 
Hirschberg (l.c.) supposes a creator of 
granulation tissue (bacillus), as the ana- 
tomical examination of recent diseases of 
the injured eye shows a similarity with 
tuberculosis (giant cells,granulation tissue) 
and not the cocci of suppuration. It re- 
quires further investigations to determine 
the producer of sympathetic ophthalmia. 
All authors, even those who do not 
accept Deutschmann’s experiments as 
convincing proof in regard to the way of 
propagation, consider the sympathetic 
ophthalmia as an infectious disease, so 
that it will express best the present state 
of the pathology and etiology of sympathe- 
tic ophthalmia, if we quote Deutchmann’s 
conclusions of his latest work (p. 95:) 
“ Sympathetic ophthalmia,as it was called, 
is a process of microphytic origin, pro- 
pagated in the continuity of tissues from 
one eye to the other by the optic nerve; 
exceptionally a chemical action may be 
communicated from one eye to the other 
on the same track.” He suggests instead 
of sympathetic inflammation, a name 
designating the disease better: ophthalmia 
migratoria.